Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The class I IgG receptor (Fc gamma RI or CD64 receptor), which is present on key cytotoxic effector cells, has been shown to initiate the destruction of tumor cells in vitro and has been hypothesized to play a role in the destruction of antibody-coated cells such as platelets in idiopathic thrombocytopenia purpura (ITP). This overview summarizes the clinical experience with CD64-directed immunotherapy in cancer patients with the bispecific antibodies MDX-447 [humanized Fab anti-CD64 x humanized Fab anti-(epidermal growth factor receptor, EGFR)] and MDX-H210 (humanized Fab anti-DC64 x Fab anti-HER2/neu), and with the anti-CD64 monoclonal antibody (mAB) MDX-33 (H22) in the modulation of monocyte CD64 in vivo. In an ongoing phase I/II open-label trial with progressive dose escalation (1-15 mg/m2), patients with treatment refractory EGFR-positive cancers (renal cell carcinoma (RCC), head and neck, bladder, ovarian, prostate cancer and skin cancer) are treated weekly with intravenous MDX-447, with and without granulocyte-colony-stimulating factor (G-CSF). MDX-447 has been found to be immunologically active at all doses, binding to circulating monocytes and neutrophils (when given with G-CSF), causing monocytopenia and stimulating increases in circulating plasma cytokines. MDX-447 is well tolerated, the primary toxicities being fever, chills, blood pressure lability, and pain/ myalgias. Of 36 patients evaluable for response, 9 have experienced stable disease of 3-6 month's duration. The optimal dose and the maximal tolerated dose (MTD) have yet to be defined; dose escalation continues to define better the dose, toxicity, and the potential therapeutic role of this bispecific antibody. Three MDX-H210 phase II trials are currently in progress, all using the intravenous dose of 15 mg/m2 given with granulocyte/macrophage (GM-CSF). These consist of one trial each in the treatment of RCC patients, patients with prostate cancer, and colorectal cancer patients, all of whom have failed standard therapy. At the time of writing, 11 patients have been treated in these phase II trials. Four patients have demonstrated antitumor effects. Patients demonstrating responses include 2 with RCC and 2 with prostate cancer. One RCC patient has had a 54% reduction in size of a hepatic metastatic lesion and the other has had a 49% decrease in the size of a lung metastasis with simultaneous clearing of other non-measurable lung lesions. Regarding the two patients with prostate cancer, one has had a 90% reduction in serum prostate-specific antigen (PSA; 118-11 ng/ml), which has persisted for several months; the other patient with prostate has had a 70% reduction of serum PSA (872 ng/ml to 208 ng/ml) within the first month of treatment. Both patients have also demonstrated symptomatic improvement. In a completed phase I and in ongoing phase I/II clinical trials, patients with treatment-refractory HER2/neu positive cancers (breast, ovarian, colorectal, prostate) have been treated with MDX-H210, which has been given alone and in conjunction with G-CSF, GM-CSF, and interferon gamma (IFN gamma). These trials have been open-label, progressive dose-escalation (0.35-135 mg/m2) studies in which single, and more often, multiple weekly doses have been administered. MDX-H210 has been well tolerated, with untoward effects being primarily mild-to-moderate flu-like symptoms. The MTD has not yet been defined. MDX-H210 is immunologically active, binding to circulating monocytes, causing monocytopenia, as well as stimulating increases in plasma cytokine levels. Furthermore, some patients have evidence of active antitumor immunity following treatment with MDX-210. Antitumor effects have been seen in response to MDX-H210 administration; these include 1 partial, 2 minor, and 1 mixed tumor response; 15 protocol-defined stable disease responses have occurred. (ABSTRACT TRUNCATED)
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PMID:Clinical experience with CD64-directed immunotherapy. An overview. 943 76

Using data from a case-control study in the United States (the Selected Cancers Study), we examined the relationship between non-Hodgkin's lymphoma (NHL) and family history of different cancers. Cases were 1,511 men aged 31 to 59 years and diagnosed pathologically with non-Hodgkin's lymphoma during 1984-88. Controls were men, frequency-matched to cases by age range and cancer registry (n = 1,910). All study subjects with acquired immunodeficiency syndrome were excluded from analyses. Our results showed that the risk of NHL is associated with a history of lymphoma (odds ratio [OR] = 3.0, 95 percent confidence interval [CI] = 1.7-5.2) and hematologic cancer (OR = 2.0, CI = 1.2-3.4) in first-degree relatives after adjustment for age, ethnic background, and educational level. Further analyses were performed for the subgroups defined by age at diagnosis (younger than 45 years cf 45 years or older). The association of NHL with a family history of lymphoma and hematologic cancer was found primarily among men aged 45 and older (OR = 4.1, CI = 1.9-8.8 for lymphoma and OR = 2.3, CI = 1.3-4.0 for hematologic cancer). The association among men aged 45 and older did not vary by whether or not there were any familial patients diagnosed at the age of 45 or older. No significant associations could be found for a family history of lung cancer, breast cancer, prostate cancer, colon cancer, skin cancer, liver cancer, stomach cancer, brain cancer, thyroid cancer, or myeloma. This study suggests that the familial risk of NHL is influenced primarily by hematolymphoproliferative malignancies rather than other cancers. The familial effects of hematolymphoproliferative malignancies may be stronger for men aged 45 to 59, compared with those aged 31 to 44.
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PMID:Non-Hodgkin's lymphoma and family history of malignant tumors in a case-control study (United States). 948 66

Prostate cancer is the most commonly diagnosed cancer among Canadian men, excluding non-melanoma skin cancer. Prostate cancer incidence increases almost exponentially with age; most cases are diagnosed in men aged 65 years or older. With the possible exception of animal fat consumption, no known widespread modifiable risk factors have been identified. Although the prognosis is good if appropriate treatment occurs in the early stages of disease, the ability of existing early detection techniques to decrease mortality has not yet been demonstrated. The considerable economic and societal burden of prostate cancer and its treatment, coupled with the projected large increase in the number of new prostate cancer cases as the population ages, make this disease a very important public health issue.
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PMID:Monograph series on aging-related diseases: X. Prostate cancer. 955 Jul 30

Almost all studies which have reported variation in cancer incidence and mortality rates across urbanization gradients have found higher rates in urban populations than in rural areas. Findings are presented from a study conducted to identify urban-rural trends in cancer mortality rates during 1982-91 for municipalities in Taiwan. The countries municipalities were classified as rural, suburban, urban, or metropolitan, using population density as an ordinal indicator of the degree of urbanization. Average annual age-adjusted, site-specific cancer mortality rates were calculated for both sexes within each population density group. Significant increasing trends with more urbanization were observed in mortality rates for cancers of the lung, pancreas, and kidney among both men and women, as well as male prostate cancer and female breast and ovary cancer. The study also found a significant rural excess for non-melanoma skin cancer among men and women, as well as male non-Hodgkin's lymphoma and cancers of the female bone and connective tissue.
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PMID:The relationship between population density and cancer mortality in Taiwan. 961 39

Prostate cancer is the most common form of cancer (except skin cancer) in men. Several factors have been associated with an increased risk for prostate cancer, including age, ethnicity, family history, lifestyle, and environmental exposures. Recognition of the importance of the interaction of these factors in prostate cancer has led to an interest in their evaluation as a model both for studying genetic susceptibility patterns and for studying and providing educational tools and preventive interventions. One such model has been developed at Fox Chase Cancer Center. Critical to the implementation of the model has been the establishment of the Prostate Cancer Risk Registry (PCRR) and Prostate Cancer Risk Assessment Program (PRAP). Together, they serve as a unique resource for investigating the interaction between environmental factors and genetic susceptibility patterns; exploring the early, premalignant biological markers of prostate cancer; and prospectively assessing the quality of life (QOL) of men at risk. In addition, PRAP facilitates the evaluation of models for prostate cancer risk counseling and screening in the community. This paper describes this model for early detection and risk reduction, along with preliminary data from its first two study aims. The program is particularly relevant in view of the wealth of genetic information emerging from the Human Genome Project.
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PMID:Prostate cancer risk assessment program. A model for the early detection of prostate cancer. 1020 54

Epidemiologic studies have suggested that nutrition plays an important role in carcinogenesis and that 30% of cancer morbidity and mortality can potentially be prevented with proper adjustment of diets. Resveratrol, a polyphenol present in red wines and a variety of human foods, has recently been reported to exhibit chemopreventive properties when tested in a mouse skin cancer model system. In this study, we investigated the effects of resveratrol on growth, induction of apoptosis, and modulation of prostate-specific gene expression using cultured prostate cancer cells that mimic the initial (hormone-sensitive) and advanced (hormone-refractory) stages of prostate carcinoma. Androgen-responsive LNCaP and androgen-nonresponsive DU-145, PC-3, and JCA-1 human prostate cancer cells were cultured with different concentrations of resveratrol (2. 5 x 10(-5)-10(-7) M). Cell growth, cell cycle distribution, and apoptosis were determined. Addition of 2.5 x 10(-5) M resveratrol led to a substantial decrease in growth of LNCaP and in PC-3 and DU-145 cells, but only had a modest inhibitory effect on proliferation of JCA-1 cells. Flow cytometric analysis showed resveratrol to partially disrupt G1/S transition in all three androgen-nonresponsive cell lines, but had no effect in the androgen-responsive LNCaP cells. In difference to the androgen-nonresponsive prostate cancer cells however, resveratrol causes a significant percentage of LNCaP cells to undergo apoptosis and significantly lowers both intracellular and secreted prostate-specific antigen (PSA) levels without affecting the expression of the androgen receptor (AR). These results suggest that resveratrol negatively modulates prostate cancer cell growth, by affecting mitogenesis as well as inducing apoptosis, in a prostate cell-type-specific manner. Resveratrol also regulates PSA gene expression by an AR-independent mechanism.
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PMID:Differential effects on growth, cell cycle arrest, and induction of apoptosis by resveratrol in human prostate cancer cell lines. 1032 58

Both benign hyperplasia (BPH) and cancer of the prostate are manifest in men beyond the age of 50. Approximately 50% of men greater than 50 years of age will suffer from the symptoms associated with BPH, especially from bladder outlet obstruction. With the ever-increasing proportion of the population over 65 years of age worldwide, BPH is becoming an important medical problem as the world moves into the next millennium. Cancer of the prostate is the second most commonly diagnosed cancer after skin cancer in the male population of the United States, and the second most common cause of death from cancer after that of the lung. Overall, around the world the incidence of carcinoma of the prostate is increasing annually by 2-3%. Both race and geographical location have a profound influence of the prevalence of prostate cancer worldwide. Black men in the USA have the highest incidence, while the incidence is much lower in Asian men from China, Japan and Thailand. Although the prostate gland is androgen-dependent, it is now recognized that the biological actions of endocrine-related factors, such as androgens, oestrogens, glucocorticoids and certain dietary and environmental factors, are mediated within the gland by various growth regulatory factors. The growth regulatory factors such as epidermal growth factor (EGF), keratinocyte growth factors (KGF), fibroblast growth factors (FGFs) and insulin-like growth factors II and I are mitogenic and directly stimulate cell proliferation under the modulating influence of steroid hormones. Steroids are therefore essential but not directly responsible for cell proliferation. Certain plant compounds such as isoflavonoids, flavonoids and lignans have been proposed as cancer protective compounds in populations with low incidences of prostate diseases. In particular, soya contains the isoflavone genistein, a compound with many properties which could influence both endocrine and growth factor signalling pathways.
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PMID:Phytoestrogens and diseases of the prostate gland. 1038 17

We investigated cancer incidence between 1958 and 1995 in 1873 individuals belonging to 29 consecutively identified BRCA1 and 20 BRCA2 associated families from Southern Sweden using data from parish and local tax authorities, as well as the Swedish Cancer Registry, Cause of Death Registry and Census Registry. 150 malignant tumours were analysed from 1145 relatives in the BRCA1 families and 87 tumours were analysed from 728 relatives in the BRCA2 families. After excluding index cases which led to the mutation analysis, the incidence for all malignant tumours was significantly increased for both BRCA1- standardised morbidity rate, SMR, 1.98, 95% confidence interval (CI) 1.59-2.45; P < 0.0001 and BRCA2- (SMR 1.79, 95% CI 1.35-2.31; P < 0.0001) associated family members. For women in BRCA1-associated families, the incidence of breast cancer (SMR 3.76, 95% CI 2.29-5.80, P < 0.0001), ovarian cancer (SMR 15.49, 95% CI 9.46-23.92, P < 0.0001), stomach cancer (SMR 5.86, 95% CI 1.60-15.01, P = 0.005) were significantly increased. Amongst men only invasive squamous cell cancer of the skin was significantly increased (SMR 6.02, 95% CI 1.96-14.05, P = 0.002). In BRCA2 associated families, female breast cancer (SMR 3.03, 95% CI 1.61-5.18, P = 0.0005) was increased after exclusion of index cases. If these were included, ovarian cancer (SMR 5.16, 95% CI 1.89-11.24, P = 0.001), invasive cervical cancer (SMR 4.21, 95% CI 1.15-10.79, P = 0.016), male breast cancer (SMR 290.52, 95% CI 125.42-572.43, P < 0.0001), and prostate cancer (SMR 2.21, 95% CI 0.89-4.56, P = 0.042) were significantly increased. The increased risk for ovarian cancer in BRCA2 related families were limited to the cases leading to mutation analysis. Our data suggest that apart from breast and ovarian cancer, the incidence of other cancer types do not appear to be greatly increased in BRCA1- and BRCA2-associated families and does not warrant specific clinical follow-up in carriers.
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PMID:Incidence of malignant tumours in relatives of BRCA1 and BRCA2 germline mutation carriers. 1061 37

Serum prostate-specific antigen is credited with dramatic advances in the early detection, screening, and management of men with prostatic carcinoma. There has been more than a twofold increase in the number of men diagnosed during the last decade, and prostate cancer has emerged as the most common non-skin cancer and the second leading cause of cancer death in men. This report summarizes the history and current status of prostate-specific antigen and other serum markers, incorporating consensus opinions from the Second International Consultation on Prostate Cancer held in Paris in June 1999.
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PMID:Prostate-specific antigen and other serum markers: current concepts from the World Health Organization Second International Consultation on Prostate Cancer. 1063 22

The aim of this study was to calculate the familial risk for prostate cancer (PC) for different family relationships. PC was studied in the Swedish Family-Cancer Database, updated in 1999 to cover individuals born after 1934 with their biological parents, totalling 9.6 million persons. Cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996 and included 1035 PC cases amongst offspring. 188 families were identified where a father and a son had PC, giving a familial standardised incidence ratio (SIR) of 2.44 (2.10-2.80). The proportion of familial cancers was 18.2% amongst all PC amongst all PC amongst sons. There were only 5 pairs of affected brothers, of which 3 had an affected father. Age of onset modified familial risks modestly; the highest SIR of 4.43 (1.40-9.17) was for sons diagnosed before 50 years of age when the father was diagnosed before 65 years of age. When analysed across sites, an association of PC in one generation and stomach, liver and skin cancer and myeloma in another generation was observed. The link was most consistent for skin cancer. No maternal site was associated with a son's PC, although the SIR of breast cancer was 1.22 (0.95-1.53). No increased risk of malignancy was observed in wives of affected men excluding any shared environmental effect for PC and female cancers.
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PMID:Familial prostate cancer from the family-cancer database. 1074 Dec 82


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