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10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

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50 Things About 50 Cancers

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Genetic Basis Of Hormonal Carcinogenesis

The identification and genetic characterization of families at high risk of breast cancer is the most striking example of the potential importance of inherited traits in breast cancer causation. The localization and sequencing of BRCA1 and BRCA2 has provided two important genes contributing to familial breast and ovarian can-cer.24,25 Somewhat surprisingly, mutations in these genes, which appear to be classic tumor-suppressor genes, seem to contribute little, if at all, to the causative pathway of sporadic breast cancer. Likewise, mutations in two other tumor-suppressor genes, TP53 and AT, contribute to breast cancer risk in certain families but, again, not generally to the risk of sporadic breast can-cer.26 The focus of much current breast cancer research is on susceptibility and progression, until the hormone-independent stage, by endogenous hormone stimulation (Fig. 1.2). Under the majority of circumstances, we assume that a breast epithelial cell does not contain a germline...

Anticarcinogenic Effects

Both in vitro and animal studies indicate that astragalus may have a role as adjunctive therapy in the treatment of some cancers. In vivo studies have shown that astragalus extract exerts anticarcinogenic effects in carcinogen-treated mice, mediated through activation of cytotoxic activity and the production of cytokines (Kurashige et al 1999). An extract of the root (90 and 180 mg kg) prevented the development of preneoplastic lesions and delayed hepatic cancer in chemically-induced hepatocarcinogenesis in a rat model (Cui et al 2003). The saponin, astragaloside IV, can increase the fibrinolytic potential of cultured human umbilical vein endothelial cells by downregulating the expression of plasminogen activator inhibitor type 1 (Zhang et al 1997). Another constituent (astragalan) increased the secretion of TNF-alpha and TNF-beta (Zhao and Kong 1993).

Vaccinia As A Cancer Vaccine

The experience with vaccinia in the eradication of smallpox led to research into its use as an antitumor vaccine. Vaccinia was engineered to express tumor antigens and serve as a cancer vaccine. The size of the potential transgene that can be put into the vaccinia vector allows for flexibility in engineering, such that immune enhancing genes and antigenetic genes can be recombined into the genome. The immunostimulatory effects and efficient transcriptional machinery of the virus were utilized to create various cancer vaccine vectors (Table 2). Recently, a phase I clinical trial of vaccinia expressing prostate specific antigen (PSA) in prostate cancer patients was published. In this trial the Wyeth strain virus was delivered intradermally every 4 wk for three doses without producing significant systemic toxicities. A cutaneous reaction, consistent with viral replication was seen in all patients treated with the virus at a dose of 2.65 x 107 pfu. Several patients developed T-cell immune...

Translational Or Correlative Cancer Research

The terms translational or correlative research are meant to represent that area of cancer research that brings together clinical observations, laboratory research, and the application of the product of this interaction for the treatment of patients with cancer 54 . This process also implies the potential to individualize treatment strategies that are tailored to the patient's tumor biology 55 . However, where is the optimum point, if any, to initiate this process While important and valid molecular-genetic observations are often made at cellular and subcellular levels in the laboratory, how such observations become properly integrated into the extraordinary complex panorama of human cancer is often problematic. Guidelines for research that have evolved over the centuries have culminated in an agreed upon format generally referred to as the scientific This is basically a unidirectional system and one that works best when not begun in the middle or run backward The observational step...

Adenovector Mediated Cancer Gene Therapy

Early-region (E1)-deleted, replication-defective adenovectors have been widely used in preclinical and clinical studies of cancer gene therapy. Recently, the use of conditional replicating or oncolytic adenovectors in cancer gene therapy or virotherapy has received much attention. Clinical trials with E1-deleted adenovectors and oncolytic adenovirus have shown that adenovector-mediated cancer gene therapy is well tolerated and can produce clinical responses in patients with advanced diseases. Moreover, numerous strategies to improve vector safety and therapeutic efficacy have been explored, including vector modification and the development of vector formulations to enhance transduction efficiency, to modulate tropism for vector targeting, to improve controlled or tissue-specific transgene expression, and to reduce vector-related toxicity. Yet, much has to be improved in this type of vector system to ensure its future success in clinical applications.

Molecular Mechanisms ofOncogenes in Carcinogenesis 241 Platelet Derived Growth Factor and Its Receptors

EGF receptors are commonly overexpressed in a number of epithelial malignancies and are often associated with an aggressive phenotype. They are overexpressed in over 50 of non-small-cell lung cancers (NSCLC), head and neck squamous cell carcinoma (HNSCC), and colon cancers, along with overexpression of one or more other EGFR family members (21,23,24). Karyotypic abnormalities, including the translocation, duplication deletion, and loss of chromosomes, have long been recognized. Most chromosomal abnormalities do not correlate with cancer types, suggesting that these abnormalities are likely secondary events and reflecting the inherent genetic instability of cancer cells. In contrast, some types of malignancies consistently undergo certain chromosomal changes. For example, a reciprocal translocation between chromosomes 9 and 22 occurs in the leukemia cells of more than 90 of patients with chronic myelogenous leukemia (CML) (28). As a result of this translocation, the abl proto-oncogene,...

Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common of the inherited gastrointestinal syndromes predisposing to colorectal cancer. The syndrome accounts for approximately 2 to 3 of all colo- rectal cancers (Westlake et al, 1991 Salovaara et al, 2000). HNPCC is an autosomal dominant heritable syndrome. Therefore, 50 of the children of an affected individual will develop the syndrome. The penetrance of HNPCC has been estimated to be between 80 and 85 (Lynch et al, 1983 Vasen et al, 1996) thus, not all affected individuals will develop cancer in their lifetime. HNPCC is characterized by early age at onset, excess synchronous and metachronous lesions, right-sided predominance, and extracolonic manifestations. The median age of diagnosis of colorectal cancer in persons with HNPCC is approximately 45 years. Although most patients present with right-sided colon malignancies, up to 40 of patients present with left-sided colorectal tumors. In patients with HNPCC, the risk of...

RNAi In Basic Cancer Research

The release of nearly complete human genome sequences and the identification of a large number of genes whose aberrant expression is associated with a variety of cancers by high-throughput genomic and proteomic approaches have provided both unprecedented opportunities and challenges for the development of new cancer therapeutics. For example, gene expression profiling using DNA microarray technology has identified distinct signatures of cancer gene expression that are associated with metastatic capacity and prognosis of cancer. Although the identification of a large number of genes that are up- or down-regulated in cancer has provided a large amount of information for both basic and clinical cancer research, it provides no information on whether the altered expression of a particular gene is the cause or a consequence of cancer. Because only the tumor-causing genes are the likely druggable targets, functional validation of therapeutic targets among these genes become a major challenge...

Cancer Predisposition in BRRS

The risk of malignancy in BRRS is not well defined. Historically, there is no mention of cancer predisposition in early BRRS literature (8,31), as follow up of cases into adulthood is virtually never reported. However, once it was realized that CS and BRRS are allelic (34) (discussed later), this opinion has changed. In addition, the single largest study of genotype-phenotype correlation in patients with BRRS demonstrated a strong correlation between germline PTEN mutations and both benign (fibroadenomas) and malignant breast diseases in families with BRRS or CS BRRS overlap (families consisting of individuals who meet CS criteria in addition to individuals felt to have BRRS) (35). This finding solidified the recommendation that all patients with PTEN mutations, irrespective of phenotypic presentation, be screened for cancer in the same manner as a patient with CS, and led to the evolution of the concept of PHTS.

Problems Associated With Adenoviral Retargeting In The Field Of Cancer Gene Therapy And Current Efforts

In 1995, the National Institutes of Health (NIH) director designated a special advisory panel headed by Drs. Orkin and Motulsky which produced a report about the limiting issues in the field of gene therapy and the points in the report are still valid (81). One of the main points was that vector systems still have problems and need to be improved to realize the benefit of gene therapy. Recently there have been several promising reports indicating the clinical benefits of gene therapy in severe combined immunodeficiency mice (SCID) (82) and cardiovascular disease (83,84), yet, the realization of the clinical therapeutic potential of the cancer gene therapy has not been achieved. specific sites (85). However, in the field of cancer, the requirements are totally different and much more stringent. Clinical trial outcomes indicate that current adenoviral therapeutics are well tolerated in the clinical setting but not potent enough to elicit significant and consistent therapeutic effect...

Cancers Other Than Breast and Ovarian Cancer

Table 1 groups studies, by type, that have examined the association of cancers other than breast and ovarian FT cancers with BRCA1 2 mutations, or in families with breast and or ovarian cancer. Inclusion in the table was restricted to claims of statistically significant findings. Colorectal Cancer Early linkage studies and family-based studies in which there was no genotyping of colorectal cancer cases observed significant associations between BRCA1 2 mutations Table 1 Genotype Phenotype Correlation Studies, Listed by Type (see text), Associating BRCA1 2 Mutations with Cancer Risks potential No. of Colon Kidney bile Fallopian Squamous cancers The Breast Cancer Linkage Consortium, 1999 Abbreviations'. AJ, Ashkenazi Jews BC, breast cancer CR, carriers' relatives FT, fallopian tube n, noncarriers' relatives NS, not significant PPC, primary peritoneal carcinoma R, rectal only X, not reported. and colorectal cancers. Using linkage kindreds, Ford et al. (51) estimated the RR for colon...

Head And Neck Cancer Imaging

Radiological assessment of head and neck cancer has largely depended on the demonstration of anatomical changes in the head and neck as an indication of tumor involvement. Computed tomography (CT) and magnetic resonance imaging (MRI) have both been used with similar success in evaluating head and neck cancer in this regard 1 . Distortion of normal anatomic spaces as seen on these images can imply the presence of tumor. Tumor size can be measured accurately. Destruction of bone or cartilage seen on CT can be an indication of tumor involvement. Anatomic data as obtained from CT and or MRI, although extremely helpful, does have some limitations. Identification of small volumes of tumor can be difficult in areas such as the larynx or base of tongue. Also, postoperative scans can be made difficult by the anatomic changes caused by surgery and or radiation. Assessing head and neck cancer using molecular imaging in conjunction with anatomic imaging has shown to be very helpful in the...

Cytokine Gene Therapy for Genitourinary Cancer

Challenges and Opportunities in Prostate Cancer In situ Cytokine Gene Therapy Cell Mediated Delivery of Cytokine Genes Conclusions This chapter will discuss the potential for delivery of cytokine molecules using neo-adjuvant adjuvant gene therapy strategies to achieve antitumor efficacy. It focuses on two approaches for delivery of cytokine genes to achieve effective therapy in situ delivery using adenoviral vectors also termed active vaccination, and cell based approaches using specific immune cells modified with cytokine genes. These approaches have potential advantages for prostate cancer therapy and possibly other genitourinary malignancies. Key Words Gene therapy adenoviral vectors cell therapy immunostimulatory genes prostate cancer.

Staging Head And Neck Cancer

The single most important factor in patient assessment, treatment planning, and survival prognostication is accurate staging 5,6 . The current staging guidelines in use for head and neck cancer are from the 1997 manual of the American Joint Committee on Cancer. Staging involves an accurate assessment of tumor at the primary site (T), regional lymphatic metastases (N), and distant metastases (M). Each primary tumor has a unique propensity for local and regional spread, which must be appreciated when evaluating head and neck cancer patients. The most commonly used imaging modality for head and neck cancer CT is with an intravenous iodinated contrast. Lymph nodes greater than 1 cm in diameter (1.5 cm for

Non Cancer Health Care and Health Maintenance

The IOM report suggested in its title that many cancer survivors are lost in transition and that the quality of care suffers when patients and providers do not know what is expected after primary treatment ends. While much of the focus of research and guidelines has been on cancer surveillance, non-cancer health care is equally as, and in many cases more important than surveillance. Most patients diagnosed with cancer today are expected to survive it.28 Studies have shown that potentially preventable conditions like heart disease and diabetes are actually the greatest threat to life for many of these patients.83,84 As a result, despite the fact that a diagnosis of cancer tends to subjugate all other concerns for a while, preventive care and the management of other medical conditions may actually be more important in the long run. The end of primary treatment for cancer has been called a teachable moment. 85 This recognizes that with significant events in a patient's life, there is the...

Finding lowpenetrance breast cancer alleles

The genetic association study has been promoted as the most efficient method to identify common low-penetrance disease suceptibility alleles (Risch and Merikangas, 1996). This design has been used as a method to map cancer susceptibility alleles for over four decades, but the advent of modern molecular genetics has seen a dramatic increase in the use of this type of study in the past five years (Pharoah et al., 2004). These efforts have, perhaps, been most notable for their few successes. However, most studies carried out so far have been based on the candidate gene candidate polymorphism approach, which has been limited by the availability of plausible candidates. In addition, many studies have lacked statistical power to detect moderate risks because limitations in molecular genetic technologies have limited sample sizes. In the future, improved knowledge of the molecular basis of carcinogenesis will enable better selection of candidate genes, and improvements in study design,...

Frequency Of Germ Line P53 Mutations In Breast Cancer

The earliest publications on LFS focused on childhood soft tissue sarcoma and breast cancer (1,2), with most ascertainment through the less common childhood sarcomas. However, with the opportunity to test for a specific gene, focus shifted to the far more common, and often familial, breast cancer. The question was, what fraction of breast cancer, young, familial, bilateral, or associated with other cancers, might be attributable to germ line p53 mutations A flurry of papers appeared in the literature from the early 1990s, studying different clinical groups of breast cancer and using various techniques to identify mutations. However, few p53 germ line mutations were observed using criteria of familial breast cancer (40-46), bilateral breast cancer (47), age at breast cancer diagnosis less than 31, 35, or 40 years (48-50), breast cancer associated with a personal or family history of multiple primary tumors (51), or breast cancer associated with no more than one sarcoma in the index...

Bacterial Extracts in Cancer Vaccines

Over a century ago, a New York physician, William B. Coley, noted that some cancer patients experienced tumor regression following episodes of acute bacterial illness. Dr. Coley hypothesized that the two events were linked and treated an inoperable cancer patient with a viable bacterial culture to induce a commotion in the blood. Remarkably, the patient recovered from both the bacterial infection and the tumor. From 1900 to 1936, During the period that Coley was treating cancer patients with his bacterial toxins, other scientists were documenting that antibody responses to experimental antigens were enhanced in animals infected with Mycobacterium tuberculosis. Several investigators went on to show that killed whole mycobacteria, as well as other Gram-positive and Gram-negative bacteria, enhanced the antibody response to exogenous antigens (reviewed in ref. 10). In the meantime, Arthur Johnson identified lipopolysaccharide (LPS) as the component of Gram-negative bacteria that had...

Risk Of Multiple Primary Cancers In Mutation Carriers

In the initial LFS report (1), some family members had multiple primary cancers. Many case reports and series have noted the association of LFS, p53 germ line mutations, and multiple primary tumors (60-69). The increased risk of subsequent neoplasms was clearly demonstrated in the follow-up studies of the 24 LFS kindreds (6,70), citing the high risk for those with young age of first cancer diagnosis, the occurrence not only of second but of third malignant neoplasms, the spectrum of multiple primary tumors that was primarily composed of the same component tumors observed as initial tumors, and the high frequency of tumors arising in radiation-treated areas. The analysis was not based on p53 mutation status but classic LFS, and included 8 p53 mutation kindreds, 8 non-p53 LFS, and 8 unknown genotype LFS. With an additional 10 to 30 years follow-up the cumulative risk of a second malignant neoplasm was 57 ( 10 ) SE at 30 years after the first cancer diagnosis, and for a third malignant...

Squamouscell Cancer Of The Anal Canal

Squamous-cell cancer (SCC) of the anal canal is an uncommon malignancy, with an annual incidence in the heterosexual population of one to two per 100,000. It occurs more frequently in women, with an increasing incidence in human immunodeficiency virus (HlV)-infected individuals. The majority of patients present with locoregional disease, of these 20 to 30 will develop distant metastases. What constitutes the most appropriate therapy for anal cancer has undergone significant evolution over the past three decades.

The Nonsurgical Treatment of Anal Cancer Radiation Therapy

The intent of therapy for anal cancer is cure with the least morbidity. Traditionally, the primary treatment for SCC of the anal canal was abdominoperineal resection (APR). Depending on tumor stage, five-year survival after APR was 48 to 71 (6-10). Locoregional recurrence was common and ranged from 18 to 27 . Contemporary studies for patients receiving radiotherapy alone reported similar five-year survival of 42 to 94 , but with typical sphincter preservation and colostomy-free survival of between 56 and 74 (11-16). Proponents of brachytherapy (BRT), with or without external-beam radiation therapy (EBRT), reported five-year survival rates of 60 to 65 and locoregional control rates of 75 to 79 (17-19). Retrospective studies show excellent local control and survival of 85 at five years obtained by radiotherapy alone for early stage T1-2 anal cancer (20,21). For in situ (Tis) and T1 tumors 5 cm) or nodal involvement had poorer outcome with five-year survival of

Colorectal cancer epidemiology

The multifactorial etiology of colorectal cancer involves environmental factors as well as genetic susceptibility (see Chapter 14). There are large differences in global prevalence of the disease, which is generally four times higher in developed countries than in developing countries (IARC, WHO, 1997). Incidence rates also vary according to ethnicity (American Cancer Society, 2002), however the observed variation between countries is primarily due to the role of environmental factors. In support of this, there is a rising incidence of colorectal cancer in populations undergoing rapid economic development, in association with Westernisation of diet and lifestyle. Another example of environmental influence comes from migrant data despite a historically relatively low colorectal cancer incidence in Japan, rates in Hawaiian Japanese are among the highest in the world (Parkin, 1992). Figure 17.1a demonstrates that colorectal cancer is more common in males than in females and in both sexes...

Current Issues In The Management Of Neutropenia And Infections In Patients With Cancer

As outlined in this chapter, the availability of rHuG-CSF has had profound medical and scientific implications. The ability of rHuG-CSF to accelerate bone marrow recovery has greatly altered the approach to chemotherapy and management of neutropenia risk in patients with cancer. The availability of rHuG-CSF has stimulated interest in understanding the physiology and regulation of neutrophil production, as well as other ways to enhance host resistance to bacterial infections. The availability of rHuG-CSF has also stimulated interest in defining host responses to cancer chemotherapy and specific factors (i.e., cellular components, cytokines, environmental factors, bone marrow recovery rate).It is relatively easy to measure the blood neutrophil counts, but cancer chemotherapy and the HGFs exert most of their effects on hematopoietic cells in the bone marrow. Better information is needed about the kinetics of recovery of primitive hematopoietic cells and their progeny in the bone marrow...

Assessment Of Recurrent Head And Neck Cancer

All head and neck cancer patients are at high risk for recurrence and a second primary disease. This must always be stressed in the treatment planning process. This is likely due to an underlying molecular or cellular abnormality of many of the cells lining the upper aerodigestive tract mucosal lining, which have been bathed in the previously mentioned carcinogens. Risks for recurrence arise from stage, treatment, and ongoing exposure to risk factors. The more advanced the stage of the head and neck cancer at presentation, the greater the risk for recurrence. Most recurrences occur in the first 24 months following therapy for head and neck cancer. Later occurring lesions (lesions at different locations and with distinct histology) are probably second primaries. Local recurrences can present many challenges, but can often be reexcised when detected early. Reexcision will further compromise any preexisting dysfunction (speech, voice, swallowing, or airway) and will impact negatively on...

Genetic susceptibility to colorectal cancer

Although environmental factors are clearly important in the etiology of the disease, there is a significant input from genetic factors. First-degree relatives of colorectal cancer cases are considered to have a 2-4-fold increased risk, with around 20-25 of all colorectal cancer cases being associated with a family history (Bonelli et al., 1988). Early screening studies suggested that cancer susceptibility is due to a predisposition in the development of colorectal adenomas (Cannon-Albright et al., 1988). The population frequency of the ''adenoma-prone'' allele was calculated as 19 but not all adenomas progress to cancer and dietary effects might clearly influence the expression of such an allele in terms of both adenoma and cancer. A North European twin study has now provided good evidence that about 35 of all colorectal cancer cases have a genetic component (Lichtenstein et al., 2000) (Figure 17.1b), which is intriguing as known susceptibility alleles account for only 5 of all cases....

Hereditary nonpolyposis colorectal cancer HNPCC or lynch syndrome

HNPCC, or the eponymous Lynch syndrome, is an autosomal dominant disorder with high pene-trance in which colorectal cancer develops in gene carriers but without the numerous adenomas seen in FAP (Lynch et al., 1985). Classically, HNPCC was defined as the development of carcinomas in the proximal part of the colon, however, expression of the HNPCC phenotype is far more diverse in terms of age of onset and the organs and site where malignancy can develop besides colorectal cancer, the trait can be associated with uterine, gastric, ovarian, upper urinary tract, small intestinal and other malignancies. The recognition that there is an increased risk of other cancers, in fact a greater risk for endometrial cancer in females than colorectal cancer, means that the term Lynch syndrome has gained popularity. There are no robust biomarkers for HNPCC. There is a predominance of certain tumor histolog-ical features in HNPCC, such as a lymphoid response, mucinous histology and poor differentiation...

Pretreatment Assessment of Women with Histologic Diagnosis of Cervical Cancer

Selective use of chest radiography, intravenous pyelography, cystoscopy, gastrointestinal endoscopy (ie, flexible sigmoidoscopy), lymphangiography, computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis and abdomen may be useful in appraising the degree of metastatic disease. Assessment of renal function is vital to the staging of cervical cancer. The presence of unilateral or bilateral ureteral obstruction with azotemia often heralds metastatic disease and heralds a poorer prognosis.

The Elusive Cancer Cell

The processes of malignancy, such as invasion and rapid growth of tumor cells, naturally cause inflammation. Dendritic cells (DCs), the most powerful antigen presenting cell (APC), should become activated to the presence of cancer cells and present sampled antigen in association with surface major histocompatibility complexes (MHC). The presentation of these tumor associated antigens (TAA), along with the appropriate costimulatory signals, leads to activation of antigen specific CD8+ T-cells. These T-cells recognize and bind that TAA on the MHC class I of tumor cells. Subsequent secretion of perforin and granzymes can induce caspase-dependent apop-tosis. However, in the many reported cases of human cancer, this process obviously does not seem to occur efficiently enough to destroy the tumor cells. Cancer cells may evade recognition by the immune system through several mechanisms (9) (1) down-regulation of antigen processing and presentation, (2) loss of some TAA which may alert the...

Monoclonal Antibodies for Cancer Therapy

The administration of recombinant monoclonal antibodies for cancer is based on the premise that tumor-specific antibodies can recognize and target cancer cells and, once in the tumor microenvironment, can inhibit tumor growth or induce tumor regression via mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (2,3). The anti-CD20 monoclonal antibody rituximab, for example, binds to the B-cell antigen CD20 expressed on B-cell lymphomas to kill cancer cells via ADCC and induction of apoptosis (4-6). The monoclonal antibody trastuzumab binds to the receptor for the growth factor HER-2, which is overexpressed in up to 30 of human breast cancers, to block the proliferative effects of this growth factor on breast cancer cells (7). Monoclonal antibodies have also been conjugated to tumor-killing substances such as radioisotopes, drugs, or toxins (8-10). Although monoclonal antibody therapy has yielded positive results in some...

Gut Bacterial Involvement in Colorectal Cancer

Comparisons of the fecal microbiota of healthy subjects and colon cancer patients have not revealed any consistent patterns, possibly due to the difficulties in culturing and identifying gut organisms. Elevated numbers of Bacteroides have been associated with increased colon cancer risk in humans (34,35). Similarly, lecithinase-negative Clostridium and Lactobacillus were more abundant in colon cancer patients (36) although in another study, some Lactobacillus species and Eubacterium aerofaciens have been associated with reduced risk (35). In animals, the presence of the intestinal microbiota has a major impact on colonic tumor formation (37,38). In a study conducted by Reddy and coworkers (38) the rate of tumor formation was much more rapid in conventional than in germ-free rats treated with the tumor initiator 1,2-dimethylhydrazine (DMH). After 20 weeks, 17 of conventional rats had colon carcinomas, whereas there were no tumors (adenomas or carcinomas) in the germ-free animals. At 40...

Cytokines for Cancer Therapy

Cytokines such as interferons and interleukins are administered for cancer because of their broad-based immunostimulatory effects including generation of tumor-reactive lymphocytes (11). Interleukin-2 (IL-2), or aldesleukin, which is indicated for the treatment of adults with metastatic renal cell carcinoma and melanoma, is the most studied cytokine. IL-2 dose-dependently activates cellular immunity and causes release of other immune-boosting cytokines in vivo (11). Systemic cytokine therapy is generally limited by rapid degradation and elimination of the cytokine, the inability to achieve optimal concentrations in the tumor microenvironment, and dose-dependent toxicity, including life-threatening side effects such as vascular leak syndrome and orthostatic hypotension (12-15). Cytokine gene therapy, in which a cytokine gene (such as that for IL-2) is introduced into tumor cells, is being explored to overcome some of these limitations of systemic cytokine administration. However,...

Treatment of Lung Cancer Associated Anemia 161 Transfusions

Historically, treatment options for patients with lung cancer who develop severe or symptomatic anemia were primarily limited to RBC transfusions. In fact, most physicians still do not treat, unless with RBC transfusion, in case of severe anemia (5). Although RBC transfusion is the most rapid correction, especially useful in patients with severe or life-threatening anemia, several risks are associated with it, including acute transfusion reactions and transmission of infectious agents (71,72). Furthermore, the limited availability and the cost of transfusion products limit their use. Finally, there is the concern of decreased immunosurveillance of tumors by the recipient of allogeneic transfusion. A negative impact on outcome has been described in some but not all surgical series examining this issue in lung cancer (73) and other cancer types (74,75). Another treatment option for the management of anemia is the administration of rHuEPO. The Food and Drug Administration (FDA) approved...

Surrogate Markers For Dietrelated Colon Cancer Studies

As discussed above, the gut microbiota has been implicated in the etiology of CRC by a number of studies and these observations form the theoretical basis for the use of several gut microbiota biomarkers (fecal biomarkers) in studies on diet and colon cancer. They are composed of two main categories those examining the activity of bacterial enzymes or bacterial metabolites and those based on bioassays on fecal water. For a more thorough review of this subject, the reader is referred to Rafter and coworkers (67).

Ich Carcinogenicity Guidances

Within the ICH process, three carcinogenicity guidances have been developed that address different aspects of regulatory carcinogenicity testing and assessment in lifetime rodent bioassays and alternative models. The Guidance on the need for carcinogenicity studies of pharmaceuticals (S1A) was finalized by the ICH EWG in late 1995. The guidance Testing for carcinogenicity of pharmaceuticals (S1B) was finalized in July 1997. The guidance Dose selection for carcinogenicity studies of pharmaceuticals (S1C) was already agreed upon in October 1994 and an addendum Addition of a limit dose and related notes was issued in July 1997. A. Dose Selection for Carcinogenicity One issue of major concern for the carcinogenicity debate was the many positive results observed in traditional rodent bioassays. A review of the U.S. Physician's Desk Reference showed that more than half of pharmaceuticals tested for carci-nogenicity are reported to elevate the incidence of some type of tumors in rodents...

Results Of The Eortc-gtcct Phase Iii Trial Of Irradiation Vs Irradiation And Cddp In Inoperable Esophageal Cancer

1 Kelsen DP, Ginsberg R, Pajak TF, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med 1998 339(27) 1979-1984. 2. Medical Research Council Oesophageal Cancer Working Group. Surgical resection with or without preoperative chemotherapy in oesophageal cancer a randomised controlled trial. Lancet 2002 359(9319) 1727-1733. 4. Ancona E, Ruol A, Santi S, et al. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer 2001 91(11) 2165-2174. 6. Kok TC, vLanschot J, Siersema PD, vOverhagen H, Tilanus HW. Neoadjuvant chemotherapy in operable esophageal squamous cell cancer final report of a phase III multicenter randomized controlled trial. Proc Am Soc Clin Oncol 1997 17 984 (abstr). 9. Nygaard K, Hagen S, Hansen HS, et...

Risk Factors For Breast Cancer

Identification of women at risk for definitive clinical trials. Family history is probably the best-recognized risk factor for breast cancer. An inherited gene mutation is thought to account for 5 -10 of breast cancer cases.116,117 Although infrequent, these mutations are significant since they are associated with a lifetime risk of breast cancer of 50 -80 ,118,119 beginning at a young age. At present, two predisposition genes, BRCA1, located on chromosome 17q21,120 and BRCA2, located on chromosome 13q12-13,121 have been identified, both of which are inherited in an autosomal dominant pattern. Most women with a family history of breast cancer do not have the genetically transmitted form of the disease, and their risk is much less than that seen in women who have inherited a predisposing gene. The cumulative probability that a 30-year-old woman with a mother and sister with breast cancer will develop breast cancer by the age of 70 is between 7 and 18 .122,123 While this risk increases...

Filgrastim In The Treatment Of Breast Cancer

Although filgrastim was known to have an effect on hematopoetic cell lines, it was not clear whether it stimulated nonhematopoetic cells or tumor cells. Several studies were done to elucidate the effect, if any, on human breast cancer cells. Emerman and Eaves (22) evaluated human breast epithelial cells from normal and malignant tissues and evaluated the effects of eight cytokines G-CSF, GM-CSF, Steel factor, interleukin (IL)-2, IL-3, IL-6, transforming growth factor-P (TGF-P), and macrophage inflammatory protein 1-a. The authors found no effect of the cytokines on the growth of normal or malignant breast epithelial cells. Filgrastim appears to be safe in the treatment of breast cancer, but when in the course of chemotherapy is the best time for it to be given

Urogenital Conditions Associated With Testicular Cancer

Cryptorchidism is a common congenital disorder in which one or both testicles fail to descend into the scrotum before birth. Over half of the boys who are born with cryptorchidism experience spontaneous testicular descent during the first year of life. A history of persistent cryptorchidism, in which spontaneous descent does not occur, is the major established risk factor for testicular cancer. Epidemiologic studies consistently find associations between a personal history of cryptorchidism and risk of testicular cancer, and reported estimates of relative risk range from 2.5 to 18.1 5 11 42-60 Some studies found cryp-torchidism to be more strongly associated with seminoma than with other histologic types. The specific mechanisms whereby a history of cryptorchidism predisposes an individual to testicu-lar cancer are not known although two general scenarios have been postulated. The abdominal-location hypothesis asserts that pathogenic effects of the suprascrotal position are...

Integrin Regulation of Cell Proliferation and Survival Links to Cancer

The ECM plays a critical role in the altered growth and metastatic behavior of cancer cells. In the case of both normal and cancer cells, these signals contribute to the balance of cell growth and death by regulating the apoptotic machinery of the cell. Under appropriate circumstances, integrin signals regulate G0-to-Gj and Grto-S progression 52-55 , as well as the expression of growth-related gene products associated with these transition states. Transient MAPK activation stimulated by either growth factors or cell adhesion is sufficient to initiate G0-to-G1 phase transition and the coincident expression of immediate-early response genes, including c-Fos, c-Myc, and c-Jun 56-59 . Serum stimulation in the absence of adhesion to the ECM abrogates progression through G1 into S phase by increasing the accumulation of cdk2 inhibitors p21cip1 and p27kip1 60 . Cyclin D1 functions to promote G1 progression by sequestering p21cip1 and p27kip1 61 . Cyclin D1 expression requires cell adhesion...

Cell Molecular Biology Breast Cancer

Bi-directional Regulation of Human Progesterone Receptors and the Mitogen Activated Protein Kinase Pathway in Breast Cancer Cell Models Abnormal Properties of Mutants in the Hinge Region of ErV Implications in Breast Cancer Effect of Dietary Genistein on Estradiol-Induced Mammary Carcinogenesis in the ACI Rat Microarray Analysis of Estrogen-Induced Protection Against Breast Cancer Pregnancy Levels of Estrogen Prevents Mammary Cancer ENDOMETRIAL CANCER OVARY PITUITARY KIDNEY LIVER CANCERS Hormonal Regulation of ZEB-1 and Implication for Progression of Human Reproductive Cancers PROSTATE CANCER The Tumour Suppressor Gene PTEN Plays Role in Cell Cycle Regulation and Apoptosis in Prostate Cancer Cell Lines The Coactivators CBP and p300 in Androgen Independent Prostate Cancer Immunohistochemical and In Situ Detection of Sex Hormone-Binding Globulin (SHBG) Expression in Breast and Prostate Cancer Implications for Hormone Regulation Activation of Androgen Receptor in Prostate Cancer Role of...

European Organization for Research and Treatment of Cancer

A larger study performed by the European Organization for Research and Treatment of Cancer (EORTC) randomized 218 patients who had undergone curative resection of a cancer of the pancreatic head or periampullary region (including distal common bile duct, papilla of Vater, or duodenum) to receive either adjuvant chemoradiation or no further treatment (8). The treatment regimen differed somewhat from that used in the GITSG study. Radiation was again given in a split-course design. However, in this European study, 5-FU concurrently with radiotherapy was administered as a continuous infusion (25 mg kg day) for zero to five days at the start of each course of radiation, and no additional chemotherapy was given afterward. Survival data for the 114 patients with pancreatic head cancer showed a trend toward improved median survival in the treatment arm (17.1 vs. 12.6 months), although this difference did not achieve statistical significance (P 0.099). Both two- and five-year actuarial...

European Study Group for Pancreatic Cancer

A great deal of attention has recently been focused on results reported by the European Study Group for Pancreatic Cancer (ESPAC). This group undertook a large multicenter trial (referred to as ESPAC-1) with the intention of examining the roles of both chemoradiation and chemotherapy in the adjuvant setting for patients with pancreatic cancer (9,10). The study used a two-by-two factorial design whereby patients were randomly assigned after surgery to one of four options (i) chemotherapy alone (5-FU 425 mg m2 plus leucovorin 20 mg m2, both administered for five consecutive days every 28 days' time in six cycles) (ii) chemoradiation alone (given as a split course, consisting of a 20-Gy dose given in 10 daily fractions, with bolus 5-FU 500 mg m2 during the first three days of treatment, then repeated again after a two-week break) (iii) both treatments (chemoradiation followed by chemotherapy) or (iv) neither treatment. A total of 289 patients were enrolled, with the goal of yielding...

Patients with Leukemia or Cancer

Central venous catheter (CVC)-associated and soft tissue NTM infections have been reported in association with leukemias, lymphomas and solid tumors (Reilly and McGowan, 2004 Levendoglu-Tugal et al., 1998). Among hematopoietic stem cell transplant recipients, adult series suggest that the incidence of NTM infection is 50-600 times greater than in the general population (Doucette and Fishman, 2004). Usually these infections are due to rapid growing NTM but M. avium intracellular has also been reported (Reilly and McGowan, 2004 Levendoglu-Tugal et al., 1998). Occasionally NTM in blood cultures may be mistaken for Corynebac-terium or Nocardia species which leads to a delay in appropriate management or the initiation of inappropriate therapy (Levendoglu-Tugal et al., 1998). Affected patients are not necessarily neutropenic but are frequently lymphopenic (total lymphocyte count

Longterm Effects Of Cancer Diagnosis And Treatment On Survivors Family Members

The literature on the effect of cancer diagnosis and treatment on family members is sparse.74 Of studies in this area, most have focused on the impact of cancer soon after diagnosis, during recurrence, or at the terminal phase of the disease.75-77 One study shows that partners of men with prostate cancer, generally from small convenience samples, report more distress than their sick partners, but also believe that their partners are more distressed. The only reviewed study of long-term prostate cancer survivors found that couples' health-related QOL was associated with marital satisfaction.61 Distress was inversely related to levels of family support. The men's focus of concern, on their sexual functioning (i.e., impotence), was not shared to an equal degree by their non-sick partners.78,79 The most relevant study included in our review focusing on family survivorship included families from 1 to 5 years posttreatment,80 thus making specific statements about the long-term effects of...

Reducing Cancer Risk

Prostate cancer A non-randomised non-blinded trial of 38 men with clinically significant prostate cancer found that 160 mg day red clover-derived dietary isoflavones, containing a mixture of genistein, daidzein, formononetin and biochanin A, significantly increased apoptosis compared with matched controls (P 0.0018). There were no significant differences between pre- and post-treatment serum levels of prostate-specific antigen, testosterone or biochemical factors or Gleason score in the treated patients (P 0.05). The study was performed in men undergoing radical prostatectomy however, it indicates that the isoflavones may halt the progression of prostate cancer by inducing apoptosis in low to moderate-grade tumours (Gleason grade 1-3) (Jarred etal 2002).

Diagnosing A Hereditary Breast Cancer Syndrome

Armed with the cancer pedigree, the clinician can now examine the history for clues about the presence of a hereditary cancer syndrome. These syndromes in general confer very significant lifetime cancer risks due to a mutation in a single germline cancer susceptibility gene inherited in an autosomal-dominant manner. Typical families demonstrate multiple affected family members in several generations, often with early ages of onset. There may be skipped generations however, since these conditions are not 100 penetrant even those who carry a mutation in a cancer susceptibility gene may live their lives at increased risk but never develop cancer. In addition, histories of female cancers such as breast cancer may be masked due to generations with a high ratio of males to females or small sibships. CANCER LOCATION OF CANCER YEAR OF CANCER DIAGNOSIS HOSPITAL WHERE CANCER DIAGNOSED Other Relatives with Cancer Only about 5 to 10 of breast cancer is due to strong inherited risk conferred by a...

Fibulins notch signalling and cancer invasion

Fibulins are oestrogen-regulated proteins (Rochefort, 1999). They are believed to be able to influence cell growth. Gallagher et al. (1999) found that the fibulin called MBP1 interacts with mutant p53 and enhances cell transformation and growth rate. Colonic tumours have been shown to express 3- to 7-fold higher levels of fibulin-4 mRNA than control cells. Oestradiol greatly enhances the secretion of fibulin by ovarian cancer cell lines and ovarian cancers (Clinton et al., 1996). The expression of the glycoprotein increases markedly from normal ovarian epithelium to serous carcinomas (Roger et al, 1998). The nature of its participation in the neoplastic process has naturally been the subject of some studies. Fibulins seem to inhibit the invasion of ER+ breast cancer and ovarian cancer cell lines (Hayashido et al., 1998 Rochefort et al., 1998). Of the fibulin family, fibulin-1, 2 and 4 have been assigned to chromosomes 22q.l3.2-ql3.3, 3p24-p25 and llql3 respectively (Mattei et al.,...

Ribozyme Technology for Cancer Gene Target Identification and Validation

Ribozyme-Based Genomic Technology in Cancer Gene Target Discovery and Validation A. HeLa HeLaHF Cervical Cancer Cell System and Anchorage-Independent Growth D. Other Inverse Genomics Screenings for Cancer Targets Ribozymes are naturally occurring RNAs with catalytic activities including cis- or trans- cleavage of RNA at predefined sequence sites. This activity has been exploited for specific gene inactivation in cells during the last two decades, and ribozymes have been important functional genomics tools, especially in the pre-RNAi era. It has also been broadly applied in drug target identification and validation in pharmaceutical R&D. This chapter covers many application principles and case studies of ribozyme technology in the areas of cancer research. We also described RNAi applications in some of the same studies for comparison. Although RNAi may be more effective than ribozymes in many respects, they are nonetheless built on many of the same principles. 2007 Elsevier Inc.

Anticancer Effects

Emerging evidence clearly indicates that hypericin is a promising tool in the photodynamic treatment of cancers. St John's wort appears to selectively photosensitise tumour cells. More recently, evidence suggests that when hyperthermia is combined with this approach, the antitumour effects of hypericin are strengthened (Chen et al 2002). Hyperforin also exhibits antineoplastic potential based on the sum of its anticarcinogenic, antiproliferant, pro-apoptotic, anti-invasive and antimetastasic effects (Medina et al 2006). Hyperforin has been shown to effectively decrease the proliferation rates of a number of mammalian cancer cell lines, induce apoptosis of tumour cells and inhibit angiogenesis both in vitro and in vivo. Besides hypericin and hyperforin, polyphenols procyanidin B2 has also demonstrated an inhibitory effect on the growth of leukaemia cells, brain glioblastoma cells and normal human astrocytes in vitro (Hostanska et al 2003). Further, the inhibitory effects on leukaemic...

Animal Models in Head and Neck Cancer

History of Experimental Head and Neck Cancer Research 57 A. Animal Models for Head and Neck Cancer Research The Value of the Hamster Buccal Pouch Experimental Model for the Study of Oral Cancer 58 III. Genetic Models for Head and Neck Cancer Research 59 B. Other Emerging Genetic Models of Head and Neck Cancer 60 and Animal Model Testing for Head and Neck Cancer Research 61 References 61

Endogenous immune responses in breast and ovarian cancers

Initially pathologists were the first to suggest that intrinsic antitumor immune response could be generated in vivo in breast cancer. Black described lymphoid infiltration of primary breast tumors and sinus histiocytosis of regional lymph nodes (2). Tumor-infiltrating lymphocytes (TILs) have been identified in ovarian adenocarcinoma tissue as well as peritoneal malignant ascites (3-5). The isolation of TILs with activity against specific TAAs has allowed characterization of specific antigens. For example, MUC-1 is a transmembrane glycoprotein expressed on the apical surface of normal glandular epithelial cells. It has multiple tandem peptide repeats that offer potential antigen sources for dendritic cell (DC) presentation. MUC-1 is overexpressed in adenocarcinomas including breast, pancreatic, and ovarian. When expressed on cancers, MUC-1 tends to be aberrantly glycosylated and expressed on the entire cell surface, rather than luminally as on normal cells (6,7). MUC-1 overexpression...

Teratogenicity MutagenicityCarcinogenicity

The German Commission E reports that hawthorn effects are unknown during pregnancy and lactation. No experimental data have been reported concerning toxicity in the embryo or fetus, or the effects on fertility or postnatal development. Commission E also reports the lack of experimental data concerning carcinogenicity. Despite experiential data that hawthorn may be mutagenic, Commission E feels that the amount of mutagenic substances ingested would not be sufficient to pose a risk to humans. Available information presents no indication of carcinogenic risk (11).

History Of Experimental Head And Neck Cancer Research

The major form of head and neck cancer is squamous cell carcinoma of the oral cavity. Therefore, attempts to study the experimental pathology of head and neck cancer were focused on the development of experimental models for oral cancer. Because the primary risk factors for oral cancer development are tobacco and alcohol, chemical carcinogens were used to induce oral cancers in animal models. Other investigations attempted to develop experimental models for malignant tumors of salivary glands, larynx, and other head and neck sites. Head and Neck Cancer

Are Lcrs Common Mediators Of Genomic Alterations In Cancer

Genomic regions known to be meiotically unstable and resulting in the well-known constitutional microdeletion syndromes may be unstable also in cancer cells, not least because of the dysfunctional DNA repair and decreased apoptotic activity characterizing such cells in general. It is important to stress, however, that fundamentally different selection mechanisms are likely to be active in neoplastic cells and congenital microdeletion syndromes. Whereas neoplastic cells will become selected because of growth advantage at the cellular level allowing gross genomic alterations, imbalances in congenital disorders have to be compatible with embryonic development. It cannot be excluded, however, that genes contained within regions lost in microdeletion syndromes, in the haploinsufficient state may confer selective advantage to tumor cells.

Cancer Prevention

High levels of phyto-oestrogens (lignans and isoflavonoids) are frequently associated with low risk of breast, prostate and colon cancer, and breast cancer has been found to be associated with low lignan levels in the USA, Finland, Sweden and Australia. It is not clear, however, if these compounds are cancer protective or are simply biomarkers of a 'healthy' diet (Adlercreutz 1998). A review of the role of phyto-oestrogens, such as soy containing isoflavones, for the prevention of breast cancer concluded that a soy-containing diet in adult women is not or only slightly protective with regard to breast cancer, but may be beneficial if consumed in early life before puberty or during adolescence and that negative effects on the breast cannot be excluded (Adlercreutz 2002a, b). A more recent meta-analysis of published epidemiologic studies associating cancer risk with soy intake suggests statistically significant reductions in the mean overall risk estimate for breast (0.78), colon (0.70)...

Combining Viral Oncolysis With Delivery ofAnticancer Genes

Several groups have constructed genetically engineered oncolytic viruses encoding a prodrug-converting enzyme. These enzymes convert nontoxic prodrugs into cytotoxic metabolites and are often soluble to allow for spreading within the tumor. Using this approach, a tumor-selective herpes virus was engineered encoding the rat cytochrome P450 (CYP2B1) transgene (62). This liver enzyme activates the prodrug cyclophosphamide into an active anti-cancer and immunosuppressive metabolite (63). Addition of cyclophosphamide potentiated oncolytic effects of this HSV mutant against cultured tumor cells and subcutaneous tumor xenografts established in athymic mice (62). therapy containing the cytosine deaminase and HSV-Tk fusion gene markedly enhanced oncolysis relative to the isolated viral effect in cancer cells (65). The combination of HSV-TK and CYP21 gene transfer mediated by an oncolytic HSV provided anti-tumor effects that were more significant than all other treatment combinations (66)....

Integrative Humanbased Discoveries And Animal Model Testing For Head And Neck Cancer Research

In addition to being able to importantly address the detailed molecular contribution of genes and molecules in carcinogenesis, the availability of genetic mouse models for head and neck cancer will dovetail very well with the current exploration of discoveries using genome-wide approaches to identify critical molecular targets in this cancer site. Technologies to monitor thousands of gene expression or through genome-wide allele typing procedures, coupled with advances in DNA sequencing, allow investigators to identify consistent genetic alterations in head and neck cancer. For epithelial cancers, this is further aided by recently developed laser capture microdissection technology, which permits the precise procurement of normal, premalignant, and cancer cells from the same histological section 78,79 , This ability to allow histologically homogeneous epithelial populations from the same patient to be compared genetically and biochemically is a significant technological advancement...

Fibroblast Growth Factors And Bladder Cancer

Bladder cancer is the second most common malignancy of the genitourinary tract. If the metastases are present, the prognosis is poor. Therefore, there is a need to investigate the mechanisms of metastasis and invasion in that disease. In this context, expression and function of FGFs has been studied. muscle of the bladder wall. In a high percentage of superficial bladder cancer tissue bFGF could not be detected (55). In contrast, bFGF mRNA and protein expression are high in invasive tumours (56). In these cancers bFGF contributes to the degradation of extracellular matrix and angiogenesis and could therefore be considered therapeutical target. The proposed mechanism involves invasion of the basement membrane by tumour-secreted enzymes such as urokinase, cathepsin D and heparanase, involvement of the muscle layers of the bladder and release of bFGF from intracellular stores. bFGF that is released stimulates angiogenesis and is detected in blood vessels. In bladder cancer bFGF also...

Role Of Lif In Cancer

Results of in vivo animal trials shed light on some of the possible roles of LIF in cancer and cancer metastasis. Cachexia (43,44), subcutaneous and abdominal fat loss, and elevated leukocyte and platelet counts often found in patients with metastatic cancer were induced by LIF in both mice and monkeys (46-48). In addition, at a high dose, LIF induced myelosclerosis whereas a low dose induced megakaryocytosis, reduced marrow cellularity and caused lymphopenia (48) suggesting a possible role for LIF in the pathogenesis of myeloproliferative disorders such as myelofibrosis and in marrow sclerosis. Furthermore, mice engrafted with FDS-P1 cells that produce high levels of LIF developed a fatal syndrome with cachexia, atrophy of liver and kidney, and excess bone formation with increased osteoblastic activity that resulted in metastatic-type calcifications (47) implying a role for LIF in bone tumours and neoplasms metastasizing to bone. Breast Cancer MCF-7 cells bind LIF and like breast...

Medullary thyroid cancer

Expression of carcinoembryonic antigen (CEA) by medullary thyroid carcinoma (MTC), a neoplasm that arises from the parafollicular cells of the thyroid, has been used as a target of radioimmunotherapy. More recently, cancer-testis antigens, in particular NY-ESO-1, have been detected in medullary thyroid cancer (10). Thus, vaccines targeting these antigens may be useful for treatment of this malignancy. Also, because medullary thyroid cancer frequently arises as a familial syndrome, one interesting approach would be to apply immunizations as a way to prevent development of the disease as has been demonstrated in an animal model of familial human MTC (11).

Akt signalling in cancer growth and invasion

Cancer cells and transformed cells undergo apoptosis when exposed to tumour necrosis factor (TNF). The TNF family of apoptosis-inducing factors include TRAIL, which is A TNF-related apoptosis inducing ligand. TRAIL is a type II integral membrane protein (Wiley et al., 1995 Pitti et al., 1996) and bears a high degree of homology to the Fas ligand, FasL (Nagata, 1997). TRAIL induces apoptosis of cells by binding to specific receptors. Binding of TRAIL to two receptors calledTRAIL-R1 and R2 appears to induce apoptosis, whereas binding of the ligand to TRAIL-R3 and R4 seem to inhibit apoptosis by acting as decoy receptors or by activating NF-kB. R1 and R2 possess the so-called death domains in the cytoplasmic tail whilst R3 and R4 lack these death domains (Degli-Esposti, Dougallo et al., 1997 Pan, Ni et al., 1997 Pan, O'Rourke et al., Figure 8 Signalling pathway involving phosphoinositide-3 kinase and Akt in the regulation of cell proliferation and apoptosis. The Figure shows the PI-3...

Genes That Contribute to Cancer

Because cell division is affected by both accelerators and brakes, cancer can arise from mutations in either type of signal, and there are several fundamentally different routes to cancer (IFigure 21.24). A stimulatory gene can be made hyperactive or active at inappropriate times, analogously to having the accelerator of an automobile stuck in the floored position. Mutations in stimulatory genes are usually dominant, because a mutation in a single copy of the gene is usually sufficient to produce a stimulatory effect. Dominant-acting stimulatory genes that cause cancer are termed oncogenes. Cell division may also be stimulated when inhibitory genes are made inactive, analogously to having a defective brake in an automobile. Mutated inhibitory genes generally have recessive effects, because both copies must be mutated to remove all inhibition. Inhibitory genes in cancer are termed tumor-suppressor genes. Although oncogenes or mutated tumor-suppressor genes or both are required to...

Alteration or Inhibition of PP2A Is Essential in Human Cancer Development

Further evidence for the importance of SV40 small T in transformation comes from experiments showing that human mesothelial cells expressing SV40 large T and small T are easier to transform by carcinogens than cells expressing large T only 32 . The potency of small T was also demonstrated in a transgenic mouse model in which only small T is expressed in breast epithelial tissue under the control of the acidic milk protein promoter 33 . Cyclin D1 is constitutively overex-pressed in the small-T-expressing mammary epithelial cells, and mammary gland differentiation is inhibited. Importantly, 10 of the transgenic animals develop breast tumors. In contrast, transgenic mice expressing only large T in breast epithelium develop breast cancer at a lower rate and after a longer latency period 33 .

Mutation of Aa and Ap Isoforms in Human Cancer

An independent line of evidence for PP2A playing a role in human cancer development comes from recent findings that PP2A is mutated in a variety of human malignancies, including cancer of the lung, breast, colon, and skin. Wang et al. 34 discovered that the gene encoding the Ap subunit of PP2A is mutated or deleted in 15 of primary lung and colon cancers. Takagi et al. 35 described mutations in the Ap subunit gene in four colon cancer cases. Furthermore, Calin et al. 36 reported that both the Aa and Ap subunit isoforms are genetically altered in a variety of primary human cancers. These findings lend strong support to the idea that PP2A is a tumor suppressor. We investigated many of the cancer-associated Aa and Ap mutants described by Wang et al. and Calin et al. Based on the location of the mutated amino acids in intra-repeat loops or nearby, we suspected that the mutant A subunits might be defective in binding B and or C subunits. Indeed, we found that all Aa and most Ap subunit...

The Molecular Genetics of Colorectal Cancer

Mutations that contribute to colorectal cancer have received extensive study, and this cancer is an excellent example of how cancer often arises through the accumulation of successive genetic defects. Colorectal cancers arise in the cells lining the colon and rectum. More than 135,000 new cases of colorectal cancer are diagnosed in the United States each year, where this cancer is responsible for more than 56,000 deaths annually. If detected early, colorectal cancer can be treated successfully consequently, there has been much interest in identifying the molecular events responsible for the initial stages of colo-rectal cancer. Colorectal cancer is thought to originate as benign tumors called adenomatous polyps. Initially, these polyps are microscopic, but in time they enlarge, and the cells of the polyp acquire the abnormal characteristics of cancer cells. In the later stages of the disease, the tumor may invade the mus Most cases of colorectal cancer are sporadic, developing in...

Other genetic factors and skin cancer

An increasing number of studies have recently reported on associations between various candidate genes and skin cancer. Most plausible are reports of associations between genes involved in DNA repair and skin cancer. Patients with xeroderma pigmentosum (OMIM 278730), an autosomal recessive disorder characterized by mutation in one of a number of genes involved in nucleotide excision repair, have a grossly elevated risk of both melanoma and NMSC (often presenting in early childhood with multiple tumors). Various studies have recently reported associations between some of the genes implicated in xeroderma pigmento-sum and skin cancer (Dybdahl et al., 1999 Tomescu et al., 2001 Winsey et al., 2000), whilst other studies have reported on associations between polymorphisms in pathways that may play a role in oxidative damage control in skin in response to UVR (such as the glutathione transferases) (Lear et al., 1997 Ramsay et al., 2001) or skin immunity (tumour necrosis factor a) (Hajeer et...

Hrql Measures And Cancer Survivors

Both generic- and cancer-specific HRQL measures have been administered to heterogeneous and homogeneous samples of cancer survivors. Tables 1-3 provide a comprehensive list of frequently used measures with specific symptoms and HRQL domains and are included to help the user begin to select appropriate instruments for their purpose. While most investigators' needs can be more or less met by several of the available instruments, these tables enable one to consider coverage of the concepts of interest in a planned research or clinical program. This is followed by a brief review of these measures and their measurement characteristics, such as reliability and validity. The majority of these measures have been used in survivorship studies. A small group of additional measures has not been frequently used with cancer survivors, but have been included because they measure important content areas that are relevant to the survivorship experience.

Tissue Distribution Of Sultdependent Dna Damage And Carcinogenesis

Tamoxifen exerts its carcinogenic, mutagenic, and DNA-adduct-forming effects with high specificity in the liver but not in other investigated tissues of the rat (da Costa et al., 2002 Greaves et al., 1993 White et al., 1992). These findings correlate with the observation that the activation of tamoxifen is specifically dependent on rSTa, an enzyme expressed with high specificity in the liver (Dunn and Klaassen, 1998). Interestingly, rSTa is constitutively expressed in the liver of adult females, whereas it is induced by tamoxifen in male liver (Davis et al., 2000). Several other SULT-dependent carcinogens, such as 2-acetylaminofluorene and safrole, are primarily carcinogenic to the liver in the rat (Miller, 1994). Again, the SULTs involved in their activation are highly expressed in liver but low or absent in other tissues.

Chemical Modulation Of Sultdependent Genotoxic And Carcinogenic Effects In Vivo

The dependence of a mutagenic effect in recombinant test systems is usually demonstrated by conducting control experiments in the parental bacterial strain or cell line lacking the specific enzyme. As an alternative, an appropriate agent, such as pentachlorophenol with SULT1A1, can inhibit the heterologous enzyme. The test system can be used to study defined chemicals or complex samples for chemopre-ventive activity. For example, dealcoholized red wine completely suppressed the mutagenicity of N-OH-PhlP (7 Figure 13.9) and 1-hydroxymethylpyrene (1 Glatt, 2000b) to a TA1538-derived S. typhimurium strain expressing human SULT1A1. In this case, the effect was due to inhibition of the enzyme. It would be important to know whether this chemoprotection would also occur in vivo in the human. This situation is typically characterized by a low exposure to procarcinogens, a high total enzyme capacity, and limited (rather than total) inhibition by food-borne factors. With the limitation that...

Modeling Chromosomal Rearrangements ofCancer

Genomic rearrangements also play critical role in cancer. Recurrent genomic aberrations have been found in both human lymphomas and solid tumors (71,72). For technical reasons, one type of genomic aberrations, recurrent balanced chromosomal translocations, are better characterized in human leukaemia and lymphomas (73). Among the most common chromosomal translocation breakpoint regions in human leukaemia is chromosome 11q23. These translocations involve the mixed-lineage leukaemia gene, MLL, and greater than 30 different MLL fusion partners (74), whereas the identity of these partners determines the etiology of the subsequent leukaemia in humans. Based on the Cre-loxP technology, a chromosomal translocation between MLL and eleven nineteen leukaemia (Enl) was induced specifically in haematopoietic cells in mice. These translocation mice developed a rapid onset and high penetrance of leukemogenesis that models many key aspects of the human disease (75). Other chromosomal aberrations...

Breast Cancer Risk Modifiers

The incomplete penetrance associated with mutations in BRCA1 and BRCA2 suggests that environmental or genetic risk-modifying factors may exist that affect the phenotype of BRCA1 and BRCA2 mutation carriers. Initial estimates from clinic-based data indicated that around 80 of carriers of mutations in BRCA1 and BRCA2 from multiple-case families would develop breast cancer (1,2), whereas a later pooled analysis from population-based studies has suggested that for the great majority of mutation carriers, their average lifetime risk is closer to 45 to 66 (3). This pooled-analysis of BRCA1 and BRCA2 carriers also showed that in BRCA1 mutation carriers, the breast cancer penetrance for relatives ascertained through a breast cancer case was significantly higher than for those ascertained through an ovarian cancer case, and even higher if the index case was diagnosed before the age of 35 (3). Conversely, the ovarian cancer risk was higher in families ascertained through an ovarian cancer index...

Tumor Suppressor Activity of E1A in Breast Cancer Experimental Models

The initial link between E1A and tumor suppression in breast cancer was based on the observations that E1A could suppress the transformation phenotype of the neu-transformed NIH mouse 3T3 cells (10-12) by transcriptionally repressing the promoter of rat neu oncogene (9). HER-2 is amplified and overexpressed in approximately 30 human breast cancer patients with poor prognosis (29-31). Because the neu gene is a murine counterpart of the human HER-2 proto-oncogene, it was hypothesized that E1A could also repress HER-2 expression in human breast cancer. Indeed, both HER-2 protein and mRNA levels were reduced in HER-2-overexpressing breast cancer cell lines infected with an E1A-expressing adenovirus (Ad.E1A(+)) but not a mutant adenovirus (Ad.E1A(-)) in which E1A is deleted (13). To test whether the E1A-mediated HER-2 repression affects the cell growth in cell model systems, both the high-HER-2 (e.g., MDA-MB-361 and SKBR3) and the low-HER-2-expressing (e.g., MDA-MB-435 and MDA-MB-231)...

Mabs in passive immunotherapy of cancer patients

Several mAbs have successfully completed phase III clinical trials and were approved by the FDA for treatment of cancer patients (Table 2). Thus, Rituxan (anti-CD20) has been approved for the treatment of non-Hodgkin's lymphoma (32), Herceptin (anti-HER-2 neu) for breast carcinoma (33), Mylotarg (anti-CD33) for acute myeloid leukemia (34,35), and Campath (anti-CD52) for chronic lymphocytic leukemia (36,37). These MAbs have significantly enhanced survival of the treated patients. The mechanism by which these antibodies may inhibit tumor growth is through antibody-dependent cellmediated cytotoxicity (ADCC) (Rituxan 38,39 Herceptin 33 Campath 36 ) or apoptosis (Mylotarg 40 Campath 37 ). These studies clearly demonstrate a beneficial role of antibodies in the growth control of cancer. However, the biological half-life of passively administered MAb in the blood is usually short (2-3 d for mouse MAb 41 and 5-7 d for human mouse chimeric antibodies 42-44 ), making repeated MAb administration...

Association Between Antibody Induction and Tumor Growth Inhibition Increased Survival in Vaccinated Cancer Patients

Several phase I and II clinical trials have demonstrated an association between antibody induction in vaccinated cancer patients and clinical response (enhanced survival, tumor shrinkage) (Table 1). Sialyl-Tn-KLH vaccine induced IgG and IgM antibodies to the antigen in all vaccinated breast cancer patients, and antibody induction was associated with patients' survival (51). Anti-idiotypic antibodies binding to the antigen-combining site of antitumor antibodies may mimic tumor antigen. Anti-idiotypic antibody vaccine mimicking the high-molecular-weight melanoma-associated antigen (HMW-MAA) elicited anti-anti-idiotypic antibodies (Ab3 antibodies binding to anti-idiotype or Ab2) in melanoma patients, and the Ab3 responses were associated with patients' survival (52). However, in neither of the two studies were the antibodies shown to be associated with clinical responses demonstrated to bind to tumor cell-surface determinants, and, therefore, the role of these antibodies in the...

Trial Design For Molecular Cancer Therapeutics

For phase II studies, one of the key issues is the question of tumor response. We have already discussed the fact that novel molecular cancer therapeutics are more likely to act in a cytostatic manner as a result of mechanism-based cell-cycle arrest or the induction of generally modest increases in apoptosis. They will not produce several logs of cell kill as was seen with alkylating agents or radiation in responsive cancers. As a result, these agents may be active on prolonged administration without causing significant tumor shrinkage, creating difficulty in assessment of these agents by the traditional phase II endpoint of radiological response. The challenge is therefore to produce innovative designs and endpoints for phase II studies, as argued by Ratain and Eckhardt (2004). One possible solution for such agents is to use progression-free survival as an alternative endpoint and to carry out the trials with crossover or randomized discontinuation designs and involving a range of...

Hormonerelated Treatment Of Cancer

Clearly, many cancers are related to the status of hormones in the body, for example, breast cancer may or may not utilize estrogens as growth factors, prostate cancer cells may depend on a supply of androgens, etc. these dependencies usually are a feature of the presence of the cognate receptor in the tumor cell, and hormone independence becomes a feature of tumor cells that no longer express the appropriate receptor. Thus, there are two approaches to cancer treatments involving hormones in one, the gland responsible for the offensive secretion of a hormone may be removed (gland extirpation this is also a route to remove a tumor of a specific gland), and in the other, hormones and their antagonists may be used as chemotherapeutic agents. A third avenue of treatment is becoming important, and this relies on agents that block the activity

Bik Induces Apoptosis in Breast Cancer Cells

In vitro, we showed that transfection of a bik expression vector and SN2 complex (SN-bik) into breast cancer cell lines such as MDA-MB-231, MDA-MB-468, and MCF-7 resulted in a drastic increase of apoptosis as measured by sub-G1 cell population (47). As expected, the SN-bik transfected breast cancer cells exhibited drastic reduction of the number of colony in soft agar. These results suggest that bik is a potent proapoptotic agent and may be suitable for further development as a potential therapeutic gene in vivo.

Mutant bik DD Enhances Apoptosis in Breast Cancer Cells

Objective, we attempted to modify the bik gene to make it more potent than the wild type bik. It has been implicated that phosphorylation of threonine 33 (T33) and serine 35 (S35) of bik protein are required for its maximum apoptotic activity (96). We hypothesized that T33 and S35 substitutions with the negatively charged aspartic acids (D33 and D35) (i.e., bik DD) would be constitutively active and, thus, more potent. Indeed, we found that bik DD has higher binding affinity with the antiapoptotic molecules, Bcl-2 and Bcl-XL, than does the wild-type bik. Subsequently, transfection of bik DD led to higher apoptosis in breast cancer cells such as MCF-7 than did wild type bik (97). These results suggest that bik DD is a more potent apoptotic agent than the wild type bik.

Longterm Care For Cancer Survivors Inattention To Issues Impacting Hrql

Although health providers are taught measurement principles from the beginning of their clinical training (e.g., height, weight, vital signs), clinicians are not routinely taught how to measure patient-reported symptoms and health status across the cancer spectrum. Optimal cancer care throughout extended survivorship includes obtaining a complete picture of ones' physical and psychosocial health status however, assessment and subsequent communication about these issues in medical consultations is often limited.213-215 Oncology specialists may overlook symptoms due to training emphasis on cancer biology, productivity pressures, and a care reimbursement policy that offers incentives for procedures or drugs and disincentives for consultation time. Therefore, insufficient attention is paid to patient In 2005, the Centers for Medicare & Medicaid Services (CMS) conducted a 1-year demonstration project for cancer patients undergoing chemotherapy. CMS provided payment of 130 per encounter to...

Amplified in Breast Cancer

BRCA1 is a coactivator of AR, and this activation is mediated in part through an estrogen-receptor coactivator, amplified in breast cancer 1 (AIB1) (73). Rebbeck et al. studied the effect of a glutamine repeat polymorphism at the AIB1 locus, whose functional effect is unknown, using a matched case-control sample of 448 women with germline BRCA1 (n 370) or BRCA2 (n 78) mutations (29). These women were at a significantly higher breast cancer risk if they carried alleles with at least 28 or 29 polyglutamine repeats in AIB1, compared with women who carried alleles with fewer repeats (OR 1.59 95 CI 1.03-2.47 or OR 2.85 95 CI 1.64-4.96, respectively). This effect was also seen when analysis was restricted to only BRCA1 mutation carriers. Women were at an even higher risk if they had AIB1 alleles with at least 28 polyglutamine repeats and were either nulliparous or had had a late age at first live birth (OR 4.62 95 CI 2.02-10.56) compared to women with none of these risk factors. The...

Anticancer Effects Of Hdac Inhibitors

Give additional insight into mechanisms involved in proliferation, differentiation, apoptosis, and angiogenesis as well as help identify novel therapeutic approaches to combat cancer. HDAC inhibition affects protein stability through several mechanisms including promotion of apoptosis, cell cycle arrest, and prevention of tumor-mediated angiogenesis. Recent evidence shows that HDAC inhibitors increase the acetylation status of heat shock protein 90 (Hsp90) whereby the chaperone activity of the acetylated form is inactivated, leading to destabilization of its client proteins including Her-2 neu, AKT, c-Raf-1, mutant p53, and Bcr-Abl (41,44,45). Nimmanapalli et al. (44) revealed activity of NVP-LAQ824 in chronic myelogenous leukemia-blast crisis (CML-BC) cells, maintaining acetylation of Hsp90 and directing protea-somal degradation of wild-type Bcr-Abl as well as imatinib-refractory mutant Bcr-Abl. This Hsp90-mediated proteasomal degradation of Bcr-Abl in conjunction with degradation of...

Hormones Centrosomes and Genomic Instability in Mammary Carcinogenesis

Breast Cancer Carcinogenesis

The centrosome duplication cycle, like the cell cycle, is regulated by a vital system of checkpoint-signaling proteins, about which little is currently known. Errors in centrosome duplication and or distribution can result in aberrant daughter cells that either lack centrosomes (acentric cells) or receive a single centrosome, producing mono-polar spindles, or they can receive more than two centrosomes, resulting in the assembly of multipolar spindles during mitosis. These aberrations can lead to catastrophic errors in chromosome distribution resulting either in cell death or transformation to become tumor cells. Using antibodies specific for centrosome associated proteins, we and others have noted that many tumors, both in-vitro and in-vivo, display cells with a variety of centrosome aberrations (1-7). The most commonly reported defect causes cells to develop supernumerary centrosomes (greater than the expected 1-2 centrosomes cell), a process identified as centrosome amplification....

Adenovirus use in cancer vaccine strategies

The potential benefits provided by the use of Ad vectors as vaccines for the prevention of viral illnesses coincide with simultaneous efforts to use Ad vectors to vaccinate against various types of cancer. The first use of Ad against cancer occurred shortly after its discovery in 1953. In this experiment, concentrated wild-type Ad were intravenously administered into subjects affected by cervical cancer. The hypothesis was that the lytic properties of Ad infection of cancer cells might slow or halt the cancer's progression, a popular notion of the period (8). Of the subjects treated, 65 reportedly had evidence of necrosis of cancerous tissue, without appreciable side effects. Autopsy findings demonstrated that the Ad had effects only on the cervical tumors and was not able to affect growth and metastases of pelvic tumors. Thus, although showing some promise, the lytic properties of Ad did not seem sufficient to effectively fight disseminated cancer. A resurgence however has occurred...

Patients With Cancer Can Be Immunized With Class II Peptide Based Vaccines

GM-CSF is a recruitment and maturation factor for skin dendritic cells (DCs), Langerhans cells (LCs), and theoretically may allow more efficient presentation of peptide epitopes than standard adjuvants such as IFA. Six HLA-A2 patients with HER-2 neu-overexpressing cancers received six monthly vaccinations with 500 g of HER-2 neu peptide, p369-377, and mixed with 100 g of GM-CSF. The patients had either stage III or IV breast or ovarian cancer. Immune responses to the p369-377 were examined using an IFN-y ELIspot assay. Prior to vaccination, the median precursor frequency, defined as precursors 106 PBMC, to p369-377 was not detectable. Following vaccination, HER-2 neu peptide-specific precursors developed to p369-377 in just two of four evaluable subjects. The responses were short-lived and not detectable at 5 mo after the final vaccination. Immunocompetence was evident as patients had detectable T-cell responses to tetanus toxoid and influenza. These results...

Respiratory And Mediastinal Cancer

Recent advances in the diagnosis of adenocarcinoma the impact of lung cancer screening on histopathologists. Curr Diagn Pathol 2004 10 269-278. Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981 48 2485-2492. Yamakawa Y, Masuoka A, Hashimoto T, Niwa H, Mizuno T, Fujii Y, Nakahara K. A tentative tumour-node-metastasis classification of thymoma. Cancer 1991 68 1984-1987.

Real Time Symptom Monitoring With Cancer Survivors

The use of computer adaptive tests with cancer survivors would minimize burden and help focus assessment. It has potential to sharpen measurement precision with a minimum number of questions255 and has several unique advantages (1) compared to paper-and-pencil tests, computer adaptive testing technology is efficient, requiring fewer questions to arrive at an accurate estimate (2) it allows respondents and providers to receive immediate feedback on the person's HRQL status (3) with its IRT underpinnings, it allows users to communicate with one another in a common language and metric (4) the problem of excessive floor or ceiling effects is greatly reduced (yielding scores that promote accurate selection and classification decisions and reducing respondent boredom or frustration) and (5) since computer adaptive testing automates test administration, scoring and recording, human error is eliminated. For example, completed and ongoing projects in our research lab utilize computer data...

Epidemiologic Insights into the Occurrence and Causes of Testicular Cancer

Epidemiologic research has described the population distribution of testicular cancer and has suggested pathophysiologic mechanisms that are being investigated. Descriptive studies show that testicular cancer is becoming more common and that it occurs primarily in young men. This unusual age distribution accounts for much of the impact of disease and suggests some etiologic hypotheses. Analytic research has provided etiologic insights suggesting that testicular germ cell carcinoma has both environmental and genetic origins.

CMyc Deregulation in Cancer

Myc Deregulation

C-Myc overexpression is associated with neoplasms of different tissues, including breast (11,12), neuroblastoma (13), cervical carcinoma (14), malignant melanoma (15), prostate cancer (16), osteogenic sarcoma (17), and lymphoid cancer (6, 18, 19) (reviewed in 20). Thus, Myc protein overexpression is an important player in cellular transformation (21-25). Long-range Illegitimate Recombinations, c-myc deregulation in murine B-cell lymphomas has been shown to induce recombination events that involved many different chromosomes (37). These illegitimate recombinations included translocations, deletions and inversions. DNA sequencing and spectral karyotyping showed that a wide variety of chromosomal regions had been affected and many different break points involved. Recent studies have also examined whether c-myc deregulation also increased the rate of point mutations or large-scale rearrangements. Davis, et al. (38) did not observe increased mutation rates in Myc-induced liver cancers, and...

Current Issues In The Treatment Of Highrisk Germ Cell Cancer With aPSCT

The choice of a regimen remains one of the major unresolved issues in the treatment of poor-risk germ cell cancer with high-dose chemotherapy and stem cell support. Elements of regimen design include (1) the safety of each agent at the dose and schedule and in the combination selected for study, (2) the timing of this modality and the use of alternative regimens such as multicycle highdose therapy, (3) tandem cycles using different agents in each cycle, and (4) the incorporation of new pharmacologic agents. Each of these aspects

DNA methylation and cancer

In vertebrate somatic cells, epigenetic regulation of gene expression reinforces stable expression states at different loci. These ''expression states'' are associated with particular molecular signatures of DNA and chromatin modifications that are characteristic of active or repressed genes. The end result is that differentiated cells have a restricted transcriptome profile and a limited developmental potential. In cancer cells, this regulatory mechanism is altered such that the transcriptome profile is changed to one that promotes cancer progression and maintenance. In cell lines, selection for rapid cell division can impose further epigenetic changes. In general, cancer cells possess aberrant patterns of hypomethylation at repeat sequences and hypermethylation at the promoters of many genes (Baylin and Herman, 2000 Bjornsson et a ., 2004 Feinberg et a ., 2002 Feinberg and Tycko, 2004 Jones and Laird, 1999). This process can give the cell a selective growth advantage akin to...

Chemoprotective And Adjunct In Cancer Therapy

Rosemary was used topically to treat cancer in ancient Greece and South America. Although controlled trials are yet to be conducted, it has been suggested that rosemary may delay and inhibit tumour formation in women with breast cancer (Abascal & Yarnell 2001) and that it has potential as a preventive agent or as an adjunct in cancer therapy. An in vitro study in human breast cancer cells found that rosemary extract increased the intracellular accumulation of commonly used chemotherapeutic agents, including doxorubicin and vinblastine via inhibition of P-glycoprotein, thereby overcoming multidrug resistance in tumour cells (Plouzek et al 1999). Clinical studies are required to determine whether the effect is significant.

Symptom Distress in Patients with Advanced Cancer

The numerous projects that have been completed examined patient populations with a variety of advanced malignancies, requiring readers to extrapolate a generalized advanced-cancer experience to the subset of patients in which they are interested. The common symptoms reported in the advanced-cancer population include fatigue, pain, anxiety, and anorexia, each with prevalence rates reported to be greater than 50 .20-28 In addition, most patients with advanced cancer experience a multitude of symptoms simultaneously.21,24,26 Pain, Dyspnea, and Anxiety Depression in Patients with Advanced Cancer Large surveys have repeatedly documented that pain is experienced by 70 to 90 of patients with advanced cancer.34-37 The National Hospice Study (N 1,754) found that pain became more prevalent in cancer patients during the last weeks of life. Of the patients enrolled in this study who could provided self-reported data, 25 indicated that persistent or severe pain was present within 2 days of...

Cancer In Werner Syndrome

WS patients are at increased risk of developing cancer (Goto et al., 1996 Monnat, 2001 Monnat, 2002). The elevated risk of neoplasia in WS patients is of particular biological interest. As discussed later, neoplasia may be an expression of important mechanistic links between WRN function in vivo, genome stability assurance, and the limitation of cell proliferation defects. The elevated risk of neoplasia in WS is selective in that only a small subset of neoplasms are clearly elevated in incidence as compared with general population controls (see Table 80.2). The following neoplasms, in order of decreasing frequency, have been observed most often in WS patients and occur at higher or much higher frequency than in normal population controls soft tissue sarcomas, thyroid carcinoma, meningioma, malignant melanoma, malignant or preneoplastic hematologic disease, and osteosarcoma. Many other neoplasms, including common adult epithelial malignancies, have been observed in WS patients....

The Qualitative Burden Of Cancer Survivorship From The Patients Perspective

To better understand the magnitude of the qualitative burden of cancer from the patient's perspective, the LAF conducted an open invitation Internet-based survey posted on the LAF Web site (http www.laf.org). The survey was a large-scale battery of 83 queries about pathological and psychosocial topics such as medical support, emotional support, patient attitude, secondary health problems, financial issues, social relations, employment problems, and concerns about activities of daily living. From October 1-6, 2004, 1024 self-identified cancer patients responded and completed the survey. Demographics of the responders (shown in Table 1) indicated that most were Caucasian, married, college graduates, and living in or near a city. Ninety percent of responders had medical insurance and 57 had annual income greater than 50,000. Most of the responders were remote from cancer therapy with 73 more than 2 years from diagnosis and 45 as long-term survivors more than 5 years from diagnosis. Only...

Methylene Blue Dye Color Variation Esophageal Cancer

The staging of esophageal carcinoma has become a multimodal process with tests that complement rather than replace one another, in order to improve accuracy. Investigations aim to determine the clinical International Union Against Cancer tumor node metastases (TNM) stage that would help determine the prognosis and hence the management plan for each patient. The decision whether to proceed with extensive staging investigations rests with the clinician and depends on the general health and wishes of the patient, and their performance status and fitness for intervention. Preoperative staging results are typically compared with the histopathological stage of those who have undergone a resection in order to determine their sensitivity and specificity. Using more modern and sensitive spiral CT scanners and in a unit where there is a special interest in esophageal cancer, the sensitivity and specificity of staging may be increased to that obtained by EUS (17). If both investigations are used...

Relation Of Some Hormones To Carcinogens And Development Of Cancer From Inappropriate Hormonal Treatment

Some time ago it was recognized that certain well-known carcinogenic substances structurally resembled steroid hormones. These carcinogens had been shown to produce tumors in experimental animals. In this context, the structures of benzo a pyrene and 7,12-dimethylbenz anthracene can be compared to the structure of estradiol (Figure 20-1). The structural similarities are even more apparent when the molecules are aligned and overlaid as shown in Figure 20-2. It thus is not surprising that steroid hormones can cause cancer if they are administered inappropriately or in high amounts. A typical example of the carcinogenicity of hormones is tumor production in humans caused by treatment with diethylstilbestrol (DES), which is an artificial estrogen. The structure of DES is shown in Figure 20-3. In this figure, the chemical structure of DES is shown in the lower left-hand corner, and the three-dimensional models of its various forms are shown in the body of the figure. Notice that the A ring...

What Is The Role Of Radiotherapy In The Treatment Of Rectal Cancer And How Is This Role Influenced When Total

The investigation of the potential role of radiotherapy in rectal cancer was prompted by the unacceptable risk of local recurrence following conventional surgery when total excision of the mesorectum was not performed. This risk varied between 15 and 50 (1). In addition, when local recurrence occurred, it was associated with significant morbidity and was almost always fatal (1,2). Early trials employed an anterior- and posterior-field arrangement intended to treat the primary tumor, internal and common iliac, inferior mesenteric, and para-aortic lymph nodes up to the vertebral level L1 2. First described by Kligerman in 1972, the Yale, Veterians Administration Surgical Oncology Study Group (VASOG) 2, University of Bergen, European Organization for Research and Treatment of Cancer (EORTC), and Stockholm I trials all used variants of this technique known as the chimney or the inverted T (4-8). Of these studies, only the Stockholm I (n 272) (25 Gy in five fractions over five to seven...

Environmental Factors Related to Hereditary and Familial Colorectal Cancer

Familial colorectal cancer may reflect the influence of multiple genetic factors along with environmental cofactors. Fuchs et al (2002) found that women with high folate intake who had a first-degree relative with colo-rectal cancer were not at increased risk for colorectal cancer. However, women with low folate intake who had a relative with colorectal cancer had about a 2.5-fold increased relative risk for colorectal cancer compared with women with low folate intake and no family history of colorectal cancer. The effect of environmental exposures on risk for cancer among individuals with inherited susceptibility has not yet been studied. However, exposures, such as low folate intake, that are thought to impair DNA repair capacity would be expected to further increase the risk for colorectal cancer among individuals with mismatch repair defects. Several studies have elucidated relationships between certain environmental exposures and genetic markers in colorectal carcinogenesis. For...

Carbohydrate Cell Surface Cancer Antigens The Mskcc Experience

We have screened a variety of malignancies and normal tissues with a series of 40 monoclonal antibodies against 25 antigens that were potential target antigens for immunotherapy (18-21). Results for the 12 defined antigens expressed strongly in 50 or more of biopsy specimens of breast, ovary, prostate cancer, melanoma, sarcoma, and small-cell lung cancer (SCLC) are shown as examples in Table 2. The 13 excluded antigens (including CEA carcinoembryonic antigen and HER2 neu) were expressed in 0-2 of the 5-10 specimens. With the exception of MUC1 and KSA, all of the widely expressed antigens on these cancers were carbohydrates. Our results are consistent with those from other centers with one exception We did not find increased levels of GD2 or GD3 in SCLC. There is a striking similarity in expression of these 12 antigens among tumors of similar embryo-logic background (i.e., epithelial vs neuroectodermal). Epithelial cancers (breast, ovary, Carbohydrate Cancer Cell-Surface Targets for...

Deregulation of the Centrosome Cycle in Cancer

Centrosome abnormalities in cancer are correlated with loss of p53 function in carcinomas of the breast, head and neck, and prostate, and in neuroectodermal tumors (14, 34, 71). In tumors that retained wild-type p53, amplified centrosomes were frequently associated with overexpression of MDM2, which abrogates p53 function by promoting its degradation (71). Furthermore, gain-of-function p53 mutations and p53 null mice can result in deregulation of centrosome duplication leading to the generation of functionally amplified centrosomes and aberrant mitoses (72-74). Interestingly, in some cancers p53 mutations and cyclin E overexpression may act synergistically since together they increased the frequency of centrosome defects in cultured cells and in mouse models (75). embryonic fibroblasts re-established centrosome homeostasis, overexpression of p21 waf1 only partially restored control of centrosome duplication in p53-null fibroblasts, suggesting that alternative downstream p53 targets...

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