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 ultraviolet-B (UVB)-vitamin D-cancer hypothesis was proposed in 1980. Since then, several ecological and observational studies have examined the hypothesis, in addition to one good randomized, controlled trial. Also, the mechanisms whereby vitamin D reduces the risk of cancer have been elucidated. This report aims to examine the evidence to date with respect to the criteria for causality in a biological system first proposed by Robert Koch and later systematized by A. Bradford Hill. The criteria of most relevance are strength of association, consistency, biological gradient, plausibility/mechanisms and experimental verification. Results for several cancers generally satisfy these criteria. Results for breast and colorectal cancer satisfy the criteria best, but there is also good evidence that other cancers do as well, including bladder, esophageal, gallbladder, gastric, ovarian, rectal, renal and uterine corpus cancer, as well as Hodgkin's and non-Hodgkin's lymphoma. Several cancers have mixed findings with respect to UVB and/or vitamin D, including pancreatic and prostate cancer and melanoma. Even for these, the benefit of vitamin D seems reasonably strong. Although ecological and observational studies are not generally regarded as able to provide convincing evidence of causality, the fact that humanity has always existed with vitamin D from solar UVB irradiance means that there is a wealth of evidence to be harvested using the ecological and observational approaches. Nonetheless, additional randomized, controlled trials are warranted to further examine the link between vitamin D and cancer incidence, survival and mortality.
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PMID:How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk of cancer?: An examination using Hill's criteria for causality. 2004 84

Antitumor activities of YM155, a novel small-molecule survivin suppressant, were investigated in a wide variety of human cancer cell lines and xenograft models. YM155 inhibited the growth of 119 human cancer cell lines, with the greatest activity in lines derived from non-Hodgkin's lymphoma, hormone-refractory prostate cancer, ovarian cancer, sarcoma, non-small-cell lung cancer, breast cancer, leukemia and melanoma. The mean log growth inhibition of 50% (GI(50) ) value was 15 nM. The mean GI(50) values of YM155 were 11 nM for p53 mut/null cell lines and 16 nM for p53 WT cell lines, suggesting that YM155 inhibits the growth of human tumor cell lines regardless of their p53 status. In non-small-cell lung cancer (Calu 6, NCI-H358), melanoma (A375), breast cancer (MDA-MB-231) and bladder cancer (UM-UC-3) xenograft models, 3- or 7-day continuous infusions of YM155 (1-10 mg/kg) demonstrated significant antitumor activity without showing significant bodyweight loss. Tumor regressions induced by YM155 were associated with reduced intratumoral survivin expression levels, increased apoptosis and decreased mitotic indices. The broad and potent antitumor activity presented in the present study is indicative of the therapeutic potential of YM155 in the clinical setting.
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PMID:Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models. 2120 82

Lenalidomide (REVLIMID), an immunomodulatory compound targeting both cancer cells and their microenvironment, has substantial activity in several difficult-to-manage hematological malignancies. In previously treated multiple myeloma, lenalidomide produces high-quality responses combined with sustained disease control. Recently, several randomized studies have demonstrated a clinical benefit of continuous lenalidomide treatment in newly diagnosed multiple myeloma. In many patients with refractory anemia associated with lower risk myelodysplastic syndromes and a 5q chromosome deletion, lenalidomide leads to transfusion independence, considerably improving quality of life. It has a manageable safety profile, and its oral formulation reduces the burden on patients. Several phase III trials are ongoing in other indications currently underserved by conventional therapy, such as chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and prostate cancer. Several early-stage studies are exploring lenalidomide alone and in combination across different hematological malignancies, solid tumors, and immune-related disorders.
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PMID:A review of the history, properties, and use of the immunomodulatory compound lenalidomide. 2143 45

Frank Caldwell Garland, Ph.D., died August 17, 2010 after a year-long battle with cancer. He will be remembered for his seminal work with his brother Cedric F. Garland in proposing the ultraviolet-B (UVB)-vitamin D-cancer hypothesis to explain the geographical variation of colon cancer mortality rates in the United States in 1980. This hypothesis has been extended to about 20 types of cancer using the ecological approach, and supported strongly by observational studies of prediagnostic serum 25-hydroxyvitamin D [25(OH) D] for incidence of breast, colorectal and ovarian cancer, and a randomized controlled trial that used sufficient vitamin D (1,150 IU/day) to and found a strongly beneficial effect on cancer incidence. The UVB-vitamin D-cancer hypothesis is also supported by studies that used as the index of solar UVB irradiance the amount of sunlight exposure in childhood or incidence of non-melanoma skin cancer. Survival after diagnosis was increased for individuals with higher serum 25(OH)D levels at the time of cancer diagnosis for six types of cancer: breast, colorectal, lung and prostate cancer; melanoma and non-Hodgkin's lymphoma. The ecological study approach is ideally suited to studying cancer risk-modifying factors since the lag between cancer initiation and detection or death can be 20-40 years or more, making ordinary observational studies difficult. The impact on vitamin D research by both Frank Garland and Cedric Garland has been immense. Health policy leaders will realize this in the near future, providing a rich legacy for humanity.
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PMID:Dr. Frank caldwell garland, june 20, 1950-august 17, 2010. 2154 96

About 15-20% of the employees in Europe and in the USA are engaged in shift work that involves night work. Some experimental and observational data indicate that this type of work might lead to circadian disruption, including disruption in the melatonin synthesis - a hormone of anticarcinogenic and antioxidative properties. A hypothesis that there is a potential link between exposure to light at night and the risk of breast cancer was formulated for the first time by Stevens in 1987. Since then, relatively few epidemiological studies have been carried out in this area (15 studies including 8 cohort and 7 case-control studies). All of them are reviewed in this article. The majority of the epidemiological studies performed to date have focused on the association between shift work and breast cancer risk, few studies have reported an increased risk of other cancers, including colorectal cancer, endometrial cancer, prostate cancer and non-Hodgkin's lymphoma. In six out of ten studies, a statistically significant association between night shift work and risk of breast cancer has been shown (OR = 2.2; 95% CI: 1.1-4.5 in nurses in Norway with > 30 years of night shift work). The increased cancer risk has been reported in nurses, radio-telephone operators, flight attendants, and women employed in the enterprises, in which 60% of employees work at night. Most of the analyses have been based on the data from the registries, with limited potential for the exposure assessment and confounders adjustment. Although some epidemiological studies suggest an increased risk of breast cancer among nurses, we are still far from drawing final conclusions. Therefore, further epidemiological studies are warranted.
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PMID:[Night shift work and cancer risk: a literature review]. 2187 Apr 22

Ultraviolet (UV) radiation in sunlight may influence risk of prostate cancer. In New South Wales (NSW), Australia, we examined the relationship between sun exposure at 30 and 50 years of age and risk of prostate cancer in a case-control study combining the NSW prostate cancer care and outcome study (cases) and the NSW non-Hodgkin's lymphoma study (controls). Prostate cancer risk increased with increasing estimated sun exposure (adjusted OR for highest vs. lowest quartiles of average weekly sun exposure in the warmer months 2.07 95% CI: 1.36-3.15) and this increase was most evident with weekend sun exposure (adjusted OR=5.55, 95% CI: 2.94-10.48). High sun sensitivity was also positively associated with risk for prostate cancer (adjusted OR=1.63, 95% CI: 1.09-2.44). The apparent effects of weekly sun exposure did not vary by disease aggressiveness. Our results suggest that increasing sun exposure in mid-adult years increases prostate cancer risk in a high ambient solar UV environment. Given that previous studies, conducted mainly in low solar UV environments, have generally found evidence of a negative association, our findings suggest there may be a U-shaped relationship between solar UV exposure and prostate cancer. Further studies are needed to test the hypothesis that high solar UV exposure is a risk factor for prostate cancer and to explore possible mechanisms for such an association.
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PMID:Sun exposure may increase risk of prostate cancer in the high UV environment of New South Wales, Australia: a case-control study. 2232 1

The initial aim of this study was to identify novel serum diagnostic markers for the human ovarian granulosa cell tumor (GCT), a tumor that represents up to 5% of all ovarian cancers. To circumvent the paucity of human tissues available for analyses, we used the Ctnnb1(tm1Mmt/+);Pten(tm1Hwu/tmiHwu);Amhr2(tm3(cre)Bhr/+) transgenic mouse model, which features the constitutive activation of CTNNB1 signaling combined with the loss of Pten in granulosa cells and develops GCTs that mimic aggressive forms of the human disease. Proteomic profiling by mass spectrometry showed that vinculin, enolase 1, several heat shock proteins, and valosin containing protein (VCP) were more abundantly secreted by cultured mouse GCT cells compared to primary cultured GC. Among these proteins, only VCP was present in significantly increased levels in the preoperative serum of GCT cancer patients compared to normal subjects. To determine the specificity of VCP, serum levels were also measured in ovarian carcinoma, non-Hodgkin's lymphoma and breast, colon, pancreatic, lung, and prostate cancer patients. Increased serum VCP levels were observed in the majority of cancer cases, with the exception of patients with lung or prostate cancer. Moreover, serum VCP levels were increased in some GCT, ovarian carcinoma, breast cancer, and colon cancer patients who did not otherwise display increased levels of widely used serum tumor markers for their cancer type (e.g. inhibin A, inhibin B, CA125, CEA, or CA15.3). These results demonstrate the potential use of VCP as highly sensitive serum marker for GCT as well as several other human cancers.
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PMID:Proteomic profiling of a mouse model for ovarian granulosa cell tumor identifies VCP as a highly sensitive serum tumor marker in several human cancers. 2287 Mar 30

We compared the incidence of cancer among Turkish, Chilean, and North African (NA) first-generation immigrants with residents in their countries of origin and native Swedes. The Swedish Family-Cancer Database was used to calculate age-standardized incidence rates. We compared the age-standardized incidence rates for immigrants with those in the Cancer Incidence in Five Continents report. All-cancer rates were decreased in Turks (men) and Chileans and increased in NAs compared with the residents in their countries of origin. The rates of stomach cancer in Chileans and lung cancer in Turkish men were decreased, whereas Turkish women had an increased rate of lung cancer. Furthermore, the rate of prostate cancer in Turks and NAs and nervous system tumors in NA men and Turkish women were increased. Chileans had higher rates of stomach and testicular cancers and lower rates of colon cancer, nervous system tumors, and non-Hodgkin's lymphoma compared with Swedes. Higher rates of male lung cancer and female thyroid cancer, and lower rates of male rectal and kidney cancers and nervous system tumors, and female stomach and colon cancers were observed among Turks compared with Swedes. The differences observed in all-cancer rates among immigrants were mostly attributable to decreased rates of stomach and lung cancers or an increased rate of prostate cancer after migration. We observed increased rates of colon, breast, and nervous system cancers after migration, whereas the rates of testicular, kidney and thyroid cancers, and non-Hodgkin's lymphoma remained unchanged.
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PMID:Cancer incidence among Turkish, Chilean, and North African first-generation immigrants in Sweden compared with residents in the countries of origin and native Swedes. 2295 39

Night work might influence cancer risk, possibly via suppression of melatonin release. In a population-based case-control study conducted in Montreal, Quebec, Canada, between 1979 and 1985, job histories, including work hours, were elicited from 3,137 males with incident cancer at one of 11 anatomic sites and from 512 controls. Compared with men who never worked at night, the adjusted odds ratios among men who ever worked at night were 1.76 (95% confidence interval (CI): 1.25, 2.47) for lung cancer, 2.03 (95% CI: 1.43, 2.89) for colon cancer, 1.74 (95% CI: 1.22, 2.49) for bladder cancer, 2.77 (95% CI: 1.96, 3.92) for prostate cancer, 2.09 (95% CI: 1.40, 3.14) for rectal cancer, 2.27 (95% CI: 1.24, 4.15) for pancreatic cancer, and 2.31 (95% CI: 1.48, 3.61) for non-Hodgkin's lymphoma. Equivocal evidence or no evidence was observed for cancers of the stomach (odds ratio (OR) = 1.34, 95% CI: 0.85, 2.10), kidney (OR = 1.42, 95% CI: 0.86, 2.35), and esophagus (OR = 1.51, 95% CI: 0.80, 2.84) and for melanoma (OR = 1.04, 95% CI: 0.49, 2.22). There was no evidence of increasing risk with increasing duration of night work, with risks generally being increased across all duration categories. Results suggest that night work may increase cancer risk at several sites among men.
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PMID:Night work and the risk of cancer among men. 2380 83

The ultraviolet-B (UVB)-vitamin D-cancer hypothesis was proposed in 1980 yet has not been fully accepted. Ecological studies based on geographical variations of cancer rates with respect to solar UVB doses have supported the hypothesis for about 20 cancers. This paper reviews the evidence from studies of personal or group UVB irradiance. Studies have associated personal UVB irradiance with reduced risk for breast, colon, endometrial, prostate, and renal cancer, as well as non-Hodgkin's lymphoma (NHL). However, some studies have also found increased risk of NHL from UV irradiance, probably due to immunosuppression by UVA near 370 nm. Several related approaches have also been used to study the hypothesis. Studies in Norway and the UK found that diagnosis in summer or fall is associated with increased survival rates for breast, colon, lung, and prostate cancer, as well as Hodgkin's lymphoma. Diagnosis of nonmelanoma skin cancer is associated with reduced risk of several cancers in sunny countries, but not often in highlatitude countries. Living at higher surface elevation is associated with reduced risk of some cancers. In a recent analyzed study of cancer rates for 54 occupations in Nordic countries, a UVB index based on standardized incidence ratios of lip cancer less those for lung cancer was inversely correlated with 15 types of cancer for males, but only four types for females. This ecological study provides additional evidence that UVB doses at high latitudes are adequate to reduce the risk of cancer, but requires considerable time outside to produce sufficient vitamin D. Because only vitamin D production has been proposed to explain the UVB-cancer link, studies reviewed in this paper should be considered strong evidence for the hypothesis.
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PMID:Update on evidence that support a role of solar ultraviolet-B irradiance in reducing cancer risk. 2309 27


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