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Sample records for prostate cancer chemoprevention

  1. Chemoprevention of prostate cancer.

    PubMed

    Vemana, Goutham; Hamilton, Robert J; Andriole, Gerald L; Freedland, Stephen J

    2014-01-01

    Large prospective randomized trials, such as the Prostate Cancer Prevention Trial (PCPT), Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, and Selenium and Vitamin E Cancer Prevention Trial (SELECT), have provided practitioners with considerable data regarding methods of treatment and prevention of prostate cancer. The best-studied medications for prevention are 5 alpha-reductase inhibitors. Their efficacy and side effects are well characterized. Other medications, dietary nutrients, and supplements have not been as well studied and generally do not demonstrate efficacy for disease prevention with an acceptable level of evidence.

  2. Chemoprevention of prostate cancer.

    PubMed

    Brand, Timothy C; Canby-Hagino, Edith D; Pratap Kumar, A; Ghosh, Rita; Leach, Robin J; Thompson, Ian M

    2006-08-01

    Prostate cancer is a common malignancy with multiple potential opportunities for cancer prevention. As the genetic basis of this malignancy is further understood, prevention strategies will be developed for individual patients based on specific risk factors and pathways of carcinogenesis. The PCPT has conclusively proven that prostate cancer prevention is possible. The results of the SELECT should be available within several years. An enormous challenge for the medical community will be the development of an efficient strategy to evaluate the substantial number of dietary, behavioral, and pharmacologic prevention opportunities. Ultimately, the goal of prostate can-cer prevention is to (1) identify men who are destined to develop clinically significant prostate cancer, and (2) provide individualized agents to prevent disease development.

  3. Polyphenols and Prostate Cancer Chemoprevention

    DTIC Science & Technology

    2005-03-01

    prostate chemoprevention are the soy isoflavone , genistein, and the tea catechin, (-)- epigallocatechin-3-gallate (EGCG). Another polyphenol that has...resveratrol in female rats , where the low doses did not exert chemopreventive effects, we concentrated on determining if single exposure to the proposed

  4. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols

    PubMed Central

    2011-01-01

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicon esculentum Mill) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries. Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years. PMID:21992488

  5. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols.

    PubMed

    Atawodi, Sunday Eneojo

    2011-09-23

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicon esculentum Mill) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries. Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years.

  6. Biomarkers of Selenium Chemoprevention of Prostate Cancer

    DTIC Science & Technology

    2003-01-01

    C 134 2.1 MCM6 0.5 receptor of retinoic acid 5.0 Ki67a 0.2 dual spec ificity phosphatase MKP-S 6.4 DNA prisnose 0.4 caltnodulin-dependent protein...to impaired function of the endoplasmic reticulum, Genes Dev., 12: 982-995, 1998. methylseleninic acid : evidence that a monomethylated selenium ...AD_____ Award Number: DAMD17-02-1-0134 TITLE: Biomarkers of Selenium Chemoprevention of Prostate Cancer PRINCIPAL INVESTIGATOR: Yan Dong, Ph.D

  7. Prostate cancer chemoprevention: Current status and future prospects

    SciTech Connect

    Gupta, Sanjay

    2007-11-01

    Chemoprevention is a strategy that aims to reduce the incidence and burden of cancer through the development of agents to prevent, reverse or delay the carcinogenic process. Prostate cancer is a suitable target for prevention because it has a high incidence and prevalence, as well as a long latency and disease-related mortality, and furthermore it is a disease in which lifestyle and environmental factors may play critical roles. The development of chemoprevention strategies against prostate cancer will have a huge impact, both medically and economically. Large-scale clinical trials suggest that some agents such as selenium, lycopene, soy, green tea, vitamins D and E, anti-inflammatory and inhibitors of 5{alpha}-reductase are effective in preventing prostate cancer. Although each agent has the potential to affect the natural history of the disease, it is important to develop strategies to strategically proceed for the design and selection of test agents in order to demonstrate clinical benefit with the minimum of adverse effects. Appropriate selection of agent(s), disease stage, trial design and endpoints is critical in selecting the most promising regimens to accomplish these goals. This review highlights the present status of prostate cancer chemoprevention and discusses future prospects for chemopreventive strategies that are safe and clinically beneficial.

  8. Complementary medicine, chemoprevention, and staging of prostate cancer.

    PubMed

    Crawford, E David

    2003-01-01

    The 13th International Prostate Cancer Update was held in Vail, Colorado, in February 2003. This article provides an overview of the high points in the areas of complementary medicine, chemoprevention, and staging that were discussed at this meeting. M. Scott Lucia, MD, addressed the use of various hormonal agents, antiproliferative or differentiating agents, antiinflammatory agents, and antioxidants in patients with prostate cancer. Wael A. Sakr, MD, provided an overview of prognostic markers for this disease. Arturo Mendoza-Valdes, MD, explored the potential role of exercise for patients with prostate cancer, and Bruce Sodee, MD, described some exciting new developments in prostate imaging. E. David Crawford, MD, discussed the ongoing Prostate Cancer Prevention Trial.

  9. Chemoprevention of Prostate Cancer: Soy Isoflavones and Curcumin

    PubMed Central

    2012-01-01

    The burden of increasing morbidity and mortality due to prostate cancer imposes a need for new, effective measures of prevention in daily life. The influence of lifestyle on carcinogenesis in Asian men who migrate to Western cultures supports a causal role for dietary, environmental, and genetic factors in the epidemiology of prostate cancer. Chemoprevention, a prophylactic approach that uses nontoxic natural or synthetic compounds to reverse, inhibit, or prevent cancer by targeting specific steps in the carcinogenic pathway, is gaining traction among health care practitioners. Soy isoflavones and curcumin, staples of the Asian diet, have shown promise as functional factors for the chemoprevention of prostate cancer because of their ability to modulate multiple intracellular signaling pathways, including cellular proliferation, apoptosis, inflammation, and androgen receptor signaling. Recent evidence has revealed the DNA damage response (DDR) to be one of the earliest events in the multistep progression of human epithelial carcinomas to invasive malignancy. Soy isoflavones and curcumin activate the DDR, providing an opportunity and rationale for the clinical application of these nutraceuticals in the chemoprevention of prostate cancer. PMID:23136625

  10. Mechanisms of action of novel agents for prostate cancer chemoprevention.

    PubMed

    Singh, Rana P; Agarwal, Rajesh

    2006-09-01

    Despite advances in the understanding of prostate cancer (PCa) growth and development, it is still the leading incidence of cases and the second leading cause of mortality due to cancer in men. The problem of early diagnosis compounded with the emergence of androgen independence during commonly used anti-androgen therapy of PCa, have been discouraging for optimal therapeutic response. Recently, many chemopreventive agents, including silibinin, inositol hexaphosphate, decursin, apigenin, acacetin, grape seed extract, curcumin, and epigallocatechin-3 gallate have been identified in laboratory studies, which could be useful in the management of PCa. In vivo pre-clinical studies have indicated chemopreventive effect of many such agents in PCa xenograft and transgenic mouse models. The molecular targets of these agents include cell signaling, cell-cycle regulators, and survival/apoptotic molecules, which are implicated in uncontrolled PCa growth and progression. Furthermore, angiogenic and metastatic targets, including vascular endothelial growth factor, hypoxia-inducing factor-1alpha, matrix metalloproteinase, and urokinase-type plasminogen activator are also modulated by many chemopreventive agents to suppress the growth and invasive potential of PCa. This review focuses on novel PCa chemopreventive observations in laboratory studies, which could provide the rationale for the prospective use of chemopreventive agents in translational studies.

  11. Novel targets for prostate cancer chemoprevention

    PubMed Central

    Sarkar, Fazlul H; Li, Yiwei; Wang, Zhiwei; Kong, Dejuan

    2010-01-01

    Among many endocrine-related cancers, prostate cancer (PCa) is the most frequent male malignancy, and it is the second most common cause of cancer-related death in men in the United States. Therefore, this review focuses on summarizing the knowledge of molecular signaling pathways in PCa because, in order to better design new preventive strategies for the fight against PCa, documentation of the knowledge on the pathogenesis of PCa at the molecular level is very important. Cancer cells are known to have alterations in multiple cellular signaling pathways; indeed, the development and the progression of PCa are known to be caused by the deregulation of several selective signaling pathways such as the androgen receptor, Akt, nuclear factor-κB, Wnt, Hedgehog, and Notch. Therefore, strategies targeting these important pathways and their upstream and downstream signaling could be promising for the prevention of PCa progression. In this review, we summarize the current knowledge regarding the alterations in cell signaling pathways during the development and progression of PCa, and document compelling evidence showing that these are the targets of several natural agents against PCa progression and its metastases. PMID:20576802

  12. Novel targets for prostate cancer chemoprevention.

    PubMed

    Sarkar, Fazlul H; Li, Yiwei; Wang, Zhiwei; Kong, Dejuan

    2010-09-01

    Among many endocrine-related cancers, prostate cancer (PCa) is the most frequent male malignancy, and it is the second most common cause of cancer-related death in men in the United States. Therefore, this review focuses on summarizing the knowledge of molecular signaling pathways in PCa because, in order to better design new preventive strategies for the fight against PCa, documentation of the knowledge on the pathogenesis of PCa at the molecular level is very important. Cancer cells are known to have alterations in multiple cellular signaling pathways; indeed, the development and the progression of PCa are known to be caused by the deregulation of several selective signaling pathways such as the androgen receptor, Akt, nuclear factor-kappaB, Wnt, Hedgehog, and Notch. Therefore, strategies targeting these important pathways and their upstream and downstream signaling could be promising for the prevention of PCa progression. In this review, we summarize the current knowledge regarding the alterations in cell signaling pathways during the development and progression of PCa, and document compelling evidence showing that these are the targets of several natural agents against PCa progression and its metastases.

  13. Green tea polyphenols for prostate cancer chemoprevention: A translational perspective

    PubMed Central

    Johnson, J.J.; Bailey, H.H.; Mukhtar, H.

    2009-01-01

    Every year nearly 200,000 men in the United States are diagnosed with prostate cancer (PCa), and another 29,000 men succumb to the disease. Within certain regions of the world population based studies have identified a possible role for green tea in the prevention of certain cancers, especially PCa. One constituent in particular, epigallocatechin-3-gallate also known as EGCG has been shown in cell culture models to decrease cell viability and promote apoptosis in multiple cancer cell lines including PCa with no effect on non-cancerous cell lines. In addition, animal models have consistently shown that standardized green tea polyphenols when administered in drinking water delay the development and progression of PCa. Altogether, three clinical trials have been performed in PCa patients and suggest that green tea may have a distinct role as a chemopreventive agent. This review will present the available data for standardized green tea polyphenols in regard to PCa chemoprevention that will include epidemiological, mechanism based studies, safety, pharmacokinetics, and applicable clinical trials. The data that has been collected so far suggests that green tea may be a promising agent for PCa chemoprevention and further clinical trials of participants at risk of PCa or early stage PCa are warranted. PMID:19959000

  14. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer

    PubMed Central

    Malik, Arshi; Afaq, Farrukh; Sarfaraz, Sami; Adhami, Vaqar M.; Syed, Deeba N.; Mukhtar, Hasan

    2005-01-01

    Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin. In this study, employing human prostate cancer cells, we evaluated the antiproliferative and proapoptotic properties of PFE. PFE (10-100 μg/ml; 48 h) treatment of highly aggressive human prostate cancer PC3 cells resulted in a dose-dependent inhibition of cell growth/cell viability and induction of apoptosis. Immunoblot analysis revealed that PFE treatment of PC3 cells resulted in (i) induction of Bax and Bak (proapoptotic); (ii) down-regulation of Bcl-XL and Bcl-2 (antiapoptotic); (iii) induction of WAF1/p21 and KIP1/p27; (iv) a decrease in cyclins D1, D2, and E; and (v) a decrease in cyclin-dependent kinase (cdk) 2, cdk4, and cdk6 expression. These data establish the involvement of the cyclin kinase inhibitor-cyclin-cdk network during the antiproliferative effects of PFE. Oral administration of PFE (0.1% and 0.2%, wt/vol) to athymic nude mice implanted with androgen-sensitive CWR22Rν1 cells resulted in a significant inhibition in tumor growth concomitant with a significant decrease in serum prostate-specific antigen levels. We suggest that pomegranate juice may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against prostate cancer in humans. PMID:16192356

  15. New answers from the Prostate Cancer Prevention Trial on the chemoprevention of prostate cancer.

    PubMed

    Ankerst, Donna Pauler; Thompson, Ian M

    2006-12-01

    In this paper, we report ongoing investigations concerning the increased number of high-grade (Gleason grade > or = 7) prostate cancer, despite a reduction in all prostate cancer, found on the finasteride arm of the Prostate Cancer Prevention Trial (PCPT). There was a statistically significant 24.8% reduction in prostate cancer found on biopsy on the finasteride arm compared to placebo, and the reduction was also observed in both groups of end-of-study and for-cause biopsies. However, when the prostate cancers were examined by Gleason score, there was an increased number of high-grade prostate cancers found on the finasteride arm than on the placebo arm. This observation was emphasized in the editorial to the first publication of PCPT results and has dampened enthusiasm for recommendation of finasteride for chemoprevention. So, what are the potential reasons for increased grade on the finasteride arm? The number of high-grade cancers that are detected following a PSA prompt is directly proportional to the sensitivity of PSA for high-grade disease times the actual but unknown number of high-grade disease cases. So the higher the sensitivity the more likely one is to detect more of the existing high-grade cases irrespective of the true number of cases, i.e., there is an ascertainment bias. We are currently performing a quantitative investigation of whether or not this ascertainment bias could explain the higher number of high-grade disease cases observed on the finasteride arm.

  16. The strategies to control prostate cancer by chemoprevention approaches

    PubMed Central

    Ting, Harold; Deep, Gagan; Agarwal, Chapla; Agarwal, Rajesh

    2014-01-01

    Prostate cancer (PCA) is the most commonly diagnosed cancer in men in the United States with growing worldwide incidence. Despite intensive investment in improving early detection, PCA often escapes timely detection and mortality remains high; this malignancy being the second highest cancer-associated mortality in American men. Collectively, health care costs of PCA results in an immense financial burden that is only expected to grow. Additionally, even in cases of successful treatment, PCA is associated with long-term and pervasive effects on patients. A proactive alternative to treating PCA is to prevent its occurrence and progression prior to symptomatic malignancy. This may serve to address the issue of burgeoning healthcare costs and increasing number of sufferers. One potential regimen in service of this alternative is PCA chemoprevention. Here, chemical compounds with cancer preventive efficacy are identified on the basis of their potential in a host of categories: their historical medicinal use, correlation with reduced risk in population studies, non-toxicity, their unique chemical properties, or their role in biological systems. PCA chemopreventive agents are drawn from multiple broad classes of chemicals, themselves further subdivided based on source or potential effect, with most derived from natural products. Many such compounds have shown efficacy, varying from inhibiting deregulated PCA cell signaling, proliferation, epithelial to mesenchymal transition (EMT), invasion, metastasis, tumor growth and angiogenesis and inducing apoptosis. Overall, these chemopreventive agents show great promise in PCA pre-clinical models, though additional work remains to be done in effectively translating these findings into clinical use. PMID:24389535

  17. Prostate cancer chemoprevention: Strategies for designing efficient clinical trials.

    PubMed

    Lieberman, R

    2001-04-01

    A chemoprevention (CP) strategy has evolved for conducting efficient clinical trials for prostate cancer (PCa) prevention. It integrates five key components, including agents, biomarkers, cohorts, designs, and endpoints. The rationale for the CP strategy relates to the natural history of prostate cancer. There is a wide array of natural and synthetic agents that hold promise for inhibiting, reversing, or modulating the transition from normal to precancer and from precancer to cancer. These agent classes include antiandrogens, antiestrogens, phytoestrogens, antioxidants, anti-inflammatory (proapoptotic) agents, antiproliferation/antidifferentiation agents, signal transduction modulators of receptor tyrosine kinase and ras farnesylation, antiangiogenesis agents, insulinlike growth factor (IGF)-1, peroxisome proliferator-activator receptor modulators (-gamma and -delta), and gene-based interventions. Biomarkers and endpoints are guided by the level of evidence required (eg, phase 1, 2, 3). Two candidate surrogate endpoints (SE) based on histology are high-grade prostatic intraepithelial neoplasia (HGPIN) and computer-assisted image analysis of dysplastic lesions. Phase 1 trials use standard endpoints of safety, pharmacokinetics and limited pharmacodynamics. Phase 2 trials use endpoints of modulation of biomarkers and correlation with histology. Phase 3 trials use endpoints of clinical benefit, such as cancer incidence reduction and quality of life. Validation of a biomarker as a SE involves correlation of the biomarker with clinical benefit. Cohorts (target populations) for phase 2/3 trials include the general population of men over age 50 with a normal prostate-specific antigen (PSA), subjects with a strong family history of PCa, subjects with elevated PSA/negative biopsy, and subjects with HGPIN/negative biopsy. These at-risk populations reflect key individual risk factors (age, race, serum PSA [free/total]; serum IGF-1/IGF binding protein (IGFBP)-3; 1, 25(OH)(2) D3

  18. Chemoprevention of hormone-dependent prostate cancer in the Wistar-Unilever rat.

    PubMed

    McCormick, D L; Rao, K V

    1999-01-01

    The high incidence and long latent period of prostate cancer make it an ideal target for chemoprevention. We have evaluated a series of agents for chemopreventive efficacy using a model in which hormone-dependent prostate cancers are induced in the Wistar-Unilever (WU) rat by sequential treatment with antiandrogen (cyproterone acetate), androgen (testosterone propionate), and direct-acting chemical carcinogen (N-methyl-N-nitrosourea), followed by chronic androgen stimulation (testosterone). This regimen reproducibly induces prostate cancers in high incidence, with no gross toxicity and a low incidence of neoplasia in the seminal vesicle and other non-target tissues. Dehydroepiandrosterone (DHEA) and 9-cis-retinoic acid (9-cis-RA) are the most active agents identified to date. DHEA inhibits prostate cancer induction both when chronic administration is begun prior to carcinogen exposure, and when administration is delayed until preneoplastic prostate lesions are present. 9-cis-RA is the most potent inhibitor of prostate carcinogenesis identified; a study to determine the efficacy of delayed administration of 9-cis-RA is in progress. Liarozole fumarate confers modest protection against prostate carcinogenesis, while N-(4-hydroxyphenyl)retinamide (fenretinide), alpha-difluoromethylornithine, oltipraz, DL-alpha-tocopherol acetate (vitamin E), and L-selenomethionine are inactive. Chemoprevention efficacy evaluations in the WU rat will support the identification of agents that merit study for prostate cancer chemoprevention in humans.

  19. Dietary Pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer

    USDA-ARS?s Scientific Manuscript database

    Dietary nutrients with ability to reverse adverse epigenetic events have great potential for cancer chemoprevention. Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1-d...

  20. Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population.

    PubMed

    Luk, Sze-Ue; Lee, Terence Kin-Wah; Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

    2011-01-01

    Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

  1. Fatty Acid Synthesis Intermediates Represent Novel Noninvasive Biomarkers of Prostate Cancer Chemoprevention by Phenethyl Isothiocyanate.

    PubMed

    Singh, Krishna B; Singh, Shivendra V

    2017-03-14

    Increased de novo synthesis of fatty acids is a distinctive feature of prostate cancer, which continues to be a leading cause of cancer-related deaths among American men. Therefore, inhibition of de novo fatty acid synthesis represents an attractive strategy for chemoprevention of prostate cancer. We have shown previously that dietary feeding of phenethyl isothiocyanate (PEITC), a phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model. The present study was designed to test the hypothesis of whether fatty acid intermediate(s) can serve as noninvasive biomarker(s) of prostate cancer chemoprevention by PEITC using archived plasma and tumor specimens from the TRAMP study as well as cellular models of prostate cancer. Exposure of prostate cancer cells (LNCaP and 22Rv1) to pharmacological concentrations of PEITC resulted in downregulation of key fatty acid metabolism proteins, including acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A). The mRNA expression of FASN and CPT1A as well as acetyl-CoA levels were decreased by PEITC treatment in both cell lines. PEITC administration to TRAMP mice also resulted in a significant decrease in tumor expression of FASN protein. Consistent with these findings, the levels of total free fatty acids, total phospholipids, triglyceride, and ATP were significantly lower in the plasma and/or prostate tumors of PEITC-treated TRAMP mice compared with controls. The present study is the first to implicate inhibition of fatty acid synthesis in prostate cancer chemoprevention by PEITC.

  2. Prostate cancer chemoprevention in men of African descent: current state of the art and opportunities for future research.

    PubMed

    Chornokur, Ganna; Kumar, Nagi B

    2013-08-01

    Prostate cancer is the most frequently diagnosed malignancy in men. However, African American/Black men are 60 % more likely to be diagnosed with and 2.4 times more likely to die from prostate cancer, compared to Non-Hispanic White men. Despite the increased burden of this malignancy, no evidence-based recommendation regarding prostate cancer screening exists for the high-risk population. Moreover, in addition to screening and detection, African American men may constitute a prime population for chemoprevention. Early detection and chemoprevention may thus represent an integral part of prostate cancer control in this population. Importantly, recent research has elucidated biological differences in the prostate tumors of African American compared to European American men. The latter may enable a more favorable response in African American men to specific chemopreventive agents that target relevant signal transduction pathways. Based on this evolving evidence, the aims of this review are threefold. First, we aim to summarize the biological differences that were reported in the prostate tumors of African American and European American men. Second, we will review the single- and multi-target chemopreventive agents placing specific emphasis on the pathways implicated in prostate carcinogenesis. And lastly, we will discuss the most promising nutraceutical chemopreventive compounds. Our review underscores the promise of chemoprevention in prostate cancer control, as well as provides justification for further investment in this filed to ultimately reduce prostate cancer morbidity and mortality in this high-risk population of African American men.

  3. Null activity of selenium and vitamin e as cancer chemopreventive agents in the rat prostate.

    PubMed

    McCormick, David L; Rao, K V N; Johnson, William D; Bosland, Maarten C; Lubet, Ronald A; Steele, Vernon E

    2010-03-01

    To evaluate the potential efficacy of selenium and vitamin E as inhibitors of prostate carcinogenesis, four chemoprevention studies using a common protocol were done in a rat model of androgen-dependent prostate cancer. After stimulation of prostate epithelial cell proliferation by a sequential regimen of cyproterone acetate followed by testosterone propionate, male Wistar-Unilever rats received a single i.v. injection of N-methyl-N-nitrosourea (MNU) followed by chronic androgen stimulation via subcutaneous implantation of testosterone pellets. At 1 week post-MNU, groups of carcinogen-treated rats (39-44/group) were fed either a basal diet or a basal diet supplemented with l-selenomethionine (3 or 1.5 mg/kg diet; study 1), dl-alpha-tocopherol (vitamin E, 4,000 or 2,000 mg/kg diet; study 2), l-selenomethionine + vitamin E (3 + 2,000 mg/kg diet or 3 + 500 mg/kg diet; study 3), or selenized yeast (target selenium levels of 9 or 3 mg/kg diet; study 4). Each chemoprevention study was terminated at 13 months post-MNU, and prostate cancer incidence was determined by histopathologic evaluation. No statistically significant reductions in prostate cancer incidence were identified in any group receiving dietary supplementation with selenium and/or vitamin E. These data do not support the hypotheses that selenium and vitamin E are potent cancer chemopreventive agents in the prostate, and when considered with the recent clinical data reported in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), show the predictive nature of this animal model for human prostate cancer chemoprevention.

  4. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model By Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2011-02-01

    chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore, the FLiMP...polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer, Array, Genes. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing PCa growth by altering ω-6/ ω-3 ratios via diet

  5. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2010-02-01

    provide a valuable pre-clinical model for chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly...polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer, Array, Genes. 16. SECURITY CLASSIFICATION OF: 17...FLiMP+/+ mice fed a normal diet (PIN observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing PCa growth

  6. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2012-02-01

    chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore... acids effects on PIN development. 15. SUBJECT TERMS Diet, polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer...compared to FLiMP+/+ mice fed a normal diet (PIN observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing

  7. Chemopreventive Potential of Ethanolic Extracts of Luobuma Leaves (Apocynum venetum L.) in Androgen Insensitive Prostate Cancer.

    PubMed

    Huang, Szu-Ping; Ho, Tzu-Ming; Yang, Chih-Wen; Chang, Ya-Ju; Chen, Jie-Fu; Shaw, Ning-Sing; Horng, Jia-Cherng; Hsu, Shih-Lan; Liao, Ming-Yuan; Wu, Li-Chen; Ho, Ja-An Annie

    2017-08-28

    Luobuma (Apocynum venetum L. (AVL)) is a popular beverage in Asia and has been reportedly to be associated with the bioactivities such as cardiotonic, diuretic, antioxidative, and antihypertensive. However, its biofunction as chemoprevention activity is seldom addressed. Herein, we aimed to characterize the anti-androgen-insensitive-prostate-cancer (anti-AIPC) bioactive compounds of Luobuma, and to investigate the associated molecular mechanisms. Activity-guided-fractionation (antioxidative activity and cell survivability) of Luobuma ethanolic extracts was performed to isolate and characterize the major bioactive compounds using Ultra Performance Liquid Chromatography (UPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR). Plant sterols (lupeol, stigamasterol and β-sitosterol) and polyphenolics (isorhamnetin, kaempferol, and quercetin) were identified. Lupeol, a triterpene found in the fraction (F8) eluted by 10% ethyl acetate/90% hexane and accounted for 19.3% (w/w) of F8, inhibited the proliferation of PC3 cells. Both lupeol and F8 induced G2/M arrest, inhibition of β-catenin signaling, regulation of apoptotic signal molecules (cytochrome c, Bcl-2, P53, and caspase 3 and 8), and suppression DNA repair enzyme expression (Uracil-DNA glycosylase (UNG)). To our knowledge, our study is the first report that lupeol inhibited the expression of UNG to elicit the cytotoxicity against androgen-insensitive-prostate-cancer cells. Collectively, Luobuma, which contains several antitumor bioactive compounds, holds the potential to be a dietary chemopreventive agent for prostate cancer.

  8. Chemopreventive Effects of Tea in Prostate Cancer: Green Tea vs. Black Tea

    PubMed Central

    Henning, Susanne M.; Wang, Piwen; Heber, David

    2011-01-01

    The polyphenol compositions of green tea (GT) and black tea (BT) are very different due to post-harvest processing. GT contains higher concentrations of monomeric polyphenols, which affect numerous intracellular signaling pathways involved in prostate cancer (CaP) development. BT polymers, on the other hand, are poorly absorbed and are converted to phenolic acids by the colonic microflora. Therefore, after consumption of GT higher concentrations of polyphenols are found in the circulation while after BT consumption the phenolic acid levels in the circulation are higher. The majority of in vitro cell culture, in vivo animal, and clinical intervention studies examine the effects of extracts of GT or purified (-)-epigallocatechin-3-gallate (EGCG) on prostate carcinogenesis. These studies provide strong evidence supporting a chemopreventive effect of GT, but results from epidemiological studies of GT consumption are mixed. While the evidence for a chemopreventive effect of BT is much weaker than the body of evidence with regard to GT, there are several animal BT intervention studies demonstrating inhibition of CaP growth. This article will review in detail the available epidemiological and human clinical studies, as well as animal and basic mechanistic studies on GT and BT supporting a chemopreventive role in CaP. PMID:21538852

  9. Effects of Family History and Genetic Polymorphism on the Cost-Effectiveness of Chemoprevention With Finasteride for Prostate Cancer

    PubMed Central

    Reed, Shelby D.; Scales, Charles D.; Stewart, Suzanne B.; Sun, Jielin; Moul, Judd W.; Schulman, Kevin A.; Xu, Jianfeng

    2010-01-01

    Purpose Improvement in the cost-effectiveness of chemoprevention for prostate cancer could be realized through the identification of patients at higher risk. We estimated the cost-effectiveness of prostate cancer chemoprevention across risk groups defined by family history and number of risk alleles and the cost-effectiveness of targeting chemoprevention to higher-risk groups. Materials and Methods We developed a probabilistic Markov model to estimate costs, survival, and quality-adjusted survival across risk groups for patients receiving or not receiving chemoprevention with finasteride. The model uses data from national cancer registries, online sources, and the medical literature. Results The incremental cost-effectiveness of 25 years of chemoprevention with finasteride in patients aged 50 years was an estimated $89,300 per quality-adjusted life-year (95% confidence interval, $58,800-$149,800), assuming finasteride reduced all grades of prostate cancer by 24.8%. Among patients with positive family history (without genetic testing), chemoprevention provided 1 additional QALY at a cost of $64,200. Among patients with negative family history, at $400 per person tested, the cost-effectiveness of genetically targeted chemoprevention ranged from $98,100 per QALY when limiting finasteride to patients with 14 or more risk alleles to $103,200 per QALY when including patients with 8 or more risk alleles. Conclusions Although there are small differences in the cost-effectiveness of genetically targeted chemoprevention strategies in patients with negative family history, genetic testing could reduce total expenditures if used to target chemoprevention for higher-risk groups. PMID:21239023

  10. Effects of family history and genetic polymorphism on the cost-effectiveness of chemoprevention with finasteride for prostate cancer.

    PubMed

    Reed, Shelby D; Scales, Charles D; Stewart, Suzanne B; Sun, Jielin; Moul, Judd W; Schulman, Kevin A; Xu, Jianfeng

    2011-03-01

    Improvement in the cost-effectiveness of chemoprevention for prostate cancer could be realized through the identification of patients at higher risk. We estimated the cost-effectiveness of prostate cancer chemoprevention across risk groups defined by family history and number of risk alleles, and the cost-effectiveness of targeting chemoprevention to higher risk groups. We developed a probabilistic Markov model to estimate costs, survival and quality adjusted survival across risk groups for patients receiving or not receiving chemoprevention with finasteride. The model uses data from national cancer registries, online sources and the medical literature. The incremental cost-effectiveness of 25 years of chemoprevention with finasteride in patients 50 years old was an estimated $89,300 per quality adjusted life-year (95% CI $58,800-$149,800), assuming finasteride decreased all grades of prostate cancer by 24.8%. Among patients with a positive family history (without genetic testing) chemoprevention provided 1 additional quality adjusted life-year at a cost of $64,200. Among patients with a negative family history at $400 per person tested, the cost-effectiveness of genetically targeted chemoprevention ranged from $98,100 per quality adjusted life-year when limiting finasteride to individuals with 14 or more risk alleles, to $103,200 per quality adjusted life-year when including those with 8 or more risk alleles. Although there are small differences in the cost-effectiveness of genetically targeted chemoprevention strategies in patients with a negative family history, genetic testing could reduce total expenditures if used to target chemoprevention for higher risk groups. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Chemopreventive effect of quercetin in MNU and testosterone induced prostate cancer of Sprague-Dawley rats.

    PubMed

    Sharmila, Govindaraj; Athirai, Thavadurainathan; Kiruthiga, Balakrishnan; Senthilkumar, Kalimuthu; Elumalai, Perumal; Arunkumar, Ramachandran; Arunakaran, Jagadeesan

    2014-01-01

    Prostate cancer becomes an ideal target for chemoprevention because of its high incidence and extended natural history. The consumption of quercetin (plant flavonoid) in diet is associated with decreased risk of disease and many cancers but then this was not elucidated in prostate malignancy. Hence, a study in which the male Sprague-Dawley rats were induced prostate cancer by hormone (testosterone) and carcinogen (MNU) and simultaneously supplemented with quercetin (200 mg/Kg body weight) thrice a week, was conducted. After the treatment period, rats were killed; ventral and dorsolateral lobes of the prostate were dissected. Histology and oxidative stress markers LPO, H2O2, and antioxidant GSH level were measured in both lobes. The lipid peroxidation, H2O2, in (MNU+T) treated rats were increased and GSH level was decreased, whereas simultaneous quercetin-treated rats reverted back to normal level in both ventral and dorsolateral regions. The different patterns of PIN were observed with associated hyperplasia and dysplasia; changes in these regions and the occurrence of this lesion were reduced in simultaneous quercetin-treated rats. The study concluded that dietary quercetin prevented MNU + T-induced prostate carcinogenesis on both ventral and dorsolateral lobes of Sprague-Dawley rats.

  12. Variability in the androgen response of prostate epithelium to 5-alpha reductase inhibition: implications for prostate cancer chemoprevention

    PubMed Central

    Mostaghel, Elahe A.; Geng, Linda; Holcomb, Ilona; Coleman, Ilsa M.; Lucas, Jared; True, Lawrence D.; Nelson, Peter S.

    2009-01-01

    Androgens and the androgen receptor (AR) influence prostate carcinogenesis. Lowering intraprostatic dihydrotestosterone (DHT) by inhibiting 5-alpha-reductase (SRD5A) reduces prostate cancer (PCa) incidence, but is not uniformly effective. Mechanisms by which SRD5A inhibition influences PCa initiation and/or progression among different individuals have not been established. We sought to identify molecular alterations underlying the differential chemo-preventive activity of SRD5A inhibition. Men with clinically-localized PCa were randomized to prostatectomy alone (n=25) or 4 months treatment with the SRD5A-inhibitor dutasteride (0.5mg (n=26) or 3.5mg (n=24)) preceding prostatectomy. Serum and prostate androgens were measured using mass spectrometry. We evaluated benign epithelial gene expression using expression profiling and immunohistochemistry, and characterized tumor TMPRSS2-ERG fusion status using FISH. Dutasteride at 0.5 or 3.5mg decreased prostatic DHT by 93% (0.23ng/g; p<0.001) and 98.8% (0.04ng/g; p<0.001) vs. untreated patients (3.33ng/g). Despite significant and uniform suppression of tissue DHT, unsupervised clustering based on prostatic gene expression did not allow us to discriminate dutasteride-treated from untreated individuals. However, we could resolve subjects into distinct cohorts characterized by high or low expression of AR-regulated genes (irrespective of treatment dose) based solely on AR transcript expression. The high-dose dutasteride treatment group comprised significantly fewer cancers with TMPRSS2-ERG fusions. Despite substantial and uniform reductions in prostatic DHT, dutasteride was associated with highly variable alterations in benign epithelial gene expression. Segregation of subjects based on AR and androgen-regulated gene expression indicates patients are differentially sensitive to SRD5A inhibition. Tissue AR levels may serve as a pretreatment predictor of SRD5A chemo-preventive efficacy. PMID:20124490

  13. Mechanism of Selenium Chemoprevention and Therapy in Prostate Cancer

    DTIC Science & Technology

    2007-11-01

    913 Mol Cancer Ther 2006;5(4). April 2006 which is required for conversion of selenomethionine to the active methylselenol (12). The effect of...to very low levels of β- lyase activity which is required for conversion of selenomethionine to the active methylselenol . The effect of

  14. A Perspective on Prostate Carcinogenesis and Chemoprevention

    PubMed Central

    Bosland, Maarten C.; Ozten, Nur; Eskra, Jillian N.; Mahmoud, Abeer M.

    2015-01-01

    In this perspective, modifiable carcinogenic factors for the prostate are summarized. This is followed by a discussion of how current knowledge about causation of prostate cancer and chemoprevention of prostate cancer can be used to develop preventive strategies. Prostate cancer is a slowly developing cancer which offers opportunities for preventive interventions. Only a few randomized clinical trials of prostate cancer prevention have been completed. The SELECT study with selenium and vitamin E did not find protective effects, but in two trials with 5α-reductase inhibitors risk was reduced about 25%, showing that chemoprevention is possible and indicating that the androgen receptor is a suitable target. Besides smoking cessation and reduction of obesity, there are no known dietary or life style interventions that will have a major impact on prostate cancer risk. Inflammation of the prostate is an attractive target and aspirin may be a promising candidate agent, but has not been addressed yet in preclinical and clinical studies. Antioxidants other than selenium and vitamin E are unlikely to be very effective and data on several dietary supplements are not encouraging. More candidate agents need to be identified and tested in relevant and adequate preclinical models and Phase II trials that have predictive value for outcome of Phase III randomized studies. Doing this will require a systematic approach comparing preclinical and clinical study outcomes to determine their predictive value of preventive efficacy. PMID:26442200

  15. Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer

    DTIC Science & Technology

    2009-05-01

    samples and in all human prostate cancer cell lines, but not in normal or benign prostatic hyperplasia tissues (1-5). The inhibition of telomerase by...clinical implications. Telomerase activation has been reported in >90% of prostate cancer samples, but not in normal or benign prostatic hyperplasia tissues

  16. Dietary Supplement 4-Methylumbelliferone: An Effective Chemopreventive and Therapeutic Agent for Prostate Cancer

    PubMed Central

    Yates, Travis J.; Lopez, Luis E.; Lokeshwar, Soum D.; Ortiz, Nicolas; Kallifatidis, Georgios; Jordan, Andre; Hoye, Kelly; Altman, Norman

    2015-01-01

    Background: Prevention and treatment of advanced prostate cancer (PCa) by a nontoxic agent can improve outcome, while maintaining quality of life. 4-methylumbelliferone (4-MU) is a dietary supplement that inhibits hyaluronic acid (HA) synthesis. We evaluated the chemopreventive and therapeutic efficacy and mechanism of action of 4-MU. Methods: TRAMP mice (7–28 per group) were gavaged with 4-MU (450mg/kg/day) in a stage-specific treatment design (8–28, 12–28, 22–28 weeks). Efficacy of 4-MU (200–450mg/kg/day) was also evaluated in the PC3-ML/Luc+ intracardiac injection and DU145 subcutaneous models. PCa cells and tissues were analyzed for HA and Phosphoinositide 3-kinase (PI-3K)/Akt signaling and apoptosis effectors. HA add-back and myristoylated Akt (mAkt) overexpression studies evaluated the mechanism of action of 4-MU. Data were analyzed with one-way analysis of variance and unpaired t test or Tukey’s multiple comparison test. All statistical tests were two-sided. Results: While vehicle-treated transgenic adenocarcinoma of the prostate (TRAMP) mice developed prostate tumors and metastases at 28 weeks, both were abrogated in treatment groups, without serum/organ toxicity or weight loss; no tumors developed at one year, even after stopping the treatment at 28 weeks. 4-MU did not alter the transgene or neuroendocrine marker expression but downregulated HA levels. However, 4-MU decreased microvessel density and proliferative index (P < .0001,). 4-MU completely prevented/inhibited skeletal metastasis in the PC3-ML/Luc+ model and DU145-tumor growth (85–90% inhibition, P = .002). 4-MU also statistically significantly downregulated HA receptors, PI-3K/CD44 complex and activity, Akt signaling, and β-catenin levels/activation, but upregulated GSK-3 function, E-cadherin, and apoptosis effectors (P < .001); HA addition or mAkt overexpression rescued these effects. Conclusion: 4-MU is an effective nontoxic, oral chemopreventive, and therapeutic agent that

  17. Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures

    PubMed Central

    Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Connors, Shahnjayla; Pow-Sang, Julio; Spiess, Philippe E.; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R.; Schreiber, Fred; Anderson, Kyle

    2014-01-01

    In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention. PMID:24533253

  18. A Review of the Potential of Phytochemicals from Prunus africana (Hook f.) Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer

    PubMed Central

    Komakech, Richard; Omujal, Francis

    2017-01-01

    Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer. PMID:28286531

  19. Perspectives in cancer chemoprevention.

    PubMed Central

    Stoner, G D; Morse, M A; Kelloff, G J

    1997-01-01

    Cancer chemoprevention can be defined as prevention of cancer by the administration of one or more chemical entities, either as individual drugs or as naturally occurring constituents of the diet. Based largely on the time period that chemopreventive agents exhibit activity in animal models of carcinogenesis, they can be classified as inhibitors of carcinogen formation, blocking agents, and suppressing agents. The majority of compounds that inhibit the formation of carcinogens prevent the formation of nitrosamines from secondary amines and nitrite in an acidic environment. Blocking agents are inhibitors of tumor initiation, while suppressing agents are inhibitors of tumor promotion/progression. Many well-characterized chemopreventive agents act at one or more steps in both tumor initiation and promotion/progression. The objective of this paper is to provide a general discussion of the mechanisms through which chemopreventive agents inhibit carcinogenesis. Examples of agents that act through these mechanisms are given; however, a complete listing of effective chemopreventive agents is not possible within the context of this paper. At the conclusion is a brief discussion of future prospects in cancer chemoprevention and obstacles to overcome. PMID:9255586

  20. Chemoprevention of bladder cancer.

    PubMed

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    possibility with long-term administration, the dose should be decreased to 16,000 IU after 3 years. High doses of beta-carotene should be avoided based on a large clinical trial reporting a 25% increase in the number of cases of prostate cancer and a statistically significant increase in the incidence of lung cancer. Vitamin B6 has been studied in several clinical trials in bladder cancer. The US-based Veterans Administration cooperative study found benefit for vitamin B6 when given as a single agent. Data for vitamins C and E are insufficient to recommend either agent as stand-alone treatment. Nonetheless, each of these vitamins is known to have beneficial effects, including improved function of the immune system. It is possible that only a small percentage of patients with bladder cancer respond to vitamins B6, C, or E, yet each is safe, nontoxic, and inexpensive. In an effort to pool the efficacy of individual agents and to increase the power of study, the authors evaluated the combination of vitamins A, B6, C, and E in a double-blind trial. The observed 50% 5-year reduction in tumor recurrence was highly significant and greater than would be expected for any of the individual ingredients and suggests that combinations of nutritional agents may be most appropriate. A large-volume study along similar lines is being conducted. Among the numerous other compounds and dietary substances purported to have chemopreventive effect, soybeans, garlic, and green tea stand out as having the greatest promise and can freely be recommended to patients. For synthetically synthesized agents such as celecoxib, piroxicam, or DFMO, recommendations must be deferred until the results of clinical trials are conclusively in favor of their use. Many of the dietary factors found to be protective against bladder cancer are being investigated in other cancers and are beneficial to general health. Although naturally occurring nutrients are ideal, especially because the delicate balance of various

  1. [Chemoprevention of colorectal cancer].

    PubMed

    Herszényi, László; Juhász, Márk; Prónai, László; Tulassay, Zsolt

    2004-03-21

    Although colorectal cancer is one of the most preventable forms of cancer, it remains the second leading cause of cancer death worldwide. Primary prevention involves the identification and elimination of factors, which cause or promote colorectal cancer. The goal of screening is to prevent colorectal cancer mortality through the detection and treatment of premalignant adenomas and curable-stage cancer. Most colorectal cancers are believed to arise from adenomatous polyps. Early identification and removal of adenomas can prevent the development of colorectal cancer. Chemoprevention is the use of specific chemical compounds to prevent, inhibit, or reverse carcinogenesis. Several chemoprevention options have been investigated and confirmed as effective. Aspirin and other nonsteroidal anti-inflammatory drugs are the most widely studied agents, their use has been consistently associated with reduction in the risk of mortality and the incidence of colorectal adenomas and cancers. The selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) have been demonstrated to decrease the number and the size of polyps in patients with familial adenomatous polyposis syndrome. Because the gastrointestinal toxicity of coxibs is lower, it might be safer than aspirin or other non-selective nonsteroidal anti-inflammatory drugs for long-term use. This review aims to summarize the recent theoretical and practical advances in the chemoprevention of colorectal cancer.

  2. Chemoprevention of Lung Cancer

    PubMed Central

    Szabo, Eva; Mao, Jenny T.; Lam, Stephen; Reid, Mary E.

    2013-01-01

    Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers. Chemoprevention refers to the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results. To facilitate the evaluation of promising agents and to lessen the need for a large sample size, extensive time commitment, and expense, surrogate end point biomarker trials are being conducted to assist in identifying the most promising agents for later-stage chemoprevention trials. With the understanding of important cellular signaling pathways and the expansion of potentially important targets, agents (many of which target inflammation and the arachidonic acid pathway) are being developed and tested which may prevent or reverse lung carcinogenesis. Conclusions: By integrating biologic knowledge, additional early-phase trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID:23649449

  3. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells.

    PubMed

    Wang, Piwen; Wang, Bin; Chung, Seyung; Wu, Yanyuan; Henning, Susanne M; Vadgama, Jaydutt V

    2014-08-05

    The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (-)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2-4 mg/L (about 5-10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.

  4. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells

    PubMed Central

    Wang, Piwen; Wang, Bin; Chung, Seyung; Wu, Yanyuan; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (−)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2–4 mg/L (about 5–10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer. PMID:25243063

  5. Teriflunomide (leflunomide) promotes cytostatic, antioxidant, and apoptotic effects in transformed prostate epithelial cells: evidence supporting a role for teriflunomide in prostate cancer chemoprevention.

    PubMed

    Hail, Numsen; Chen, Ping; Bushman, Lane R

    2010-06-01

    Teriflunomide (TFN) is an inhibitor of de novo pyrimidine synthesis and the active metabolite of leflunomide. Leflunomide is prescribed to patients worldwide as an immunomodulatory and anti-inflammatory disease-modifying prodrug. Leflunomide inhibited the growth of human prostate cancer xenographs in mice, and leflunomide or TFN promoted cytostasis and/or apoptosis in cultured cells. These findings suggest that TFN could be useful in prostate cancer chemoprevention. We investigated the possible mechanistic aspects of this tenet by characterizing the effects of TFN using premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. TFN promoted a dose- and time-dependent cytostasis or apoptosis induction in these cells. The cytostatic effects of TFN, which were reversible but not by the presence of excess uridine in the culture medium, included diminished cellular uridine levels, an inhibition in oxygen consumption, a suppression of reactive oxygen species (ROS) generation, S-phase cell cycle arrest, and a conspicuous reduction in the size and number of the nucleoli in the nuclei of these cells. Conversely, TFN's apoptogenic effects were characteristic of catastrophic mitochondrial disruption (i.e., a dissipation of mitochondrial inner transmembrane potential, enhanced ROS production, mitochondrial cytochrome c release, and cytoplasmic vacuolization) and followed by DNA fragmentation. The respiration-deficient derivatives of the DU-145 cells, which are also uridine auxotrophs, were markedly resistant to the cytostatic and apoptotic effects of TFN, implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiration competent cells. These mechanistic findings advocate a role for TFN and mitochondrial bioenergetics in prostate cancer chemoprevention.

  6. Teriflunomide (Leflunomide) Promotes Cytostatic, Antioxidant, and Apoptotic Effects in Transformed Prostate Epithelial Cells: Evidence Supporting a Role for Teriflunomide in Prostate Cancer Chemoprevention1

    PubMed Central

    Hail, Numsen; Chen, Ping; Bushman, Lane R

    2010-01-01

    Teriflunomide (TFN) is an inhibitor of de novo pyrimidine synthesis and the active metabolite of leflunomide. Leflunomide is prescribed to patients worldwide as an immunomodulatory and anti-inflammatory disease-modifying prodrug. Leflunomide inhibited the growth of human prostate cancer xenographs in mice, and leflunomide or TFN promoted cytostasis and/or apoptosis in cultured cells. These findings suggest that TFN could be useful in prostate cancer chemoprevention. We investigated the possible mechanistic aspects of this tenet by characterizing the effects of TFN using premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. TFN promoted a dose- and time-dependent cytostasis or apoptosis induction in these cells. The cytostatic effects of TFN, which were reversible but not by the presence of excess uridine in the culture medium, included diminished cellular uridine levels, an inhibition in oxygen consumption, a suppression of reactive oxygen species (ROS) generation, S-phase cell cycle arrest, and a conspicuous reduction in the size and number of the nucleoli in the nuclei of these cells. Conversely, TFN's apoptogenic effects were characteristic of catastrophic mitochondrial disruption (i.e., a dissipation of mitochondrial inner transmembrane potential, enhanced ROS production, mitochondrial cytochrome c release, and cytoplasmic vacuolization) and followed by DNA fragmentation. The respiration-deficient derivatives of the DU-145 cells, which are also uridine auxotrophs, were markedly resistant to the cytostatic and apoptotic effects of TFN, implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiration competent cells. These mechanistic findings advocate a role for TFN and mitochondrial bioenergetics in prostate cancer chemoprevention. PMID:20563249

  7. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2012-12-01

    omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa...development. 15. SUBJECT TERMS Diet, polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer, Array, Genes. 16...competing with ω-6 fatty acids for 15-LO-1, and COX-2 activities. REPORTABLE OUTCOMES: None. CONCLUSION: Omega (ω)-3 fatty acids can

  8. GKLF as a Novel Target in Selenium Chemoprevention of Prostate Cancer

    DTIC Science & Technology

    2007-02-01

    development and treatment of prostate cancer, J.Mol.Med., 77: 419- 426, 1999. 3 Heinlein ,C.A. and Chang,C. Androgen receptor (AR) coregulators: an...the androgen receptor. Biochemistry 2002;41: 11824–31. 16. Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview. Endocr Rev 2002;23

  9. Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention.

    PubMed

    Beaver, Laura M; Buchanan, Alex; Sokolowski, Elizabeth I; Riscoe, Allison N; Wong, Carmen P; Chang, Jeff H; Löhr, Christiane V; Williams, David E; Dashwood, Roderick H; Ho, Emily

    2014-10-01

    Epidemiological studies provide evidence that consumption of cruciferous vegetables, like broccoli, can reduce the risk of cancer development. Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for this cancer-specific cytotoxicity remain unclear. We utilized RNA sequencing and determined the transcriptomes of normal prostate epithelial cells, androgen-dependent prostate cancer cells, and androgen-independent prostate cancer cells treated with SFN. SFN treatment dynamically altered gene expression and resulted in distinct transcriptome profiles depending on prostate cell line. SFN also down-regulated the expression of genes that were up-regulated in prostate cancer cells. Network analysis of genes altered by SFN treatment revealed that the transcription factor Specificity protein 1 (Sp1) was present in an average of 90.5% of networks. Sp1 protein was significantly decreased by SFN treatment in prostate cancer cells and Sp1 may be an important mediator of SFN-induced changes in expression. Overall, the data show that SFN alters gene expression differentially in normal and cancer cells with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2008-02-01

    either omega (n)-3 or n-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore, the FLiMP mice, which overexpress human 15...effects of excessive n-6 LA diet consumption in the progression of PCa. 15. SUBJECT TERMS Linoleic acid ; LO or LOX, lipoxygenase; PUFA , Polyunsaturated... fatty acid ; PCa, Prostate Cancer, MMHCC, Mouse Models of Human Cancer Consortium; IHC, immunohistochemistry; H & E, Hematoxylin and Eosin; FLiMP

  11. [Coffee in Cancer Chemoprevention].

    PubMed

    Neuwirthová, J; Gál, B; Smilek, P; Urbánková, P

    Coffee consumption is associated with a reduced risk of several diseases including cancer. Its chemopreventive effect has been studied in vitro, in animal models, and more recently in humans. Several modes of action have been proposed, namely, inhibition of oxidative stress and damage, activation of metabolizing liver enzymes involved in carcinogen detoxification processes, and anti-inflammatory effects. The antioxidant activity of coffee relies partly on its chlorogenic acid content and is increased during the roasting process. Maximum antioxidant activity is observed for medium-roasted coffee. The roasting process leads to the formation of several components, e.g., melanoidins, which have antioxidant and anti-inflammatory properties. Coffee also contains two specific diterpenes, cafestol and kahweol, which have anticarcinogenic properties. Roasted coffee is a complex mixture of various chemicals. Previous studies have reported that the chemopreventive components present in coffee induce apoptosis, inhibit growth and metastasis of tumor cells, and elicit antiangiogenic effects. A meta-analysis of epidemiological studies showed that coffee consumption is associated with a lower risk of developing various malignant tumors. This review summarizes the molecular mechanisms and the experimental and epidemiological evidence supporting the chemopreventive effect of coffee.Key words: coffee - chemoprevention - antioxidative enzyme - detoxification enzyme - anti-inflammatory effect The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 9. 2016Accepted: 24. 11. 2016.

  12. Vitamin D in cancer chemoprevention.

    PubMed

    Giammanco, Marco; Di Majo, Danila; La Guardia, Maurizio; Aiello, Stefania; Crescimannno, Marilena; Flandina, Carla; Tumminello, Francesca M; Leto, Gaetano

    2015-01-01

    There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo. The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy. A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar. Experimental and clinical observations suggest that Vit D and its analogues may be effective in preventing the malignant transformation and/or the progression of various types of human tumors including breast cancer, prostate cancer, colorectal cancer, and some hematological malignances. These findings suggest the possibility of the clinical use of these molecules as novel potential chemopreventive and anticancer agents.

  13. Use of 5-α-Reductase Inhibitors for Prostate Cancer Chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline

    PubMed Central

    Kramer, Barnett S.; Hagerty, Karen L.; Justman, Stewart; Somerfield, Mark R.; Albertsen, Peter C.; Blot, William J.; Ballentine Carter, H.; Costantino, Joseph P.; Epstein, Jonathan I.; Godley, Paul A.; Harris, Russell P.; Wilt, Timothy J.; Wittes, Janet; Zon, Robin; Schellhammer, Paul

    2009-01-01

    Purpose To develop an evidence-based guideline on the use of 5-α-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. Methods The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. Results The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. Conclusion Asymptomatic men with a prostate-specific antigen (PSA) ≤ 3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI. PMID:19252137

  14. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2009-02-01

    in either omega (ω)-3 or ω-6 polyunsaturated fatty acids (PUFAs) directly impact PCa tumor growth. Furthermore, the FLiMP mice, which overexpress ...monounsaturated fatty acid pathway enzyme, Δ-9-desaturase which is a member in the fatty acid synthase (FASN) pathway, increased in tumors from SDA... Overexpression of 15-lipoxygenase-1 in PC-3 human prostate cancer cells increases tumorigenesis. Carcinogenesis, 22, 1765-73. 6. Ziboh A and VangK

  15. Challenges and Potential Solutions to Meeting Accrual Goals in a Phase II Chemoprevention Trial for Prostate Cancer

    PubMed Central

    Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Pow-Sang, Julio; Spiess, Philippe E.; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R.; Schreiber, Fred; Slaton, Joel; Anderson, J Kyle

    2011-01-01

    Objective The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. Methods We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. Results Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. Conclusion A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials. PMID:22101219

  16. Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer.

    PubMed

    Kallifatidis, Georgios; Hoy, James J; Lokeshwar, Bal L

    2016-10-01

    Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, surveillance and palliative care of PCa have significantly increased quality of life and survival following diagnosis. However, over 20% of patients initially diagnosed with PCa still develop an aggressive and treatment-refractory disease. Prevention or treatment for hormone-refractory PCa using bioactive compounds from marine sponges, mushrooms, and edible plants either as single agents or as adjuvants to existing therapy, has not been clinically successful. Major advancements have been made in the identification, testing and modification of the existing molecular structures of natural products. Additionally, conjugation of these compounds to novel matrices has enhanced their bio-availability; a big step towards bringing natural products to clinical trials. Natural products derived from edible plants (nutraceuticals), and common folk-medicines might offer advantages over synthetic compounds due to their broader range of targets, as compared to mostly single target synthetic anticancer compounds; e.g. kinase inhibitors. The use of synthetic inhibitors or antibodies that target a single aberrant molecule in cancer cells might be in part responsible for emergence of treatment refractory cancers. Nutraceuticals that target AR signaling (epigallocatechin gallate [EGCG], curcumin, and 5α-reductase inhibitors), AR synthesis (ericifolin, capsaicin and others) or AR degradation (betulinic acid, di-indolyl diamine, sulphoraphane, silibinin and others) are prime candidates for use as adjuvant or mono-therapies. Nutraceuticals target multiple pathophysiological mechanisms involved during cancer development and progression and thus have potential to simultaneously

  17. Mitochondrial structure alteration in human prostate cancer cells upon initial interaction with a chemopreventive agent phenethyl isothiocyanate.

    PubMed

    Xue, Chengsen; Pasolli, Hilda A; Piscopo, Irene; Gros, Daniel J; Liu, Christina; Chen, Yamei; Chiao, Jen Wei

    2014-03-31

    Phenethyl isothiocyanate (PEITC), present naturally in cruciferous vegetables, is a chemopreventive agent. It blocks initiation and post-initiation progression of carcinogenesis. Mechanism study in human prostate cancer cells revealed that PEITC is a dual inhibitor of aberrant DNA hypermethylation and histone deacetylases, reactivating silenced genes and regulating the androgen-mediated growth of tumor cells. The identity of the cellular organelle that initially interacts with PEITC has not been fully described. Human prostate cancer LNCaP cells were exposed to PEITC and the effects on cellular fine structure examined by transmission electron microscopic studies. Alteration of mitochondrial membrane potential and cytochrome c release were evaluated as early events of apoptosis, and the TUNEL method for quantifying apoptotic cells. Mitochondria were isolated for determining their protein expression. Ultrastructural analyses have revealed condensed mitochondria and a perturbed mitochondrial cristae structure, which assumed a rounded and dilated shape within 4-hours of PEITC contact, and became more pronounced with longer PEITC exposure. They presented as the most prominent intracellular alterations in the early hours. Mitochondria structure alterations were demonstrated, for the first time, with the isothiocyanates. An increase in the number of smooth endoplasmic reticulum and vacuoles were also noted that is consistent with the presence of autophagy. Early events of apoptosis were detected, with cytochrome c released along with the appearance of mitochondrial alteration. Mitochondrial membrane potential was disrupted within 18 hours of PEITC exposure, preceding the appearance of apoptotic cells with DNA strand breaks. In parallel, the expression of the mitochondrial class III ß-tubulin in the outer membrane, which associates with the permeability transition pore, was significantly reduced as examined with isolated mitochondria. Mitochondria may represent the

  18. Chemoprevention strategies for pancreatic cancer

    PubMed Central

    Stan, Silvia D.; Singh, Shivendra V.; Brand, Randall E.

    2010-01-01

    Pancreatic cancer has a poor prognosis and it is often diagnosed at advanced stages, which makes it very difficult to treat. The low survival rate of patients with pancreatic cancer points toward an increased need for novel therapeutic and chemopreventive strategies and early detection. Increased consumption of fruits and vegetables has been associated with a reduced risk of pancreatic cancer. Both synthetic as well as natural, diet-derived bioactive compounds have been evaluated as pancreatic cancer chemopreventive agents and have been shown to have various degrees of efficacy in cellular and in vivo animal models. Some chemopreventive agents (for example curcumin, resveratrol, B-DIM) have also been reported to sensitize pancreatic cancer cells to standard chemotherapeutic drugs (for example gemcitabine or erlotinib), which suggests the potential use of chemopreventive agents as potentiators of standard chemotherapy. Very few clinical trials with pancreatic cancer chemopreventive agents have been completed and some are in early phases. Further development of pancreatic cancer chemopreventive agents may prove to be tremendously valuable for individuals at high-risk of developing pancreatic cancer and patients who present with premalignant lesions. This Review discusses the current state of the pancreatic cancer chemoprevention field and highlights the challenges ahead. PMID:20440279

  19. The challenges for cancer chemoprevention.

    PubMed

    Penny, Lewis K; Wallace, Heather M

    2015-12-21

    The incidence of cancer is rising in parallel with an ageing populous thus increasing the strain on both treatment options and budgets for healthcare providers worldwide. New cancer therapies are being developed but at what cost? The new treatments are expensive and poor survival rates still exist for some cancers. What is needed now is to prevent or at least limit the disease occurring in the first place. This review evaluates the current situation and the progress in upcoming strategies as well as suggesting some areas for further research within the increasingly important field of cancer chemoprevention. The key principles of cancer chemoprevention are discussed and areas for improvement highlighted. Despite significant progress, chemoprevention has not been widely adopted. Cancer chemoprevention has many challenges to face but this only emphasises the size of the task. These hurdles include a lack of awareness of the benefits, a lack of interest and a lack of investment in taking prevention forward. Despite the huge potential importance of cancer prevention and clinical success stories such as the well-publicised HPV vaccine, the challenges remain significant. With cancer and its treatment being a global issue, the opportunities offered by chemoprevention must be re-evaluated and uptake of chemoprevention actively encouraged. If chemoprevention is to be adopted successfully, a holistic approach is required. This approach will involve multidisciplinary teams of healthcare providers and scientists with the big challenge particularly for medicinal chemists being to design and synthesise the ideal chemopreventative agent.

  20. Orange juice and cancer chemoprevention.

    PubMed

    Franke, Silvia Isabel Rech; Guecheva, Temenouga Nikolova; Henriques, João Antonio Pêgas; Prá, Daniel

    2013-01-01

    Orange juice (OJ) is among the most consumed fruit juices worldwide, and its chemopreventive action is fairly addressed in the literature. This review critically presents the available evidence linking OJ with cancer chemoprevention and on discussing the putative mechanisms and negative health effects. The chemopreventive action of OJ is related to its effect on metabolic enzymes and its antiinflammatory, cytoprotective/apoptotic, hormonal, cell signaling-modulating, antioxidant, and antigenotoxic effects. Most studies on OJ are in vitro, and few are conducted in vivo. Results from in vitro studies must be interpreted carefully because these findings do not consider in vivo bioavailability. However, such results are useful for studying the impact of different processing and storage methods on OJ's chemopreventive effect. Evidence of OJ's chemoprevention in humans is limited. OJ is antimutagenic in bacteria and antigenotoxic in humans and rodents. Studies using rodent cancer models showed that OJ is cancer chemopreventive, influencing either the induction stage or the promotion stage. The composition and, therefore, the chemopreventive action of OJ might be influenced by different cultivars, climates, extraction methods, packaging, storage temperatures, and shelf lives, among other factors. Epidemiological studies and randomized controlled intervention studies in humans evaluating the chemopreventive effect of OJ, taking into consideration variability in OJ composition, are needed.

  1. The failure of cancer chemoprevention.

    PubMed

    Potter, John D

    2014-05-01

    Chemoprevention is proposed as a clinical analogue of population prevention, aimed at reducing likelihood of disease progression, not across the population, but in identified high-risk individuals and not by behavioral or lifestyle modification, but by the use of pharmaceutical agents. Cardiovascular chemoprevention is successful via control of hyperlipidemias and hypertension. However, chemoprevention of cancer is an almost universal failure: not only are some results null; even more frequently, there is an excess of disease, including disease that the agents were chosen specifically to reduce. A brief introduction is followed by the evidence for a wide variety of agents and their largely deleterious, sometimes null, and in one case, largely beneficial, consequences as possible chemopreventives. The agents include (i) those that are food derived and their synthetic analogues: β-carotene, folic acid, retinol and retinoids, vitamin E, multivitamin supplements, vitamin C, calcium and selenium and (ii) agents targeted at metabolic and hormonal pathways: statins, estrogen and antagonists, 5α-reductase inhibitors. There are two agents for which there is good evidence of benefit when the strategy is focused on those at defined high risk but where wider application is much more problematic: aspirin and tamoxifen. The major problems with cancer chemoprevention are presented. This is followed by a hypothesis to explain the failure of cancer chemoprevention as an enterprise, arguing that the central tenets that underpin it are flawed and showing why, far from doing good, cancer chemoprevention causes harm.

  2. Cancer chemoprevention - selected molecular mechanisms.

    PubMed

    Walczak, Katarzyna; Marciniak, Sebastian; Rajtar, Grażyna

    2017-03-02

    The effect of diet on cancer formation and prevention of carcinogenesis has attracted considerable attention for years and is the subject of several studies. Some components of the daily diet, such as resveratrol, curcumin, genistein, gingerol, can significantly reduce the risk of cancer or affect the rate of tumor progression. Cancer chemoprevention assumes the use of natural or synthetic biologically active substances in order to prevent, inhibit or reverse the progression of cancer. There are many biologically active compounds in several natural products, i.e. garlic, ginger, soy, curcuma, tomatoes, cruciferous plants or green tea. Their chemopreventive activity is based on the inhibition of processes underlying carcinogenesis (inflammation, transformation and proliferation), but also affects the final phase of carcinogenesis - angiogenesis and metastasis. Despite the relatively low toxicity of chemopreventive agents, their molecular targets often coincide with the objectives of the currently used cancer therapies. The widespread use of chemopreventive agents may contribute to reduction of the rate of cancer incidence, and increase the effectiveness of conventional cancer therapies. In the present study, selected molecular mechanisms of the chemopreventive activity have been discussed, especially their involvement in the regulation of signal transduction, cell cycle regulation, apoptosis, metastasis and angiogenesis. The role of chemopreventive agents in the inflammatory process, the metabolism of xenobiotics and multidrug resistance has been also characterized.

  3. Selective apoptosis induction by the cancer chemopreventive agent N-(4-hydroxyphenyl)retinamide is achieved by modulating mitochondrial bioenergetics in premalignant and malignant human prostate epithelial cells.

    PubMed

    Hail, Numsen; Chen, Ping; Kepa, Jadwiga J

    2009-07-01

    Prostate tumorigenesis is coupled with an early metabolic switch in transformed prostate epithelial cells that effectively increases their mitochondrial bioenergetic capacity. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) inhibits prostate cancer development in vivo, and triggers reactive oxygen species (ROS)-dependent prostate cancer cell apoptosis in vitro. The possibility that 4HPR-induced ROS production is associated with mitochondrial bioenergetics and required for apoptosis induction in transformed prostate epithelial cells in vitro would advocate a prospective mechanistic basis for 4HPR-mediated prostate cancer chemoprevention in vivo. We investigated this tenet by comparing and contrasting 4HPR's effects on premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. 4HPR promoted a dose- and/or time-dependent apoptosis induction in PWR-1E and DU-145 cells, which was preceded by and dependent on an increase in mitochondrial ROS production. In this regard, the PWR-1E cells were more sensitive than the DU-145 cells, and they consumed roughly twice as much oxygen as the DU-145 cells suggesting oxidative phosphorylation was higher in the premalignant cells. Interestingly, increasing the [Ca(2+)] in the culture medium of the PWR-1E cells attenuated their proliferation as well as their mitochondrial bioenergetic capacity and 4HPR's cytotoxic effects. Correspondingly, the respiration-deficient derivatives (i.e., rho(0) cells lacking mitochondrial DNA) of DU-145 cells were markedly resistant to 4HPR-induced ROS production and apoptosis. Together, these observations implied that the reduction of mitochondrial bioenergetics protected PWR-1E and DU-145 cells against the cytotoxic effects of 4HPR, and support the concept that oxidative phosphorylation is an essential determinant in 4HPR's apoptogenic signaling in transformed human prostate epithelial cells.

  4. Selective apoptosis induction by the cancer chemopreventive agent N-(4-hydroxyphenyl)retinamide is achieved by modulating mitochondrial bioenergetics in premalignant and malignant human prostate epithelial cells

    PubMed Central

    Hail, Numsen; Chen, Ping; Kepa, Jadwiga J.

    2010-01-01

    Prostate tumorigenesis is coupled with an early metabolic switch in transformed prostate epithelial cells that effectively increases their mitochondrial bioenergetic capacity. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) inhibits prostate cancer development in vivo, and triggers reactive oxygen species (ROS)-dependent prostate cancer cell apoptosis in vitro. The possibility that 4HPR-induced ROS production is associated with mitochondrial bioenergetics and required for apoptosis induction in transformed prostate epithelial cells in vitro would advocate a prospective mechanistic basis for 4HPR-mediated prostate cancer chemoprevention in vivo. We investigated this tenet by comparing and contrasting 4HPR's effects on premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. 4HPR promoted a dose- and/or time-dependent apoptosis induction in PWR-1E and DU-145 cells, which was preceded by and dependent on an increase in mitochondrial ROS production. In this regard, the PWR-1E cells were more sensitive than the DU-145 cells, and they consumed roughly twice as much oxygen as the DU-145 cells suggesting oxidative phosphorylation was higher in the premalignant cells. Interestingly, increasing the [Ca2+] in the culture medium of the PWR-1E cells attenuated their proliferation as well as their mitochondrial bioenergetic capacity and 4HPR's cytotoxic effects. Correspondingly, the respiration-deficient derivatives (i.e., ρ0 cells lacking mitochondrial DNA) of DU-145 cells were markedly resistant to 4HPR-induced ROS production and apoptosis. Together, these observations implied that the reduction of mitochondrial bioenergetics protected PWR-1E and DU-145 cells against the cytotoxic effects of 4HPR, and support the concept that oxidative phosphorylation is an essential determinant in 4HPR's apoptogenic signaling in transformed human prostate epithelial cells. PMID:19421858

  5. Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer

    DTIC Science & Technology

    2011-04-01

    primers and Taqman probes for β-actin (a housekeeping gene), prostate- specific antigen (PSA), and hTERT were products of Applied Biosystems. Western...inactivation telomerase control was tested to ensure the specificity of the reaction. The PCR products were separated on a 28 × 20 cm 12% nondenaturing...Chem Res Toxicol 2009;22:1795–801. 25. Institute of Medicine FaNB. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids . Washington

  6. Evaluation of the cancer chemopreventive efficacy of rice bran in genetic mouse models of breast, prostate and intestinal carcinogenesis

    PubMed Central

    Verschoyle, R D; Greaves, P; Cai, H; Edwards, R E; Steward, W P; Gescher, A J

    2007-01-01

    Brown rice is a staple dietary constituent in Asia, whereas rice consumed in the Western world is generally white, obtained from brown rice by removal of the bran. We tested the hypothesis that rice bran interferes with development of tumours in TAg, TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) or ApcMin mice, genetic models of mammary, prostate and intestinal carcinogenesis, respectively. Mice received rice bran (30%) in AIN-93G diet throughout their post-weaning lifespan. In TAg and TRAMP mice, rice bran did not affect carcinoma development. In TRAMP or wild-type C57Bl6/J mice, dietary rice bran increased kidney weight by 18 and 20%, respectively. Consumption of rice bran reduced numbers of intestinal adenomas in ApcMin mice by 51% (P<0.01), compared to mice on control diet. In parallel, dietary rice bran decreased intestinal haemorrhage in these mice, as reflected by increased haematocrit. At 10% in the diet, rice bran did not significantly retard ApcMin adenoma development. Likewise, low-fibre rice bran (30% in the diet) did not affect intestinal carcinogenesis, suggesting that the fibrous constituents of the bran mediate chemopreventive efficacy. The results suggest that rice bran might be beneficially evaluated as a putative chemopreventive intervention in humans with intestinal polyps. PMID:17211473

  7. Prostate Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Prostate Cancer What is Prostate Cancer? How Tumors Form The body is made up ... the Escape (Esc) button on your keyboard.) How Prostate Cancer Occurs Prostate cancer occurs when a tumor forms ...

  8. Chemoprevention: a primary cancer prevention strategy.

    PubMed

    Smith, Judith J; Tully, Patricia; Padberg, Rose Mary

    2005-11-01

    To review cancer chemoprevention clinical trials, and to discuss associated roles, responsibilities, and challenges for nursing. Journal articles, textbooks, and government reports. Chemoprevention offers a promising approach to primary cancer prevention for a variety of organ systems. Candidate agents are rigorously evaluated for safety and efficacy through the chemoprevention clinical trials process. Chemoprevention is an emerging discipline in which complex clinical trials are being conducted. Nurses play key roles in planning, coordinating, and implementing these studies.

  9. Cancer chemoprevention: a radical perspective.

    PubMed

    Hail, Numsen; Cortes, Marcela; Drake, Edgar N; Spallholz, Julian E

    2008-07-15

    Cancer chemopreventive agents block the transformation of normal cells and/or suppress the promotion of premalignant cells to malignant cells. Certain agents may achieve these objectives by modulating xenobiotic biotransformation, protecting cellular elements from oxidative damage, or promoting a more differentiated phenotype in target cells. Conversely, various cancer chemopreventive agents can encourage apoptosis in premalignant and malignant cells in vivo and/or in vitro, which is conceivably another anticancer mechanism. Furthermore, it is evident that many of these apoptogenic agents function as prooxidants in vitro. The constitutive intracellular redox environment dictates a cell's response to an agent that alters this environment. Thus, it is highly probable that normal cells, through adaption, could acquire resistance to transformation via exposure to a chemopreventive agent that promotes oxidative stress or disrupts the normal redox tone of these cells. In contrast, transformed cells, which typically endure an oxidizing intracellular environment, would ultimately succumb to apoptosis due to an uncontrollable production of reactive oxygen species caused by the same agent. Here, we provide evidence to support the hypothesis that reactive oxygen species and cellular redox tone are exploitable targets in cancer chemoprevention via the stimulation of cytoprotection in normal cells and/or the induction of apoptosis in transformed cells.

  10. Nicotinamide for skin cancer chemoprevention.

    PubMed

    Damian, Diona L

    2017-03-20

    Nicotinamide (vitamin B3 ) has a range of photoprotective effects in vitro and in vivo; it enhances DNA repair, reduces UV radiation-induced suppression of skin immune responses, modulates inflammatory cytokine production and skin barrier function and restores cellular energy levels after UV exposure. Pharmacological doses of nicotinamide have been shown to reduce actinic keratoses and nonmelanoma skin cancer incidence in high-risk individuals, making this a nontoxic and accessible option for skin cancer chemoprevention in this population.

  11. Chemoprevention of nonmelanoma skin cancer.

    PubMed

    Wright, Tina I; Spencer, James M; Flowers, Franklin P

    2006-06-01

    Skin cancer is the most common cancer in human beings. The increased incidence of skin cancer has brought much attention to the process by which these tumors develop and how they can be prevented. Efforts have been made to educate the public about the importance of protecting skin from excessive ultraviolet light. Despite this work, the incidence of skin cancer continues to increase. Available compounds may be useful in the chemoprevention of skin cancer. Chemoprevention is defined as oral or topical use of dietary or pharmacologic agents to inhibit or reverse the development of cancer. Potential agents included are the retinoids; difluoromethylornithine; T4 endonuclease V; polyphenolic antioxidants, such as (-)-epigallocatechin gallate, found in green tea and grape seed extract; silymarin; isoflavone genestein; nonsteroidal anti-inflammatory drugs; curcumin; lycopene; vitamin E; beta-carotene; and selenium. Many of these agents are available over the counter as topical or oral preparations. At the conclusion of this activity, participants should be familiar with the chemopreventive agents and their efficacy, as well as any significant side effects associated with them.

  12. The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer.

    PubMed

    Niu, Yi-Nong; Wang, Kai; Jin, Song; Fan, Dong-Dong; Wang, Ming-Shuai; Xing, Nian-Zeng; Xia, Shu-Jie

    2016-01-01

    In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer (PCa) while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP (PC3) cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERK1/2 were evaluated. In LNCaP (PC3) mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, fibroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERK1/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERK1/2 were noted in the presence of c-Jun-/- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride's therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

  13. Recent advances in cancer chemoprevention.

    PubMed

    Lippman, S M; Hittelman, W N; Lotan, R; Pastorino, U; Hong, W K

    1991-02-01

    The CCPC 90 conference and workshop included presentations by basic scientists describing the key in vitro and in vivo model systems used to study epithelial carcinogenesis and its associated biochemical and molecular alterations. A major conference theme was the identification of markers identifying specific carcinogenic stages. Current work focuses on defining the biology of preneoplasia, the critical specific molecular events in multistep carcinogenesis, and the dynamic interplay between viral, behavioral, dietary, and genetic factors in human carcinogenesis. Studies of molecular epidemiology and genetic susceptibility are identifying new risk groups and contributing to preventive strategies. Another major theme of the conference was the concept of field carcinogenesis and the study of carcinogen-exposed tissue "at risk" for the development of cancer. A specific example discussed by several investigators was the issue of SPT development in head and neck and lung cancers. Novel studies of biologic markers for use in early detection and as intermediate end points were described. The latter application, if validated in human trials, may allow short-term screening of chemopreventive agents and determinations of optimal doses/schedules for phase III chemoprevention trials. These biomarker trials may serve as a bridge between preclinical work and full-scale randomized trials. The status of the major phase III clinical trials was presented. Major problems in chemoprevention trials include (1) selection of agents, doses, and schedules, (2) lack of pharmacologic and pharma quality control, (5) adherence (drop-out and drop-in), and (6) trial-specific feasibility/recruitment, issues.

  14. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2005-02-01

    15. NUMBER OF PAGES Selenium, methylselenol , prostate cancer chemoprevention, apoptosis 15 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY...that Methylselenol has been implicated as an active metabolite inhibit one or more steps in the natural history of prostate for the anticancer effect of...in PCa chemoprevention and therapy activity) for their apoptosis responses to the methylselenol by selenium compounds (8). Methylselenol has been impli

  15. Tea in chemoprevention of cancer.

    PubMed

    Katiyar, S; Mukhtar, H

    1996-02-01

    This review summarizes available information on epidemiological and experimental data showing an association of tea consumption with cancer prevention. Studies showing cancer risk associated with tea consumption are also summarized. Tea is grown in about 30 countries and, next to water, is the most widely consumed beverage in the world. Experimental studies demonstrating the chemopreventive effects of tea have been conducted principally with green tea; limited studies have also assessed the usefulness of black tea. Majority of these studies have been carried out in skin tumor model system where consumption through drinking water of water extracts of tea or a polyphenolic fraction isolated from tea has been shown to afford protection against chemical carcinogen- or ultraviolet radiation-induced skin tumorigenesis. Tea consumption has also been shown to afford protection against chemical carcinogen-induced lung, forestomach, esophagus, duodenum, pancreas, liver, breast and colon carcinogenesis in specific bioassay models. Evidence has also accumulated showing that tea polyphenols prevent tumor promoter- and ultraviolet B-induced inflammatory responses in murine skin. The species and strains of animals, dose, route, frequency and duration of carcinogen administration, as well as types, route of administration and duration of tea or its polyphenolic component(s) treatment are described in detail. A brief description regarding mechanism(s) responsible for the broad chemopreventive effects of tea is provided. Epidemiologic studies, though inconclusive, in general suggest a possible preventive effect of tea consumption on human cancer. On the basis of available information, epidemiologic and experimental studies are ongoing to draw the possible relationship between tea consumption and cancer causation and prevention. Appropriate strategies for future clinical chemoprevention trials to translate animal data to human cancer risk are warranted.

  16. Natural chemopreventive alternatives in oral cancer chemoprevention.

    PubMed

    Scrobota, I; Bolfa, P; Filip, A G; Catoi, C; Alb, C; Pop, O; Tatomir, C; Baciut, G

    2016-02-01

    We studied the effect of grape seed extract Burgund Mare (BM) on oral carcinogenesis and compared it with that of curcumin (CU). Wistar rats were divided into six groups (n = 10): 4-nitro-quinoline-1-oxide (4NQO) oral carcinogenesis was induced to groups 1 - 5; groups 2 and 3 received BM and CU respectively during initiation and groups 4 and 5 BM and CU during post-initiation of carcinogenesis; group 6 represented the negative control group. Total malondialdehyde (MDA) and reduced glutathione (GSH) were assayed fluorometrically in oral tissue (gingival, jugal, palatal, lingual mucosa) and serum. Histopathological exam was performed and a dysplasia score given to each oral mucosal lesion. Ki67, cyclin D1, p63, Bcl2 and p53 were immunohistochemically evaluated. BM and CU reduced tissue MDA values elevated by 4NQO (P = 0.000). The difference between CU and BM effect was significant in the initiation (P = 0.02) but not in the post-initiation phase of carcinogenesis (P = 0.58). Tissue GSH levels decreased by 4NQO (P < 0.001) were not significantly modified by BM or CU. Serum MDA levels increased by 4NQO (P = 0.000) were significantly lowered by CU (P = 0.04) and BM (P = 0.04) during initiation and by CU during post-initiation of carcinogenesis (P = 0.01). CU was more potent than BM during post-initiation of carcinogenesis (P = 0.01). Serum GSH lowered by 4NQO (P = 0.55) was significantly decreased by BM and CU (P < 0.012), with no significant difference between groups receiving BM or CU. Moderate dysplasia was the most advanced dysplasia induced and gingival localization the most frequent. Both BM and CU lowered dysplasia scores, with BM being the most efficient during post-initiation of carcinogenesis (P = 0.001). Ki67, cyclin D1, p63, Bcl2 and p53 expression increased with dysplasia scores. BM showed chemopreventive properties during initiation and post-initiation of oral carcinogenesis, reducing local and general oxidative stress and the intensity of dysplasia

  17. Chemoprevention of colorectal cancer

    PubMed Central

    LANGMAN, M; BOYLE, P

    1998-01-01

    Department of Medicine, Queen Elizabeth Hospital, Birmingham B15 2TH, UK P BOYLE Colorectal cancer is the fourth commonest form of cancer in men with 678 000 estimated new cases per year worldwide, representing 8.9% of all new cancers. The disease is most frequent in Occidental countries and particularly so in North America, Australia, New Zealand, and parts of Europe. Prospects for colorectal cancer control are bright and a number of possible approaches could prove fruitful. Among these, pharmaceutical measures seem to be valid and logical approaches to the prevention of colorectal cancer and diminishing its impact. Such approaches could concentrate in primary prevention in at-risk subjects or be applied in altering the course of precursor or established disease. Treatments used must fulfil basic requirements of biological plausibility and safety in continued use in large numbers of subjects. Those available include vitamins and minerals, and other drugs with potential as antioxidants, immune modulators or promoters of cell differentiation or apoptosis. Of the various regimens suggested, vitamin A supplementation may even predispose to adverse outcomes, and antioxidant vitamins in general have no coherent body of evidence to support their use. N-acetylcysteine and ursodeoxycholic acid have promising characteristics but there are as yet no clinical data to support the use of the former in gut epithelial cancer, and formal dose ranging studies must be carried out before the latter is submitted to large scale trial. Folate shows promising characteristics but non-steroidal anti-inflammatory drugs and vitamin D seem the most promising agents. Both seem to reduce the incidence of disease, and to reduce growth rates and/or induce differentiation or apoptosis in gut epithelial cancer cells. Both are also well understood pharmacologically. They may be preferred to newer selective compounds in the same class until these newer compounds are confirmed as safe for widespread

  18. Prostate Cancer

    MedlinePlus

    Prostate cancer Overview Prostate cancer is cancer that occurs in the prostate — a small walnut-shaped gland in men that produces the seminal fluid that nourishes and transports sperm. Prostate cancer is one of the most common types of ...

  19. Proteomic Analysis of Genistein Mammary Cancer Chemoprevention

    DTIC Science & Technology

    2007-07-01

    to collect a higher yield of proteins and hopefully allow success. 15. SUBJECT TERMS Genistein , Breast Cancer Chemoprevention, Proteomics, Rats ...AD_________________ Award Number: DAMD17-03-1-0433 TITLE: Proteomic Analysis of Genistein ...SUBTITLE 5a. CONTRACT NUMBER Proteomic Analysis of Genistein Mammary Cancer Chemoprevention 5b. GRANT NUMBER DAMD17-03-1-0433 5c. PROGRAM

  20. Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    2005-10-01

    coupled device camera . The interrogated tissue area was 2 mm in diameter. Fluorescence emission spectra ranging from 320 to 850 nm were collected...properties of normal and neoplastic human cervical tissue," Laser Surg. Med. 13, 646-655 (1993). 48. K. T. Schomacker, J. K. Frisoli, C. C. Compton , T. J...undergo apoptosis in response to certain physio- in mitochondrial finction in both normal and cancer cells. In logical stimuli and cytotoxic agents

  1. Nutritional aspects regarding lung cancer chemoprevention.

    PubMed

    Thanopoulou, E; Baltayiannis, N; Lykogianni, V

    2006-01-01

    Lung cancer is still one of the major causes of cancer-related deaths and its mortality figures argue powerfully for new approaches to control this leading cancer threat. Chemoprevention can be defined as the use of specific agents to reverse, or prevent premalignancy from progressing to invasive cancer. The use of foods and dietary supplements present a safe chemopreventive strategy. Data for this review were identified by searches of PubMed and references from relevant articles. Articles were identified by use of the search terms "lung cancer", "chemoprevention", "carcinogenesis", and "retinoids". Only papers published in English were included. Trials in lung cancer chemoprevention have so far produced either neutral or harmful primary endpoint results, whether in the primary, secondary, or tertiary settings. Lung cancer was not prevented by beta-carotene, alpha-tocopherol, retinol, retinyl palmitate, N-acetylcysteine, or isotretinoin in smokers. Ongoing trials may help define new avenues for chemoprevention. The concept of chemoprevention in lung cancer is still in its infancy, but in the future it may have a significant impact on the incidence and mortality of lung cancer. In addition to epidemiologic studies, basic science research to detect mechanisms and evaluate the chemopreventive potential of food components is necessary. The overwhelming evidence of a major role of nutrition in carcinogenesis, the many leads that nutritional intervention may reduce cancer incidence, and the growth and increasing sophistication of clinical trials networks point to a very promising future for nutritional intervention trials leading to substantial public benefit.

  2. Cancer Chemoprevention: Current State of the Art

    PubMed Central

    Landis-Piwowar, Kristin R; Iyer, Neena R

    2014-01-01

    The aim of cancer chemoprevention is disruption or delay of the molecular pathways that lead to carcinogenesis. Chemopreventive blocking and/or suppressing agents disrupt the molecular mechanisms that drive carcinogenesis such as DNA damage by reactive oxygen species, increased signal transduction to NF-κB, epigenomic deregulation, and the epithelial mesenchymal transition that leads to metastatic progression. Numerous dietary phytochemicals have been observed to inhibit the initiation phase of carcinogenesis, and therefore are useful in primary chemoprevention. Moreover, phytochemicals are capable of interfering with the molecular mechanisms of metastasis. Likewise, numerous synthetic compounds are relevant and clinically viable as chemopreventive agents during the fundamental stages of carcinogenesis. While molecularly targeted anti-cancer therapies are in constant stages of development, superior patient outcomes are observed if carcinogenic processes are prevented altogether. This article reviews the role of chemopreventive compounds in inhibition of cancer initiation and their ability to reduce cancer progression. PMID:24987270

  3. Prostate cancer

    SciTech Connect

    Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

  4. Comet Assay in Cancer Chemoprevention.

    PubMed

    Santoro, Raffaela; Ferraiuolo, Maria; Morgano, Gian Paolo; Muti, Paola; Strano, Sabrina

    2016-01-01

    The comet assay can be useful in monitoring DNA damage in single cells caused by exposure to genotoxic agents, such as those causing air, water, and soil pollution (e.g., pesticides, dioxins, electromagnetic fields) and chemo- and radiotherapy in cancer patients, or in the assessment of genoprotective effects of chemopreventive molecules. Therefore, it has particular importance in the fields of pharmacology and toxicology, and in both environmental and human biomonitoring. It allows the detection of single strand breaks as well as double-strand breaks and can be used in both normal and cancer cells. Here we describe the alkali method for comet assay, which allows to detect both single- and double-strand DNA breaks.

  5. Prostate Cancer

    MedlinePlus

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  6. Alternate dosing schedules for cancer chemopreventive agents.

    PubMed

    Lazzeroni, Matteo; DeCensi, Andrea

    2016-02-01

    Pharmacologic interventions for cancer risk reduction involve the chronic administration of synthetic or natural agents to reduce or delay the occurrence of malignancy. Despite the strong evidence for a favorable risk-benefit ratio for a number of agents in several common malignancies such as breast and prostate cancer, the public's attitude toward cancer chemoprevention remains ambivalent, with the issue of toxicity associated with drugs being perceived as the main barrier to widespread use of preventive therapy by high-risk subjects. Among the strategies to overcome such obstacles to preventive therapies, two novel and potentially safer modes of administering agents are discussed in this paper. The first strategy is to lower the dose of drugs that are in common use in the adjuvant setting based on the notion that prevention of cancer cells from developing should require a lower dose than eradicating established tumor cells. A second approach is to adopt an intermittent administration similar to what is used in the chemotherapy setting in an attempt to minimize risks while retaining benefits. This article provides a detailed discussion of the principles and future development of these two approaches in the direction of a precision preventive medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Natural Products for Chemoprevention of Breast Cancer

    PubMed Central

    Ko, Eun-Yi; Moon, Aree

    2015-01-01

    Breast cancer is the primary cause of cancer death in women. Although current therapies have shown some promise against breast cancer, there is still no effective cure for the majority of patients in the advanced stages of breast cancer. Development of effective agents to slow, reduce, or reverse the incidence of breast cancer in high-risk women is necessary. Chemoprevention of breast cancer by natural products is advantageous, as these compounds have few side effects and low toxicity compared to synthetic compounds. In the present review, we summarize natural products which exert chemopreventive activities against breast cancer, such as curcumin, sauchinone, lycopene, denbinobin, genipin, capsaicin, and ursolic acid. This review examines the current knowledge about natural compounds and their mechanisms that underlie breast cancer chemopreventive activity both in vitro and in vivo. The present review may provide information on the use of these compounds for the prevention of breast cancer. PMID:26734584

  8. Biological Basis for Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    2000-10-01

    Since reduction of ovulation is protective against ovarian cancer, prevention may represent a feasible approach to decreasing mortality . To achieve a...potent apoptotic effect on ovarian epithelial cells, the use of levonorgestrel in chemoprevention of ovarian cancer is being explored in chickens and women...A chemoprevention trial is ongoing in chickens and we will begin a trial to determine whether levonorgestrel induces apoptosis in the ovarian epithelium of women undergoing oophorectomy.

  9. Dietary chemoprevention of colorectal cancer.

    PubMed

    Forte, Angelo; De Sanctis, Rita; Leonetti, Giovanni; Manfredelli, Simone; Urbano, Vincenzo; Bezzi, Marcello

    2008-01-01

    Colorectal cancer is the second cause of morbidity and death in Italy. Genetic and environmental factors, i.e. inappropriate nutrition, are strongly involved in the aetiology of colon cancer. In the present review the authors analyze the possible mechanisms by which certain nutritive factors may interfere with the complex process of carcinogenesis. The authors identify studies by a literature search of Medline from January 1, 1970, through December 31, 2006. The mechanism of every protective compound is detailed, in particular the impact of antioxidant vitamins and minerals on tumor development. At present, the data suggest that vegetables are associated with lower risk and that their fbre content alone does not account for this association. Further, meat consumption is associated with an increased risk but this, too, is not explained solely by its fat content. Several microconstituents of the diet may be associated with reduced risk, including folate, methionine, calcium and vitamin D. Short chain fatty acids also contribute to colonic health. Nevertheless agricultural products contain several dangerous pesticides. Mutagenic compounds, particularly heterocyclic amines, produced when protein is cooked, plausibly explain the meat association. Healthy nutrition is a necessary but not sufficient condition for colon cancer prevention: accepted the feasibility of an accurate control on every patient's diet, fequently the difficulty encountered in nutritional chemoprevention is to establish individual metabolic profiles.

  10. Prostate Cancer Screening

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Prostate Cancer Key Points Prostate cancer is a disease in ...

  11. Chemoprevention of rat prostate carcinogenesis by soy isoflavones and by Bowman-Birk inhibitor.

    PubMed

    McCormick, David L; Johnson, William D; Bosland, Maarten C; Lubet, Ronald A; Steele, Vernon E

    2007-01-01

    Epidemiology studies suggest that soy consumption confers protection against human prostate cancer. To identify the soy component(s) that may be responsible for this chemopreventive activity, studies were conducted to determine the influence of a soy isoflavone mixture (PTI G-2535; 45% genistein, 22% daidzein, 2% glycitein) and a soy-derived protease inhibitor (Bowman-Birk Inhibitor Concentrate; BBIC) on prostate carcinogenesis in rats. Prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate and testosterone propionate, followed by a single intravenous injection of N-methyl-N-nitrosourea (MNU) and chronic androgen stimulation. In separate studies, PTI G-2535 and BBIC were administered continuously at 0 (control), 200, or 2000 mg/kg diet, beginning 1 wk post-MNU. PTI G-2535 and BBIC both conferred modest, but statistically significant and dose-related protection against carcinogenesis in the dorsolateral+anterior prostate. These data demonstrate that both the isoflavone and protein (protease inhibitor) components of soy can inhibit prostate carcinogenesis in the rat. However, the modest individual activities of soy isoflavones and BBIC suggest that while both components may contribute to the chemopreventive activity of soy, combination administration (or exposure to whole soy) may be more effective in prostate cancer prevention than is administration of either component alone.

  12. Pancreatic Cancer Chemoprevention Translational Workshop: Meeting Report.

    PubMed

    Miller, Mark Steven; Allen, Peter; Brentnall, Teresa A; Goggins, Michael; Hruban, Ralph H; Petersen, Gloria M; Rao, Chinthalapally V; Whitcomb, David C; Brand, Randall E; Chari, Suresh T; Klein, Alison P; Lubman, David M; Rhim, Andrew D; Simeone, Diane M; Wolpin, Brian M; Umar, Asad; Srivastava, Sudhir; Steele, Vernon E; Rinaudo, Jo Ann S

    2016-09-01

    Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a 5-year survival rate of less than 10%. The Division of Cancer Prevention of the National Cancer Institute sponsored the Pancreatic Cancer Chemoprevention Translational Workshop on September 10 to 11, 2015. The goal of the workshop was to obtain information regarding the current state of the science and future scientific areas that should be prioritized for pancreatic cancer prevention research, including early detection and intervention for high-risk precancerous lesions. The workshop addressed the molecular/genetic landscape of pancreatic cancer and precursor lesions, high-risk populations and criteria to identify a high-risk population for potential chemoprevention trials, identification of chemopreventative/immunopreventative agents, and use of potential biomarkers and imaging for assessing short-term efficacy of a preventative agent. The field of chemoprevention for pancreatic cancer is emerging, and this workshop was organized to begin to address these important issues and promote multi-institutional efforts in this area. The meeting participants recommended the development of an National Cancer Institute working group to coordinate efforts, provide a framework, and identify opportunities for chemoprevention of pancreatic cancer.

  13. Biological Basis for Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    2001-10-01

    Prevention may represent a feasible approach to decreasing ovarian cancer mortality . To achieve a better understanding of the etiology of ovarian...Progestins have a potent apoptotic effect on ovarian epithelial cells and we have shown that levonorgestrel dramatically decreases ovarian cancer incidence...effective chemoprevention strategies that might decrease mortality from this disease.

  14. Meeting Report: Pancreatic Cancer Chemoprevention Translational Workshop

    PubMed Central

    Miller, Mark Steven; Allen, Peter; Brentnall, Teresa; Goggins, Michael; Hruban, Ralph H.; Petersen, Gloria M.; Rao, Chinthalapally V.; Whitcomb, David C.; Brand, Randall E.; Chari, Suresh; Klein, Alison; Lubman, David; Rhim, Andrew; Simeone, Diane M.; Wolpin, Brian; Umar, Asad; Srivastava, Sudhir; Steele, Vernon E.; Ann Rinaudo, Jo

    2016-01-01

    Pancreatic cancer is the 4th leading cause of cancer related deaths in the US with a 5 year survival rate of <10%. The Division of Cancer Prevention of the NCI sponsored the Pancreatic Cancer Chemoprevention Translational Workshop on September 10–11th 2015. The goal of the workshop was to obtain information regarding the current state of the science and future scientific areas that should be prioritized for pancreatic cancer prevention research, including early detection and intervention for high-risk precancerous lesions. The workshop addressed the molecular/genetic landscape of pancreatic cancer and precursor lesions; high risk populations and criteria to identify a high risk population for potential chemoprevention trials; identification of chemopreventative/immuopreventative agents; and use of potential biomarkers and imaging for assessing short term efficacy of a preventative agent. The field of chemoprevention for pancreatic cancer is emerging and this workshop was organized to begin to address these important issues and promote multi-institutional efforts in this area. The meeting participants recommended the development of an NCI working group to coordinate efforts, provide a framework, and identify opportunities for chemoprevention of pancreatic cancer. PMID:27518363

  15. Pathobiology and Chemoprevention of Bladder Cancer

    PubMed Central

    Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

    2011-01-01

    Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

  16. Polyphenols as cancer chemopreventive agents.

    PubMed

    Stoner, G D; Mukhtar, H

    1995-01-01

    This article summarizes available data on the chemopreventive efficacies of tea polyphenols, curcumin and ellagic acid in various model systems. Emphasis is placed upon the anticarcinogenic activity of these polyphenols and their proposed mechanism(s) of action. Tea is grown in about 30 countries and, next to water, is the most widely consumed beverage in the world. Tea is manufactured as either green, black, or oolong; black tea represents approximately 80% of tea products. Epidemiological studies, though inconclusive, suggest a protective effect of tea consumption on human cancer. Experimental studies of the antimutagenic and anticarcinogenic effects of tea have been conducted principally with green tea polyphenols (GTPs). GTPs exhibit antimutagenic activity in vitro, and they inhibit carcinogen-induced skin, lung, forestomach, esophagus, duodenum and colon tumors in rodents. In addition, GTPs inhibit TPA-induced skin tumor promotion in mice. Although several GTPs possess anticarcinogenic activity, the most active is (-)-epigallocatechin-3-gallate (EGCG), the major constituent in the GTP fraction. Several mechanisms appear to be responsible for the tumor-inhibitory properties of GTPs, including enhancement of antioxidant (glutathione peroxidase, catalase and quinone reductase) and phase II (glutathione-S-transferase) enzyme activities; inhibition of chemically induced lipid peroxidation; inhibition of irradiation- and TPA-induced epidermal ornithine decarboxylase (ODC) and cyclooxygenase activities; inhibition of protein kinase C and cellular proliferation; antiinflammatory activity; and enhancement of gap junction intercellular communication. Curcumin is the yellow coloring agent in the spice tumeric. It exhibits antimutagenic activity in the Ames Salmonella test and has anticarcinogenic activity, inhibiting chemically induced preneoplastic lesions in the breast and colon and neoplastic lesions in the skin, forestomach, duodenum and colon of rodents. In addition

  17. Dietary derived compounds in cancer chemoprevention

    PubMed Central

    Rzeski, Wojciech

    2012-01-01

    Cancer chemoprevention is defined as the application of natural or synthetic agents to suppress or reverse cancer development and progression. In this field especially diet derived compounds have recently attracted researchers’ attention as potential therapeutics generally exerting low toxicity compared with regular drugs. This review presents a survey of recent findings concerning the most promising dietary chemopreventive agents such as green tea polyphenols (i.e. catechins), long-chain polyunsaturated fatty acids, carotenoids, glucosinolates/isothiocyanates, vitamins (i.e. vitamin D and folate) and minerals (i.e. calcium and selenium). Molecular targets involved in intrinsic pathways affected by these natural compounds are also shortly discussed. PMID:23788916

  18. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2008-02-01

    methylselenol , prostate cancer chemoprevention, apoptosis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...considered an immediate precursor to the in vivo active anticancer selenium metabolite methylselenol , greatly sensitized HRPCa cells to undergo

  19. Ellagitannins in Cancer Chemoprevention and Therapy

    PubMed Central

    Ismail, Tariq; Calcabrini, Cinzia; Diaz, Anna Rita; Fimognari, Carmela; Turrini, Eleonora; Catanzaro, Elena; Akhtar, Saeed; Sestili, Piero

    2016-01-01

    It is universally accepted that diets rich in fruit and vegetables lead to reduction in the risk of common forms of cancer and are useful in cancer prevention. Indeed edible vegetables and fruits contain a wide variety of phytochemicals with proven antioxidant, anti-carcinogenic, and chemopreventive activity; moreover, some of these phytochemicals also display direct antiproliferative activity towards tumor cells, with the additional advantage of high tolerability and low toxicity. The most important dietary phytochemicals are isothiocyanates, ellagitannins (ET), polyphenols, indoles, flavonoids, retinoids, tocopherols. Among this very wide panel of compounds, ET represent an important class of phytochemicals which are being increasingly investigated for their chemopreventive and anticancer activities. This article reviews the chemistry, the dietary sources, the pharmacokinetics, the evidence on chemopreventive efficacy and the anticancer activity of ET with regard to the most sensitive tumors, as well as the mechanisms underlying their clinically-valuable properties. PMID:27187472

  20. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate.

    PubMed

    Lamartiniere, Coral A; Cotroneo, Michelle S; Fritz, Wayne A; Wang, Jun; Mentor-Marcel, Roycelynn; Elgavish, Ada

    2002-03-01

    We investigated the potential of genistein, the primary isoflavone of soy, to protect against breast and prostate cancers in animal models. For mammary cancer studies, Sprague-Dawley rats were fed AIN-76A diet plus minus 250 mg genistein/kg diet. Dimethylbenz[a]anthracene was administered by gavage at d 50 postpartum to induce mammary tumors. Mammary cancer chemoprevention was demonstrated after prepubertal and combined prepubertal and adult genistein treatments but not after prenatal- or adult-only treatments, demonstrating that the timing of exposure to genistein is important for mammary cancer chemoprevention. The cellular mechanism of action was found to be mammary gland and cell differentiation, as shown by whole-mount analysis and beta-casein expression. An imprinting effect was shown for epidermal growth factor receptor expression in mammary terminal end buds. For prostate cancer studies, we used two models. The first was a chemically (N-methylnitrosourea) induced prostate cancer rat model. Genistein in the diet inhibited the development of invasive adenocarcinomas in a dose-dependent manner. The second model was a transgenic mouse model that resulted in spontaneously developing adenocarcinoma tumor of the prostate. Genistein in the diet reduced the incidence of poorly differentiated prostatic adenocarcinomas in a dose-dependent manner and down-regulated androgen receptor, estrogen receptor-alpha, progesterone receptor, epidermal growth factor receptor, insulin-like growth factor-I, and extracellular signal-regulated kinase-1 but not estrogen receptor-beta and transforming growth factor-alpha mRNA expressions. We conclude that dietary genistein protects against mammary and prostate cancers by regulating specific sex steroid receptors and growth factor signaling pathways.

  1. Chemopreventive efficacy of inositol hexaphosphate against prostate tumor growth and progression in TRAMP mice.

    PubMed

    Raina, Komal; Rajamanickam, Subapriya; Singh, Rana P; Agarwal, Rajesh

    2008-05-15

    Herein, for the first time, we evaluated the in vivo chemopreventive efficacy of inositol hexaphosphate (IP6), a major constituent of high-fiber diets, against prostate tumor growth and progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Beginning at 4 weeks of age, male TRAMP mice were fed 2% (w/v) IP6 in drinking water or only drinking water till 24 weeks of age, and then sacrificed. Prostate tissue was subjected to histopathologic analysis and to immunohistochemical analyses for proliferation and apoptosis. IP6 feeding did not show any adverse effect on fluid and diet consumption and body weight. There was a significant reduction (40%; P < 0.01) in lower urogenital tract weight in IP6-fed mice. IP6 inhibited prostate cancer progression at prostatic intraepithelial neoplasia stage and strongly reduced the incidence of adenocarcinoma (prostatic intraepithelial neoplasia/adenocarcinoma, 75:25% in the IP6 group versus 39:61% in the control group; P < 0.05). The incidences of well-differentiated and poorly differentiated adenocarcinomas in the IP6-fed group were reduced by 44% and 62%, respectively. Immunohistochemical analysis of prostate tissue showed a 26% decrease (P < 0.05) in proliferation cell nuclear antigen-positive cells and a 3.5-fold increase in apoptotic cells with no effect on Tag expression by IP6. These findings are both novel and highly significant in establishing for the first time that oral IP6, without any toxicity, suppresses prostate tumor growth and progression at the neoplastic stage, thereby reducing the incidence of adenocarcinoma through its antiproliferative and proapoptotic effects, and thus indicating that IP6 could have potential chemopreventive effects against human prostate cancer.

  2. Trimethoxy-resveratrol and piceatannol administered orally suppress and inhibit tumor formation and growth in prostate cancer xenografts

    USDA-ARS?s Scientific Manuscript database

    Resveratrol (Res) is recognized as a promising cancer chemoprevention dietary polyphenol with antioxidative, anti-inflammatory and anticancer properties. However, the role of its analogues in prostate cancer (PCa) chemoprevention is still unknown. METHODS. We synthesized natural and synthetic anal...

  3. Intermediate endpoint biomarkers for lung cancer chemoprevention

    NASA Astrophysics Data System (ADS)

    MacAulay, Calum E.; Lam, Stephen; Klein-Parker, Helga; Gazdar, Adi; Guillaud, Martial; Payne, Peter W.; Le Riche, Jean C.; Dawe, Chris; Band, Pierre; Palcic, Branko

    1998-04-01

    Given the demographics of current and ex-smoking populations in North America, lung cancer will be a major problem in the foreseeable future. Early detection and treatment of lung cancer holds great promise for the management of this disease. Unlike cervical cancer, the physical, complete removal/destruction of all dysplastic lesions in the bronchial tree is not possible; however, treatment of the lesions using a chemopreventive agent is. Intermediate biomarkers have been used to screen promising chemopreventive agents for larger population studies. We have examined the natural history of lung cancer development by following a group of subjects at high risk of developing lung cancer using fluorescence endoscopy to identify the areas of abnormality for biopsy. Approximately 900 biopsies have been collected in this fashion and graded by at least two experienced, expert pathologists. Using an interactive version of the Cyto-Savant (Oncometrics Imaging Corp.), cytometric and tissue architectural data were collected from these biopsies. Using only the data from the normal and invasive cancer biopsies, quantitative morphometric and architectural indices were generated and calculated for all the collected biopsies. These indices were compared with Loss of Heterozygosity (LOH) of ten sites commonly associated with cancer. These results and the application of these quantitative measures to two small chemoprevention studies will be reported.

  4. Prostate cancer screening

    MedlinePlus

    Prostate cancer screening - PSA; Prostate cancer screening - digital rectal exam; Prostate cancer screening - DRE ... level of PSA could mean you have prostate cancer. But other conditions can also cause a high ...

  5. Biological Basis for Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    1999-10-01

    Since reduction of ovulation is protective against ovarian cancer, prevention may represent a feasible approach to decreasing mortality . To achieve a...cells, the use of levonorgestrel in chemoprevention of ovarian cancer is being explored in chickens and women. A chernoprevention trial is ongoing in...chickens and we will begin a trial to determine whether levonorgestrel induces apoptosis in the ovarian epithelium of women undergoing oophorectomy.

  6. Targeting NRF2 signaling for cancer chemoprevention

    SciTech Connect

    Kwak, Mi-Kyoung; Kensler, Thomas W.

    2010-04-01

    Modulation of the metabolism and disposition of carcinogens through induction of cytoprotective enzymes is one of several promising strategies to prevent cancer. Chemopreventive efficacies of inducers such as dithiolethiones and sulforaphane have been extensively studied in animals as well as in humans. The KEAP1-NRF2 system is a key, but not unilateral, molecular target for these chemopreventive agents. The transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of the expression of a subset of genes, which produce proteins responsible for the detoxication of electrophiles and reactive oxygen species as well as the removal or repair of some of their damage products. It is believed that chemopreventive enzyme inducers affect the interaction between KEAP1 and NRF2 through either mediating conformational changes of the KEAP1 protein or activating phosphorylation cascades targeting the KEAP1-NRF2 complex. These events in turn affect NRF2 stability and trafficking. Recent advances elucidating the underlying structural biology of KEAP1-NRF2 signaling and identification of the gene clusters under the transcriptional control of NRF2 are facilitating understanding of the potential pleiotropic effects of NRF2 activators and discovery of novel classes of potent chemopreventive agents such as the triterpenoids. Although there is appropriately a concern regarding a deleterious role of the KEAP1-NRF2 system in cancer cell biology, especially as the pathway affects cell survival and drug resistance, the development and the use of NRF2 activators as chemopreventive agents still holds a great promise for protection of normal cells from a diversity of environmental stresses that contribute to the burden of cancer and other chronic, degenerative diseases.

  7. [Prostate cancer].

    PubMed

    Bey, P; Beckendorf, V; Stinès, J

    2001-10-01

    Radiation therapy of prostate carcinoma with a curative intent implies to treat the whole prostate at high dose (at least 66 Gy). According to clinical stage, PSA level, Gleason's score, the clinical target volume may include seminal vesicles and less often pelvic lymph nodes. Microscopic extracapsular extension is found in 15 to 60% of T1-T2 operated on, specially in apex tumors. On contrary, cancers developing from the transitional zone may stay limited to the prostate even with a big volume and with a high PSA level. Zonal anatomy of the prostate identifies internal prostate, including the transitional zone (5% of the prostate in young people). External prostate includes central and peripheral zones. The inferior limit of the prostate is not lower than the inferior border of the pubic symphysis. Clinical and radiological examination: ultrasonography, nuclear magnetic resonance (NMR), CT-scan identify prognostic factors as tumor volume, capsule effraction, seminal vesicles invasion and lymph node extension. The identification of the clinical target volume is now done mainly by CT-Scan which identifies prostate and seminal vesicles. NMR could be helpful to identify more precisely prostate apex. The definition of margins around the clinical target volume has to take in account daily reproducibility and organ motion and of course the maximum tolerable dose for organs at risk.

  8. Cancer chemoprevention by nuts: evidence and promises.

    PubMed

    Falasca, Marco; Casari, Ilaria

    2012-01-01

    Chemoprevention is the use of chemical compounds to interfere with the early precancerous stages of carcinogenesis and thereby reverse tumor formation. Many chemopreventive agents, either natural or synthetic, have been identified. Some of the most promising compounds are found in vegetables and fruits. There are numerous mechanisms of action by which these components can intervene in the prevention of cancer, although they have not been fully elucidated. It is worth to note that some foods contain different bioactive compounds. Therefore the possibility exists that combinations of compounds, naturally occurring in those foods, may have a cumulative or even synergistic effect. Nuts are very rich in different bioactive compounds whose anti-cancer properties have already been described. Epidemiologic studies have already suggested that nuts consumption may be potentially beneficial in the incidence of other diseases, such as coronary heart disease and diabetes. Although the results are not conclusive, recent studies show possible cancer protective effects of nuts. This review will focus on the laboratory and clinical evidence of nuts chemopreventive and therapeutic properties.

  9. Retinoids in lung cancer chemoprevention and treatment.

    PubMed

    Toma, S; Raffo, P; Isnardi, L; Palumbo, R

    1999-01-01

    In this review, we aim to synthesize the emerging picture of retinoids in lung cancer through a summary of ongoing investigations in biology, chemoprevention and therapy settings, in an attempt to clarify the possible role of these agents in such a disease. Early work in head and neck cancer has evidenced the capability of retinoids to interrupt field carcinogenesis by reversing premalignant lesions and decreasing the incidence of second primary tumors (SPTs). At this time, the completed randomized trials in lung cancer have failed to demonstrate an evident chemopreventive effect of the tested agents on different study end points, although both a marginally significant benefit of retinol palmitate in time-to-development rates for smoke-related SPTs and a potential preventive effect of retinol supplementation against mesothelioma in selected populations of asbestos-exposed workers have been recently reported. Concerning the role of retinoids in lung cancer treatment, a moderate activity of 13-cis-retinoic acid (13cRA) or all-transretinoic acid (ATRA) as single agents has been reported in small series of advanced, mostly pretreated lung cancer patients. More encouraging findings derive from combination studies, in which retinoids, especially ATRA, are added to either alpha-interferon or chemotherapy and radiotherapy. Major recent advances have been made towards the understanding of retinoids mechanisms of action; at this regard, the role of RAR-beta basal or treatment-induced levels seems to be of particular interest as intermediate end point and/or independent prognostic factor, besides their known importance in lung carcinogenesis. Future research for chemopreventive and therapeutic programs with retinoids in lung cancer should be focused on the investigation of new generation compounds with a specificity for individual retinoid nuclear receptors. Such selective molecules may have a greater activity against lung cancer, with a more favourable toxicity profile, as

  10. Prostate cancer

    PubMed Central

    Mazhar, D; Waxman, J

    2002-01-01

    It is a paradigm in cancer treatment that early detection and treatment improves survival. However, although screening measures lead to a higher rate of detection, for small bulk localised prostate cancer it remains unclear whether early detection and early treatment will lead to an overall decrease in mortality. The management options include surveillance, radiotherapy, and radical prostatectomy but there is no evidence base to evaluate the benefits of each approach. Advanced prostate cancer is managed by hormonal therapy. There have been major changes in treatment over the last two decades with the use of more humane treatment and developments in both chemotherapy and radiation. In this article we review the natural history and management of prostate cancer. PMID:12415080

  11. Medicinal Plants and Cancer Chemoprevention

    PubMed Central

    Desai, Avni G.; Qazi, Ghulam N.; Ganju, Ramesh K.; El-Tamer, Mahmoud; Singh, Jaswant; Saxena, Ajit K.; Bedi, Yashbir S.; Taneja, Subhash C.; Bhat, Hari K.

    2014-01-01

    Cancer is the second leading cause of death worldwide. Although great advancements have been made in the treatment and control of cancer progression, significant deficiencies and room for improvement remain. A number of undesired side effects sometimes occur during chemotherapy. Natural therapies, such as the use of plant-derived products in cancer treatment, may reduce adverse side effects. Currently, a few plant products are being used to treat cancer. However, a myriad of many plant products exist that have shown very promising anti-cancer properties in vitro, but have yet to be evaluated in humans. Further study is required to determine the efficacy of these plant products in treating cancers in humans. This review will focus on the various plant-derived chemical compounds that have, in recent years, shown promise as anticancer agents and will outline their potential mechanism of action. PMID:18781909

  12. Chemoprevention of cancer: current evidence and future prospects

    PubMed Central

    Benetou, Vassiliki; Lagiou, Areti; Lagiou, Pagona

    2015-01-01

    Cancer chemoprevention refers to the use of agents for the inhibition, delay, or reversal of carcinogenesis before invasion. In the present review, agents examined in the context of cancer chemoprevention are classified in four major categories—hormonal, medications, diet-related agents, and vaccines—and the main representatives of each category are presented. Although there are serious constraints in the documentation of effectiveness of chemopreventive agents, mainly stemming from the long latency of the condition they are addressing and the frequent lack of intermediate biomarkers, there is little disagreement about the role of aspirin, whereas a diet rich in vegetables and fruits appears to convey more protection than individual micronutrients. Among categories of cancer chemopreventive agents, hormonal ones and vaccines might hold more promise for the future. Also, the identification of individuals who would benefit most from chemopreventive interventions on the basis of their genetic profiles could open new prospects for cancer chemoprevention. PMID:27006756

  13. Cancer chemoprevention: selenium as a prooxidant, not an antioxidant.

    PubMed

    Drake, E N

    2006-01-01

    Although the average daily dietary selenium (Se) intake in the United States is consistently above the adult RDA of 55 microg Se/day, supranutritional supplements of 200 microg Se/day have been shown to provide chemopreventive benefits against several cancers, particularly prostate cancer. The hypothesis herein contends that selenium compounds with the greatest anticarcinogenic potency are likely to be sodium selenite with Se in the +4 oxidation state and methylseleninic acid. These compounds exert their cancer chemopreventive effects by directly oxidizing critical thiol-containing cellular substrates, and are more effective than the more frequently preferred (used) supplements of selenomethionine and Se-methylselenocysteine that lack oxidation capability. Selenate (+6 Se) the immediate precursor of selenite (+4 Se) can be metabolically reduced, and although less potent than the +4 Se compounds cited above, appears to be a more effective anticarcinogen than organic forms of dietary selenium. Apoptosis, an important, Se-induced anticarcinogenic mechanism, is accomplished by the direct oxidation of vicinal sulfhydryl groups in cysteine clusters within the catalytic domains of cellular enzymes (e.g., protein kinase C), and by the production of CH3Se-, which reacts with O2 to generate superoxide and other reactive oxygen species (ROS). Activated oncogenes "prime" cells for Se-induced prooxidative apoptosis thereby providing the needed margin for "killing" cancer cells while leaving normal, healthy cells unharmed. Selenoethers, such as selenomethionine and Se-methylselenocysteine are not oxidizing agents, and first, must be converted to methylselenol (CH3Se-) that can be directly oxidized to methylseleninic acid. The addition of methioninase, to selenomethionine, or beta-lyase to Se-methylselenocysteine, rapidly produces significant amounts of methylselenol, which may be oxidized to methylseleninic acid or may react with O2 to produce superoxide and ROS, resulting in

  14. Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer.

    PubMed

    Marin, Jose J G; Sanchez de Medina, Fermin; Castaño, Beatriz; Bujanda, Luis; Romero, Marta R; Martinez-Augustin, Olga; Moral-Avila, Rosario Del; Briz, Oscar

    2012-05-01

    Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.

  15. Phyto-oestrogens and breast cancer chemoprevention

    PubMed Central

    Limer, Jane L; Speirs, Valerie

    2004-01-01

    Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed. PMID:15084232

  16. Chemoprevention of lung cancer by tea.

    PubMed

    Clark, Julie; You, Ming

    2006-02-01

    Tea is the second only to water as the most consumed beverage in the world. Both green and black teas have been studied for their health benefits for a variety of diseases, particularly cancer. Lung cancer is the predominant cause of cancer mortality in developed countries. Smokers' risk of lung cancer is 20 times that of persons who have never smoked. Epidemiological studies on the cancer-preventive effects of tea produce inconsistent results, which could in part be attributed to the lack of a universal standard for tea preparations. However, most animal studies indicate that tea has strong chemopreventive effects against lung tumorigenesis. The reported mechanisms for chemopreventive activity of green tea are antioxidation, induction of phase II enzymes, inhibition of TNFalpha expression and release, inhibition of cell proliferation, and induction of apoptosis. Cell cycle arrest and apoptosis induced by green tea are probably the two most significant factors. Future studies are needed to determine how green tea affects the genes associated with cell cycle regulation and apoptosis during the mouse lung carcinogenesis process.

  17. MicroRNA and Cancer Chemoprevention

    PubMed Central

    Yi, Bin; Piazza, Gary A.; Su, Xiulan; Xi, Yaguang

    2013-01-01

    MicroRNAs (miRNAs) are a group of naturally occurring, small, non-coding, and single-strand RNA molecules that regulate gene expression at the post-transcriptional and translational levels. By controlling the expression of oncogenic and tumor suppressor proteins, miRNAs are believed to play an important role in pathological processes associated with malignant progression including tumor cell proliferation, apoptosis, differentiation, angiogenesis, invasion and metastasis. However, relatively few studies have investigated the influence of chemopreventive agents on miRNA expression and their regulation of target genes. Given the significance of miRNAs in modulating gene expression, such research can provide insight into the pleiotropic biological effects that chemopreventive agents often display and a deeper understanding of their mechanism of action to inhibit carcinogenesis. Additionally, miRNAs can provide useful biomarkers for assessing antineoplastic activity of these agents in preclinical and clinical observations. In this review, we summarize recent publications that highlight a potentially important role of miRNAs in cancer chemoprevention research. PMID:23531448

  18. Prostate cancer - resources

    MedlinePlus

    Resources - prostate cancer ... The following organizations are good resources for information on prostate cancer : American Cancer Society -- www.cancer.org/cancer/prostatecancer/index National Cancer Institute -- www.cancer.gov/cancertopics/ ...

  19. Grape seeds: ripe for cancer chemoprevention.

    PubMed

    Katiyar, Santosh K; Athar, Mohammad

    2013-07-01

    A wide variety of phytochemicals, mostly flavonoids or polyphenolics, have been shown to possess anticarcinogenic activities. Among these are the grape seed proanthocyanidins (GSPs), which are the active ingredients of grape seed extract (GSE). Substantial in vitro and preclinical in vivo studies have shown the chemopreventive efficacy of GSPs against various forms of cancers in different tumor models. In this issue of the journal, Derry and colleagues show that administration of GSE in the diet reduces azoxymethane-induced colon carcinogenesis in an A/J mouse model. The results of this innovative and comprehensive study indicate that inhibition of azoxymethane-induced colon cancer by dietary GSE is mediated through the induction of apoptosis that is associated with alterations in microRNA (miRNA) and cytokine expression profiles as well as β-catenin signaling. Notably, the demonstration that miRNA expression is affected by dietary GSE suggests a novel underlying mechanism for the chemopreventive action of GSE in colon cancer and, potentially, other cancers. ©2013 AACR.

  20. Risks of Prostate Cancer Screening

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Prostate Cancer Key Points Prostate cancer is a disease in ...

  1. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  2. Breast Cancer Profile among Patients with a History of Chemoprevention

    PubMed Central

    Pivo, Sarah; Refinetti, Ana Paula; Guth, Amber

    2016-01-01

    Purpose. This study identifies women with breast cancer who utilized chemoprevention agents prior to diagnosis and describes their patterns of disease. Methods. Our database was queried retrospectively for patients with breast cancer who reported prior use of chemoprevention. Patients were divided into primary (no history of breast cancer) and secondary (previous history of breast cancer) groups and compared to patients who never took chemoprevention. Results. 135 (6%) of 2430 women used chemoprevention. In the primary chemoprevention group (n = 18, 1%), 39% had completed >5 years of treatment, and fully 50% were on treatment at time of diagnosis. These patients were overwhelmingly diagnosed with ER/PR positive cancers (88%/65%) and were diagnosed with equal percentages (44%) of IDC and DCIS. 117 (87%) used secondary chemoprevention. Patients in this group were diagnosed with earlier stage disease and had lower rates of ER/PR-positivity (73%/65%) than the nonchemoprevention group (84%/72%). In the secondary group, 24% were on chemoprevention at time of diagnosis; 73% had completed >5 years of treatment. Conclusions. The majority of patients who used primary chemoprevention had not completed treatment prior to diagnosis, suggesting that the timing of initiation and compliance to prevention strategies are important in defining the pattern of disease in these patients. PMID:28078143

  3. Breast Cancer Profile among Patients with a History of Chemoprevention.

    PubMed

    Schnabel, Freya R; Pivo, Sarah; Chun, Jennifer; Schwartz, Shira; Refinetti, Ana Paula; Axelrod, Deborah; Guth, Amber

    2016-01-01

    Purpose. This study identifies women with breast cancer who utilized chemoprevention agents prior to diagnosis and describes their patterns of disease. Methods. Our database was queried retrospectively for patients with breast cancer who reported prior use of chemoprevention. Patients were divided into primary (no history of breast cancer) and secondary (previous history of breast cancer) groups and compared to patients who never took chemoprevention. Results. 135 (6%) of 2430 women used chemoprevention. In the primary chemoprevention group (n = 18, 1%), 39% had completed >5 years of treatment, and fully 50% were on treatment at time of diagnosis. These patients were overwhelmingly diagnosed with ER/PR positive cancers (88%/65%) and were diagnosed with equal percentages (44%) of IDC and DCIS. 117 (87%) used secondary chemoprevention. Patients in this group were diagnosed with earlier stage disease and had lower rates of ER/PR-positivity (73%/65%) than the nonchemoprevention group (84%/72%). In the secondary group, 24% were on chemoprevention at time of diagnosis; 73% had completed >5 years of treatment. Conclusions. The majority of patients who used primary chemoprevention had not completed treatment prior to diagnosis, suggesting that the timing of initiation and compliance to prevention strategies are important in defining the pattern of disease in these patients.

  4. Modulation of apoptosis by cancer chemopreventive agents.

    PubMed

    D'Agostini, Francesco; Izzotti, Alberto; Balansky, Roumen M; Bennicelli, Carlo; De Flora, Silvio

    2005-12-11

    A review of almost 2000 studies showed that the large majority of 39 putative cancer chemopreventive agents induced "spontaneous" apoptosis. Inhibition of the programmed cell death triggered by a variety of stimuli was consistently reported only with ascorbic acid, alpha-tocopherol, and N-acetylcysteine (NAC). We performed experimental studies in rodents exposed to cigarette smoke, either mainstream (MCS) or environmental (ECS), and UV-A/B-containing light. The nonsteroidal anti-inflammatory drug sulindac did not affect the apoptotic process in the skin of light-exposed mice and in the lungs of ECS-exposed mice. Likewise, 5,6-benzoflavone, indole-3-carbinol, 1,2-dithiole-3-thione and oltipraz failed to modulate apoptosis in the respiratory tract of ECS-exposed rats. Phenethyl isothiocyanate further enhanced the frequency of apoptosis in pulmonary alveolar macrophages and bronchial epithelial cells, and upregulated several genes in the lung of ECS-exposed rats. Both individually and in combination with oltipraz, NAC inhibited apoptosis in the respiratory tract of rats exposed either to MCS or ECS. Moreover, NAC attenuated the ECS-related overexpression of proapoptotic genes and normalized the levels of proapoptotic proteins in rat lung. The transplacental administration of NAC to mice considerably attenuated gene overexpression in the liver of fetuses exposed to ECS throughout pregnancy. Inhibition of apoptosis by chemopreventive agents reflects their ability to counteract certain upstream signals, such as genotoxic damage, redox imbalances, and other forms of cellular stress that trigger apoptosis. On the other hand, enhancement of apoptosis is a double-edged sword, since it represents a protective mechanism in carcinogenesis but may contribute to the pathogenesis of other degenerative diseases. We suggest that stimulation of apoptosis by so many chemopreventive agents, as reported in the literature, may often reflect the occurrence of toxic effects at high doses.

  5. Localized Prostate Cancer

    MedlinePlus

    ... a decision aid for men with clinically localized prostate cancer (available at http://effectivehealthcare.ahrq.gov/prostate_da) ... A Decision Aid for Men With Clinically Localized Prostate Cancer Page 1 of 24 Introduction Men with clinically ...

  6. Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain;numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. |

  7. Chemoprevention of oral cancer by lyophilized strawberries.

    PubMed

    Casto, Bruce C; Knobloch, Thomas J; Galioto, Rebecca L; Yu, Zhangsheng; Accurso, Brent T; Warner, Blake M

    2013-11-01

    Oral cancer represents approximately 2.5% of all cancers in the United States, with five- and 10-year survival rates of 62% and 51%. In the present study, lyophilized strawberries (LS) were evaluated for their potential to inhibit tumorigenesis in the hamster cheek pouch (HCP) model of oral cancer and for their ability to modify expression of several genes relevant to oral cancer development. HCPs were painted three times a week for six weeks with 0.2% 7,12-dimethylbenz(a)anthracene (DMBA). Hamsters were given 5% or 10% LS in their diet prior to, during, and after, or only after carcinogen treatment. Animals were sacrificed 12 weeks from the beginning of DMBA treatment and the number of total lesions and tumors was determined. A significant difference (p<0.01-0.04) in the number of tumors was found between the LS-treated groups and the carcinogen controls. Histological examination of HCPs revealed a significant reduction in mild and severe dysplasia following 12 weeks of treatment with LS. Molecular analysis revealed that genes related to tumor development were modulated by LS. These experiments support previous studies in HCP that demonstrated a chemopreventive activity by black raspberries and show, to our knowledge for the first time, that strawberries can inhibit tumor formation in an animal model of oral cancer.

  8. Chemoprevention of Oral Cancer by Lyophilized Strawberries

    PubMed Central

    Casto, Bruce C.; Knobloch, Thomas J.; Galioto, Rebecca L.; Yu, Zhangsheng; Accurso, Brent T.; Warner, Blake M.

    2014-01-01

    Background/Aim Oral cancer represents approximately 2.5% of all cancer in the United States, with five- and 10-year survival rates of 62% and 51%. In the present study, lyophilized strawberries (LS) were evaluated for their potential to inhibit tumorigenesis in the hamster cheek pouch (HCP) model of oral cancer and for their ability to modify expression of several genes relevant to oral cancer development. Materials and Methods HCPs were painted three times a week for six weeks with 0.2% 7,12-dimethylbenz(a)anthracene (DMBA). Hamsters were given 5% LS or 10% LS in their diet prior to, during, and after, or only after carcinogen treatment. Animals were sacrificed 12 weeks from the beginning of DMBA treatment and the number of total lesions and tumors determined. Results A significant difference (p-value <0.01–0.04) in the number of tumors was found between the LS-treated groups and the carcinogen controls. Histological examination of HCPs revealed a significant reduction in mild and severe dysplasia following 12 weeks of treatment with LS. Molecular analysis revealed that genes related to tumor development were modulated by LS. Conclusions These experiments support previous studies in HCPs that demonstrated a chemopreventive activity by black raspberries and show, to our knowledge for the first time, that strawberries can inhibit tumor formation in an animal model of oral cancer. PMID:24222110

  9. Green tea in chemoprevention of cancer.

    PubMed

    Mukhtar, H; Ahmad, N

    1999-12-01

    The concept of prevention of cancer using naturally occurring substances that could be included in the diet consumed by the human population is gaining increasing attention. Tea, next to water, is the most popularly consumed beverage in the world and it is grown in about 30 countries. Abundant data, amassed from several laboratories around the world in the last ten years, provided convincing evidence that polyphenolic antioxidants present in tea afford protection against cancer risk in many animal-tumor bioassay systems. The epidemiological studies, though inconclusive, have also suggested that the consumption of tea is associated with a lowered risk of cancer. Much of this work has been done on green tea; less is known about black tea. Green tea contains many polyphenolic antioxidants, and (-)-epigallocatechin-3-gallate (EGCG) is the key polyphenolic antioxidant believed to be responsible for most of the cancer chemopreventive properties of green tea. This review will discuss these effects and the molecular mechanisms associated with the biological response to green-tea polyphenols.

  10. About the Prostate and Urologic Cancer Research Group | Division of Cancer Prevention

    Cancer.gov

    The Prostate and Urologic Cancer Research Group conducts and supports research on prostate and bladder cancers, and new approaches to clinical prevention studies including cancer immunoprevention. The group develops, implements and monitors research efforts in chemoprevention, nutrition, genetic, and immunologic interventions, screening, early detection and other prevention strategies. |

  11. Hereditary cancer syndromes as model systems for chemopreventive agent development.

    PubMed

    Walcott, Farzana L; Patel, Jigar; Lubet, Ronald; Rodriguez, Luz; Calzone, Kathleen A

    2016-02-01

    Research in chemoprevention has undergone a shift in emphasis for pragmatic reasons from large, phase III randomized studies to earlier phase studies focused on safety, mechanisms, and utilization of surrogate endpoints such as biomarkers instead of cancer incidence. This transition permits trials to be conducted in smaller populations and at substantially reduced costs while still yielding valuable information. This article will summarize some of the current chemoprevention challenges and the justification for the use of animal models to facilitate identification and testing of chemopreventive agents as illustrated though four inherited cancer syndromes. Preclinical models of inherited cancer syndromes serve as prototypical systems in which chemopreventive agents can be developed for ultimate application to both the sporadic and inherited cancer settings.

  12. [Prostate cancer].

    PubMed

    Morote, Joan; Maldonado, Xavier; Morales-Bárrera, Rafael

    2016-02-05

    The Vall d'Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  13. Development of New Treatments for Prostate Cancer

    SciTech Connect

    DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

    2005-02-01

    The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention

  14. What is Prostate Cancer?

    MedlinePlus

    ... their doctors even knew they had it. Possible pre-cancerous conditions of the prostate Some research suggests that prostate cancer starts out as a pre-cancerous condition, although this is not yet known ...

  15. Comprehensive Population-Specific Marker Panel for Early Prostate Cancer Diagnostics and Risk Assessment

    DTIC Science & Technology

    2012-06-01

    of Green Tea Catechins in the Chemoprevention of Prostate Cancer. Nutrition and cancer. 1112011; 64(1):4-22; PMID: 22098273 2. Kumar NB, Crocker, T...Nagi Kumar. New Insights to the Mechanisms of Green Tea Catechins in the Chemoprevention ofProstate Cancer. Nutrition and cancer. 11/2011; 64(1):4-22...decreased diabetes risk and associated BMI increase; 4a and 4b ( green line): association mediated through increased BMI. Short description of the gene

  16. Future directions in the prevention of prostate cancer

    PubMed Central

    Thompson, Ian M.; Cabang, April B.; Wargovich, Michael J.

    2016-01-01

    The high global incidence of prostate cancer has led to a focus on chemoprevention strategies to reduce the public health impact of the disease. Early studies indicating that selenium and vitamin E might protect against prostate cancer encouraged large-scale studies that produced mixed clinical results. Next-generation prostate cancer prevention trials validated the impact of 5α-reductase inhibitors in hormone-responsive prostate cancer, and these results were confirmed in follow-up studies. Other interventions on the horizon, involving both dietary and pharmacological agents, hold some promise but require further investigation to validate their efficacy. In this Review, we discuss the clinical and preclinical evidence for dietary and pharmacological prevention of prostate cancer and give an overview of future opportunities for chemoprevention. PMID:24281061

  17. Cancer chemoprevention using natural vitamin D and synthetic analogs.

    PubMed

    Guyton, K Z; Kensler, T W; Posner, G H

    2001-01-01

    Substantial epidemiologic data support a role for vitamin D in cancer prevention. However, dose-limiting hypercalcemic effects have proved a major obstacle to the development of natural vitamin D as a cancer chemopreventive. Structure-activity studies have sought to disassociate the toxicities and chemopreventive activities of vitamin D, and a number of synthetic deltanoids (vitamin D analogs) have shown considerable promise in this regard. Several such compounds have chemopreventive efficacy in preclinical studies, as does natural vitamin D. Data supporting further development of agents of this class include in vitro and in vivo evidence of antiproliferative, proapoptotic, prodifferentiating and antiangiogenic activities. Ongoing studies are aimed at further defining the molecular mechanisms through which vitamin D and synthetic deltanoids affect gene expression and cellular fate. Additional efforts are focused on establishing the chemopreventive index (efficacy vs toxicity) of each synthetic deltanoid.

  18. Collaborative Undergraduate HBCU Student Summer Prostate Cancer Training Program

    DTIC Science & Technology

    2011-03-01

    Injury Dr. Narendra Banik, PhD Aug 3 (N) Schizophrenia Dr. Antonieta Lavin, PhD Aug 4 (C) Pathology Museum TBA Aug 5 H) Aspirin ...viral receptor but later found to be an adhesion molecule Do cancer cells adhere? Question Do prostate cancer cells adhere? Downregulation of adhesion... aspirin ) to reduce the risk of developing cancer Examples of chemoprevention: Prostate Cancer • SELECT Trial –Bad news: no evidence that either

  19. Cancer chemoprevention by natural carotenoids as an efficient strategy.

    PubMed

    Bolhassani, Azam

    2015-01-01

    The use of specific compounds to suppress the growth of tumors or reverse carcinogenesis is defined as chemoprevention. Natural products have been known as one of the most important resources of anticancer agents. Among them, carotenoids are lipophilic molecules accumulating in lipophilic compartments including lipoproteins and/or membranes. Various carotenoids were used as major phytonutrients to inhibit the development of tumors in vitro and in vivo. They have shown different functions such as scavenging free radicals, inhibition of angiogenesis, prevention of cell propagation, and apoptosis induction in lung, colon, breast and prostate. Regarding these roles, most carotenoids possess anti-oxidant properties. However, their therapeutic use is problematic due to the lack of solubility of carotenoids in water. Hence, recent studies have been focused on uncommon carotenoids soluble in water because of their glycosylated form, such as crocin(s) extracted from saffron. These structures with their cytotoxicity effects on human cancer cells are suggested as the most suitable compounds for cancer treatment. Herein, we summarize different functions of carotenoids for suppressing tumor growth.

  20. Chemoprevention of Gastrointestinal Cancer: The Reality and the Dream

    PubMed Central

    Chun, Kyung-Soo; Kim, Eun-Hee; Lee, Sooyeon

    2013-01-01

    Despite substantial progress in screening, early diagnosis, and the development of noninvasive technology, gastrointestinal (GI) cancer remains a major cause of cancer-associated mortality. Chemoprevention is thought to be a realistic approach for reducing the global burden of GI cancer, and efforts have been made to search for chemopreventive agents that suppress acid reflux, GI inflammation and the eradication of Helicobacter pylori. Thus, proton pump inhibitors, statins, monoclonal antibodies targeting tumor necrosis factor-alpha, and nonsteroidal anti-inflammatory agents have been investigated for their potential to prevent GI cancer. Besides the development of these synthetic agents, a wide variety of the natural products present in a plant-based diet, which are commonly called phytoceuticals, have also sparked hope for the chemoprevention of GI cancer. To perform successful searches of chemopreventive agents for GI cancer, it is of the utmost importance to understand the factors contributing to GI carcinogenesis. Emerging evidence has highlighted the role of chronic inflammation in inducing genomic instability and telomere shortening and affecting polyamine metabolism and DNA repair, which may help in the search for new chemopreventive agents for GI cancer. PMID:23560148

  1. Chemoprevention of rat prostate carcinogenesis by dietary 16alpha-fluoro-5-androsten-17-one (fluasterone), a minimally androgenic analog of dehydroepiandrosterone.

    PubMed

    McCormick, David L; Johnson, William D; Kozub, Nicole M; Rao, K V N; Lubet, Ronald A; Steele, Vernon E; Bosland, Maarten C

    2007-02-01

    Dehydroepiandrosterone (DHEA) is a potent inhibitor of prostate carcinogenesis in rats. However, concerns related to the possible androgenicity of DHEA may preclude its use for chemoprevention of human prostate cancer. Studies were performed to compare the androgenicity of DHEA and a fluorinated DHEA analog, 16alpha-fluoro-5-androsten-17-one (fluasterone), and to determine the chemopreventive activity of fluasterone in the rat prostate. Comparisons of accessory sex gland weight and histology in gonadectomized male rats demonstrated that fluasterone is less androgenic than is DHEA. Fluasterone conferred significant protection against prostate carcinogenesis induced in Wistar-Unilever rats by a sequential regimen of N-methyl-N-nitrosourea+testosterone. Chronic administration of fluasterone at levels of 2000 and 1000 mg/kg diet reduced the incidence of adenocarcinoma in the dorsolateral/anterior prostate from 64% in dietary controls to 28 and 31%, respectively. Other than a dose-related suppression of body weight gain, chronic exposure to fluasterone induced no clinical evidence of toxicity; suppression of body weight gain may be either a pharmacological effect or a minimally toxic effect of the compound. These data demonstrate that a minimally androgenic analog of DHEA protects against prostate carcinogenesis induced in rats by a chemical carcinogen + androgen. The reduced androgenicity of fluasterone may obviate toxicities associated with the androgenicity of the parent compound. On this basis, fluasterone merits consideration for evaluation in clinical trials for prostate cancer prevention. The chemopreventive activity of a non-androgenic DHEA analog suggests that at least a portion of the chemopreventive activity of DHEA in the rat prostate is unrelated to hormonal effects.

  2. Screening for Prostate Cancer

    MedlinePlus

    Understanding Task Force Recommendations Screening for Prostate Cancer The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation on Screening for Prostate Cancer . This recommendation is for ...

  3. Prostate Cancer FAQs

    MedlinePlus

    ... Coffey – Holden Prostate Cancer Academy Awards Challenge Awards Creativity Awards Young Investigator Awards Scientific Retreat – Meeting Agenda ... Retreat Coffey – Holden Prostate Cancer Academy Challenge Awards Creativity Awards Young Investigator Awards Featured Scientific Retreat – Meeting ...

  4. Prostate Cancer Symptoms

    MedlinePlus

    ... Coffey – Holden Prostate Cancer Academy Awards Challenge Awards Creativity Awards Young Investigator Awards Scientific Retreat – Meeting Agenda ... Retreat Coffey – Holden Prostate Cancer Academy Challenge Awards Creativity Awards Young Investigator Awards Featured Scientific Retreat – Meeting ...

  5. Cryotherapy for prostate cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000907.htm Cryotherapy for prostate cancer To use the sharing features ... first treatment for prostate cancer. What Happens During Cryotherapy Before the procedure, you will be given medicine ...

  6. Mitochondria: A novel target for the chemoprevention of cancer.

    PubMed

    Hail, N

    2005-08-01

    The mitochondria have emerged as a novel target for anticancer chemotherapy. This tenet is based on the observations that several conventional and experimental chemotherapeutic agents promote the permeabilization of mitochondrial membranes in cancerous cells to initiate the release of apoptogenic mitochondrial proteins. This ability to engage mitochondrial-mediated apoptosis directly using chemotherapy may be responsible for overcoming aberrant apoptosis regulatory mechanisms commonly encountered in cancerous cells. Interestingly, several putative cancer chemopreventive agents also possess the ability to trigger apoptosis in transformed, premalignant, or malignant cells in vitro via mitochondrial membrane permeabilization. This process may occur through the regulation of Bcl-2 family members, or by the induction of the mitochondrial permeability transition. Thus, by exploiting endogenous mitochondrial-mediated apoptosis-inducing mechanisms, certain chemopreventive agents may be able to block the progression of premalignant cells to malignant cells or the dissemination of malignant cells to distant organ sites as means of modulating carcinogenesis in vivo. This review will examine cancer chemoprevention with respect to apoptosis, carcinogenesis, and the proapoptotic activity of various chemopreventive agents observed in vitro. In doing so, I will construct a paradigm supporting the notion that the mitochondria are a novel target for the chemoprevention of cancer.

  7. In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis

    DTIC Science & Technology

    2001-03-01

    FUNDING NUMBERS In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous DAMD1 7-98-1-8550 Prostate Carcinogenesis 6. AUTHOR( S ... castration (n= 9 dogs ). Interventions were well tolerated by all dogs . Although the final data analysis is not yet completed, our project has generated...Waters DJ, Shen S , Glickman LT. Life expectancy, antagonistic pleiotropy, and the testis of dogs and men. Prostate 2000;43:272-277. DNA damage-sparing

  8. Polyamines and cancer: Implications for chemoprevention and chemotherapy

    PubMed Central

    Nowotarski, Shannon L.; Woster, Patrick M.; Casero, Robert A.

    2013-01-01

    Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes and a poorly characterized transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate, and skin cancers, and altered levels of the rate limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway specific drugs, and ongoing clinical trials targeting polyamine biosynthesis. PMID:23432971

  9. Polyamines and cancer: implications for chemotherapy and chemoprevention.

    PubMed

    Nowotarski, Shannon L; Woster, Patrick M; Casero, Robert A

    2013-02-22

    Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes, and a poorly characterised transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate and skin cancers, and altered levels of rate-limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway-specific drugs and ongoing clinical trials targeting polyamine biosynthesis.

  10. The epidemiology of prostate cancer.

    PubMed

    Boyle, Peter; Severi, Gianluca; Giles, Graham G

    2003-05-01

    attraction than do prophylactic mastectomies for women at high risk of breast cancer. This issue becomes more complex when considering counseling on the basis of a genetic profile involving many low-risk polymorphisms. Hopefully, such genetic screening should occur only after its efficacy has been established; when there is a better understanding of prostate biology, tumor heterogeneity, and prognosis; and when there are proven treatment or prevention options available. Prevention is held to be better than cure, and there are some potentially interesting chemopreventive agents that require careful trial before public health initiatives can be promoted. Potential candidates include vitamin E, selenium, zinc, and lycopene as dietary supplements. There are other agents that may be appropriate for pharmaceutical development, including inhibitors of COX-2 and IGF-1 activity. It is important that chemoprevention trials are followed-up for a sufficient period of time and that other endpoints also are captured, because the supplementation of diets with superphysiologic doses of individual micronutrients sometimes has caused unexpected and unwanted results--for example, an 18% increase in lung cancers observed in the beta-carotene arm of the ATBC trial.

  11. Chemoprevention of asbestos-linked cancers: a systematic review.

    PubMed

    Neri, Monica; Ugolini, Donatella; Boccia, Stefania; Canessa, Pier Aldo; Cesario, Alfredo; Leoncini, Giacomo; Mutti, Luciano; Bonassi, Stefano

    2012-03-01

    Asbestos has been used extensively and, in spite of many countries having banned most of its uses, professional, domestic and environmental exposure has not ceased worldwide. Inhaled asbestos fibers can lead to malignant mesothelioma, lung cancer and non-cancerous conditions, while the substance persists indefinitely in the lung and pleural tissue, resulting in continuous damage. Exposed individuals may be offered medical surveillance or compensation, but nothing is currently being done to lower their specific cancer risk: chemoprevention seems a promising approach. A web search and a PubMed review of the literature on chemoprevention trials in individuals exposed to asbestos have been conducted. Forty-six articles on five projects were found and newly reviewed but, surprisingly, no novel trials have been set up for twenty years, although considerable advances have been gained in cancer chemoprevention. A re-consideration of possibilities offered by chemoprevention should be encouraged. New trials based on the most recently characterized molecules should be planned, taking into account specific issues such as the need for a very large number of participants and a long follow up or, alternatively, the use of biomarkers as surrogate endpoints. The long latency of asbestos related diseases may offer delayed intervention opportunities. The lack of chemoprevention trials for asbestos exposure highlights the urgent need for research in this field.

  12. Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways.

    PubMed

    Ramos, Sonia

    2008-05-01

    Prevention of cancer through dietary intervention recently has received an increasing interest, and dietary polyphenols have become not only important potential chemopreventive, but also therapeutic, natural agents. Polyphenols have been reported to interfere at the initiation, promotion and progression of cancer. They might lead to the modulation of proteins in diverse pathways and require the integration of different signals for the final chemopreventive or therapeutic effect. Polyphenols have been demonstrated to act on multiple key elements in signal transduction pathways related to cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis and metastasis; however, these molecular mechanisms of action are not completely characterized and many features remain to be elucidated. The aim of this review is to provide insights into the molecular basis of potential chemopreventive and therapeutic activities of dietary polyphenols with emphasis in their ability to control intracellular signalling cascades considered as relevant targets in a cancer preventive approach.

  13. Cancer chemoprevention research with selenium in the post-SELECT era: Promises and challenges

    PubMed Central

    Lü, Junxuan; Zhang, Jinhui; Jiang, Cheng; Deng, Yibin; Özten, Nur; Bosland, Maarten C.

    2016-01-01

    The negative efficacy outcomes of double-blinded, randomized, placebo-controlled Phase III human clinical trials with selenomethionine (SeMet) and SeMet-rich selenized-yeast (Se-yeast) for prostate cancer prevention and Se-yeast for prevention of non-small cell lung cancer (NSCLC) in North America lead to rejection of SeMet/Se-yeast for cancer prevention in Se-adequate populations. We identify two major lessons from the outcomes of these trials: 1) The antioxidant hypothesis was tested in wrong subjects or patient populations. 2) The selection of Se agents was not supported by cell culture and preclinical animal efficacy data as is common in drug development. We propose that next-generation forms of Se (next-gen Se), such as methylselenol precursors, offer biologically appropriate approaches for cancer chemoprevention but these are faced with formidable challenges. Solid mechanism-based preclinical efficacy assessments and comprehensive safety studies with next-gen Se will be essential to re-vitalize the idea of cancer chemoprevention with Se in the post-SELECT era. We advocate smaller mechanism-driven Phase I/II trials with these next-gen Se to guide and justify future decisions for definitive Phase III chemoprevention efficacy trials. PMID:26595411

  14. Cancer chemoprevention research with selenium in the post-SELECT era: Promises and challenges.

    PubMed

    Lü, Junxuan; Zhang, Jinhui; Jiang, Cheng; Deng, Yibin; Özten, Nur; Bosland, Maarten C

    2016-01-01

    The negative efficacy outcomes of double-blinded, randomized, placebo-controlled Phase III human clinical trials with selenomethionine (SeMet) and SeMet-rich selenized-yeast (Se-yeast) for prostate cancer prevention and Se-yeast for prevention of nonsmall cell lung cancer (NSCLC) in North America lead to rejection of SeMet/Se-yeast for cancer prevention in Se-adequate populations. We identify 2 major lessons from the outcomes of these trials: 1) the antioxidant hypothesis was tested in wrong subjects or patient populations, and 2) the selection of Se agents was not supported by cell culture and preclinical animal efficacy data as is common in drug development. We propose that next-generation forms of Se (next-gen Se), such as methylselenol precursors, offer biologically appropriate approaches for cancer chemoprevention but these are faced with formidable challenges. Solid mechanism-based preclinical efficacy assessments and comprehensive safety studies with next-gen Se will be essential to revitalize the idea of cancer chemoprevention with Se in the post-SELECT era. We advocate smaller mechanism-driven Phase I/II trials with these next-gen Se to guide and justify future decisions for definitive Phase III chemoprevention efficacy trials.

  15. Molecular medicine and the development of cancer chemopreventive agents.

    PubMed

    Izzotti, Alberto

    2012-07-01

    Chemoprevention is effective in inhibiting the onset of cancer in experimental animal models, but the transferability of similar results to humans is questionable. Therefore, reliable intermediate molecular biomarkers are needed to evaluate the efficacy of chemopreventive agents before the onset of cancer. The use of genomic biomarkers is limited by their poor predictive value. Although post-genomic biomarkers (i.e., gene-expression analyses) are useful for evaluating the safety, efficacy, and mechanistic basis of chemopreventive agents, the biomarkers are often poorly related to the phenotype, due to posttranscriptional regulation. Proteome analyses can evaluate preclinical phenotype alterations, but only at low protein counts. MicroRNA alterations, which are essential for the development of cancer, may be modulated by chemopreventive agents. Furthermore, microRNA delivery may be used to counteract carcinogenesis. Exposure to cigarette smoke induces microRNA let-7 downregulation and cell proliferation that can be converted to cell growth arrest and apoptosis upon let-7a transfection. Therefore, microRNAs are reliable biomarkers for evaluating chemoprevention efficacy and may be used to counteract carcinogenesis. © 2012 New York Academy of Sciences.

  16. Plant flavonoids in cancer chemoprevention: role in genome stability.

    PubMed

    George, Vazhappilly Cijo; Dellaire, Graham; Rupasinghe, H P Vasantha

    2016-11-28

    Carcinogenesis is a multistage process that involves a series of events comprising of genetic and epigenetic changes leading to the initiation, promotion and progression of cancer. Chemoprevention is referred to as the use of nontoxic natural compounds, synthetic chemicals or their combinations to intervene in multistage carcinogenesis. Chemoprevention through diet modification, i.e., increased consumption of plant-based food, has emerged as a most promising and potentially cost-effective approach to reducing the risk of cancer. Flavonoids are naturally occurring polyphenols that are ubiquitous in plant-based food such as fruits, vegetables and teas as well as in most medicinal plants. Over 10,000 flavonoids have been characterized over the last few decades. Flavonoids comprise of several subclasses including flavonols, flavan-3-ols, anthocyanins, flavanones, flavones, isoflavones and proanthocyanidins. This review describes the most efficacious plant flavonoids, including luteolin, epigallocatechin gallate, quercetin, apigenin and chrysin; their hormetic effects; and the molecular basis of how these flavonoids contribute to the chemoprevention with a focus on protection against DNA damage caused by various carcinogenic factors. The present knowledge on the role of flavonoids in chemoprevention can be used in developing effective dietary strategies and natural health products targeted for cancer chemoprevention.

  17. Epigenetic potential of resveratrol and analogs in preclinical models of prostate cancer

    USDA-ARS?s Scientific Manuscript database

    Prostate cancer is affected by lifestyle, particularly diet. Dietary polyphenols such as resveratrol possess anticancer properties and, therefore, chemopreventive and therapeutic potentials. Resveratrol has pleiotropic effect exerting its biological activity through multiple pathways and targets ass...

  18. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention

    PubMed Central

    Piazza, Gary A.

    2015-01-01

    Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. PMID:26021807

  19. Selenoproteins and Prostate Cancer

    DTIC Science & Technology

    2005-11-01

    1-0009 TITLE: Selenoproteins and Prostate Cancer PRINCIPAL INVESTIGATOR: Veda Navsariwala, Ph.D...Annual Summary 3. DATES COVERED (From - To) 15 Oct 2004 – 14 Oct 2005 4. TITLE AND SUBTITLE Selenoproteins and Prostate Cancer 5a. CONTRACT NUMBER...ABSTRACT For this postdoctoral fellowship the specific role of selenoproteins in prostate carcinogenesis is being investigated using a cell

  20. Screening for prostate cancer

    NASA Technical Reports Server (NTRS)

    Weirich, Stephen A.

    1993-01-01

    Despite recent advances in both the survival and cure rates for many forms of cancer, unfortunately the same has not been true for prostate cancer. In fact, the age-adjusted death rate from prostate cancer has not significantly improved since 1949, and prostate cancer remains the most common cancer in American men, causing the second highest cancer mortality rate. Topics discussed include the following: serum testosterone levels; diagnosis; mortality statistics; prostate-sppecific antigen (PSA) tests; and the Occupational Medicine Services policy at LeRC.

  1. Review paper: Cancer chemopreventive compounds and canine cancer.

    PubMed

    Baek, S J; McEntee, M F; Legendre, A M

    2009-07-01

    Canine cancer has become more prevalent in recent years because of increased life expectancy and greater attention to the health of pets. The range of cancers seen in dogs is as diverse as that in human patients, and despite more intensive therapeutic interventions, fatality rates remain unacceptably high in both species. Chemoprevention is therefore an important means of confronting this disease. Because domestic pets share our environment, greater cross-application and study of the protumorigenic and antitumorigenic factors in our shared environment will benefit all species, leading to the development of new families of less toxic antitumorigenic compounds based on novel and established molecular targets. Currently, the most interesting cancer preventive agents are nonsteroidal anti-inflammatory drugs, peroxisome proliferator-activated receptor-gamma ligands, and dietary compounds. This article provides an overview of what is known about how these agents affect molecular signaling in neoplastic disease, with reference to reported application and/or study in dogs where available.

  2. Diet and Epigenetic Interactions in Prostate Cancer Prevention

    DTIC Science & Technology

    2011-06-01

    for pathology. In this study, dietary SFN, fed as freeze-dried broccoli sprouts, increased SFN content in the prostate (Figure 5A) and decreased the...and Exercise Sciences seminar (April 2010) “Cancer Prevention with Broccoli – from Cellular to Human Studies” Cancer chemoprevention seminar...mice. (A) Liver, kidney, colon and prostates were collected from mice fed standard diet and mice fed a 15% broccoli diet and processed according to

  3. Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer Prevention

    DTIC Science & Technology

    2013-05-01

    Green Tea for Prostate Cancer Prevention PRINCIPAL INVESTIGATOR: Hasan Mukhtar, Ph.D. CONTRACTING ORGANIZATION: University of...Nanoformulated Green Tea for Prostate Cancer Prevention 5b. GRANT NUMBER W81XWH-10-1-0245 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Principal...chemopreventive properties green tea has shown promise in preclinical, epidemiological and initial clinical studies. However, absolute clinical success

  4. Evaluation of Brazilian plants on cancer chemoprevention targets in vitro.

    PubMed

    Endringer, Denise C; Valadares, Ydia M; Campana, Priscilla R V; Campos, Jussara J; Guimarães, Keller G; Pezzuto, John M; Braga, Fernão C

    2010-06-01

    Cancer is a leading cause of death worldwide. Cancer chemoprevention is one of the promising strategies to decrease its incidence and both plant extracts and natural products may constitute sources of new chemoprevention agents. Some Brazilian species popularly used to treat inflammatory conditions were selected for evaluation for cancer chemoprevention. A total of 32 extracts/fractions from Hancornia speciosa, Davilla elliptica, Jacaranda caroba, Mansoa hirsuta, Remija ferrugina, Solanum paniculatum and Xyris pterygoblephara, along with a mixture of ursolic and oleanolic acids obtained from J. caroba and a dihydroisocoumarin isolated from aerial parts of X. pterygoblephara were tested for their cancer chemoprevention activity [inhibition of 12-O-tetradecanoyl-13-acetate (TPA)-mediated NF-kappaB activation, ornithine decarboxylase (ODC) and cyclooxygenase-1 (COX-1); induction of antioxidant response element (ARE)]. Several extracts/fractions were active in more than one assay and those from H. speciosa, M. hirsuta and J. caroba mediated strong responses with NF-kappaB, COX-1 and ARE, respectively.

  5. Shrimp lipids: a source of cancer chemopreventive compounds.

    PubMed

    López-Saiz, Carmen-María; Suárez-Jiménez, Guadalupe-Miroslava; Plascencia-Jatomea, Maribel; Burgos-Hernández, Armando

    2013-10-16

    Shrimp is one of the most popular seafoods worldwide, and its lipids have been studied for biological activity in both, muscle and exoskeleton. Free fatty acids, triglycerides, carotenoids, and other lipids integrate this fraction, and some of these compounds have been reported with cancer chemopreventive activities. Carotenoids and polyunsaturated fatty acids have been extensively studied for chemopreventive properties, in both in vivo and in vitro studies. Their mechanisms of action depend on the lipid chemical structure and include antioxidant, anti-proliferative, anti-mutagenic, and anti-inflammatory activities, among others. The purpose of this review is to lay groundwork for future research about the properties of the lipid fraction of shrimp.

  6. Role of saffron and its constituents on cancer chemoprevention

    PubMed Central

    Zhang, Zhiyu; Wang, Chong-Zhi; Wen, Xiao-Dong; Shoyama, Yukihiro; Yuan, Chun-Su

    2014-01-01

    Context Cancer dramatically impacts human life expectancy and quality of life. Natural substances from vegetables, herbs and spices could be beneficial in the prevention or treatment of a variety of cancers. Crocus sativus, which has been used as a folk medicine for treating diseases for ages, showed obvious cancer chemoprevention potential. Objective This article focuses on the effects of Crocus sativus and its main ingredients, such as crocin, on cancer therapeutics. Methods We reviewed research data from saffron, a spice derived from the flower of Crocus sativus, and its constituents using the major databases, viz., Web of Science, SciFinder, and PubMed. Results and conclusion Saffron possesses free radical-scavenging properties and antitumor activities. Significant cancer chemopreventive effects have been shown in both in vitro and in vivo models. Based on current data, saffron and its ingredients could be considered as a promising candidate for clinical anticancer trials. PMID:23570520

  7. Diet and prostate cancer - a holistic approach to management.

    PubMed

    Cheetham, Philippa J; Katz, Aaron E

    2011-10-01

    There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemo-preventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemoprevention agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers.

  8. Evaluation of the chemopreventive potential of retinoids using a novel in vitro human prostate carcinogenesis model.

    PubMed

    Quader, S T; Bello-DeOcampo, D; Williams, D E; Kleinman, H K; Webber, M M

    2001-09-20

    The prevalence of prostatic intraepithelial neoplasia (PIN) and latent prostatic carcinoma, representing multiple steps in carcinogenesis and progression to invasive carcinoma, makes them relevant targets for prevention. A unique family of human prostate epithelial cell lines, which mimic steps in prostate carcinogenesis and progression, were used to evaluate the chemopreventive potential of all-trans-retinoic acid (RA) and N-(4-hydroxyphenyl)retinamide (4-HPR). The effects of RA and 4-HPR on anchorage-dependent growth of an immortalized, non-tumorigenic cell line RWPE-1 and two tumorigenic cell lines, WPE1-NB14 and WPE1-NB11, derived from RWPE-1 by exposure to N-methyl-N-nitrosourea (MNU), were examined. Both tumorigenic cell lines grow more rapidly than the parent RWPE-1 cell line in monolayer culture. Further, while RWPE-1 cells do not form colonies in agar, both tumorigenic cell lines do, with a colony forming efficiency (CFE) of 1.85 and 2.04% for WPE1-NB14 and WPE1-NB11 cells, respectively. Both RA and 4-HPR inhibited anchorage-dependent growth of all cell lines and anchorage-independent growth of WPE1-NB14 and WPE1-NB11 cells, in a dose-dependent manner, however, 10 times more RA than 4-HPR was required to produce the same effect. RWPE-1 cells are not invasive but WPE1-NB11 cells are significantly more invasive than WPE1-NB14 cells. Both RA and 4-HPR inhibited invasion in vitro by WPE1-NB11 and WPE1-NB14 cells where the more malignant WPE1-NB11 cells showed greater inhibition of invasion by 4-HPR than by RA. Overall, 4-HPR was more effective than RA in inhibiting growth and invasion but the response varied amongst the cell lines. These three cell lines mimic progressive steps in carcinogenesis and progression, from immortalized, non-tumorigenic RWPE-1 cells, to the less malignant WPE1-NB14 to the more malignant WPE1-NB11 cells, and provide powerful models for studies on secondary and tertiary prevention, i.e. promotion and progression stages, respectively

  9. Advanced drug delivery systems of curcumin for cancer chemoprevention.

    PubMed

    Bansal, Shyam S; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V; Gupta, Ramesh C

    2011-08-01

    Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium.

  10. Genetics Home Reference: prostate cancer

    MedlinePlus

    ... Email Facebook Twitter Home Health Conditions prostate cancer prostate cancer Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Prostate cancer is a common disease that affects men, usually ...

  11. Hormone therapy for prostate cancer

    MedlinePlus

    ... gov/ency/patientinstructions/000908.htm Hormone therapy for prostate cancer To use the sharing features on this page, ... the growth of prostate cancer. Male Hormones and Prostate Cancer Androgens are male sex hormones. Testosterone is one ...

  12. Collaborative Undergraduate HBCU Student Summer Prostate Cancer Training Program

    DTIC Science & Technology

    2010-03-01

    Smothers July 17 H - Aspirin & NSAIDS Dr. Halushka July 20 C – Herbals & Cancer Dr. Wargovich July 21 N – Neuroimaging Dr. George...receptor CAR - originally discovered as a viral receptor but later found to be an adhesion molecule Do cancer cells adhere? Problems Do cancer cells...synthetic (e.g., aspirin ) to reduce the risk of developing cancer Examples of chemoprevention: Prostate Cancer • SELECT Trial –Bad news: no evidence

  13. Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass?

    PubMed Central

    Walle, Thomas

    2007-01-01

    Dietary flavonoids and other polyphenols show great potential as cancer chemopreventive agents in cell culture studies. This does not translate well into in vivo activity, because of extensive conjugative metabolism of these compounds in the intestine and liver. This paper presents a review of a flavonoid subclass in which all hydroxyl groups are capped by methylation. This results in dramatically increased metabolic stability and membrane transport in the intestine/liver, thus improving oral bioavailability. The methoxyflavones also show increased cancer chemopreventive properties. At the cancer initiation stage, bioactivation of polyaromatic hydrocarbon carcinogens and binding to DNA are markedly diminished through effects on CYP1A1/1B1 transcription but also through direct interactions with the proteins. At the cancer promotion stage, the proliferation of cancer cells, but not normal cells, is inhibited with greater potency than with the unmethylated flavones. Limited mechanistic experiments, such as of effects on cell cycle regulation, indicate that the mechanisms of methoxyflavone activities are unique, including aromatase inhibition. The cancer preventive effects and mechanisms of the polymethoxyflavones, such as tangeretin and nobiletin, are discussed in comparison. It is concluded that the methoxyflavones have properties that may make them particularly useful as cancer chemopreventive agents. PMID:17574860

  14. Chemopreventive Agent Development | Division of Cancer Prevention

    Cancer.gov

    [[{"fid":"174","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Chemoprevenentive Agent Development Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Chemoprevenentive Agent Development Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Chemoprevenentive Agent Development Research Group Homepage Logo","title":"Chemoprevenentive Agent Development Research Group Homepage Logo","heigh | Research on early chemopreventive agent development, from preclinical studies to phase I clinical trials.

  15. Cancer risk factors for selecting cohorts for large-scale chemoprevention trials.

    PubMed

    Greenwald, P

    1996-01-01

    for cancer; and chemopreventive agent selection and development. A comprehensive database is being established to support the PTDN's decision-making process and will help to determine which agents investigated in preclinical and early phase clinical trials should move to large-scale testing. Cohorts for large-scale chemoprevention trials include individuals who are determined to be at high risk as a result of genetic predisposition, carcinogenic exposure, or the presence of biomarkers indicative of increased risk. Current large-scale trials in well-defined, high-risk populations include the Breast Cancer Prevention Trial (tamoxifen), the Prostate Cancer Prevention Trial (finasteride), and the N-(4-hydroxyphenyl) retinamide (4-HPR) breast cancer prevention study being conducted in Milan. Biomarker studies will provide valuable information for refining the design and facilitating the implementation of future large-scale trials. For example, potential biomarkers are being assessed at biopsy in women with ductal carcinoma in situ (DCIS). The women are then randomized to either placebo, tamoxifen, 4-HPR, or tamoxifen plus 4-HPR for 2-4 weeks, at which time surgery is performed and the biomarkers reassessed to determine biomarker modulation by the interventions. For prostate cancer, modulation of prostatic intraepithelial neoplasia (PIN) by 4-HPR and difluoromethylornithine is being investigated; similar studies are being planned for oltipraz, dehydroepiandrosterone, and vitamin E plus selenomethionine. The validation of biomarkers as surrogate endpoints for cancer incidence in high-risk cohorts will allow more agents to be evaluated in shorter studies that use fewer subjects to achieve the desired statistical power.

  16. Selenoproteins and Prostate Cancer

    DTIC Science & Technology

    2006-11-01

    W81XWH-05-1-0009 TITLE: Selenoproteins and Prostate Cancer PRINCIPAL INVESTIGATOR: Veda Diwadkar-Navsariwala, Ph.D. CONTRACTING...From - To) 14 Oct 2004 – 14 Oct 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Selenoproteins and Prostate Cancer 5b. GRANT NUMBER W81XWH-05...SUPPLEMENTARY NOTES 14. ABSTRACT For this postdoctoral fellowship the specific role of selenoproteins (SP) in prostate cancer (PCa) was

  17. Cactus pear: a natural product in cancer chemoprevention

    PubMed Central

    Zou, Da-ming; Brewer, Molly; Garcia, Francisco; Feugang, Jean M; Wang, Jian; Zang, Roungyu; Liu, Huaguang; Zou, Changping

    2005-01-01

    Background Cancer chemoprevention is a new approach in cancer prevention, in which chemical agents are used to prevent cancer in normal and/or high-risk populations. Although chemoprevention has shown promise in some epithelial cancers, currently available preventive agents are limited and the agents are costly, generally with side effects. Natural products, such as grape seed, green tea, and certain herbs have demonstrated anti-cancer effects. To find a natural product that can be used in chemoprevention of cancer, we tested Arizona cactus fruit solution, the aqueous extracts of cactus pear, for its anti-cancer effects in cultured cells and in an animal model. Method Aqueous extracts of cactus pear were used to treat immortalized ovarian and cervical epithelial cells, as well as ovarian, cervical, and bladder cancer cells. Aqueous extracts of cactus pear were used at six concentrations (0, 0.5, 1, 5, 10 or 25%) to treat cells for 1, 3, or 5 days. Growth inhibition, apoptosis induction, and cell cycle changes were analyzed in the cultured cells; the suppression of tumor growth in nude mice was evaluated and compared with the effect of a synthetic retinoid N-(4-hydroxyphernyl) retinamide (4-HPR), which is currently used as a chemoprevention agent. Immunohistochemistry staining of tissue samples from animal tumors was performed to examine the gene expression. Results Cells exposed to cactus pear extracts had a significant increase in apoptosis and growth inhibition in both immortalized epithelial cells and cancer cells in a dose- and time-dependent manner. It also affected cell cycle of cancer cells by increasing G1 and decreasing G2 and S phases. Both 4-HPR and cactus pear extracts significantly suppressed tumor growth in nude mice, increased annexin IV expression, and decreased VEGF expression. Conclusion Arizona cactus pear extracts effectively inhibited cell growth in several different immortalized and cancer cell cultures, suppressed tumor growth in nude mice

  18. Cactus pear: a natural product in cancer chemoprevention.

    PubMed

    Zou, Da-ming; Brewer, Molly; Garcia, Francisco; Feugang, Jean M; Wang, Jian; Zang, Roungyu; Liu, Huaguang; Zou, Changping

    2005-09-08

    Cancer chemoprevention is a new approach in cancer prevention, in which chemical agents are used to prevent cancer in normal and/or high-risk populations. Although chemoprevention has shown promise in some epithelial cancers, currently available preventive agents are limited and the agents are costly, generally with side effects. Natural products, such as grape seed, green tea, and certain herbs have demonstrated anti-cancer effects. To find a natural product that can be used in chemoprevention of cancer, we tested Arizona cactus fruit solution, the aqueous extracts of cactus pear, for its anti-cancer effects in cultured cells and in an animal model. Aqueous extracts of cactus pear were used to treat immortalized ovarian and cervical epithelial cells, as well as ovarian, cervical, and bladder cancer cells. Aqueous extracts of cactus pear were used at six concentrations (0, 0.5, 1, 5, 10 or 25%) to treat cells for 1, 3, or 5 days. Growth inhibition, apoptosis induction, and cell cycle changes were analyzed in the cultured cells; the suppression of tumor growth in nude mice was evaluated and compared with the effect of a synthetic retinoid N-(4-hydroxyphernyl) retinamide (4-HPR), which is currently used as a chemoprevention agent. Immunohistochemistry staining of tissue samples from animal tumors was performed to examine the gene expression. Cells exposed to cactus pear extracts had a significant increase in apoptosis and growth inhibition in both immortalized epithelial cells and cancer cells in a dose- and time-dependent manner. It also affected cell cycle of cancer cells by increasing G1 and decreasing G2 and S phases. Both 4-HPR and cactus pear extracts significantly suppressed tumor growth in nude mice, increased annexin IV expression, and decreased VEGF expression. Arizona cactus pear extracts effectively inhibited cell growth in several different immortalized and cancer cell cultures, suppressed tumor growth in nude mice, and modulated expression of tumor

  19. [Aberrant crypt foci as biomarkers in chemoprevention for colorectal cancer].

    PubMed

    Katsuki, S; Oui, M; Takayama, T; Takahashi, Y; Shuichi, N; Niitsu, Y

    1998-06-01

    Aberrant crypt foci (ACF) are small lesions identifiable in whole-mount preparations of normal-appearing human colonic mucosa with the aid of methyleneblue staining under stereoscopic microscope. Highly frequent mutations of K-ras genes were found, and increased proliferative activities were also observed. Therefore, K-ras gene mutation may have some role in formation of ACF. Using rat experimental model, formation of ACF was shown to be enhanced by cancer promoters (such as secondary bile acids), and to be suppressed by chemopreventive agents (deoxycholic acid and aspirin). Based on these findings, ACF are considered to be precursors of colon cancer. We demonstrated that ACF are the precursors of adenoma-carcinoma sequence. Moreover, we showed that ACF may be suitable biomarkers of chemopreventive agents for colon cancers.

  20. Lipids and Prostate Cancer

    PubMed Central

    Suburu, Janel; Chen, Yong Q.

    2012-01-01

    The role of lipid metabolism has gained particular interest in prostate cancer research. A large body of literature has outlined the unique upregulation of de novo lipid synthesis in prostate cancer. Concordant with this lipogenic phenotype is a metabolic shift, in which cancer cells use alternative enzymes and pathways to facilitate the production of fatty acids. These newly synthesized lipids may support a number of cellular processes to promote cancer cell proliferation and survival. Hence, de novo lipogenesis is under intense investigation as a therapeutic target. Epidemiologic studies suggest dietary fat may also contribute to prostate cancer; however, whether dietary lipids and de novo synthesized lipids are differentially metabolized remains unclear. Here, we highlight the lipogenic nature of prostate cancer, especially the promotion of de novo lipid synthesis, and the significance of various dietary lipids in prostate cancer development and progression. PMID:22503963

  1. Prostate Cancer

    MedlinePlus

    ... cancers that don't respond to hormone therapy. Biological therapy Biological therapy (immunotherapy) uses your body's immune system to fight cancer cells. One type of biological therapy called sipuleucel-T (Provenge) has been developed ...

  2. [Prostate cancer screening].

    PubMed

    Villers, Arnauld; Rébillard, Xavier; Soulié, Michel; Davin, Jean-Louis; Coloby, Patrick; Moreau, Jean-Luc; Mejean, Arnaud; Irani, Jacques; Coulange, Christian; Mangin, Philippe

    2003-04-01

    Prostate cancer has become the most frequent cancer and the second cause of cancer mortality in men. This public health problem is becoming increasingly important due to the increasing life expectancy. At the present time, prostate cancer will be discovered in one in every eight men during their lifetime. Prostate cancer represents 25% of all new cases of male cancers. Prostate cancer screening is designed to detect early stage, asymptomatic prostate cancer, as the patient's chances of cure are higher when the cancer is diagnosed at an early stage. The conclusions of the ANAES evaluation in 1998 did not recommend mass screening for prostate cancer. Several international prospective randomized studies based on serum PSA assay, sometimes associated with digital rectal examination, are currently underway. France is participating in the European ERSPC study (European Randomized Study of Screening for Cancer Prostate) and is organizing a national study on high-risk populations. While waiting for the final results of these studies, a recommendation needs to be proposed to inform general practitioners and specialists about optimal use of the currently available tests. Based on the conclusions of its oncology committee (composed of urologists, medical oncologists, radiotherapists, pathologists and radiologists), the Association Française d'Urologie proposes a recommendation concerning prostate cancer screening and defines its modalities, especially concerning the target population, screening tests and the information given to men before screening. The Association Française d'Urologie recommends prostate cancer screening by PSA assay (prostate specific antigen) and digital rectal examination annually between the ages of 50 and 75 years, and from the age of 45 years in men with a family or ethnic risk. If total PSA is above the normal value of the test or if digital rectal examination is abnormal, referral to a urologist is recommended. Information concerning the limits

  3. The Dean and Betty Gallo Prostate Cancer Center

    DTIC Science & Technology

    2004-07-01

    Department of the Army position , policy or decision unless so designated by other documentation. 20051013 021 Form Approved SREPORT DOCUMENTATION PAGE OMB No...mon non- 3. To improve the control of prostate cancer through early detection, chemoprevention, outreach /// cutaneous malignancy afflicting men in and...mutant mice to malignant transformation of the prostate. These studies Deleted: Drs. provide important insights linking the control of differentiation to

  4. Nanoformulation of natural products for prevention and therapy of prostate cancer.

    PubMed

    Sanna, Vanna; Siddiqui, Imtiaz A; Sechi, Mario; Mukhtar, Hasan

    2013-06-28

    There is a need for developing improved therapeutic options for the management of prostate cancer, able to inhibit proliferation of precancerous and malignant lesions and/or to improve the effectiveness of conventional chemopreventive and chemotherapeutic agents. In this perspective, application of nanotechnology based strategies for the delivery of natural compounds for effective management of the disease is being actively researched. Here, after highlighting the most promising natural compounds for chemoprevention and chemotherapy of prostate cancer, the state of the art nanotherapeutics and the recent proof-of-concept of "nanochemoprevention", as well as the clinical development of promising targeted nanoprototypes for use in the prostate cancer treatment are being discussed.

  5. Prostate Cancer Biorepository Network

    DTIC Science & Technology

    2015-10-01

    annotated with the biospecimens. Specialized processing consists of tissue microarray design and construction. Biospecimens (mainly tissue ...provide much sought after biospecimens for prostate cancer research. 15. SUBJECT TERMS Prostate Cancer, Biorepository, tissue microarrays, tissue ...and harmonizing a set of common data elements (CDEs): Completed in 1st quarter (October 2014) Task 3. Submit SOPs currently in use to Coordinating

  6. Prostate cancer staging

    MedlinePlus

    ... test. A faster increase could show a more aggressive tumor. A prostate biopsy is done in your ... suggest the cancer is slow growing and not aggressive. Higher numbers indicate a faster growing cancer that ...

  7. Randomized Phase II Trial of Sulindac for Lung Cancer Chemoprevention

    PubMed Central

    Limburg, Paul J.; Mandrekar, Sumithra J.; Aubry, Marie Christine; Ziegler, Katie L. Allen; Zhang, Jun; Yi, Joanne E.; Henry, Michael; Tazelaar, Henry D.; Lam, Stephen; McWilliams, Annette; Midthun, David E.; Edell, Eric S.; Rickman, Otis B.; Mazzone, Peter; Tockman, Melvyn; Beamis, John F.; Lamb, Carla; Simoff, Michael; Loprinzi, Charles; Szabo, Eva; Jett, James

    2012-01-01

    Introduction Sulindac represents a promising candidate agent for lung cancer chemoprevention, but clinical trial data have not been previously reported. We conducted a randomized, phase II chemoprevention trial involving current or former cigarette smokers (≥ 30 pack-years) utilizing the multi-center, inter-disciplinary infrastructure of the Cancer Prevention Network (CPN). Methods At least 1 bronchial dysplastic lesion identified by fluorescence bronchoscopy was required for randomization. Intervention assignments were sulindac 150 mg bid or an identical placebo bid for six months. Trial endpoints included changes in histologic grade of dysplasia (per-participant as primary endpoint and per lesion as secondary endpoint), number of dysplastic lesions (per-participant), and Ki67 labeling index. Results Slower than anticipated recruitment led to trial closure after randomizing participants (n = 31 and n = 30 in the sulindac and placebo arms, respectively). Pre- and post-intervention fluorescence bronchoscopy data were available for 53/61 (87%) randomized, eligible participants. The median (range) of dysplastic lesions at baseline was 2 (1-12) in the sulindac arm and 2 (1-7) in the placebo arm. Change in dysplasia was categorized as regression:stable:progression for 15:3:8 (58%:12%:31%) subjects in the sulindac arm and 15:2:10 (56%:7%:37%) subjects in the placebo arm; these distributions were not statistically different (p=0.85). Median Ki67 expression (% cells stained positive) was significantly reduced in both the placebo (30 versus 5; p = 0.0005) and sulindac (30 versus 10; p = 0.0003) arms, but the difference between arms was not statistically significant (p = 0.92). Conclusions Data from this multi-center, phase II squamous cell lung cancer chemoprevention trial do not demonstrate sufficient benefits from sulindac 150 mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention

  8. Randomized phase II trial of sulindac for lung cancer chemoprevention.

    PubMed

    Limburg, Paul J; Mandrekar, Sumithra J; Aubry, Marie Christine; Ziegler, Katie L Allen; Zhang, Jun; Yi, Joanne E; Henry, Michael; Tazelaar, Henry D; Lam, Stephen; McWilliams, Annette; Midthun, David E; Edell, Eric S; Rickman, Otis B; Mazzone, Peter; Tockman, Melvyn; Beamis, John F; Lamb, Carla; Simoff, Michael; Loprinzi, Charles; Szabo, Eva; Jett, James

    2013-03-01

    Sulindac represents a promising candidate agent for lung cancer chemoprevention, but clinical trial data have not been previously reported. We conducted a randomized, phase II chemoprevention trial involving current or former cigarette smokers (≥30 pack-years) utilizing the multi-center, inter-disciplinary infrastructure of the Cancer Prevention Network (CPN). At least 1 bronchial dysplastic lesion identified by fluorescence bronchoscopy was required for randomization. Intervention assignments were sulindac 150mg bid or an identical placebo bid for 6 months. Trial endpoints included changes in histologic grade of dysplasia (per-participant as primary endpoint and per lesion as secondary endpoint), number of dysplastic lesions (per-participant), and Ki67 labeling index. Slower than anticipated recruitment led to trial closure after randomizing participants (n=31 and n=30 in the sulindac and placebo arms, respectively). Pre- and post-intervention fluorescence bronchoscopy data were available for 53/61 (87%) randomized, eligible participants. The median (range) of dysplastic lesions at baseline was 2 (1-12) in the sulindac arm and 2 (1-7) in the placebo arm. Change in dysplasia was categorized as regression:stable:progression for 15:3:8 (58%:12%:31%) subjects in the sulindac arm and 15:2:10 (56%:7%:37%) subjects in the placebo arm; these distributions were not statistically different (p=0.85). Median Ki67 expression (% cells stained positive) was significantly reduced in both the placebo (30 versus 5; p=0.0005) and sulindac (30 versus 10; p=0.0003) arms, but the difference between arms was not statistically significant (p=0.92). Data from this multi-center, phase II squamous cell lung cancer chemoprevention trial do not demonstrate sufficient benefits from sulindac 150mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention. Copyright © 2012 Elsevier Ireland Ltd. All rights

  9. Downstream carcinogenesis signaling pathways by green tea polyphenols: a translational perspective of chemoprevention and treatment for cancers.

    PubMed

    Hu, Guohua; Zhang, Lei; Rong, Yefei; Ni, Xiaoling; Sun, Yihong

    2014-01-01

    Green tea is one of the most popular beverages around the world. For several decades, numerous epidemiological, preclinical and clinical studies have demonstrated that green tea polyphenols (GTPs), especially epigallocatechin-3-gallate (EGCG) have cancer-preventing effects on various cancers. In this review, we present inhibition of carcinogenesis in different animal models by GTPs or EGCG, including prostate cancer, bladder cancer, breast cancer, intestinal cancer, colon cancer, gastric cancer, lung cancer, oral cancer and skin cancer. In vitro studies showed that GTPs/EGCG potently induces apoptosis, cell cycle arrest and suppresses metastasis in tumor cells but not in their normal cell counterparts. The molecular mechanisms of these activities are discussed in detail to elucidate GTPs/EGCG downstream carcinogenesis signaling pathways and their values of perspective of chemoprevention and treatment for cancers.

  10. Chain elongation analog of resveratrol as potent cancer chemoprevention agent.

    PubMed

    Kang, Yan-Fei; Qiao, Hai-Xia; Xin, Long-Zuo; Ge, Li-Ping

    2016-09-01

    Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism.

  11. Cancer Chemoprevention by Dietary Polyphenols: Promising Role for Epigenetics

    PubMed Central

    Link, Alexander; Balaguer, Francesc; Goel, Ajay

    2010-01-01

    Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression. In mammals, epigenetic mechanisms include changes in DNA methylation, histone modifications and non-coding RNAs. Although epigenetic changes are heritable in somatic cells, these modifications are also potentially reversible, which makes them attractive and promising avenues for tailoring cancer preventive and therapeutic strategies. Burgeoning evidence in the last decade has provided unprecedented clues that diet and environmental factors directly influence epigenetic mechanisms in humans. Dietary polyphenols from green tea, turmeric, soybeans, broccoli and others have shown to possess multiple cell-regulatory activities within cancer cells. More recently, we have begun to understand that some of the dietary polyphenols may exert their chemopreventive effects in part by modulating various components of the epigenetic machinery in humans. In this article, we first discuss the contribution of diet and environmental factors on epigenetic alterations; subsequently, we provide a comprehensive review of literature on the role of various dietary polyphenols. In particular, we summarize the current knowledge on a large number of dietary agents and their effects on DNA methylation, histone modifications and regulation of expression of non-coding miRNAs in various in vitro and in vivo models. We emphasize how increased understanding of the chemopreventive effects of dietary polyphenols on specific epigenetic alterations may provide unique and yet unexplored novel and highly effective chemopreventive strategies for reducing the health burden of cancer and other diseases in humans. PMID:20599773

  12. Keap1 eye on the target: chemoprevention of liver cancer.

    PubMed

    Yates, Melinda Sue; Kensler, Thomas Wells

    2007-09-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, causing nearly 600,000 deaths each year. Increased risk of HCC due to chronic infection with hepatitis B virus (HBV) and exposure to dietary aflatoxins is responsible for many of these deaths. Prevention strategies targeting HBV infection and aflatoxin exposure could dramatically impact the rates of HCC. Universal HBV vaccination programs have begun in some high-risk areas. Strategies to reduce aflatoxin contamination in food stores have also been implemented. However, complete elimination of aflatoxin contamination might not be possible. For this reason, chemoprevention strategies which alter aflatoxin disposition are a practical strategy to reduce the incidence of HCC in populations with high dietary aflatoxin exposure. The mechanisms of aflatoxin-induced hepatocarcinogenesis are well known. This knowledge provides the basis for evaluation of both exposures to aflatoxin, as well as modulation of aflatoxin disposition by chemopreventive agents. Products of aflatoxin DNA damage and toxicity as well as other metabolites can be used as biomarkers to evaluate modulation of aflatoxin disposition. Modulation of aflatoxin disposition can be achieved through induction of conjugating and cytoprotective enzymes. Many of these enzymes are regulated through Kelch ECH-associating protein 1 (Keap1)-NF-E2-related factor 2(Nrf2)-antioxidant response element (ARE) signaling, making this pathway an important molecular target for chemoprevention. Rodent studies have identified several classes of chemopreventive agents which induce cytoprotective genes. These inducers include phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids. Furthermore, clinical interventions have shown that inducers of Keap1-Nrf2- ARE signaling increase cytoprotective enzyme expression, resulting in modulation of aflatoxin disposition. Much work remains to be done in order to take promising chemopreventive agents

  13. Chemoprevention Trial of Selenium and Prostate Cancer

    DTIC Science & Technology

    1999-10-01

    i Green peppers , green chilies, jalapenos, and green chili salsa 0 O 0 0 .-*"> G ^>* O O 1/4 cup •-.-j J*™1; O Red peppers and red chilies 0 0 0...program they are using. Color-coding is used to visually show the coordinator which trial they are working with ( cyan background). The menu items on...is the main menu stating what program they are using. Color-coding is used to visually show the coordinator which trial they are working with ( cyan

  14. Biomarkers of Selenium Chemoprevention of Prostate Cancer

    DTIC Science & Technology

    2005-01-01

    metabolite, methylseleninic acid (MSA). MSA retarded cell cycle progression at multiple transition points without changing the proportion of cells in...their expression profiles across multiple time points, we used the Self Organizing Map (SOM) algorithm to do the analysis on all the genes that are 4...expression of the gut-enriched Kruppel-like factor gene in intestinal adenomas of multiple intestinal neoplasia mice and in colonic adenomas of

  15. [Benign prostatic hypertrophy and prostate cancer].

    PubMed

    Mourey, Loïc; Doumerc, Nicolas; Gaudin, Clément; Gérard, Stéphane; Balardy, Laurent

    2014-01-01

    Prostatic diseases are extremely common, especially in older men. Amongst them, benign prostatic hypertrophy may affect significantly the quality of life of patients by the symptoms it causes. It requires appropriate care. Prostate cancer is the second most common cancer in men after lung cancer and the fifth leading cause of cancer deaths in the world. It affects preferentially older men. An oncogeriatric approach is required for personalised care.

  16. Biomarkers for prostate cancer.

    PubMed

    Leman, Eddy S; Getzenberg, Robert H

    2009-09-01

    The detection of prostate cancer using a blood test has by many standards changed the face of the disease. Despite this tremendous success, there are limitations attributed to the use of prostate specific antigen (PSA) as a means to screen and detect prostate cancer. PSA, as its name implies, is not specific for prostate cancer and as such is often found elevated in other prostatic diseases/symptoms associated with the aging male. Clearly, more specific marker(s) that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value. The search for more accurate and clinically useful biomarkers of prostate cancer has been extensive. This has focused on individual markers, as well as groups of markers. Included among these are PSA isoforms, pathological indicators and stains, nucleic acids and others. This article highlights the discovery of PSA as a first blood-based biomarker for prostate cancer detection, as well as other molecular biomarkers and their potential application in detection of the disease. (c) 2009 Wiley-Liss, Inc.

  17. Cryosurgery for prostate cancer.

    PubMed

    Fahmy, W E; Bissada, N K

    2003-01-01

    Choice of management for patients with prostate cancer is influenced by patient and disease characteristics and life expectancy. Management options include expectance (watchful waiting), radical prostatectomy, external beam radiotherapy, brachytherapy, and cryosurgical ablation of the prostate (CSAP). The role of cryotherapy in the management of prostate cancer is still evolving. Continued research has allowed the introduction of efficient and safe cryosurgical equipment exemplified by the current third-generation cryosurgical machines. CSAP can be performed in an ambulatory surgery setting or as inpatient surgery with overnight stay. The procedure is performed under continuous ultrasonic monitoring. Mature data from the use of second-generation cryosurgical equipment indicate that CSAP is an effective therapeutic modality for managing patients with prostate cancer. Current data with the third-generation cryosurgical equipment are not mature. However, the favorable side effect profile and the good early responses seem to indicate that this modality will have a prominent role in the management of patients with prostate cancer.

  18. Epigenomics of Ovarian Cancer and Its Chemoprevention

    PubMed Central

    Chen, Huaping; Hardy, Tabitha M.; Tollefsbol, Trygve O.

    2011-01-01

    Ovarian cancer is a major cause of death among gynecological cancers and its etiology is still unclear. Currently, the two principle obstacles in treating this life threatening disease are lack of effective biomarkers for early detection and drug resistance after initial chemotherapy. Similar to other cancers, the initiation and development of ovarian cancer is characterized by disruption of oncogenes and tumor suppressor genes by both genetic and epigenetic mechanisms. While it is well known that it is challenging to treat ovarian cancer through a genetic strategy due in part to its heterogeneity, the reversibility of epigenetic mechanisms involved in ovarian cancer opens exciting new avenues for treatment. The epigenomics of ovarian cancer has therefore become a rapidly expanding field leading to intense investigation. A review on the current status of the field is thus warranted. In this analysis, we will evaluate the current status of epigenomics of ovarian cancer and will include epigenetic mechanisms involved in ovarian cancer development such as DNA methylation, histone modifications, and non-coding microRNA. Development of biomarkers, the epigenetic basis for drug resistance and improved chemotherapy for ovarian cancer will also be assessed. In addition, the potential use of natural compounds as epigenetic modulators in chemotherapy shows promise in moving to the forefront of ovarian cancer treatment strategies. PMID:22303362

  19. Chemical genomics of cancer chemopreventive dithiolethiones

    PubMed Central

    Tran, Quynh T.; Xu, Lijing; Phan, Vinhthuy; Goodwin, Shirlean B.; Rahman, Mostafizur; Jin, Victor X.; Sutter, Carrie H.; Roebuck, Bill D.; Kensler, Thomas W.; George, E.Olusegun; Sutter, Thomas R.

    2009-01-01

    3H-1,2-dithiole-3-thione (D3T) and its analogues 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (OLT) and 5-tert-butyl-3H-1,2-dithiole-3-thione (TBD) are chemopreventive agents that block or diminish early stages of carcinogenesis by inducing activities of detoxication enzymes. While OLT has been used in clinical trials, TBD has been shown to be more efficacious and possibly less toxic than OLT in animals. Here, we utilize a robust and high-resolution chemical genomics procedure to examine the pharmacological structure–activity relationships of these compounds in livers of male rats by microarray analyses. We identified 226 differentially expressed genes that were common to all treatments. Functional analysis identified the relation of these genes to glutathione metabolism and the nuclear factor, erythroid derived 2-related factor 2 pathway (Nrf2) that is known to regulate many of the protective actions of dithiolethiones. OLT and TBD were shown to have similar efficacies and both were weaker than D3T. In addition, we identified 40 genes whose responses were common to OLT and TBD, yet distinct from D3T. As inhibition of cytochrome P450 (CYP) has been associated with the effects of OLT on CYP expression, we determined the half maximal inhibitory concentration (IC50) values for inhibition of CYP1A2. The rank order of inhibitor potency was OLT ≫ TBD ≫ D3T, with IC50 values estimated as 0.2, 12.8 and >100 μM, respectively. Functional analysis revealed that OLT and TBD, in addition to their effects on CYP, modulate liver lipid metabolism, especially fatty acids. Together, these findings provide new insight into the actions of clinically relevant and lead dithiolethione analogues. PMID:19126641

  20. Evidence supporting the conceptual framework of cancer chemoprevention in canines

    PubMed Central

    Kondratyuk, Tamara P.; Adrian, Julie Ann Luiz; Wright, Brian; Park, Eun-Jung; van Breemen, Richard B.; Morris, Kenneth R.; Pezzuto, John M.

    2016-01-01

    As with human beings, dogs suffer from the consequences of cancer. We investigated the potential of a formulation comprised of resveratrol, ellagic acid, genistein, curcumin and quercetin to modulate biomarkers indicative of disease prevention. Dog biscuits were evaluated for palatability and ability to deliver the chemopreventive agents. The extent of endogenous DNA damage in peripheral blood lymphocytes from dogs given the dietary supplement or placebo showed no change. However, H2O2-inducible DNA damage was significantly decreased after consumption of the supplement. The expression of 11 of 84 genes related to oxidative stress was altered. Hematological parameters remained in the reference range. The concept of chemoprevention for the explicit benefit of the canine is compelling since dogs are an important part of our culture. Our results establish a proof-of-principle and provide a framework for improving the health and well-being of “man’s best friend”. PMID:27216246

  1. Shrimp Lipids: A Source of Cancer Chemopreventive Compounds

    PubMed Central

    López-Saiz, Carmen-María; Suárez-Jiménez, Guadalupe-Miroslava; Plascencia-Jatomea, Maribel; Burgos-Hernández, Armando

    2013-01-01

    Shrimp is one of the most popular seafoods worldwide, and its lipids have been studied for biological activity in both, muscle and exoskeleton. Free fatty acids, triglycerides, carotenoids, and other lipids integrate this fraction, and some of these compounds have been reported with cancer chemopreventive activities. Carotenoids and polyunsaturated fatty acids have been extensively studied for chemopreventive properties, in both in vivo and in vitro studies. Their mechanisms of action depend on the lipid chemical structure and include antioxidant, anti-proliferative, anti-mutagenic, and anti-inflammatory activities, among others. The purpose of this review is to lay groundwork for future research about the properties of the lipid fraction of shrimp. PMID:24135910

  2. Evidence supporting the conceptual framework of cancer chemoprevention in canines.

    PubMed

    Kondratyuk, Tamara P; Adrian, Julie Ann Luiz; Wright, Brian; Park, Eun-Jung; van Breemen, Richard B; Morris, Kenneth R; Pezzuto, John M

    2016-05-24

    As with human beings, dogs suffer from the consequences of cancer. We investigated the potential of a formulation comprised of resveratrol, ellagic acid, genistein, curcumin and quercetin to modulate biomarkers indicative of disease prevention. Dog biscuits were evaluated for palatability and ability to deliver the chemopreventive agents. The extent of endogenous DNA damage in peripheral blood lymphocytes from dogs given the dietary supplement or placebo showed no change. However, H2O2-inducible DNA damage was significantly decreased after consumption of the supplement. The expression of 11 of 84 genes related to oxidative stress was altered. Hematological parameters remained in the reference range. The concept of chemoprevention for the explicit benefit of the canine is compelling since dogs are an important part of our culture. Our results establish a proof-of-principle and provide a framework for improving the health and well-being of "man's best friend".

  3. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    PubMed

    Wang, Chong-Zhi; Cai, Yi; Anderson, Samantha; Yuan, Chun-Su

    2015-09-01

    Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possess antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

  4. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    PubMed Central

    Wang, Chong-Zhi; Cai, Yi; Anderson, Samantha; Yuan, Chun-Su

    2015-01-01

    Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possess antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management. PMID:26941993

  5. The potential of statins for individualized colorectal cancer chemoprevention.

    PubMed

    Jacobs, Rutger J; Kodach, Liudmila L; Hardwick, James C H

    2011-12-01

    Colorectal cancer is a leading cause of death by cancer in the western world. Despite major progress, even new chemotherapeutic regimens have had relatively little impact on long term survival in the approximately 50% of patients with advanced disease at presentation meaning that prevention is the only realistic way to reduce the burden of this disease. Many countries have implemented population-based screening methods to prevent colorectal cancer by the physical removal of its precursor lesion the adenoma, or to detect cancer at an earlier stage when it is amenable to surgical cure. However these programs have only been shown to reduce colorectal cancer deaths by 30% in those screened and therefore new or complimentary approaches are needed. One such approach is chemoprevention. A number of compounds have shown potential in reducing the incidence of colorectal cancer. Most widely known are NSAIDs but recently inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also known as statins, commonly prescribed medications that lower serum cholesterol, have been shown to reduce colorectal cancer incidence. A critical issue in chemoprevention is the weighing of benefits against risks. In chemoprevention this balance is likely to be unfavourable when used in a wide unselected population even for the safest of compounds. Therapy should therefore be tailored to the individual patient. The balance will be more favourable in high risk groups such as individuals especially susceptible to neoplasia because of environmental risk factors, patients with inflammatory bowel disease, those with a hereditary predisposition and patients with a previous history of colorectal cancer or polyps. Furthermore colorectal cancer is not one disease but a heterogeneous group of diseases with different underlying molecular mechanisms. It is likely that both prevention and therapy will need to be tailored to the molecular subtype of the cancer in question. This may explain

  6. Drugs Approved for Prostate Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Prostate Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Prostate Cancer Abiraterone Acetate Bicalutamide Cabazitaxel Casodex (Bicalutamide) Degarelix Docetaxel ...

  7. Concepts of epigenetics in prostate cancer development

    PubMed Central

    Cooper, C S; Foster, C S

    2008-01-01

    Substantial evidence now supports the view that epigenetic changes have a role in the development of human prostate cancer. Analyses of the patterns of epigenetic alteration are providing important insights into the origin of this disease and have identified specific alterations that may serve as useful diagnostic and prognostic biomarkers. Examination of cancer methylation patterns supports a stem cell origin of prostate cancer. It is well established that methylation of GSTpi is a marker of prostate cancer, and global patterns of histone marking appear to be linked to cancer prognosis with levels of acetylated histones H3K9, H3K18, and H4K12, and of dimethylated H4R3 and H3K4, dividing low-grade prostate cancer (Gleason 6 or less) into two prognostically separate groups. Elevated levels of several components of the polycomb group protein complex, EZH2, BMI1, and RING1, can also act as biomarkers of poor clinical outcome. Many components of the epigenetic machinery, including histone deacetylase (whose expression level is linked to the TMPRSS2:ERG translocation) and the histone methylase EZH2, are potential therapeutic targets. The recent discovery of the role of small RNAs in governing the epigenetic status of individual genes offers exciting new possibilities in therapeutics and chemoprevention. PMID:19002169

  8. Current Challenges and Opportunities for Chemoprevention of Pancreatic Cancer.

    PubMed

    Mohammed, Altaf; Janakiram, Naveena B; Madka, Venkateshwar; Li, Min; Asch, Adam S; Rao, Chinthalapally V

    2017-02-08

    The incidence of pancreatic cancer (PC) is rising in parallel with the deaths caused by this malignant disease largely due to limited improvement in current treatment strategies. In spite of aggressive PC research, for the past three decades, there has been no significant improvement in the five-year survival for this cancer. Like many other cancers, it takes several years for normal pancreatic cells to transform into pancreatic precursor lesions and to further progress into invasive carcinoma. Hence there is a scope for development of chemoprevention strategies to inhibit/delay/prevent progression of this disease into an advanced stage cancer. Availability of various genetically engineered mouse (GEM) models of PC has led to accelerated progress in understanding the disease and developing intervention strategies otherwise stalled for a long time. These GEM models spontaneously develop PC in a stepwise manner and mimic the disease etiology in humans. Understanding PC development from initiation to progression to metastasis is very important for early detection and prevention of PC. In this review, we focus on the current situation, the potential challenges, the progress in existing strategies and available opportunities as well as suggest key areas for research within the increasingly important area of pancreatic cancer chemoprevention.

  9. Preventing and Treating Prostate Cancer Spread to Bone

    MedlinePlus

    ... Prostate Cancer Treating Prostate Cancer Preventing and Treating Prostate Cancer Spread to Bones If prostate cancer spreads to ... Away or Comes Back After Treatment More In Prostate Cancer About Prostate Cancer Causes, Risk Factors, and Prevention ...

  10. Biomarkers and their use in cervical cancer chemoprevention.

    PubMed

    Vlastos, Anne Thérèse; Schottenfeld, David; Follen, Michele

    2003-06-01

    Cervical cancer chemoprevention agents under study include diet and micronutrients (particularly beta-carotene, folate, and vitamins A, C, and E); medications such as retinoids (retinyl acetate gel, all-trans-retinoic acid, and 4-hydroxyphenylretinamide) that are chemically related to micronutrients; and other chemopreventives meant to affect the carcinogenic process at the cellular level, including such polyamine synthesis inhibitors as alpha-difluoromethylornithine. Agents become reasonable candidates for study when they have a biologic rationale, they are of low toxicity, and they can be taken for a long period of time. Since the human papillomavirus (HPV) is the major etiologic agent, the medication should show activity against HPV-positive preinvasive and invasive cell lines. The medication needs to be of low toxicity because it may be taken for long periods of time and less toxicity is tolerated in the precancerous setting. Until 1995, none of the studies used surrogate end point biomarkers (SEBs), relying instead on histologic and colposcopic regression as end points. All studies typically included subjects with cervical intraepithelial neoplasia. Conclusions to be drawn from these studies include the following: Though micronutrients are logical candidates for chemoprevention, they haven't worked consistently, and the reasons remain unclear. Furthermore, SEBs need to be validated in phase I trials. Finally, a better understanding of the role of HPV needs elucidation, including an understanding of the relationship of the medication to HPV status and of the immunobiology of HPV throughout the trial.

  11. Chemoprevention of Breast Cancer by Dietary Polyphenols.

    PubMed

    Mocanu, Maria-Magdalena; Nagy, Péter; Szöllősi, János

    2015-12-17

    The review will discuss in detail the effects of polyphenols on breast cancer, including both the advantages and disadvantages of the applications of these natural compounds. First, we focus on the characterization of the main classes of polyphenols and then on in vitro and in vivo experiments carried out in breast cancer models. Since the therapeutic effects of the administration of a single type of polyphenol might be limited because of the reduced bioavailability of these drugs, investigations on combination of several polyphenols or polyphenols with conventional therapy will also be discussed. In addition, we present recent data focusing on clinical trials with polyphenols and new approaches with nanoparticles in breast cancer. Besides the clinical and translational findings this review systematically summarizes our current knowledge about the molecular mechanisms of anti-cancer effects of polyphenols, which are related to apoptosis, cell cycle regulation, plasma membrane receptors, signaling pathways and epigenetic mechanisms. At the same time the effects of polyphenols on primary tumor, metastasis and angiogenesis in breast cancer are discussed. The increasing enthusiasm regarding the combination of polyphenols and conventional therapy in breast cancer might lead to additional efforts to motivate further research in this field.

  12. Biological Basis for Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    2004-10-01

    birth control pill use are strongly protective. To achieve a better understanding of the etiology of ovarian cancer, which can then be translated into effective prevention strategies, we have initiated a case-control study that considers genetic susceptibility, epidemiologic risk factors and acquired genetic alterations. Subjects are interviewed in their homes and about 750 cases and 750 controls have been accrued thus far. Blood and cancer samples have been collected and molecular analyses of genetic polymorphisms (BRCA1/2, progesterone receptor, vitamin D receptor,

  13. Biological Basis for Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    2003-10-01

    birth control pill use are strongly protective. To achieve a better understanding of the etiology of ovarian cancer, which can then be translated into effective prevention strategies, we have initiated a case-control study that considers genetic susceptibility, epidemiologic risk factors and acquired genetic alterations. Subjects are interviewed in their homes and about 650 cases and 650 controls have been accrued thus far. Blood and cancer samples have been collected and molecular analyses of genetic polymorphisms (BRCA1/2, progesterone receptor) have been performed. An

  14. Cholesterol and prostate cancer.

    PubMed

    Pelton, Kristine; Freeman, Michael R; Solomon, Keith R

    2012-12-01

    Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models, which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations.

  15. Advanced Prostate Cancer

    MedlinePlus

    ... if it has spread to: • Bones • Lungs • Liver • Brain • Lymph nodes outside the pelvis • Other organs You may be diagnosed with metastatic prostate cancer when you are first diagnosed, after having completed ...

  16. Zinc and prostatic cancer

    PubMed Central

    Song, Yang; Ho, Emily

    2014-01-01

    Purpose of review Aim to understand the connection between zinc and prostatic cancer, and to summarize the recent findings about the functions of zinc in the maintenance of prostate health. Recent findings Contradictory findings have been reported by epidemiologic studies examining the association between zinc intake and the risk of prostate cancer. However, a growing body of experimental evidence support that high zinc levels are essential for prostate health. The possible mechanisms include the effects of zinc on the inhibition of terminal oxidation, induction of mitochondrial apoptogenesis, and suppression of NFκB activity. The most recent finding is the effects of zinc in the maintenance of DNA integrity in normal prostate epithelial cells (PrEC) by modulating the expression and activity of DNA repair and damage response proteins, especially p53. Zinc depletion in PrEC increased p53 expression but compromised p53 DNA binding activity resulting an impaired DNA repair function. Moreover, recent findings support the role of zinc transporters as tumor suppressors in the prostate. Summary Future studies need to discover sensitive and specific zinc biomarkers and perform more in vivo studies on the effects of zinc on prostate functions in normal animals or prostate cancer models. PMID:19684515

  17. Cancer Chemoprevention by Phytochemicals: Nature's Healing Touch.

    PubMed

    Zubair, Haseeb; Azim, Shafquat; Ahmad, Aamir; Khan, Mohammad Aslam; Patel, Girijesh Kumar; Singh, Seema; Singh, Ajay Pratap

    2017-03-03

    Phytochemicals are an important part of traditional medicine and have been investigated in detail for possible inclusion in modern medicine as well. These compounds often serve as the backbone for the synthesis of novel therapeutic agents. For many years, phytochemicals have demonstrated encouraging activity against various human cancer models in pre-clinical assays. Here, we discuss select phytochemicals-curcumin, epigallocatechin-3-gallate (EGCG), resveratrol, plumbagin and honokiol-in the context of their reported effects on the processes of inflammation and oxidative stress, which play a key role in tumorigenesis. We also discuss the emerging evidence on modulation of tumor microenvironment by these phytochemicals which can possibly define their cancer-specific action. Finally, we provide recent updates on how low bioavailability, a major concern with phytochemicals, is being circumvented and the general efficacy being improved, by synthesis of novel chemical analogs and nanoformulations.

  18. Biological Basis for Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    2006-10-01

    Source: American Cancer Society 14 summarized in Figure 1, the human body obtains vitamin D (specifically vitamin D3 or “cholecalciferol... vitamin D3 . Both pre- vitamin D3 and vitamin D3 can be further converted by UVB radiation to a number of degradation products (e.g., Upper right...Figure 1, Lumisterol and Suprasterol). This serves as a regulatory mechanism to limit the excess production of vitamin D3 in skin. Although skin has

  19. New Approaches to Chemoprevention of Breast Cancer.

    DTIC Science & Technology

    1997-09-01

    chemotherapy of breast cancer. Although the naturally occurring triterpenoids, ursolic acid (UA) and oleanolic acid (OA), have been shown to have some...formed in nature by the cyclization of squalene, with the retention of all 30 carbon atoms in molecules such as oleanolic acid (OA) and ursolic acid ...and ursolic acids is described in detail in the attached manuscript, "New Enone Derivatives of Oleanolic Acid and Ursolic Acid as Inhibitors of Nitric

  20. New Approaches to Chemoprevention of Breast Cancer.

    DTIC Science & Technology

    1998-09-01

    breast cancer. Although the naturally occurring triterpenoids, ursolic acid (UA) and oleanolic acid (OA), have been shown to have some anti-carcinogenic...nature by the cyclization of squalene, with the retention of all 30 carbon atoms in molecules such as oleanolic acid (OA) and ursolic acid (UA). Although...manuscript. b) Results and Discussion 1. Synthesis of New Triterpenoids The synthesis of new triterpenoid derivatives of oleanolic and ursolic acids is

  1. Obesity and Prostate Cancer.

    PubMed

    Cao, Yin; Giovannucci, Edward

    Prostate cancer is a complex, heterogeneous disease. Factors related to detection, particularly PSA screening, further increase heterogeneity in the manifestation of the disease. It is thus not possible to provide a simple summary of the relationship between obesity and prostate cancer. Findings on obesity, often defined using body mass index (BMI), and total prostate cancer risk have been mixed; however, obesity is relatively consistently associated with a higher risk of aggressive prostate cancer, with aggressiveness defined in various ways (e.g., advanced stage, fatal, poorer prognosis in men with prostate cancer). Many methodologic issues (e.g., influence of PSA screening, detection bias and treatment) need to be thoroughly considered in both existing and future etiologic and prognostic research. Biological mechanisms supporting the link are under investigation, but may involve insulin and IGF axis, sex steroid hormones and alterations in metabolism. Some promising data suggest that molecular sub-types of prostate cancer may offer insights into etiology, but further study is required. A full evaluation of body fatness and weight change over the life course would not only provide insights to the underlying mechanisms but also allow more effective interventions.

  2. Prostate Cancer Pathology Resource Network

    DTIC Science & Technology

    2015-12-01

    researchers. Specimens include prostatectomy tissues (frozen, paraffin embedded, and tissue microarrays (TMAs), serum, plasma, buffy coat, prostatic fluid...Prostate Cancer, biorepository, biomarkers, tissue microarrays 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...usage by the prostate cancer research community. The specimens in the PCBN include tissues from prostatectomies, serum, plasma, buffy coat, prostatic

  3. Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines.

    PubMed

    Araújo, João R; Gonçalves, Pedro; Martel, Fátima

    2011-02-01

    Colorectal cancer (CRC) is the second most fatal and the third most diagnosed type of cancer worldwide. Despite having multifactorial causes, most CRC cases are mainly determined by dietary factors. In recent years, a large number of studies have attributed a protective effect to polyphenols and foods containing these compounds (fruits and vegetables) against CRC. Indeed, polyphenols have been reported to interfere with cancer initiation, promotion, and progression, acting as chemopreventive agents. The aim of this review is to summarize the main chemopreventive properties of some polyphenols (quercetin, rutin, myricetin, chrysin, epigallocatechin-3-gallate, epicatechin, catechin, resveratrol, and xanthohumol) against CRC, observed in cell culture models. From the data reviewed in this article, it can be concluded that these compounds inhibit cell growth, by inducing cell cycle arrest and/or apoptosis; inhibit proliferation, angiogenesis, and/or metastasis; and exhibit anti-inflammatory and/or antioxidant effects. In turn, these effects involve multiple molecular and biochemical mechanisms of action, which are still not completely characterized. Thus, caution is mandatory when attempting to extrapolate the observations obtained in CRC cell line studies to humans. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. The role of aspirin in colorectal cancer chemoprevention.

    PubMed

    Singh Ranger, Gurpreet

    2016-08-01

    Considerable interest has emerged over the last decade regarding the role of aspirin in prevention of colorectal cancer. This disease is one of the commonest cancers in the Western World, therefore, the existence of a simple "everyday" agent, which could have the ability to prevent the disease, represents an invaluable opportunity clinicians may be able to exploit. Evidence from case-control and cohort studies, and recent updates of randomised controlled trials have been very encouraging-indicating benefit from long term use of aspirin at low dose. Possible mechanisms of chemoprevention include inhibition of the cyclooxygenase (COX) pathway, or COX-independent mechanisms, for example, the PIK3CA pathway, or therapy-induced senescence of cancer cells. The most serious side effect of prolonged aspirin treatment is haemorrhage, especially from the GI tract. This is likely to be less of a problem with chemoprevention at lower doses. One also needs to consider the impact if aspirin resistance, an increasingly recognised clinical entity.

  5. Interactions of the Major Metabolite of the Cancer Chemopreventive Drug Oltipraz with Cytochrome C: A Novel Pathway for Cancer Chemoprevention

    PubMed Central

    Velayutham, Murugesan; Muthukumaran, Rajendra B.; Sostaric, Joe Z.; McCraken, John; Fishbein, James C.; Zweier, Jay L.

    2009-01-01

    The major metabolite of the cancer chemopreventive agent oltipraz (OLT), a pyrrolopyrazine thione (PPD), has been shown to be a phase two enzyme inducer, an activity thought to be key to the cancer chemopreventive action of the parent compound. In cells, mitochondria are the major source of reactive oxygen species (ROS) and cytochrome c (cyt c) is known to participate in mitochondrial electron transport and confer antioxidant and peroxidase activities. To understand possible mechanisms by which PPD acts as a phase two enzyme inducer, a study of its interaction with cyt c was undertaken. UV-visible spectroscopic results demonstrate that PPD is capable of reducing oxidized cyt c. The reduced cyt c is stable for a long period of time in the absence of an oxidizing agent. In the presence of ferricyanide, the reduced cyt c is rapidly oxidized back to its oxidized form. Further, UV-visible spectroscopic studies show that during the reduction process the co-ordination environment and redox state of iron in cyt c is changed. Low temperature EPR studies show that during the reduction process, the heme iron changes from a low spin state of s = ½ to a low spin state of s = 0. Room temperature EPR studies demonstrate that PPD inhibits the peroxidase activity of cyt c. EPR spin trapping experiments using DMPO show that PPD inhibits the superoxide radical scavenging activity of oxidized cyt c. From these results, we propose that PPD interacts with cyt c, binding to and then reducing the heme, and this may enhance ROS levels in mitochondria. This in turn could contribute to the mechanism by which the parent compound, oltipraz, might trigger the cancer chemopreventive increase in transcription of phase 2 enzymes. The modifications of cyt c function by the oltipraz metabolite may have implications for the regulation of apoptotic cell death. PMID:17761303

  6. New Prostate Cancer Treatment Target

    Cancer.gov

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

  7. Understanding your prostate cancer risk

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000931.htm Understanding your prostate cancer risk To use the sharing features on this ... enable JavaScript. Are you at risk for developing prostate cancer in your lifetime? Learn about the risk factors ...

  8. Targeting HER2 Positive Breast Cancer with Chemopreventive Agents

    PubMed Central

    Wahler, Joseph; Suh, Nanjoo

    2015-01-01

    Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a subtype of breast cancer that is exhibited in approximately 20-30% of breast cancer cases. The overexpression of HER2 is typically associated with a more aggressive disease and poor prognosis. Currently, the therapeutic drugs trastuzumab and lapatinib are the most commonly used to combat HER2+ breast cancer. However, tumors can develop resistance to these drugs. A better understanding of the mechanism of how HER2+ breast cancer works will help aid the development for new therapeutic approaches which more closely target the source of the signaling dysfunction. This review summarizes four major points in the context of HER2 over-expressing breast cancer (i) HER2 as a molecular target in breast cancer therapy, (ii) current treatment options as well as ongoing clinical studies, (iii) animal and cellular models for the study of HER2 over-expressing breast cancer, and (iv) future therapies and chemopreventive agents used to target HER2+ breast cancer. PMID:26442201

  9. Prostate cancer and the influence of dietary factors and supplements: a systematic review

    PubMed Central

    2014-01-01

    Background Prostate cancer is the second most common cause of cancer worldwide after lung cancer. There is increasing evidence that diet and lifestyle plays a crucial role in prostate cancer biology and tumourigenesis. Prostate cancer itself represents a good model of cancer in which to look for chemopreventive agents due to the high disease prevalence, slowly progressive nature, and long latency period. Dietary agents have gained considerable attention, often receiving much publicity in the media. Aim To review the key evidence available for potential chemopreventive nutrients. Methods The methodology for this review involved a PubMed search from 1990 to 2013 using the key-words “diet and prostate cancer”, “nutrition and prostate cancer”, “dietary factors and prostate cancer”, “prostate cancer epidemiology”, “prostate cancer prevention”, “prostate cancer progression”. Results Red meat, dietary fat and milk intake should be minimised as they appear to increase the risk of prostate cancer. Fruit and vegetables and polyphenols may be preventive in prostate cancer, but further studies are needed to draw more solid conclusions and to clarify their role in patients with an established diagnosis of prostate cancer. Selenium and vitamin supplements cannot be advocated for the prevention of prostate cancer and indeed higher doses may be associated with a worse prognosis. There is no specific evidence regarding benefits of probiotics or prebiotics in prostate cancer. Conclusions From the wealth of evidence available, many recommendations can be made although more randomised control trials are required. These need to be carefully designed due to the many confounding factors and heterogeneity of the population. PMID:24976856

  10. Neoflavonoids and tetrahydroquinolones as possible cancer chemopreventive agents

    PubMed Central

    Luqman, Suaib; Meena, Abha; Singh, Pragya; Kondratyuk, Tamara P.; Marler, Laura E.; Pezzuto, John M.; Negi, Arvind Singh

    2012-01-01

    Several lactone and lactam based neoflavonoids and tetrahydroquinolones were synthesized and evaluated for cancer chemopreventive studies using cell and molecular target based in vitro bioassays, namely NFκB, aromatase, and quinone reductase 1 (QR1). These analogues blocked TNF-α-induced NFκB activation in a dose-dependent manner with IC50 values in the range of 0.11–3.2 μM. In addition, compound 8 inhibited aromatase activity with an IC50 value of 12.12 μM and compound 10 affected QR1 induction (IR: 3.6, CD: 19.57 μM). Neoflavonoids 8 and 10 exhibiting good results, can further be optimized for improved therapeutic profiles. However, investigations into the actions of neoflavonoids and tetrahydroquinolones, especially those related to the NFκB signaling pathway, aromatase inhibition, induction of QR1 expression and in vivo studies could provide new insights into the cancer chemopreventive ability of these molecules. PMID:22726671

  11. Update from Asia. Asian studies on cancer chemoprevention.

    PubMed

    Yun, T K

    1999-01-01

    In Asia, nontoxic dietary products are considered desirable primary prevention vehicles for conquering cancer. As early as 1978, investigators in Korea carried out extensive long-term anticarcinogenicity experiments using the mouse lung tumor model and observed an anticarcinogenic effect of Panax ginseng C.A. Meyer extract in 1980. The results showed that natural products can provide hope for human cancer prevention. A newly established nine-week medium-term model using mouse lung tumors (Yun's model) could confirm the anticarcinogenicity of ginseng that varies according to its type and age. Subsequently, the ginseng was shown by epidemiological studies to be a nonorgan-specific cancer preventive agent associated with a dose-response relationship. The anticarcinogenic effects of vegetarian foods common at every dining table in Korea and some synthetics were also studied using Yun's nine-week model. In brief, ascorbic acid, soybean lecithin, capsaicin, biochanin A, Ganoderma lucidum, caffeine, and a novel synthetic 2-(allylthio)pyrazine decrease the incidence of mouse lung tumors, whereas fresh ginseng (4 years old), carrot, spinach, Sesamum indicum, beta-carotene, and 13-cis retinoic acid do not. This result regarding beta-carotene is consistent with the ineffective findings of the ATBC trial, the CARET trial, and the Physicians' Health Study. In 1983, a cancer chemoprevention study group was first established in Japan. Subsequently, (-)-epigallocatechin gallate, cryptoporic acid E, and sarcophytol A from natural products, and synthetic acyclic retinoid and canventol were shown to be anticarcinogenic or chemopreventive in human subjects. Despite the frequent consumption of tea wordwide as a beverage and current experimental evidence of anticarcinogenesis, including controversial results of epidemiological studies, more systematic clinical trials for confirmation of preventive activity of tea against cancer are needed. Placebo-controlled intervention trials of

  12. Prognostic factors, predictive markers and cancer biology: the triad for successful oral cancer chemoprevention.

    PubMed

    Monteiro de Oliveira Novaes, Jose Augusto; William, William N

    2016-10-01

    Oral squamous cell carcinomas represent a significant cancer burden worldwide. Unfortunately, chemoprevention strategies investigated to date have failed to produce an agent considered standard of care to prevent oral cancers. Nonetheless, recent advances in clinical trial design may streamline drug development in this setting. In this manuscript, we review some of these improvements, including risk prediction tools based on molecular markers that help select patients most suitable for chemoprevention. We also discuss the opportunities that novel preclinical models and modern molecular profiling techniques will bring to the prevention field in the near future, and propose a clinical trials framework that incorporates molecular prognostic factors, predictive markers and cancer biology as a roadmap to improve chemoprevention strategies for oral cancers.

  13. MYC and Prostate Cancer

    PubMed Central

    Koh, Cheryl M.; Bieberich, Charles J.; Dang, Chi V.; Nelson, William G.; Yegnasubramanian, Srinivasan; De Marzo, Angelo M.

    2010-01-01

    Prostate cancer, the majority of which is adenocarcinoma, is the most common epithelial cancer affecting a majority of elderly men in Western nations. Its manifestation, however, varies from clinically asymptomatic insidious neoplasms that progress slowly and do not threaten life to one that is highly aggressive with a propensity for metastatic spread and lethality if not treated in time. A number of somatic genetic and epigenetic alterations occur in prostate cancer cells. Some of these changes, such as loss of the tumor suppressors PTEN and p53, are linked to disease progression. Others, such as ETS gene fusions, appear to be linked more with early phases of the disease, such as invasion. Alterations in chromosome 8q24 in the region of MYC have also been linked to disease aggressiveness for many years. However, a number of recent studies in human tissues have indicated that MYC appears to be activated at the earliest phases of prostate cancer (e.g., in tumor-initiating cells) in prostatic intraepithelial neoplasia, a key precursor lesion to invasive prostatic adenocarcinoma. The initiation and early progression of prostate cancer can be recapitulated in genetically engineered mouse models, permitting a richer understanding of the cause and effects of loss of tumor suppressors and activation of MYC. The combination of studies using human tissues and mouse models paints an emerging molecular picture of prostate cancer development and early progression. This picture reveals that MYC contributes to disease initiation and progression by stimulating an embryonic stem cell–like signature characterized by an enrichment of genes involved in ribosome biogenesis and by repressing differentiation. These insights pave the way to potential novel therapeutic concepts based on MYC biology. PMID:21779461

  14. Colorectal Cancer Chemoprevention: Is This the Future of Colorectal Cancer Prevention?

    PubMed Central

    Manzano, A.; Pérez-Segura, P.

    2012-01-01

    Colorectal cancer (CRC) is presently one of the most common causes of cancer-related death in our setting and affects a great number of people each year. Screening strategies are commonly used but they do not seem enough to avoid CRC development or prevent completely its mortality. Because of this fact other prevention strategies have gained interest in recent years. Chemoprevention seems to be an attractive option in this setting and several drugs have been studied in this field. This review is focused on salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs) and cycloxygenase-2 inhibitors (COXIBs), whose mechanism of action could be directly related to colon cancer chemoprevention. PMID:22649288

  15. [Sexuality and prostate cancer].

    PubMed

    Colson, M-H; Lechevallier, E; Rambeaud, J-J; Alimi, J-C; Faix, A; Gravis, G; Hannoun-Levi, J-M; Quintens, H; Rébillard, X; Droupy, S

    2012-09-01

    All treatments of prostate cancer have a negative effect on both sexuality and male fertility. There is a specific profile of changes in the fields of quality of life, sexual, urinary, bowel and vitality according to the treatment modalities chosen. Maintain a satisfying sex is the main concern of a majority of men facing prostate cancer and its treatment. It is essential to assess the couple's sexuality before diagnosis of prostate cancer in order to deliver complete information and to consider early and appropriate treatment options at the request of the couple. Forms of sexuality sexual preference settings stored (orgasm) may, when the erection is not yet recovered, be an alternative to the couple to maintain intimacy and complicity. In all cases, a specific management and networking will in many cases to find a satisfactory sexuality. Consequences of the treatment on male fertility should be part of the information of patients with prostate cancer and their partners. The choice of treatment must take into account the desire of paternity of the couple. A semen analysis with sperm cryopreservation before any therapy should be routinely offered in men with prostate cancer, particularly among men under 55, with a partner under 43 years old or without children. If the desire for parenthood among couples, sperm cryopreservation before treatment and medical assisted reproduction are recommended.

  16. Modulating Polo-Like Kinase 1 as a Means for Cancer Chemoprevention

    PubMed Central

    Schmit, Travis L.; Ledesma, Mark C.; Ahmad, Nihal

    2010-01-01

    Naturally occurring agents have always been appreciated for their medicinal value for both their chemopreventive and therapeutic effects against cancer. In fact, the majority of the drugs we use today, including the anti-cancer agents, were originally derived from natural compounds, either in their native form or modified to enhance their bioavailability or specificity. It is believed that for maximum effectiveness, it will useful to design novel target-based agents for chemoprevention as well as the treatment of cancer. Recent studies have shown that the serine/threonine kinase polo-like kinase (Plk) 1 is widely overexpressed in a variety of cancers and is being increasingly appreciated as a target for cancer management. Additionally, several chemopreventive agents have been shown to inhibit Plk1 in cancer cells. In this review, we will discuss if Plk1 could also be a target for designing novel strategies for cancer chemoprevention. PMID:20107874

  17. Chemopreventive effect of apple and berry fruits against colon cancer

    PubMed Central

    Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko; Octorina Dewi, Dyah Ekashanti; Narayanan, Aqilah Leela T; Balaji, Arunpandian; Subramanian, Aruna Priyadarshini; Yusof, Mustafa

    2014-01-01

    Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon. Prevention is better than cure, and this is very true with respect to colon cancer. Various epidemiologic studies have linked colorectal cancer with food intake. Apple and berry juices are widely consumed among various ethnicities because of their nutritious values. In this review article, chemopreventive effects of these fruit juices against colon cancer are discussed. Studies dealing with bioavailability, in vitro and in vivo effects of apple and berry juices are emphasized in this article. A thorough literature survey indicated that various phenolic phytochemicals present in these fruit juices have the innate potential to inhibit colon cancer cell lines. This review proposes the need for more preclinical evidence for the effects of fruit juices against different colon cancer cells, and also strives to facilitate clinical studies using these juices in humans in large trials. The conclusion of the review is that these apple and berry juices will be possible candidates in the campaign against colon cancer. PMID:25493015

  18. Chemopreventive effect of apple and berry fruits against colon cancer.

    PubMed

    Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko; Octorina Dewi, Dyah Ekashanti; Narayanan, Aqilah Leela T; Balaji, Arunpandian; Subramanian, Aruna Priyadarshini; Yusof, Mustafa

    2014-12-07

    Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon. Prevention is better than cure, and this is very true with respect to colon cancer. Various epidemiologic studies have linked colorectal cancer with food intake. Apple and berry juices are widely consumed among various ethnicities because of their nutritious values. In this review article, chemopreventive effects of these fruit juices against colon cancer are discussed. Studies dealing with bioavailability, in vitro and in vivo effects of apple and berry juices are emphasized in this article. A thorough literature survey indicated that various phenolic phytochemicals present in these fruit juices have the innate potential to inhibit colon cancer cell lines. This review proposes the need for more preclinical evidence for the effects of fruit juices against different colon cancer cells, and also strives to facilitate clinical studies using these juices in humans in large trials. The conclusion of the review is that these apple and berry juices will be possible candidates in the campaign against colon cancer.

  19. Promoter Hypermethylation in Prostate Cancer

    PubMed Central

    Park, Jong Y.

    2011-01-01

    Background The prostate gland is the most common site of cancer and the second leading cause of cancer mortality in American men. It is well known that epigenetic alterations such as DNA methylation within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could be potential biomarkers and therapeutic targets for prostate cancer. Methods This review discusses current information on methylated genes associated with prostate cancer development and progression. Results Over 30 genes have been investigated for promoter methylation in prostate cancer. These methylated genes are involved in critical pathways, such as DNA repair, metabolism, and invasion/metastasis. The role of hypermethylated genes in regulation of critical pathways in prostate cancer is reviewed. Conclusions These findings may provide new information of the pathogenesis of prostate cancer. Certain epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use. PMID:20861812

  20. Prostate Cancer Rates by Race and Ethnicity

    MedlinePlus

    ... HPV-Associated Lung Ovarian Skin Uterine Cancer Home Prostate Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of men getting prostate cancer or dying from prostate cancer varies by race ...

  1. [Overdiagnosis in prostate cancer].

    PubMed

    Villeda, Christian; Gomez, Martha Olivia; Sotomayor, Mariano

    2014-06-01

    Prostate cancer screening is an absolutely controversial topic and under debate. The points of view from which the problem is analyzed also influence this issue; patient, physician and Health Care authorities have different interests that most of the times are not comprehensively analyzed. Currently, no clinical guideline supports the performance of a population screening with active recruitment, but they do support the credible information to the man who desires its performance of potential benefits and risks (opportunistic screening), as well as its performance in certain risk groups. Nevertheless, what is inherent to any screening program is the overdiagnosis of clinically irrelevant disease, which in prostate cancer has been calculated around 50%, and that, from our point of view, gives cause to the correct implementation of active surveillance programs to tamponade the potential deleterious effects of active therapies of prostate cancer.

  2. Hypofractionation for prostate cancer.

    PubMed

    Ritter, Mark; Forman, Jeffrey; Kupelian, Patrick; Lawton, Colleen; Petereit, Daniel

    2009-01-01

    Hypofractionation for prostate cancer was originally carried out in the pursuit of efficiency and convenience but has now attracted greatly renewed interest based upon a hypothesis that prostate cancers have a higher sensitivity to fraction size, reflected in a low alpha/beta ratio, than do late responding organs at risk such as the rectum or bladder. Tumor control and acceptable toxicity outcomes from several hypofractionation or brachytherapy analyses do in fact support an alpha/beta ratio for prostate cancer that is low, perhaps even lower that that for the normal organs that ordinarily constrain the delivery of radiation therapy. However, many of these studies lack sufficient patient numbers and follow-up, are clouded by dose inhomogeneity issues in the case of brachytherapy, or delivered effective doses that were too low by contemporary standards. Thus, the clinical efficacy of the approach has yet to be fully validated. However, a number of newer prospective trials, some randomized, are underway or have reached accrual but await sufficient follow-up for analysis. These studies, which cover a wide range of doses per fraction, should ultimately be capable of validating the utility of prostate hypofractionation and the models that predict its effects. With hypofractionation's significant potential for therapeutic gain, cost savings, and improved patient convenience, the future management of localized prostate cancer could be profoundly altered in the process.

  3. Non-dietary environmental risk factors in prostate cancer

    PubMed Central

    Ferrís-i-Tortajada, J; Berbel-Tornero, O; Garcia-i-Castell, J; López-Andreu, J.A.; Sobrino-Najul, E; Ortega-García, J.A.

    2016-01-01

    Introduction The aim is to update and disclose the main environmental risk factors, excluding dietary factors, involved in the etiopathology of prostate cancer. Materials and methods Bibliographic review of the last 25 years of non-dietary environmental risk factors associated with prostate cancer between 1985 and 2010, obtained from MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Environmental Risk Factors/Tobacco/Infectious-Inflammatory Factors/Pesticides/Vasectomy/Occupational Exposures/ Chemoprevention Agents/Radiation and Prostate Cancer. Results While some non-dietary environmental risk factors increase the risk of acquiring the disease, others decrease it. Of the former, it is worth mentioning exposal to tobacco smoke, chronic infectious-inflammatory prostatic processes and occupational exposure to cadmium, herbicides and pesticides. The first factors that reduce the risk are the use of chemopreventive drugs (Finasterida, Dutasteride) and exposure to ultraviolet solar radiation. With the current data, a vasectomy does not influence the risk of developing the disease. Conclusions The slow process of prostate carcinogenesis is the final result of the interaction of constitutional risk and environmental factors. Non-dietary environmental factors play an important role in the etiopathology of this disease. To appropriately assess the risk factors, extensive case studies that include all the possible variables must be analyzed. PMID:21439685

  4. [Diet and prostate cancer].

    PubMed

    Romero Cagigal, I; Ferruelo Alonso, A; Berenguer Sánchez, A

    2003-06-01

    Prostate cancer is the first neoplasia in the United States accounting the second in cancer deaths. With all the treatments strategies in debate because of their side effects, is very important try to elucidate prevention mechanisms that may be implicate in the development of this disease, between these, nutrients have been of mayor importance. In the present review we tried to study the most important nutritional factors implicated in the development and prevention of prostate carcinoma. We focus our attention over the polyphenols of the red wine, which influence over cellular proliferation and apoptosis in LNCaP cells have been studied in our Department.

  5. Implications of cancer stem cell theory for cancer chemoprevention by natural dietary compounds.

    PubMed

    Li, Yanyan; Wicha, Max S; Schwartz, Steven J; Sun, Duxin

    2011-09-01

    The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anticancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anticancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine and vitamin D(3), are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor-initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival.

  6. Black tea: Phytochemicals, cancer chemoprevention, and clinical studies.

    PubMed

    Singh, Brahma N; Rawat, A K S; Bhagat, R M; Singh, B R

    2017-05-03

    Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-κB, Bcl-xL, caspases, p53, FOXO1, TNFα, PARP, and MAPK, which may be the basis of how dose of black tea prevents and cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea to reveal its anti-cancer effect.

  7. Crocus sativus L. (saffron) for cancer chemoprevention: A mini review.

    PubMed

    Bhandari, Prasan R

    2015-04-01

    Cancer is one of the most feared diseases globally and there has been a sustained rise in its incidence in both developing and developed countries. Despite the growing therapeutic options for patients with cancer, their efficacy is time-limited and non-curative. Hence to overcome these drawbacks, an incessant screening for superior and safer drugs has been ongoing for numerous decades, resulting in the detection of anti-cancer properties of several phytochemicals. Chemoprevention using readily available natural substances from vegetables, fruits, herbs and spices is one of the significantly important approaches for cancer prevention in the present era. Among the spices, Crocus sativus L. (saffron; fān hóng huā) has generated interest because pharmacological experiments have established numerous beneficial properties including radical scavenging, anti-mutagenic and immuno-modulating effects. The more powerful components of saffron are crocin, crocetin and safranal. Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and cancer preventive activities of saffron and its main ingredients. This review provides a brief insight into the anticancer properties of saffron and its components.

  8. Chemoprevention of ultraviolet radiation-induced skin cancer.

    PubMed Central

    Ley, R D; Reeve, V E

    1997-01-01

    The use of chemical and physical sunscreening agents has increased dramatically during the last two to three decades as an effective means of preventing sunbum. The use of high sunprotection factor sunscreens has also been widely promoted for the prevention of skin cancer, including melanoma. Whereas sunscreens are undoubtedly effective in preventing sunbum, their efficacy in preventing skin cancer, especially melanoma, is currently under considerable debate. Sunscreens have been shown to prevent the induction of DNA damage that presumably results from the direct effects of ultraviolet radiation (UVR) on DNA. DNA damage has been identified as an initiator of skin cancer formation. However, both laboratory and epidemiological studies indicate that sunscreens may not block the initiation or promotion of melanoma formation. These studies suggest that the action spectrum for erythema induction is different than the action spectrum for the induction of melanoma. Indeed, recent reports on the wavelength dependency for the induction of melanoma in a fish model indicate that the efficacy of ultraviolet A wavelengths (320-400 nm) to induce melanoma is orders of magnitude higher than would be predicted from the induction of erythema in man or nonmelanoma skin tumors in mice. Other strategies for the chemoprevention of skin cancer have also been reported. Low levels and degree of unsaturation of dietary fats protect against UVR-induced skin cancer in mice humens. Compounds with antioxidant activity, including green tea extracts (polyphenols), have been reported to inhibit UVR-induced skin carcinogenesis. PMID:9255591

  9. Assessment of information to substantiate a health claim on the prevention of prostate cancer by lignans.

    PubMed

    Saarinen, Niina M; Tuominen, Juhani; Pylkkänen, Liisa; Santti, Risto

    2010-02-01

    Lignans and their in vivo metabolites, especially enterolactone (ENL), have attracted substantial interest as potential chemopreventive agents for prostate cancer. Preclinical and clinical interventions performed with lignan-rich flaxseed that use surrogate biomarkers as endpoints suggest that lignans may attenuate prostate carcinogenesis in individuals with increased risk or with diagnosed cancer. No unequivocal prostate cancer risk reduction has been found for lignans in epidemiological studies, suggesting that lignan concentrations found in populations consuming a regular non-supplemented diet are not chemopreventive in prostate cancer. Presumably, the main obstacles in assessing the efficacy of food lignans is limited knowledge of the serum and tissue lignan concentrations required for the putative prevention. Further clinical studies performed with the purified compounds are required to substantiate a health claim.

  10. American Cancer Society Recommendations for Prostate Cancer Early Detection

    MedlinePlus

    ... Prostate Cancer Prevention and Early Detection American Cancer Society Recommendations for Prostate Cancer Early Detection The American Cancer Society (ACS) recommends that men have a chance to ...

  11. Dietary aflatoxin exposure and chemoprevention of cancer: a clinical review.

    PubMed

    Sudakin, Daniel L

    2003-01-01

    Exposure to dietary aflatoxins is considered to be an important risk factor for the development of hepatocellular carcinoma in certain regions of the world. Significant advances have recently been made in understanding the clinical toxicology of aflatoxins. These include the development and validation of biomarkers of exposure and genotoxic effect. These biomarkers are currently being utilized to explore the potential that pharmaceutical interventions may have in modifying the toxicokinetics of dietary aflatoxin exposure. Preliminary results of clinical trials with the drug oltipraz suggest that it may modify the genotoxic effects of aflatoxin B1 by inhibiting bioactivation pathways and stimulating detoxification pathways. More recent results of a clinical trial with chlorophyllin suggest that this drug may have a role in preventing dietary exposure to aflatoxin B1 by reducing its oral bioavailability. The preliminary results of these chemoprevention studies may ultimately have implications for cancer prevention in high-risk populations in the future.

  12. Acceptance and adherence to chemoprevention among women at increased risk of breast cancer.

    PubMed

    Roetzheim, Richard G; Lee, Ji-Hyun; Fulp, William; Matos Gomez, Elizabeth; Clayton, Elissa; Tollin, Sharon; Khakpour, Nazanin; Laronga, Christine; Lee, Marie Catherine; Kiluk, John V

    2015-02-01

    Chemoprevention is an option for women who are at increased risk of breast cancer (five year risk ≥1.7%). It is uncertain, however, how often women accept and complete five years of therapy and whether clinical or demographic factors predict completion. Medical records were abstracted for 219 women whose five year risk of breast cancer was ≥1.7% and who were offered chemoprevention while attending a high risk breast clinic at the Moffitt Cancer Center. We examined the likelihood of accepting chemoprevention and completing five years of therapy, and potential clinical and demographic predictors of these outcomes, using multivariable logistic regression and survival analysis models. There were 118/219 women (54.4%) who accepted a recommendation for chemoprevention and began therapy. The likelihood of accepting chemoprevention was associated with lifetime breast cancer risk and was higher for women with specific high risk conditions (lobular carcinoma in situ and atypical ductal hyperplasia). Women with osteoporosis and those that consumed alcohol were also more likely to accept medication. There were 58/118 (49.2%) women who stopped medication at least temporarily after starting therapy. Based on survival curves, an estimated 60% of women who begin chemoprevention will complete five years of therapy. A substantial percentage of women at increased risk of breast cancer will decline chemoprevention and among those that accept therapy, approximately 40% will not be able to complete five years of therapy because of side effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Effects of Brassicaceae Isothiocyanates on Prostate Cancer.

    PubMed

    Novío, Silvia; Cartea, María Elena; Soengas, Pilar; Freire-Garabal, Manuel; Núñez-Iglesias, María Jesús

    2016-05-12

    Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models.

  14. Vitamin E and Prostate Cancer

    USDA-ARS?s Scientific Manuscript database

    Vitamin E, its metabolites or its analogs, might help prevent prostate cancer initiation or progression. Prostate cancer is the most common non-skin malignancy and the second leading cause of cancer deaths among men in the United States, exceeded only by lung cancer. About 218,890 new cases of prost...

  15. [Grading of prostate cancer].

    PubMed

    Kristiansen, G; Roth, W; Helpap, B

    2016-07-01

    The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system.

  16. Prostate Cancer for the Internist.

    PubMed

    Jaiswal, Shikha; Sarmad, Rehan; Arora, Sumant; Dasaraju, Radhikha; Sarmad, Komal

    2015-10-01

    In the United States, approximately 240,000 men are diagnosed annually with prostate cancer. Although effective treatment options are available for clinically localized cancer, the potential burdensome co-morbidities and attendant healthcare costs from over diagnosis and over treatment have escalated the discussion and controversy regarding appropriate screening, diagnosis, and optimal management of prostate cancer. Although the lifetime risk of developing prostate cancer is approximately 1 in 6 (~16%), the risk of dying from the disease is only ~2%. The discrepancy between the cancer incidence and lethality has led to widespread scrutiny of prostate cancer patient management, particularly for low-grade, low-stage (indolent) disease. The vast majority of men diagnosed with clinically localized prostate cancer are treated with interventional therapies despite studies demonstrating that even without treatment, prostate cancer-specific mortality is low. A MedLine/PubMed search was performed using PICO format (Patient, Intervention, Comparison and Outcome) identifying all relevant articles. No restrictions were used for publication dates. The terms "Prostate Cancer", "Screening", "Mortality", "Morbidity" yielded 307 results. "Diagnosis", "Prognosis" and "Survival" yielded 1504 results. Further filters were applied to narrow down the results using keywords "Prostate cancer screening guidelines 2014", "Beyond PSA", "NCCN Guidelines prostate", "MRI guided Prostate biopsy" yielding 72, 274, 54 and 568 results respectively. Of these, approximately 137 articles were found relevant and were reviewed. References from the reviewed articles were included in the final article.

  17. Ascorbic acid in cancer chemoprevention: translational perspectives and efficacy.

    PubMed

    Ullah, Mohammad F; Bhat, Showket H; Hussain, Eram; Abu-Duhier, Faisel; Ahmad, Aamir; Hadi, S M

    2012-12-01

    Chemoprevention, which is referred to as the use of nontoxic natural or synthetic chemicals to intervene in multistage carcinogenesis has since decades attracted a considerable interest in plant-derived chemical constituents often termed as "phytochemicals" or sometimes as "Nutraceuticals" in case they are derived from dietary sources. A comprehensive search of the literature show that such an interest in natural product pharmacology has surged in the last 25 years and particularly risen at exponential rates since the last one decade. Phytochemicals such as curcumin (from spice turmeric), resveratrol (from red wine) and genistein (from soy) share the major efforts as indicated by overwhelming publications, despite skepticism concerning their bioavailability. Ascorbic acid (AA), the popular anti-oxidant in fruits and vegetables, has even a longer historical perspective than these dietary agents as for more than 35 years; there had been lingering questions about the efficacy of AA in cancer therapy. The footprints of AA from "scurvy" to "cancer" though complex seems to carry potential provided the puzzle could be set right. The use of AA in cancer treatment has been debated extensively as evident from the literature but surprisingly the complementing early phase bench work on the mechanistic studies for anticancer action was rather retarded. Proposed mechanisms of action for AA in the prevention and treatment of cancer includes antioxidant as well as pro-oxidant properties, stimulation of the immune system, altering carcinogen metabolism, enhancement of collagen synthesis necessary for tumor encapsulation and interference with cancer cell signaling. The observation that the intravenous administration of AA enhances its bioavailability to the extent of deriving pharmacological benefits against cancer has in recent years partially supported the clinical plausibility (efficacy) of AA towards realizing its translational advantage. Here, we provide an overview of AA with

  18. Survival in prostate cancer prevention trial detailed

    Cancer.gov

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  19. Survival in prostate cancer prevention trial detailed

    Cancer.gov

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  20. Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention.

    PubMed

    W Watson, Gregory; M Beaver, Laura; E Williams, David; H Dashwood, Roderick; Ho, Emily

    2013-10-01

    Epidemiological evidence has demonstrated a reduced risk of prostate cancer associated with cruciferous vegetable intake. Follow-up studies have attributed this protective activity to the metabolic products of glucosinolates, a class of secondary metabolites produced by crucifers. The metabolic products of glucoraphanin and glucobrassicin, sulforaphane, and indole-3-carbinol respectively, have been the subject of intense investigation by cancer researchers. Sulforaphane and indole-3-carbinol inhibit prostate cancer by both blocking initiation and suppressing prostate cancer progression in vitro and in vivo. Research has largely focused on the anti-initiation and cytoprotective effects of sulforaphane and indole-3-carbinol through induction of phases I and II detoxification pathways. With regards to suppressive activity, research has focused on the ability of sulforaphane and indole-3-carbinol to antagonize cell signaling pathways known to be dysregulated in prostate cancer. Recent investigations have characterized the ability of sulforaphane and indole-3-carbinol derivatives to modulate the activity of enzymes controlling the epigenetic status of prostate cancer cells. In this review, we will summarize the well-established, "classic" non-epigenetic targets of sulforaphane and indole-3-carbinol, and highlight more recent evidence supporting these phytochemicals as epigenetic modulators for prostate cancer chemoprevention.

  1. Chemopreventive and metabolic effects of inulin on colon cancer development

    PubMed Central

    Szabadosova, Viktória; Štofilová, Jana; Hrčková, Gabriela

    2013-01-01

    Prebiotics modulate microbial composition and ensure a healthy gastrointestinal tract environment that can prevent colon cancer development. These natural dietary compounds are therefore potential chemopreventive agents. Thirty Sprague-Dawley rats (4 months old) were experimentally treated with procarcinogen dimethylhydrazine to induce colon cancer development. The rats were randomly assigned to three groups: a control group (CG), a group treated with dimethylhydrazine (DMH), and a group given DMH and inulin, a prebiotic (DMH+PRE). The effects of inulin on the activities of bacterial glycolytic enzymes, short-chain fatty acids, coliform and lactobacilli counts, cytokine levels, and cyclooxygenase-2 (COX-2) and transcription nuclear factor kappa beta (NFκB) immunoreactivity were measured. Inulin significantly decreased coliform counts (p < 0.01), increased lactobacilli counts (p < 0.001), and decreased the activity of β-glucuronidase (p < 0.01). Butyric and propionic concentrations were decreased in the DMH group. Inulin increased its concentration that had been reduced by DMH. Inulin decreased the numbers of COX-2- and NFκB-positive cells in the tunica mucosae and tela submucosae of the colon. The expression of IL-2, TNFα, and IL-10 was also diminished. This 28-week study showed that dietary intake of inulin prevents preneoplastic changes and inflammation that promote colon cancer development. PMID:23820222

  2. Plant Polyphenols as Chemopreventive Agents for Lung Cancer

    PubMed Central

    Amararathna, Madumani; Johnston, Michael R.; Rupasinghe, H. P. Vasantha

    2016-01-01

    Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases. PMID:27548149

  3. Plant Polyphenols as Chemopreventive Agents for Lung Cancer.

    PubMed

    Amararathna, Madumani; Johnston, Michael R; Rupasinghe, H P Vasantha

    2016-08-19

    Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases.

  4. Tuberculous prostatitis: mimicking a cancer.

    PubMed

    Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay

    2016-01-01

    Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions.

  5. [Mediterranean diet, micronutrients and prostate carcinoma: a rationale approach to primary prevention of prostate cancer].

    PubMed

    Miano, Lucio

    2003-09-01

    Cancer of the prostate is one of the most commonly diagnosed solid malignancies and the fourth leading cause of cancer-related deaths in men living in Italy. With an ageing population, the number of men living with early stages of prostate cancer is expected to increase. There is an impelling need to prevent the onset of the cancer or delay the progression of carcinogenesis in this organ. The chemoprevention of cancer is a relatively new concept defined as the administration of pharmacological agents (drug or diet-derived supplements) to prevent, delay or reverse the carcinogenesis. Epidemiological data showing ethnic and geographic variations in the incidence of, and mortality from, prostate cancer have suggested that the consumption of dietary factors may be protective. There is increasing evidence that diet (particularly dietary fat intake) may play a significant role in early prostate carcinogenesis. Dietary micronutrients and antioxidants are under intense scrutiny. These factors include the vitamin D and E, lycopene, selenium, zinc, poliphenols, isoflavonoids, and phytoestrogens (especially soy products and green tea). The old Mediterranean diet (based on cereals, vegetables, polyunsaturated fats, fruits, fish and low quantities of dairy products and meat) is now sparingly adopted because of the globalisation of the food chain which now involves also our country. Nevertheless, our traditional dietary habits are considered of great value in the prevention of cardiovascular or cancerous diseases and particularly of prostate cancer.

  6. Cholesterol and prostate cancer.

    PubMed

    Freeman, Michael R; Solomon, Keith R

    2004-01-01

    Cholesterol is a neutral lipid that accumulates in liquid-ordered, detergent-resistant membrane domains called lipid rafts. Lipid rafts serve as membrane platforms for signal transduction mechanisms that mediate cell growth, survival, and a variety of other processes relevant to cancer. A number of studies, going back many years, demonstrate that cholesterol accumulates in solid tumors and that cholesterol homeostasis breaks down in the prostate with aging and with the transition to the malignant state. This review summarizes the established links between cholesterol and prostate cancer (PCa), with a focus on how accumulation of cholesterol within the lipid raft component of the plasma membrane may stimulate signaling pathways that promote progression to hormone refractory disease. We propose that increases in cholesterol in prostate tumor cell membranes, resulting from increases in circulating levels or from dysregulation of endogenous synthesis, results in the coalescence of raft domains. This would have the effect of sequestering positive regulators of oncogenic signaling within rafts, while maintaining negative regulators in the liquid-disordered membrane fraction. This approach toward examining the function of lipid rafts in prostate cancer cells may provide insight into the role of circulating cholesterol in malignant growth and on the potential relationship between diet and aggressive disease. Large-scale characterization of proteins that localize to cholesterol-rich domains may help unveil signaling networks and pathways that will lead to identification of new biomarkers for disease progression and potentially to novel targets for therapeutic intervention.

  7. Protein Kinase Cβ Is an Effective Target for Chemoprevention of Colon Cancer

    PubMed Central

    Fields, Alan P.; Calcagno, Shelly R.; Krishna, Murli; Rak, Sofija; Leitges, Michael; Murray, Nicole R.

    2009-01-01

    Colon cancer develops over a period of 10 to 15 years, providing a window of opportunity for chemoprevention and early intervention. However, few molecular targets for effective colon cancer chemoprevention have been characterized and validated. Protein kinase CβII (PKCβII) plays a requisite role in the initiation of colon carcinogenesis in a preclinical mouse model by promoting proliferation and increased β-catenin accumulation. In this study, we test the hypothesis that PKCβII is an effective target for colon cancer chemoprevention using enzastaurin (LY317615), a PKCβ-selective inhibitor, in a mouse model of colon carcinogenesis. We find that enzastaurin potently reduces azoxymethane-induced colon tumor initiation and progression by inhibiting PKCβII-mediated tumor cell proliferation and β-catenin accumulation. Biochemically, enzastaurin reduces expression of the PKCβII- and β-catenin/T-cell factor–regulated genes PKCβII, cyclooxygenase II, and vascular endothelial growth factor, three genes implicated in colon carcinogenesis. Our results show that enzastaurin is an effective chemopreventive agent in a mouse model of sporadic colon cancer that significantly reduces both tumor initiation and progression by inhibiting expression of proproliferative genes. Thus, PKCβII is an important target for colon cancer chemoprevention and the PKCβ-selective inhibitor enzastaurin may represent an effective chemopreventive agent in patients at high risk for colon cancer. PMID:19221092

  8. Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention

    PubMed Central

    Ziv, Elad; Tice, Jeffrey A.; Sprague, Brian; Vachon, Celine M.; Cummings, Steven R.; Kerlikowske, Karla

    2017-01-01

    Background Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs) and aromatase inhibitors (AIs). The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs) have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention. Methods We used the risk distribution among women ages 35–69 estimated by the Breast Cancer Surveillance Consortium (BCSC) risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention. Results We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (~21% of all women), ~75% of the benefit of testing all women (shifting women above or below 3% 5-year risk) would be derived. If women with a 5-year risk of >1.5% are tested (~36% of all women), ~90% of the benefit of testing all women would be derived. Conclusion SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention. PMID:28107349

  9. Cancer chemoprevention with green tea catechins: from bench to bed.

    PubMed

    Shirakami, Yohei; Shimizu, Masahito; Moriwaki, Hisataka

    2012-12-01

    Many epidemiological studies and a large number of experimental studies using a variety of animal models have observed that consumption or administration of green tea appears to exert cancer chemopreventive activity. Based on the results of numerous laboratory cell culture investigations, several mechanisms have been hypothesized to underlie the anti-cancer activity of green tea catechins, especially that of (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active constituent in green tea. These mechanisms include promotion of anti-oxidant activity, inhibition of NF-κB and AP-1, regulation of the cell cycle, inhibition of receptor tyrosine kinase pathways, control of epigenetic modifications, and modulation of the immune system. Several recent interventional studies examining the anti-carcinogenic properties of green tea catechins in humans have yielded promising results that suggest the possibility of their application to human clinical trials. This review article analyzes the results of these studies to explicate the effects of consumption or administration of green tea and its constituents on malignancies observed to date and discuss future directions in this research field.

  10. Testosterone Therapy and Prostate Cancer.

    PubMed

    Davidson, Emily; Morgentaler, Abraham

    2016-05-01

    Changes in understanding regarding the relationship of androgens and prostate cancer have led to changes in the use of testosterone therapy. The evidence supports a finite ability of androgens to stimulate prostate cancer growth, with a maximum achieved at low testosterone concentrations, called the saturation model. The saturation point corresponds with maximal androgenic stimulation at 250 ng/dL. Evidence is reviewed herein regarding the relationship of testosterone to prostate cancer and the relatively new practice of offering testosterone therapy to men with a history of prostate cancer. Although no prospective controlled trials have been performed, results have been reassuring.

  11. Mouse Models of Prostate Cancer

    PubMed Central

    Valkenburg, Kenneth C.; Williams, Bart O.

    2011-01-01

    The development and optimization of high-throughput screening methods has identified a multitude of genetic changes associated with human disease. The use of immunodeficient and genetically engineered mouse models that mimic the human disease has been crucial in validating the importance of these genetic pathways in prostate cancer. These models provide a platform for finding novel therapies to treat human patients afflicted with prostate cancer as well as those who have debilitating bone metastases. In this paper, we focus on the historical development and phenotypic descriptions of mouse models used to study prostate cancer. We also comment on how closely each model recapitulates human prostate cancer. PMID:22111002

  12. Biomarkers in Prostate Cancer Epidemiology

    PubMed Central

    Verma, Mukesh; Patel, Payal; Verma, Mudit

    2011-01-01

    Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person's genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed. PMID:24213111

  13. Implications of Cancer Stem Cell Theory for Cancer Chemoprevention by Natural Dietary Compounds

    PubMed Central

    Li, Yanyan; Wicha, Max S.; Schwartz, Steven J.; Sun, Duxin

    2011-01-01

    The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anti-cancer drugs targeting cancer stem cells. Naturally-occurring dietary compounds have received increasing attention in cancer chemoprevention. The anti-cancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog, and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine, and vitamin D3, are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival. PMID:21295962

  14. Prostate Cancer MR Imaging

    NASA Astrophysics Data System (ADS)

    Fütterer, Jurgen J.

    With a total of 192,280 new cases predicted for 2009, prostate cancer (PC) now accounts for 25% of all new male cancers diagnosed in the United States [1]. Furthermore, in their lifetime, one in six men will be clinically diagnosed with having PC, although many more men are found to have histological evidence of PC at autopsy [2,3,4]. Presently, approximately 1 in 10 men will die of PC [5,6]. The ever-aging population and wider spread use of the blood prostate-specific antigen (PSA) test [7,8], as well as the tendency to apply lower cut-off levels for this test [9], will further increase the diagnosis of this disease [10].

  15. Androgen receptor in prostate cancer.

    PubMed

    Heinlein, Cynthia A; Chang, Chawnshang

    2004-04-01

    The normal development and maintenance of the prostate is dependent on androgen acting through the androgen receptor (AR). AR remains important in the development and progression of prostate cancer. AR expression is maintained throughout prostate cancer progression, and the majority of androgen-independent or hormone refractory prostate cancers express AR. Mutation of AR, especially mutations that result in a relaxation of AR ligand specificity, may contribute to the progression of prostate cancer and the failure of endocrine therapy by allowing AR transcriptional activation in response to antiandrogens or other endogenous hormones. Similarly, alterations in the relative expression of AR coregulators have been found to occur with prostate cancer progression and may contribute to differences in AR ligand specificity or transcriptional activity. Prostate cancer progression is also associated with increased growth factor production and an altered response to growth factors by prostate cancer cells. The kinase signal transduction cascades initiated by mitogenic growth factors modulate the transcriptional activity of AR and the interaction between AR and AR coactivators. The inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression.

  16. Prostate Cancer Aggressiveness Gene in Hereditary Prostate Cancer

    DTIC Science & Technology

    2007-03-01

    Ann Arbor, MI 48109-1274 REPORT DATE: March 2007 TYPE OF REPORT: Final PREPARED...REPORT DATE 01-03-2007 2. REPORT TYPE Final 3. DATES COVERED 1 Mar 2004 – 28 Feb 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate... inherited prostate cancer susceptibility. This statement is based on the identification of prostate cancer linkage to distal 7q markers in a recently

  17. Targeting Prostate Cancer Metastasis

    DTIC Science & Technology

    2015-09-01

    drug t oxi c i t y and the e ffect i ve dose i n zebrafish and found the best perf ormi ng s t rat egi es usi ng zebrafish - metastasi s model s...CLASSIFICATION OF: a. REPORT b. ABSTRACT c . THIS PAGE Unclassified Unclassified Unclassified screen, zebrafish , mouse, 17. LIMITATION 18. NUMBER OF... zebrafish -metastasis models and mouse models of prostate cancer, we aim to investigate whether FDA approved drugs that target these pathways can be

  18. Chemoprevention of Skin Cancer Program Project | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): Skin cancer is the most common malignancy in the world. One out of three new cancers is a skin cancer. More than 1 million cases of non-melanoma skin cancer (NMSC) (basal cell carcinoma [BCC] and squamous cell cancers [SCC]) occur annually. While the incidence rates for non-melanoma skin cancers continue to rise, there continues to be a substantial impact on morbidity, health and health care costs. |

  19. In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis

    DTIC Science & Technology

    2003-03-01

    or high-selenium yeast given prior (12) Waters DJ, Sakr WA, Hayden DW, Lang cancer and that were of a comparable CM, McKinney L, Murphy GP , et al...cancer. * Home Defibrillator ADHD Child? Researchers say the results show that selenium may help protect cells within the aging prostate from initial DNA...References: 1. Waters DJ, Sakr WA, Hayden DW, Lang CM, McKinney L, Murphy GP , Radinsky R, Ramoner R, Richardson RC, Tindall DJ. Workgroup 4

  20. Dietary Polyphenols in Prevention and Treatment of Prostate Cancer

    PubMed Central

    Lall, Rahul K.; Syed, Deeba N.; Adhami, Vaqar M.; Khan, Mohammad Imran; Mukhtar, Hasan

    2015-01-01

    Prostate cancer is the most prevalent disease affecting males in many Western countries, with an estimated 29,480 deaths in 2014 in the US alone. Incidence rates for prostate cancer deaths have been decreasing since the early 1990s in men of all races/ethnicities, though they remain about 60% higher in African Americans than in any other group. The relationship between dietary polyphenols and the prevention of prostate cancer has been examined previously. Although results are sometimes inconsistent and variable, there is a general agreement that polyphenols hold great promise for the future management of prostate cancer. Various dietary components, including polyphenols, have been shown to possess anti-cancer properties. Generally considered as non-toxic, dietary polyphenols act as key modulators of signaling pathways and are therefore considered ideal chemopreventive agents. Besides possessing various anti-tumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Polyphenols have also been shown to affect post-translational modifications and microRNA expressions. This article provides a systematic review of the health benefits of selected dietary polyphenols in prostate cancer, especially focusing on the subclasses of polyphenols, which have a great effect on disease prevention and treatment. PMID:25654230

  1. Potential role of gastrointestinal microbiota composition in prostate cancer risk

    PubMed Central

    2013-01-01

    Background Among men in the U.S., prostate cancer is the most common cancer and the second leading cause of cancer death. Despite its prevalence, there are few established risk factors for prostate cancer. Some studies have found that intake of certain foods/nutrients may be associated with prostate cancer risk, but few have accounted for how intake and metabolic factors may interact to influence bioavailable nutrient levels and subsequent disease risk. Presentation of the hypothesis The composition of the gastrointestinal (GI) microbiome may influence metabolism of dietary compounds and nutrients (e.g., plant phenols, calcium, choline) that may be relevant to prostate cancer risk. We, therefore, propose the hypothesis that GI microbiota may have a markedly different composition among individuals with higher prostate cancer risk. These individuals could have microbial profiles that are conducive to intestinal inflammation and/or are less favorable for the metabolism and uptake of chemopreventive agents. Testing the hypothesis Because very little preliminary data exist on this potential association, a case–control study may provide valuable information on this topic. Such a study could evaluate whether the GI microbial profile is markedly different between three groups of individuals: healthy men, those with latent prostate cancer, and those with invasive prostate cancer. Any findings could then be validated in a larger study, designed to collect a series of specimens over time. Implications of the hypothesis Given the plethora of information emerging from the Human Microbiome Project, this is an opportune time to explore associations between the microbiome and complex human diseases. Identification of profiles that alter the host’s risk for disease may clarify inconsistencies in the literature on dietary factors and cancer risk, and could provide valuable targets for novel cancer prevention strategies. PMID:24180596

  2. Hedera nepalensis K. Koch: A Novel Source of Natural Cancer Chemopreventive and Anticancerous Compounds.

    PubMed

    Jafri, Laila; Saleem, Samreen; Kondrytuk, Tamara P; Haq, Ihsan-ul; Ullah, Nazif; Pezzuto, John M; Mirza, Bushra

    2016-03-01

    Traditional medicinal plants are often used for both the prevention and the treatment of local diseases. Taking into consideration the medicinal importance of Hedera nepalensis within local Pakistani traditions, the present study was undertaken to analyze the in vitro cancer chemopreventive and cytotoxic properties of the plant. The in vitro cancer chemopreventive testing was performed using nitrite assay, NFκB assay, aromatase assay, and quinone reductase 1 (QR1) assay. The cytotoxic potential was evaluated on three cancer-cell lines: MCF-7, MDA-MB-231, and HeLa using sulforhodamine B (SRB) assay. The results of cancer chemopreventive assays show that n-hexane and ethyl acetate fractions of tested plant have promising cancer chemopreventive potential. Lupeol isolated from n-hexane as well as ethyl acetate fraction showed lowest IC50 (0.20 ± 1.9 μM) in NFκB assay. Crude extract and its fractions inhibited the growth of three cancer cell lines by more than 60%, IC50 value of lupeol varied from 2.32 to 10.2 μM. HPLC-DAD-based quantification of lupeol in different plant tissues demonstrated that leaves of H. nepalensis are a rich source of lupeol (0.196 mg/100 mg dry weight). Our data have shown that H. nepalensis harbors cancer chemopreventive and cytotoxic agents.

  3. About the Chemopreventive Agent Development Research Group | Division of Cancer Prevention

    Cancer.gov

    The Chemopreventive Agent Development Research Group promotes and supports research on early chemopreventive agent development, from preclinical studies to phase I clinical trials. The group’s projects aim to identify and develop prevention agents with the potential to block, reverse, or delay the early stages of cancer. The overarching goal is to determine positive and negative predictive values of preclinical models for clinical development. |

  4. Examination of the relationship between symptoms of prostatitis and histological inflammation: baseline data from the REDUCE chemoprevention trial.

    PubMed

    Nickel, J Curtis; Roehrborn, Claus G; O'leary, Michael P; Bostwick, David G; Somerville, Matthew C; Rittmaster, Roger S

    2007-09-01

    Symptoms of abacterial chronic prostatitis/chronic pelvic pain syndrome are considered to be associated with prostate inflammation. The ongoing Reduction by Dutasteride of Prostate Cancer Events trial is a 4-year, phase III, placebo controlled study to determine whether 0.5 mg dutasteride daily decreases the risk of biopsy detectable prostate cancer. All men underwent biopsy before study entry, allowing review of the relationship between histological prostate inflammation and prostatitis symptoms. Eligible men were 50 to 75 years old with serum prostate specific antigen 2.5 ng/ml or greater and 10 ng/ml or less (ages 50 to 60 years), or 3.0 ng/ml or greater and 10 ng/ml or less (older than 60 years), and an International Prostate Symptom Score of less than 25 (or less than 20 if already on alpha-blocker therapy). Acute prostatitis was an exclusion criterion. The National Institutes of Health Chronic Prostatitis Symptom Index was used to assess prostatitis-like symptoms. Spearman rank correlations were used to assess the relationship between acute and chronic inflammation, and Chronic Prostatitis Symptom Index scores for the pain, urinary symptoms and quality of life domains as well as average pain, total score and prostatitis-like symptoms. Data were available on 5,597 patients. The distribution of inflammation status was similar for those with and without chronic prostatitis-like symptoms. Significant correlations were found between average chronic inflammation, and total Chronic Prostatitis Symptom Index score and subscores for urinary symptoms and quality of life but the magnitude of these correlations was small. A lack of clinically meaningful association was found between prostatitis-like pain symptoms and histological inflammation in the Reduction by Dutasteride of Prostate Cancer Events population, suggesting that the view that symptoms of chronic prostatitis/chronic pelvic pain syndrome and prostate inflammation are associated needs further scrutiny.

  5. DuCLOX-2/5 inhibition: a promising target for cancer chemoprevention.

    PubMed

    Gautam, Swetlana; Roy, Subhadeep; Ansari, Mohd Nazam; Saeedan, Abdulaziz S; Saraf, Shubhini A; Kaithwas, Gaurav

    2017-03-01

    Cancer is a leading cause of death and major health concern worldwide. The animal and human studies support the presumption that inflammation directs the cancer initiation and progression. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are the key players in the inflammatory cascade contributing towards the angiogenesis, tumor cell invasiveness, and disruption in the pathways of cellular proliferation/apoptosis. Contemporary studies have particularized a promising role of COX-2 and 5-LOX inhibitors in cancer chemoprevention. The present review is a pursuit to define implications of dual COX-2 and 5-LOX (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention.

  6. Selenium and prostate cancer prevention: insights from the selenium and vitamin E cancer prevention trial (SELECT).

    PubMed

    Nicastro, Holly L; Dunn, Barbara K

    2013-04-03

    The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention.

  7. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  8. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  9. Molecular Imaging of Prostate Cancer

    PubMed Central

    Burger, Irene A.; Sala, Evis; Hricak, Hedvig; Weber, Wolfgang A.; Vargas, Hebert Alberto

    2016-01-01

    Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer–specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls. ©RSNA, 2015 PMID:26587888

  10. General Information about Prostate Cancer

    MedlinePlus

    ... problems after prostate cancer surgery include the following: Impotence . Leakage of urine from the bladder or stool ... and/or gastrointestinal cancer. Radiation therapy can cause impotence and urinary problems. Hormone therapy Hormone therapy is ...

  11. Urinary biomarkers for prostate cancer.

    PubMed

    Wei, John T

    2015-01-01

    The field of urology has been beset by several major trends that have affected the early detection of prostate cancer. These stem primarily from a backlash against overdiagnosis due to prostate specific antigen-based screening efforts and are epitomized by the US Preventive Services Task Force giving prostate specific antigen-based prostate cancer screening a 'D' recommendation. Consequently, the active surveillance strategy for low-risk prostate cancer has become commonplace, leading many to ask how best to follow these patients. More importantly, this public outcry has shifted the focus of early detection from an effort to diagnose any and all prostate cancers to an effort to diagnose only 'high-risk' cancer. Along with a trend for minimally invasive procedures, these forces have challenged the early detection field to more efficiently identify clinically significant prostate cancers at an early stage while limiting the number of biopsies. With US Food and Drug Administration approval, prostate cancer antigen 3 has emerged as the first bona-fide urinary biomarker for prostate cancer. Using the same platform, investigators have developed a second urinary test based on TMPRSS2:erg fusion. Recent literature supports the use of these biomarkers as a combined panel that improves risk evaluation in the setting of prostate cancer detection. Early works for applying urinary biomarkers for active surveillance are underway. Other biomarkers in the pipeline will require further prevalidation and validation work. Recent literature would support that urinary biomarkers have a clear role to supplement risk evaluation for men undergoing prostate biopsy and for prognostication.

  12. What's New in Prostate Cancer Research and Treatment?

    MedlinePlus

    ... Cancer Research? Prostate Cancer About Prostate Cancer What’s New in Prostate Cancer Research? Research into the causes, ... in many medical centers throughout the world. Genetics New research on gene changes linked to prostate cancer ...

  13. Biomarkers in localized prostate cancer.

    PubMed

    Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

    2016-02-01

    Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer.

  14. Biomarkers in localized prostate cancer

    PubMed Central

    Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

    2016-01-01

    Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer. PMID:26768791

  15. Mechanistic Role of MicroRNA in Cancer Chemoprevention by Nonsteroidal Anti-inflammatory Drugs

    PubMed Central

    Ma, Ruixia; Yi, Bin; Piazza, Gary A.; Xi, Yaguang

    2015-01-01

    Over the past several decades, studies have documented the significance of nonsteroidal anti-inflammatory drugs (NSAIDs) on cancer chemoprevention by lowering incidence and slowing down progression of malignant disease, which consequently lead to decline of cancer-related mortality and improvement of disease progression free survival (PFS). Inhibition of cyclooxygenase (COX) has been primarily believed to be the key mechanism responsible for anticancer activity of NSAIDs, while the serious toxicity caused by COX inhibitory effect reduces the enthusiasm to use NSAIDs as chemoprevention agents in the clinic. Recently, more and more studies demonstrate that non-COX inhibitory mechanisms may account for anticancer properties of NSAIDs, at least partially, which potentially support the indication of NSAIDs on cancer chemoprevention. MicroRNAs (miRNAs) are a set of non-coding and small RNA molecules with master regulatory effect on over 30% human genes through the post-transcriptional and translational modulation. Although miRNAs have been reported to be involved in many normal and pathological processes including cell proliferation, apoptosis, differentiation, as well as tumorigenesis, their roles in NSAIDs' properties of cancer chemoprevention have not yet been studied exclusively. Here, we will review the prior studies reporting interactions between miRNAs and COX/non-COX pathways with intent to provide insights into better understanding molecular mechanisms of cancer chemoprevention by NSAIDs. PMID:26213681

  16. Chemoprevention research: implications for primary care practice.

    PubMed

    Denicoff, A M; Padberg, R M

    2000-01-01

    The field of cancer prevention research is entering a time of growth and opportunity. This important research is identifying agents that are making a substantial difference by reducing cancer incidence in high-risk populations. Primary care providers are natural partners for this research because of their diversity, commitment to disease prevention, and long-term access to their patient population. Several national chemoprevention trials in breast and prostate cancer are open and seeking to affiliate with primary care providers. Information is provided on this research effort, the development of chemoprevention trials, and how to learn more.

  17. The Potential Role of Nitric Oxide in Halting Cancer Progression Through Chemoprevention

    PubMed Central

    Vahora, Huzefa; Khan, Munawwar Ali; Alalami, Usama; Hussain, Arif

    2016-01-01

    Nitric oxide (NO) in general plays a beneficial physiological role as a vasorelaxant and the role of NO is decided by its concentration present in physiological environments. NO either facilitates cancer-promoting characters or act as an anti-cancer agent. The dilemma in this regard still remains unanswered. This review summarizes the recent information on NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents which have NO-modulating properties with safe cytotoxic profile. Understanding the molecular mechanisms and cross-talk modulating NO effect by these chemopreventive agents can allow us to develop better therapeutic strategies for cancer treatment. PMID:27051643

  18. Pancreatic Cancer Chemoprevention Translational Workshop | Division of Cancer Prevention

    Cancer.gov

    Thursday, September 10th (6:00 to 9:30 PM) Welcome Barnett Kramer, MD, MPH (6:00 to 6:10 PM) Director of the Division of Cancer Prevention, NCI Introduction – Goals of the Workshop: ABCs of Cancer Prevention (Agents, Biomarkers, Cohorts) Mark Miller, PhD (6:10 to 6:25 PM) Program Director Division of Cancer Prevention, NCI |

  19. Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products.

    PubMed

    Kaur, Manjinder; Agarwal, Chapla; Agarwal, Rajesh

    2009-09-01

    With emerging trends in the incidence of cancer of various organ sites, additional approaches are needed to control human malignancies. Intervention or prevention of cancer by dietary constituents, a strategy defined as chemoprevention, holds great promise in our conquest to control cancer, because it can be implemented on a broader population base with less economic burden. Consistent with this, several epidemiological studies have shown that populations that consume diets rich in fruits and vegetables have an overall lower cancer incidence. Based on these encouraging observations, research efforts from across the globe have focused on identifying, characterizing, and providing scientific basis to the efficacy of various phytonutrients in an effort to develop effective strategy to control various human malignancies. Cancer induction, growth, and progression are multi-step events and numerous studies have demonstrated that various dietary agents interfere with these stages of cancer, thus blocking malignancy. Fruits and vegetables represent untapped reservoir of various nutritive and nonnutritive phytochemicals with potential cancer chemopreventive activity. Grapes and grape-based products are one such class of dietary products that have shown cancer chemopreventive potential and are also known to improve overall human health. This review focuses on recent advancements in cancer chemopreventive and anticancer efficacy of grape seed extract and other grape-based products. Overall, completed studies from various scientific groups conclude that both grapes and grape-based products are excellent sources of various anticancer agents and their regular consumption should thus be beneficial to the general population.

  20. Human Prostate Cancer Hallmarks Map.

    PubMed

    Datta, Dipamoy; Aftabuddin, Md; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-08-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process.

  1. The BESCT Lung Cancer Program (Biology, Education, Screening, Chemoprevention, and Treatment)

    DTIC Science & Technology

    2005-03-01

    early enough to be reversed with molecular targeted therapy and to develop innovative therapeutic approaches to lung cancer. Thus, the specific. aims...cancer, genetic alterations, chemoprevention, molecular therapy 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19. SECURITY... therapy , and chemotherapy of non-small cell lung cancer (NSCLC) have only led to a marginal improvement in five-year survival. To reduce lung cancer

  2. Dietary Factors and Epigenetic Regulation for Prostate Cancer Prevention12

    PubMed Central

    Ho, Emily; Beaver, Laura M.; Williams, David E.; Dashwood, Roderick H.

    2011-01-01

    The role of epigenetic alterations in various human chronic diseases has gained increasing attention and has resulted in a paradigm shift in our understanding of disease susceptibility. In the field of cancer research, e.g., genetic abnormalities/mutations historically were viewed as primary underlying causes; however, epigenetic mechanisms that alter gene expression without affecting DNA sequence are now recognized as being of equal or greater importance for oncogenesis. Methylation of DNA, modification of histones, and interfering microRNA (miRNA) collectively represent a cadre of epigenetic elements dysregulated in cancer. Targeting the epigenome with compounds that modulate DNA methylation, histone marks, and miRNA profiles represents an evolving strategy for cancer chemoprevention, and these approaches are starting to show promise in human clinical trials. Essential micronutrients such as folate, vitamin B-12, selenium, and zinc as well as the dietary phytochemicals sulforaphane, tea polyphenols, curcumin, and allyl sulfur compounds are among a growing list of agents that affect epigenetic events as novel mechanisms of chemoprevention. To illustrate these concepts, the current review highlights the interactions among nutrients, epigenetics, and prostate cancer susceptibility. In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression. PMID:22332092

  3. Dietary factors and epigenetic regulation for prostate cancer prevention.

    PubMed

    Ho, Emily; Beaver, Laura M; Williams, David E; Dashwood, Roderick H

    2011-11-01

    The role of epigenetic alterations in various human chronic diseases has gained increasing attention and has resulted in a paradigm shift in our understanding of disease susceptibility. In the field of cancer research, e.g., genetic abnormalities/mutations historically were viewed as primary underlying causes; however, epigenetic mechanisms that alter gene expression without affecting DNA sequence are now recognized as being of equal or greater importance for oncogenesis. Methylation of DNA, modification of histones, and interfering microRNA (miRNA) collectively represent a cadre of epigenetic elements dysregulated in cancer. Targeting the epigenome with compounds that modulate DNA methylation, histone marks, and miRNA profiles represents an evolving strategy for cancer chemoprevention, and these approaches are starting to show promise in human clinical trials. Essential micronutrients such as folate, vitamin B-12, selenium, and zinc as well as the dietary phytochemicals sulforaphane, tea polyphenols, curcumin, and allyl sulfur compounds are among a growing list of agents that affect epigenetic events as novel mechanisms of chemoprevention. To illustrate these concepts, the current review highlights the interactions among nutrients, epigenetics, and prostate cancer susceptibility. In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression.

  4. [Surgery of prostate cancer].

    PubMed

    Villers, Arnauld; Rébillard, Xavier

    2003-12-31

    Radical prostatectomy is one of the standard treatment of localised prostate cancer. It is considered that cure is obtain if PSA value is undetectable (< 0,1 ng/mL) for at least 5 to 7 years post surgery. 8 to 9 men out of 10 are currently cured by prostatectomy if the cancer is detected at organ confined stage, with PSA < 10 ng/mL. Major technical progress related to patient setting, surgical approach, instrumentation, periprostatic fascial exposure and surgical strategy clearly decreased perioperative morbidity and late effects (erectile dysfunction and incontinence). Laparoscopic approach was described mainly by French teams since 1997 and represents a validated alternative to the gold standard suprapubic open approach.

  5. Vitamins, metabolomics, and prostate cancer.

    PubMed

    Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

    2017-06-01

    How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease. Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

  6. Molecular imaging of prostate cancer.

    PubMed

    Fox, Josef J; Schöder, Heiko; Larson, Steven M

    2012-07-01

    Prostate cancer is a complex and biologically heterogeneous disease that is not adequately assessed with conventional imaging alone. Molecular imaging with positron emission tomography (PET) is poised to fill this unmet need through noninvasive probing of the multiple molecular and cellular processes that are active in prostate cancer patients. Several PET tracers are active in early-stage and late-stage prostate cancer in humans. F18-Fluorodeoxyglucose (FDG), C11/F18-choline and sodium F18-fluoride have been studied most extensively. There is a growing body of literature supporting the utility of choline in early-stage prostate cancer. FDG and sodium F18-fluoride are more valuable in advanced disease, especially for assessing bone metastases, the prevalent form of metastases in this patient population. F18-fluorodihydrotestosterone is active in castrate disease and is emerging as a valuable pharmacodynamic marker in the development of novel androgen receptor-targeted therapies. Prostate-specific membrane antigen PET tracers are in the early stages of clinical development. Multiple PET tracers are currently available to aid in the detection and management of prostate cancer across the clinical spectrum of the disease. Prospective, rigorously controlled, clinical imaging trials are needed to establish the optimal role of PET in prostate cancer.

  7. Vaccine Treatment for Prostate Cancer

    MedlinePlus

    ... while you are hooked up to a special machine. The cells are then sent to a lab, where they are exposed to a protein from prostate cancer cells called prostatic acid phosphatase (PAP). The cells are then sent back to the doctor’s office or hospital, where they are given back to ... Information, ...

  8. Prostate Cancer Aggressiveness Genes in Hereditary Prostate Cancer

    DTIC Science & Technology

    2006-03-01

    W81XWH-04- 1 -0314 TITLE: Prostate Cancer Aggressiveness Genes in Hereditary Prostate Cancer PRINCIPAL INVESTIGATOR: Kathleen A...burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...ADDRESS. 1 . REPORT DATE (DD-MM-YYYY) March 2006 2. REPORT TYPE Annual 3. DATES COVERED (From - To) 1 Mar 05 – 28 Feb 06 5a. CONTRACT NUMBER

  9. Prostate Cancer Skeletal Metastases: Pathobiology and Interventions

    DTIC Science & Technology

    2005-02-01

    in higher levels in prostate carcinoma than in benign prostatic hyperplasia [35, 36], and is found in human metastatic lesions in bone [37]. However...compared to normal controls, benign prostatic hyperplasia , prostatitis, and localized or recurrent disease. In an animal model, prostate tumor cells...Malakouti S, Antar S, Kukreja S. Enhanced expression of parathyroid hormone-related protein in prostate cancer as compared with benign prostatic hyperplasia . Hum

  10. Urinary Biomarkers for Prostate Cancer.

    PubMed

    Tosoian, Jeffrey J; Ross, Ashley E; Sokoll, Lori J; Partin, Alan W; Pavlovich, Christian P

    2016-02-01

    In light of the overdiagnosis and overtreatment associated with widespread prostate-specific antigen-based screening, controversy persists surrounding the detection and diagnosis of prostate cancer (PCa). Given its anatomic proximity to the prostate, urine has been proposed as a noninvasive substrate for prostatic biomarkers. With greater understanding of the molecular pathways of carcinogenesis and significant technological advances, the breadth of potential biomarkers is substantial. In this review, the authors aim to provide an evidence-based assessment of current and emerging urinary biomarkers used in the detection and prognostication of PCa and high-grade PCa, with particular attention on clinically relevant findings. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo.

    PubMed

    Shenouda, Nader S; Sakla, Mary S; Newton, Leslie G; Besch-Williford, Cynthia; Greenberg, Norman M; MacDonald, Ruth S; Lubahn, Dennis B

    2007-02-01

    Prostate cancer is an important public health problem. It is an excellent candidate disease for chemoprevention because prostate cancer is typically slow growing and is usually diagnosed in elderly males. Pygeum africanum (Prunus africana or Rosaceae) is an African prune (plum) tree found in tropical Africa. An extract from the bark of Pygeum africanum has been used in Europe as a prevention and treatment of prostate disorders including benign prostatic hypertrophy (BPH). More recently in the USA, the phytotherapeutic preparations of Pygeum africanum and Saw palmetto have been marketed for prostate health including prostate cancer prevention and treatment. The anti-cancer potential of Pygeum africanum has been tested both in vitro (PC-3 and LNCaP cells) and in vivo (TRAMP mouse model). In tissue culture, ethanolic extracts (30%) of Pygeum africanum inhibited the growth of PC-3 and LNCaP cells; induced apoptosis and altered cell kinetics; down regulated ERalpha and PKC-alpha protein, and demonstrated good binding ability to both mouse uterine estrogen receptors and LNCaP human androgen receptors. TRAMP mice fed Pygeum africanum showed a significant reduction (P = 0.034) in prostate cancer incidence (35%) compared to casein fed mice (62.5%). Pygeum africanum, which is widely used in Europe and USA for treatment of BPH, has a significant role in regulation of prostate cancer both in vitro and in vivo and therefore may be a useful supplement for people at high risk for developing prostate cancer.

  12. Prostate Cancer Screening: MedlinePlus Health Topic

    MedlinePlus

    ... Prostate Cancer Screening (National Cancer Institute) Also in Spanish Latest News Prostate Cancer Symptoms Aren't Always ... Be Found Early? (American Cancer Society) Also in Spanish Risks of Prostate Cancer Screening (National Cancer Institute) ...

  13. Bioactive natural products against prostate cancer: mechanism of action and autophagic/apoptotic molecular pathways.

    PubMed

    Gioti, Katerina; Tenta, Roxane

    2015-05-01

    Prostate cancer is one of the leading causes of death worldwide for men. There is increasing evidence that diet and lifestyle play a crucial role in prostate cancer biology and tumorigenesis. Due to the fact that conventional chemotherapy is not adequately effective against prostate cancer and has severe side effects, numerous in vitro studies have been conducted in order to identify the potent cytotoxic or chemopreventive activity of naturally occurring compounds and their respective molecular mechanisms of action. In this context, many natural compounds isolated from plants have been found to inhibit cancer growth and to induce cell cycle arrest, suppress angiogenesis, and promote apoptotic or autophagic cell death. Therefore, in this article, the most promising bioactive natural products and their respective mechanisms of action for the prevention or/and treatment of prostate cancer are presented.

  14. Molecular subtyping of prostate cancer.

    PubMed

    Kaffenberger, Samuel D; Barbieri, Christopher E

    2016-05-01

    The recent publication of The Cancer Genome Atlas molecular taxonomy of primary prostate cancer highlights the increased understanding of the genomic basis of human prostate cancer, but also emphasizes the complexity and heterogeneity of prostate cancer. Seven molecular subclasses have been defined on the basis of early genomic alterations, which are largely mutually exclusive. We review the recent advances in the genomic understanding of human prostate cancer, with focus on molecular subclassification. Broadly, prostate cancer can be classified based upon whether specific genomic rearrangements, such as the Transmembrane Protease, Serine 2-ETS-related gene fusion occur or whether specific alterations such as Speckle-type POZ protein and forkhead box A1 mutations occur. The molecular drivers remain to be identified in a further quarter of human prostate cancers. Depending upon the molecular subclassification and the coincident genomic alterations, specific clinical insights can be gained from this information, including associations with pathologic factors, race, and prognosis, as well as the possibility for future precision therapies.

  15. Photosensitizers in prostate cancer therapy

    PubMed Central

    Gheewala, Taher; Skwor, Troy; Munirathinam, Gnanasekar

    2017-01-01

    The search for new therapeutics for the treatment of prostate cancer is ongoing with a focus on the balance between the harms and benefits of treatment. New therapies are being constantly developed to offer treatments similar to radical therapies, with limited side effects. Photodynamic therapy (PDT) is a promising strategy in delivering focal treatment in primary as well as post radiotherapy prostate cancer. PDT involves activation of a photosensitizer (PS) by appropriate wavelength of light, generating transient levels of reactive oxygen species (ROS). Several photosensitizers have been developed with a focus on treating prostate cancer like mTHPC, motexafin lutetium, padoporfin and so on. This article will review newly developed photosensitizers under clinical trials for the treatment of prostate cancer, along with the potential advantages and disadvantages in delivering focal therapy. PMID:28430624

  16. Hormone Therapy for Prostate Cancer

    MedlinePlus

    ... 3-4):251-258. [PubMed Abstract] Lee RJ, Smith MR. Hormone Therapy for Prostate Cancer. In: Chabner ... 1, 2014. doi: 10.1056/NEJMoa1405095 Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus ...

  17. Chemoprevention Trial Feasibility Using Botanicals in Exceptionally High Risk Populations for Lung Cancer

    PubMed Central

    Kumar, Nagi B; Quinn, Gwendolyn P; Alexandrow, Mark G; Gray, Jhanelle; Schell, Michael; Sutton, Steve; Haura, Eric B

    2015-01-01

    While chemoprevention with botanicals shows promise in reducing cancer risk, recruitment and retention of participants for trials continues to be costly and presents unique challenges. Knowledge of interest, willingness of target populations and evaluation of design challenges are critical to improve accrual in these chemoprevention trials. Objective The study assessed interest and willingness of former smokers to participate in a chemoprevention trial using a botanical agent. Methods An introductory letter and survey instrument were mailed to 609 consecutive, former heavy smokers, with no cancer, from a database of 826 subjects at the Moffitt Cancer Center. Results 202 (40.4%) subjects returned completed surveys. 92-96% reported interest in receiving free lung exams and knowing their lung cancer risk. 88% were interested in participating in a trial evaluating a botanical agent for lung cancer prevention. Over 92% of subjects reported willingness to comply with study requirements; multiple blood draws and trips to the Center, spiral CTs and chest x-rays. Subjects were relatively less enthusiastic (73-79%) about bronchoscopy, taking multiple study agents and assignment to placebo arm. Conclusions Our study strongly suggests feasibility, highlights potential challenges and the significant interest and willingness of this exceptionally high risk population to participate in chemoprevention trials. PMID:26101725

  18. COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs

    PubMed Central

    Gurpinar, Evrim; Grizzle, William E.; Piazza, Gary A.

    2013-01-01

    Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase (COX)-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention. PMID:23875171

  19. Tuberculous prostatitis: mimicking a cancer

    PubMed Central

    Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay

    2016-01-01

    Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions. PMID:28292092

  20. Nebraska Prostate Cancer Research Program

    DTIC Science & Technology

    2014-07-01

    Effect of Metal Ion Chelators on Mannose 6-Phosphate/ Insulin -like Growth Factor II Receptor in DU145 Prostate Cancer Cells. UNMC Summer Undergraduate...Lynnette Lefall Date Published: Friday, August 6, 2010 Keidra Bryant – Abstract Effect of Metal Ion Chelators on Mannose 6-Phosphate/ Insulin ...chelators would inhibit this process in the insulin -like growth factor-responsive human prostate cancer cell line DU145. Cells were grown to 70-80

  1. Nebraska Prostate Cancer Research Program

    DTIC Science & Technology

    2012-05-01

    Expression in Prostate Cancer Cells Exposed to Heavy Metal Carcinogen. UNMC Summer Undergraduate Research Program, August 2010. • Keidra A. Bryant...Joseph R. Wheeler, Michelle A. Montgomery, and Richard G. MacDonald. (2010). Effect of Metal Ion Chelators on Mannose 6-Phosphate/Insulin-like... Effect of 4’-Bis-Thiosemicarbazide, a New Ribonucleotide Reductase Inhibitor, on Prostate Cancer Cell Proliferation. UNMC Summer Undergraduate Research

  2. Hyaluronan Biosynthesis in Prostate Cancer

    DTIC Science & Technology

    2006-01-01

    SUPPLEMENTARY NOTES 14. ABSTRACT: Despite advances in the diagnosis and treatment of prostate cancer in the last several years, metastasis represents the... metastasis to lymph nodes and bone. Metastasis to bone is especially noteworthy, not only because it reflects more advanced tumors, but also because of the...the growth and metastasis of androgen-independent tumors, it may be possible to better diagnose and treat prostate cancers by inhibiting growth of

  3. Molecular Imaging of Prostate Cancer

    PubMed Central

    Fox, Josef J.; Schöder, Heiko; Larson, Steven M.

    2015-01-01

    Purpose of review Prostate cancer is a complex and biologically heterogeneous disease that is not adequately assessed with conventional imaging alone. Molecular imaging with positron emission tomography (PET) is poised to fill this unmet need through noninvasive probing of the multiple molecular and cellular processes that are active in prostate cancer patients. Recent findings Several PET tracers are active in early and late stage prostate cancer in humans. F18-FDG, C11/F18-choline and F18-sodium fluoride (NaF) have been studied most extensively. There is a growing body of literature supporting to the utility of choline in early stage prostate cancer. FDG and NaF are more valuable in advanced disease, especially for assessing bone metastases, the prevalent form of metastases in this patient population. F18-Fluoro-dihydrotestosterone is active in castrate disease and is emerging as a valuable pharmacodynamic marker in the development of novel AR-targeted therapies. Anti-PSMA PET tracers are in the early stages of clinical development. Summary Multiple PET tracers are currently available to aid in the detection and management of prostate cancer across the clinical spectrum of the disease. Prospective, rigorously controlled, clinical imaging trials are needed to establish the optimal role of PET in prostate cancer. PMID:22617062

  4. Immunotherapy in metastatic prostate cancer

    PubMed Central

    Slovin, Susan F.

    2016-01-01

    Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit. PMID:27843208

  5. What we have learned from randomized trials of prostate cancer screening.

    PubMed

    Hoffman, Richard M; Smith, Anthony Y

    2011-05-01

    The introduction of prostate-specific antigen (PSA) for prostate cancer screening in the late 1980s led to an epidemic of prostate cancer, particularly in developed countries. However, the first valid reports from randomized controlled trials on the efficacy of screening were not published until 2009. Men in the screening group in the European Randomized Study of Screening for Prostate Cancer were 20% less likely than those in the control group to die from prostate cancer. The absolute difference was only 0.7/1000, implying that over 1400 men needed to be screened to prevent one prostate cancer death. Screening was also associated with a 70% increased risk for being diagnosed with prostate cancer. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial found no survival benefit for screening. Results were not conclusive because a substantial proportion of study subjects had previously undergone PSA testing, over half of the control group had PSA testing, follow-up was relatively short, and fewer than 100 subjects died from prostate cancer. Balancing the potential survival benefit from screening is the risk of overdiagnosis-finding cancers that would not otherwise cause clinical problems-and the risk of treatment complications, including urinary, sexual and bowel dysfunction. Prostate cancer screening efforts would benefit from improved biomarkers, which more readily identify clinically important cancers. Cancer control efforts might also need to include chemoprevention, though currently available agents are controversial. In the meantime, patients need to be supported in achieving informed decisions on whether to be screened for prostate cancer.

  6. Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment.

    PubMed

    Jordan, Brian C; Mock, Charlotta D; Thilagavathi, Ramasamy; Selvam, Chelliah

    2016-05-01

    Primary prostate cancer, also known as prostate adenocarcinoma (PCa), is a devastating cancer in men worldwide. Europe and developing countries of Asia have fewer reported cases of prostate cancer compared to increasing cases in the United States with higher incidence in Black men. Risk factors associated with prostate cancer are aging, genetics, lifestyle, high body mass index as well as carcinogenic exposure to carbon-containing fuels, tobacco, and charbroiled meats. Hormone therapy and radical prostatectomy are commonly implemented treatments. The >20.000 prostate cancer deaths of 2013 suggest that there exists a need for enhanced chemopreventive and therapeutic agents for prostate cancer treatment. Fruits, vegetables, and red wines contain high levels of polyphenolic levels. Consumption of these products may provide chemoprevetion of PCa. Curcumin, the major compound from the turmeric rhizome Curcuma longa has long been used for medicinal purposes as an antiseptic and wound healing. This review focuses on curcumin's therapeutic effectiveness in vitro and in vivo in prostate cancer models. The review will highlight the mechanisms of actions of curcumin in the signaling pathways of prostate cancer. Published by Elsevier Inc.

  7. Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis.

    PubMed

    Zhang, Ling; Ren, Xiaoyang; Alt, Eckhard; Bai, Xiaowen; Huang, Shaoyi; Xu, Zhengming; Lynch, Patrick M; Moyer, Mary P; Wen, Xian-Feng; Wu, Xiangwei

    2010-04-15

    Cancer chemoprevention uses natural, synthetic, or biological substances to reverse, suppress, or prevent either the initial phase of carcinogenesis or the progression of neoplastic cells to cancer. It holds promise for overcoming problems associated with the treatment of late-stage cancers. However, the broad application of chemoprevention is compromised at present by limited effectiveness and potential toxicity. To overcome these challenges, here we developed a new chemoprevention approach that specifically targets premalignant tumour cells for apoptosis. We show that a deficiency in the adenomatous polyposis coli (APC) gene and subsequent activation of beta-catenin lead to the repression of cellular caspase-8 inhibitor c-FLIP (also known as CFLAR) expression through activation of c-Myc, and that all-trans-retinyl acetate (RAc) independently upregulates tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors and suppresses decoy receptors. Thus, the combination of TRAIL and RAc induces apoptosis in APC-deficient premalignant cells without affecting normal cells in vitro. In addition, we show that short-term and non-continuous TRAIL and RAc treatment induce apoptosis specifically in intestinal polyps, strongly inhibit tumour growth, and prolong survival in multiple intestinal neoplasms C57BL/6J-Apc(Min)/J (Apc(Min)) mice. With our approach, we further demonstrate that TRAIL and RAc induce significant cell death in human colon polyps, providing a potentially selective approach for colorectal cancer chemoprevention by targeting APC-deficient cells for apoptosis.

  8. Lycopene: Redress for Prostate Cancer

    PubMed Central

    Pisipati, Sai Venkata Vedavyas; Pathapati, Harshavardhan; Bhukya, Ganesh; Nuthakki, Suresh; Chandu, Baburao; Nama, SreeKanth; Adeps, RajDev

    2012-01-01

    Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals. PMID:24826034

  9. Lycopene: redress for prostate cancer.

    PubMed

    Pisipati, Sai Venkata Vedavyas; Pathapati, Harshavardhan; Bhukya, Ganesh; Nuthakki, Suresh; Chandu, Baburao; Nama, SreeKanth; Adeps, RajDev

    2012-03-01

    Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals.

  10. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2016-12-01

    lipids in test controls. Key Metabolomics Research Accomplishments 1) Developed unbiased mass spectrometry methods to profile 500 lipids . 2) Completed...Award Number: W81XWH-12-1-0168 TITLE: Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer PRINCIPAL INVESTIGATOR: Jackilen...Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0168 5c. PROGRAM ELEMENT NUMBER

  11. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2016-11-01

    test controls. Key Metabolomics Research Accomplishments 1) Developed unbiased mass spectrometry methods to profile 500 lipids . 2) Completed...Award Number: W81XWH-12-1-0169 PC110361P1 TITLE: Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer PRINCIPAL INVESTIGATOR...SUBTITLE Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0169 5c. PROGRAM

  12. Prostate cancer: endogenous chemical castration.

    PubMed

    McCoy, Olugbemisola Oredein; Prasad, Michaella M; Singer, Natalie

    2016-04-28

    We report treatment of intermediate risk prostate cancer in a patient with a brief period of androgen deprivation secondary to a pituitary adenoma. This was a patient with intermediate risk prostate cancer diagnosed in the setting of an elevated prostate-specific antigen (PSA). The patient subsequently demonstrated a decline in PSA along with symptoms of hypogonadism and visual disturbance, and was consequently found to have a pituitary tumour. Trans-sphenoidal resection of the sellar mass was performed with normalisation of hormone profiles. The patient subsequently completed a course of radiation therapy for prostate cancer with PSA nadir to undetectable levels without evidence of biochemical recurrence at 7 months follow-up. 2016 BMJ Publishing Group Ltd.

  13. Sirolimus, Docetaxel, and Carboplatin in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

    ClinicalTrials.gov

    2016-11-10

    Castration Levels of Testosterone; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  14. Prostate cancer risk alleles are associated with prostate cancer volume and prostate size.

    PubMed

    Reinhardt, Daniel; Helfand, Brian T; Cooper, Phillip R; Roehl, Kimberly A; Catalona, William J; Loeb, Stacy

    2014-06-01

    Genome-wide association studies have identified an increasing number of single nucleotide polymorphisms associated with prostate cancer risk. Some of these genetic variants are also associated with serum prostate specific antigen levels and lower urinary tract symptoms, raising the question of whether they are truly prostate cancer biomarkers or simply lead to detection bias. Therefore, we determined whether single nucleotide polymorphisms associated with prostate cancer risk are more strongly associated with tumor or prostate volume. The genotypes of 38 validated prostate cancer risk single nucleotide polymorphisms were determined in 1,321 white men who underwent radical prostatectomy. Univariate and multivariate analyses were performed to compare the relationship of single nucleotide polymorphism frequency with total prostate and tumor volumes. On multivariate analysis 2 single nucleotide polymorphisms on chromosome 8q24, rs16901979 (A) and rs6983267 (G), were significantly associated with increased tumor volume (p=0.01 and 0.02, respectively). In contrast, rs17632542 (T) near the PSA gene on 19q13 was associated with significantly lower tumor volume and rs10788160 (A) on 10q26 was associated with significantly larger prostate volume (p=0.02 and 0.01, respectively). Analysis of 38 single nucleotide polymorphisms associated with prostate cancer risk revealed a significant association between several on chromosome 8q24 and increased tumor volume but not prostate volume. This suggests that they are bona fide markers of prostate cancer susceptibility and possibly more aggressive disease. Other prostate cancer risk alleles are associated with prostate specific antigen and increased prostate or decreased tumor volume, suggesting detection bias due to their phenotypic influence. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. The Danish Prostate Cancer Database

    PubMed Central

    Nguyen-Nielsen, Mary; Høyer, Søren; Friis, Søren; Hansen, Steinbjørn; Brasso, Klaus; Jakobsen, Erik Breth; Moe, Mette; Larsson, Heidi; Søgaard, Mette; Nakano, Anne; Borre, Michael

    2016-01-01

    Aim of database The Danish Prostate Cancer Database (DAPROCAdata) is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. Study population All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. Main variables The DAPROCAdata registers clinical data and selected characteristics for patients with prostate cancer at diagnosis. Data are collected from the linkage of nationwide health registries and supplemented with online registration of key clinical variables by treating physicians at urological and oncological departments. Main variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine therapy, and chemotherapy). Descriptive data In total, 22,332 patients with prostate cancer were registered in DAPROCAdata as of April 2015. A key feature of DAPROCAdata is the routine collection of patient-reported outcome measures (PROM), including data on quality-of-life (pain levels, physical activity, sexual function, depression, urine and fecal incontinence) and lifestyle factors (smoking, alcohol consumption, and body mass index). PROM data are derived from questionnaires distributed at diagnosis and at 1-year and 3-year follow-up. Hitherto, the PROM data have been limited by low completeness (26% among newly diagnosed patients in 2014). Conclusion DAPROCAdata is a comprehensive, yet still young clinical database. Efforts to improve data collection, data validity, and completeness are ongoing and of high priority. PMID:27843346

  16. Molecular therapeutics in prostate cancer.

    PubMed

    Nicholson, B; Theodorescu, D

    2003-01-01

    The purpose of this review is to provide information on the molecular basis of prostate cancer biology and to identify some of the targets for therapy, and highlight some potential strategies for molecular treatment. Here we give a synopsis of what we have learned regarding molecular biology of cancer in general and the directions research might take in the future in order to impact prostate cancer specifically. This work is certainly not encyclopedic in nature and we apologize in advance to colleagues whose work we were no able to include. Hope lies in learning to utilize some of these molecular workings for better prevention, diagnosis, and treatment of the most common solid organ cancer in men. Prostate cancer is a formidable disease and at current rates of diagnosis will affect one-in-six men living in the United States (Greenlee et al., 2000) Many of these men are diagnosed at an early stage of the disease and can be effectively treated by surgery or radiation. However, a significant fraction of men are diagnosed with later stage disease or progress despite early curative therapeutic attempts. Unfortunately, many of these men succumb to prostate cancer, as management options are limited and not always successful. Through an understanding of the molecular processes that occur in the development and progression of prostate cancer, novel therapies will arise that will provide longer survival, better quality of life, and a chance for cure in men afflicted with this disease.

  17. [The epidemiology of prostate cancer].

    PubMed

    Rébillard, Xavier; Tretarre, Brigitte; Villers, Arnauld

    2003-12-31

    Prostate cancer is a public health problem. Currently, it is the most frequent cause of cancer, and the second most common cause of cancer mortality, in men in most developed countries. Its incidence in France in 2000 is close to 40 000 new cases, a consistent increase of 7,9% per year. One man in 8 in France will be diagnosed with prostate cancer in the course of his life. More than half of these cancers are diagnosed before 75 years, most often at a localized stage accessible to a curative treatment. The increasing practice of PSA testing and systematic prostatic biopsies are responsible for this rise in incidence. The mortality is stable at around 10 000 per year in France. Hereditary risk factors permit a definition of a target population for screening. Environmental factors are little known, but a diet rich in fat seems to be associated with a more elevated risk.

  18. Prostate Cancer: Symptoms, Tests, and Treatment

    MedlinePlus

    ... Products For Consumers Home For Consumers Consumer Updates Prostate Cancer: Symptoms, Tests, and Treatment Share Tweet Linkedin Pin ... Linkedin Pin it Email Print Risk factors for prostate cancer include family history, age and race; but new ...

  19. Metabolic Risk Factors in Prostate Cancer

    PubMed Central

    Chu, David I.; Freedland, Stephen J.

    2010-01-01

    The biology of prostate cancer is influenced by the metabolic profile of each individual. We examine the evidence available interlinking prostate cancer with obesity, diabetes, and other metabolic syndrome components. PMID:21523712

  20. Chemopreventive effects of combination of honokiol and magnolol with α-santalol on skin cancer developments.

    PubMed

    Chilampalli, C; Zhang, X; Kaushik, R S; Young, A; Zeman, D; Hildreth, M B; Fahmy, H; Dwivedi, C

    2013-06-01

    α-Santalol is active component of sandalwood oil and has been shown to have chemopreventive effects against chemically and UVB-induced skin cancer development in mice. α-Santalol is also shown to have skin permeation enhancing effects. Honokiol and magnolol isolated from Magnolia officinalis bark extract have also been shown to have chemopreventive effects against chemically and UVB-induced skin cancer in mice. This study was conducted to investigate the combination effects of α-santalol, honokiol and magnolol to study any additive/synergistic effects to lower the doses required for chemoprevention. Pretreatment of combinations of α-santalol with honokiol and magnolol significantly decreased tumor multiplicity upto 75% than control, α-santalol, honokiol and magnolol alone in SKH-1 mice. Combination of α-santalol with honokiol and magnolol also decreased cell viability, proliferation, and enhanced apotosis in comparison to α-santalol, honokiol and magnolol alone in Human epidrmoid carcinoma A431 cells. Overall, the results of present study indicated combinations of α-santalol with honokiol and magnolol could provide chemoprevention of skin cancer at lower doses than given alone.

  1. Prostate cancer gene 3 urine assay for prostate cancer in Japanese men undergoing prostate biopsy.

    PubMed

    Ochiai, Atsushi; Okihara, Koji; Kamoi, Kazumi; Iwata, Tsuyoshi; Kawauchi, Akihiro; Miki, Tsuneharu; Fors, Zephyr

    2011-03-01

    To examine the clinical utility of the prostate cancer gene 3 (PCA3) urine test in predicting prostate cancer in Japanese men undergoing prostate biopsy. The study group included 105 men who underwent extended prostate biopsy based on an elevated serum prostate-specific antigen (PSA). In all cases, the patients' race was Asian. Urine specimens were collected after digital rectal examination, and PCA3 score (PCA3/PSA mRNA) was determined in the urine using the APTIMA PCA3 assay. PCA3 score was investigated for a correlation with serum PSA, prostate volume (PV), PSA density and biopsy outcome. All urine samples collected were successfully analyzed (i.e. the informative specimen rate was 100%). Biopsy showed prostate cancer in 38 men (36%). The PCA3 score was not associated with serum PSA nor PV. The median PCA3 score in prostate cancer was significantly higher than that in negative biopsy (59.5 vs 14.2 P<0.0001). The probability of prostate cancer was 69% at a PCA3 score of more than 50 and 5% at a PCA3 score of less than 20. On multivariable logistic regression, PSA density (P<0.05) and PCA3 score (P<0.0001) were the independent predictors for prostate cancer. There was no significant difference in AUC between PCA3 score and PSA density. The combination of PCA3 score and PSA density increased the AUC from 0.72 for PSA alone to 0.88. The specificity of the PCA3 urine assay for prostate cancer was excellent in Japanese men undergoing biopsy. PCA3 score could improve the prediction for prostate cancer and help to better select men who might benefit from prostate biopsy. © 2011 The Japanese Urological Association.

  2. Height and Prostate Cancer Risk

    PubMed Central

    Zuccolo, Luisa; Harris, Ross; Gunnell, David; Oliver, Steven; Lane, Jane Athene; Davis, Michael; Donovan, Jenny; Neal, David; Hamdy, Freddie; Beynon, Rebecca; Savovic, Jelena; Martin, Richard Michael

    2008-01-01

    Background Height, a marker of childhood environmental exposures, is positively associated with prostate cancer risk, perhaps through the insulin-like growth factor system. We investigated the relationship of prostate cancer with height and its components (leg and trunk length) in a nested case-control study and with height in a dose-response meta-analysis. Methods We nested a case-control study within a population-based randomized controlled trial evaluating treatments for localized prostate cancer in British men ages 50 to 69 years, including 1,357 cases detected through prostate-specific antigen testing and 7,990 controls (matched on age, general practice, assessment date). Nine bibliographic databases were searched systematically for studies on the height-prostate cancer association that were pooled in a meta-analysis. Results Based on the nested case-control, the odds ratio (OR) of prostate-specific antigen-detected prostate cancer per 10 cm increase in height was 1.06 [95% confidence interval (95% CI): 0.97-1.16; ptrend = 0.2]. There was stronger evidence of an association of height with high-grade prostate cancer (OR: 1.23; 95% CI: 1.06-1.43), mainly due to the leg component, but not with low-grade disease (OR: 0.99; 95% CI: 0.90-1.10). In general, associations with leg or trunk length were similar. A meta-analysis of 58 studies found evidence that height is positively associated with prostate cancer (random-effects OR per 10 cm: 1.06; 95% CI: 1.03-1.09), with a stronger effect for prospective studies of more advanced/aggressive cancers (random-effects OR: 1.12; 95% CI: 1.05-1.19). Conclusion These data indicate a limited role for childhood environmental exposures—as indexed by adult height—on prostate cancer incidence, while suggesting a greater role for progression, through mechanisms requiring further investigation. PMID:18768501

  3. An Overview of Ultraviolet B Radiation-Induced Skin Cancer Chemoprevention by Silibinin

    PubMed Central

    Kumar, Rahul; Deep, Gagan; Agarwal, Rajesh

    2015-01-01

    Skin cancer incidences are rising worldwide, and one of the major causative factors is excessive exposure to solar ultraviolet radiation (UVR). Annually, ~5 million skin cancer patients are treated in United States, mostly with nonmelanoma skin cancer (NMSC), which is also frequent in other Western countries. As sunscreens do not provide adequate protection against deleterious effects of UVR, additional and alternative chemoprevention strategies are urgently needed to reduce skin cancer burden. Over the last couple of decades, extensive research has been conducted to understand the molecular basis of skin carcinogenesis, and to identifying novel agents which could be useful in the chemoprevention of skin cancer. In this regard, several natural non-toxic compounds have shown promising efficacy in preventing skin carcinogenesis at initiation, promotion and progression stages, and are considered important in better management of skin cancer. Consistent with this, we and others have studied and established the notable efficacy of natural flavonolignan silibinin against UVB-induced skin carcinogenesis. Extensive pre-clinical animal and cell culture studies report strong anti-inflammatory, anti-oxidant, DNA damage repair, immune-modulatory and anti-proliferative properties of silibinin. Molecular studies have identified that silibinin targets pleotropic signaling pathways including mitogenic, cell cycle, apoptosis, autophagy, p53, NF-κB, etc. Overall, the skin cancer chemopreventive potential of silibinin is well supported by comprehensive mechanistic studies, suggesting its greater use against UV-induced cellular damages and photocarcinogenesis. PMID:26097804

  4. Epigenetics of prostate cancer.

    PubMed

    McKee, Tawnya C; Tricoli, James V

    2015-01-01

    The introduction of novel technologies that can be applied to the investigation of the molecular underpinnings of human cancer has allowed for new insights into the mechanisms associated with tumor development and progression. They have also advanced the diagnosis, prognosis and treatment of cancer. These technologies include microarray and other analysis methods for the generation of large-scale gene expression data on both mRNA and miRNA, next-generation DNA sequencing technologies utilizing a number of platforms to perform whole genome, whole exome, or targeted DNA sequencing to determine somatic mutational differences and gene rearrangements, and a variety of proteomic analysis platforms including liquid chromatography/mass spectrometry (LC/MS) analysis to survey alterations in protein profiles in tumors. One other important advancement has been our current ability to survey the methylome of human tumors in a comprehensive fashion through the use of sequence-based and array-based methylation analysis (Bock et al., Nat Biotechnol 28:1106-1114, 2010; Harris et al., Nat Biotechnol 28:1097-1105, 2010). The focus of this chapter is to present and discuss the evidence for key genes involved in prostate tumor development, progression, or resistance to therapy that are regulated by methylation-induced silencing.

  5. Urine biomarkers in prostate cancer.

    PubMed

    Ploussard, Guillaume; de la Taille, Alexandre

    2010-02-01

    The deficiencies of serum PSA as a prostate-cancer-specific diagnostic test are well recognized. Thus, the development of novel biomarkers for prostate cancer detection remains an important and exciting challenge. Noninvasive urine-based tests are particularly attractive candidates for large-scale screening protocols, and biomarker discovery programs using urine samples have emerged for detecting and predicting aggressiveness of prostate cancer. Some new biomarkers already outperform serum PSA in the diagnosis of this disease. Currently, the PCA3 (prostate cancer antigen 3) urine test is probably the best adjunct to serum PSA for predicting biopsy outcome, and has proven its clinical relevance by surpassing the predictive abilities of traditional serum biomarkers. New research methods are also emerging, and high-throughput technologies will facilitate high-dimensional biomarker discovery. Future approaches will probably integrate proteomic, transcriptomic and multiplex approaches to detect novel biomarkers, and aim to identify combinations of multiple biomarkers to optimize the detection of prostate cancer. In addition, an unmet need remains for markers that differentiate indolent from aggressive cancers, to better inform treatment decisions.

  6. Proton therapy for prostate cancer.

    PubMed

    Hoppe, Bradford; Henderson, Randal; Mendenhall, William M; Nichols, Romaine C; Li, Zuofeng; Mendenhall, Nancy P

    2011-06-01

    Proton therapy has been used in the treatment of cancer for over 50 years. Due to its unique dose distribution with its spread-out Bragg peak, proton therapy can deliver highly conformal radiation to cancers located adjacent to critical normal structures. One of the important applications of its use is in prostate cancer, since the prostate is located adjacent to the rectum and bladder. Over 30 years of data have been published on the use of proton therapy in prostate cancer; these data have demonstrated high rates of local and biochemical control as well as low rates of urinary and rectal toxicity. Although before 2000 proton therapy was available at only a couple of centers in the United States, several new proton centers have been built in the last decade. With the increased availability of proton therapy, research on its use for prostate cancer has accelerated rapidly. Current research includes explorations of dose escalation, hypofractionation, and patient-reported quality-of-life outcomes. Early results from these studies are promising and will likely help make proton therapy for the treatment of prostate cancer more cost-effective.

  7. Active surveillance for prostate cancer.

    PubMed

    Romero-Otero, Javier; García-Gómez, Borja; Duarte-Ojeda, José M; Rodríguez-Antolín, Alfredo; Vilaseca, Antoni; Carlsson, Sigrid V; Touijer, Karim A

    2016-03-01

    It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized.

  8. Reconstructing the Prostate Cancer Transcriptional Regulatory Network

    DTIC Science & Technology

    2010-07-01

    TITLE: Reconstructing the prostate cancer transcriptional regulatory network PRINCIPAL INVESTIGATOR: Keyan Salari...CONTRACT NUMBER 4. TITLE AND SUBTITLE Reconstructing the prostate cancer transcriptional regulatory network 5b. GRANT NUMBER W81XWH-09-1...of this study is to reconstruct the prostate cancer transcriptional regulatory network and to experimentally validate novel, clinically-relevant

  9. Counseling the Client with Prostate Cancer.

    ERIC Educational Resources Information Center

    Curtis, Russell C.; Juhnke, Gerald A.

    2003-01-01

    Prostate cancer is prevalent in the United States and has a far-reaching effect on men and their relationships. Being diagnosed with and treated for prostate cancer often causes men to experience side effects that induce physical, emotional, and social change. Counselors need to be aware of prostate cancer's impact on men and their families.…

  10. Counseling the Client with Prostate Cancer.

    ERIC Educational Resources Information Center

    Curtis, Russell C.; Juhnke, Gerald A.

    2003-01-01

    Prostate cancer is prevalent in the United States and has a far-reaching effect on men and their relationships. Being diagnosed with and treated for prostate cancer often causes men to experience side effects that induce physical, emotional, and social change. Counselors need to be aware of prostate cancer's impact on men and their families.…

  11. Prostate cancer brachytherapy: guidelines overview.

    PubMed

    Wojcieszek, Piotr; Białas, Brygida

    2012-06-01

    Prostate cancer, due to wide availability of PSA tests, is very often diagnosed in early stage, nowadays. This makes management of this disease even harder in every day oncology care. There is a wide range of treatment options including surgery, radiotherapy and active surveillance, but essential question is which treatment patient and oncologist should decide for. Due to recent publication of Prostate Cancer Results Study Group, in which brachytherapy is one of supreme curative options for prostate cancer, we decided to overview most present european and north american recommendations. National Comprehensive Cancer Network, American Society for Radiation Oncology, American Brachytherapy Society, European Association of Urology and Groupe Européen de Curiethérapie of European Society for Therapeutic Radiation Oncology guidelines are overviewed, particularly focusing on HDR and LDR brachytherapy.

  12. Prostate cancer brachytherapy: guidelines overview

    PubMed Central

    Białas, Brygida

    2012-01-01

    Prostate cancer, due to wide availability of PSA tests, is very often diagnosed in early stage, nowadays. This makes management of this disease even harder in every day oncology care. There is a wide range of treatment options including surgery, radiotherapy and active surveillance, but essential question is which treatment patient and oncologist should decide for. Due to recent publication of Prostate Cancer Results Study Group, in which brachytherapy is one of supreme curative options for prostate cancer, we decided to overview most present european and north american recommendations. National Comprehensive Cancer Network, American Society for Radiation Oncology, American Brachytherapy Society, European Association of Urology and Groupe Européen de Curiethérapie of European Society for Therapeutic Radiation Oncology guidelines are overviewed, particularly focusing on HDR and LDR brachytherapy. PMID:23349655

  13. Prostate Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  14. Polyamines as mediators of APC-dependent intestinal carcinogenesis and cancer chemoprevention

    PubMed Central

    Rial, Nathaniel S.; Meyskens, Frank L.; Gerner, Eugene W.

    2013-01-01

    Combination chemoprevention for cancer was proposed a quarter of a century ago, but has not been implemented in standard medical practice owing to limited efficacy and toxicity. Recent trials have targeted inflammation and polyamine biosynthesis, both of which are increased in carcinogenesis. Preclinical studies have demonstrated that DFMO (difluoromethylornithine), an irreversible inhibitor of ODC (ornithine decarboxylase) which is the first enzyme in polyamine biosynthesis, combined with NSAIDs (non-steroidal anti-inflammatory drugs) suppresses colorectal carcinogenesis in murine models. The preclinical rationale for combination chemoprevention with DFMO and the NSAID sulindac, was strengthened by the observation that a SNP (single nucleotide polymorphism) in the ODC promoter was prognostic for adenoma recurrence in patients with prior sporadic colon polyps and predicted reduced risk of adenoma in those patients taking aspirin. Recent results from a phase III clinical trial showed a dramatic reduction in metachronous adenoma number, size and grade. Combination chemoprevention with DFMO and sulindac was not associated with any serious toxicity. A non-significant trend in subclinical ototoxicity was detected by quantitative audiology in a subset of patients identified by a genetic marker. These preclinical, translational and clinical data provide compelling evidence for the efficacy of combination chemoprevention. DFMO and sulindac is a rational strategy for the prevention of metachronous adenomas, especially in patients with significant risk for colorectal cancer. Toxicities from this combination may be limited to subsets of patients identified by either past medical history or clinical tests. PMID:20095973

  15. Evaluation of chemoprevention of oral cancer with Spirulina fusiformis.

    PubMed

    Mathew, B; Sankaranarayanan, R; Nair, P P; Varghese, C; Somanathan, T; Amma, B P; Amma, N S; Nair, M K

    1995-01-01

    The blue-green microalgae Spirulina, used in daily diets of natives in Africa and America, have been found to be a rich natural source of proteins, carotenoids, and other micronutrients. Experimental studies in animal models have demonstrated an inhibitory effect of Spirulina algae on oral carcinogenesis. Studies among preschool children in India have demonstrated Spirulina fusiformis (SF) to be an effective source of dietary vitamin A. We evaluated the chemopreventive activity of SF (1 g/day for 12 mos) in reversing oral leukoplakia in pan tobacco chewers in Kerala, India. Complete regression of lesions was observed in 20 of 44 (45%) evaluable subjects supplemented with SF, as opposed to 3 of 43 (7%) in the placebo arm (p < 0.0001). When stratified by type of leukoplakia, the response was more pronounced in homogeneous lesions: complete regression was seen in 16 of 28 (57%) subjects with homogeneous leukoplakia, 2 of 8 with erythroplakia, 2 of 4 with verrucous leukoplakia, and 0 of 4 with ulcerated and nodular lesions. Within one year of discontinuing supplements, 9 of 20 (45%) complete responders with SF developed recurrent lesions. Supplementation with SF did not result in increased serum concentration of retinol or beta-carotene, nor was it associated with toxicity. This is the first human study evaluating the chemopreventive potential of SF. More studies in different settings and different populations are needed for further evaluation.

  16. Natural history of prostate cancer.

    PubMed

    Estebanez, Javier; Teyrouz, Antoin; Gutierrez, Miguel Angel; Linazasoro, Ione; Belloso, Jon; Cano, Carlos; Peralta, Jose Maria; Sanz, Juan Pablo

    2014-06-01

    Prostatic cancer can be a silent tumor, with no symptoms remaining undetectable throughout life . But when it keeps growing, enough to produce symptoms such as bladder neck obstruction, invasion of adjacent organs or distant metastasis, curative treatment is usually impossible. Since PSA emerges, data shows a dramatic increasing in the diagnosis of prostatic cancer, specially low risk tumor. Since then, We are wondering which tumors are suitable to be treated and which ones remain asymptomatic without treatment. Analysing the natural history of prostate cancer, helps us to choose the best atitude treating the tumor, this subjet has been in constant discusión in the last decade. Our article consistes of a reviewing the main publications treating natural history of prostate cancer in prehyphen;and post-PSA era. The indicated studied suggest that most prostate tumors diagnosed today are low grade cancer, as a result with a low mortality. This conclusión shows us the importance of modifying the algorithm of treatment of these tumors.

  17. Detection of DNA viruses in prostate cancer.

    PubMed

    Smelov, Vitaly; Bzhalava, Davit; Arroyo Mühr, Laila Sara; Eklund, Carina; Komyakov, Boris; Gorelov, Andrey; Dillner, Joakim; Hultin, Emilie

    2016-04-28

    We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions.

  18. National Cancer Institute Prostate Cancer Genetics Workshop.

    PubMed

    Catalona, William J; Bailey-Wilson, Joan E; Camp, Nicola J; Chanock, Stephen J; Cooney, Kathleen A; Easton, Douglas F; Eeles, Rosalind A; FitzGerald, Liesel M; Freedman, Matthew L; Gudmundsson, Julius; Kittles, Rick A; Margulies, Elliott H; McGuire, Barry B; Ostrander, Elaine A; Rebbeck, Timothy R; Stanford, Janet L; Thibodeau, Stephen N; Witte, John S; Isaacs, William B

    2011-05-15

    Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness--one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics. ©2011 AACR

  19. Decision making in the context of breast cancer chemoprevention: patient perceptions and the meaning of risk.

    PubMed

    Holmberg, Christine

    2015-01-01

    Chemoprevention with selective estrogen receptor modulators (SERMs) is considered one of the most promising risk reduction options to date in the United States. Tamoxifen and raloxifene are both approved by the U.S. Food and Drug Administration (FDA) for breast cancer risk reduction. However, despite endorsement from the American Society for Clinical Oncology and the National Comprehensive Cancer Network, uptake remains low. Decision aids have been successful in improving women's understanding and knowledge about the risk-benefit trade-offs in decision making regarding SERMs. However, increased knowledge does not lead to increased uptake of chemoprevention for the purpose of reducing breast cancer risk; instead, women become more reluctant to take medication that is itself associated with risks. Reasons for this include a lack of awareness that SERMs are effective in reducing breast cancer risk, an unwillingness to increase the risk of other disease, reluctance to take a daily medication, and the perception of tamoxifen as a "cancer drug." In studies on hypothetical decision making in the context of chemoprevention women indicate greater willingness to take a SERM when they are determined to be at risk. These findings suggest a differential understanding of what risk means among the general public, health professionals, and researchers. Feeling at risk is related to bodily signs and symptoms and not to population-derived probabilities. Such differential understanding may in part explain women's perception of the low efficacy of SERMs and their decision making regarding SERM use.

  20. Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus.

    PubMed

    Sun, Guochuan; Zheng, Zongping; Lee, Mee-Hyun; Xu, Yijuan; Kang, Soouk; Dong, Zigang; Wang, Mingfu; Gu, Zhennan; Li, Haitao; Chen, Wei

    2017-05-03

    Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.

  1. Injectable Sustained Release Microparticles of Curcumin: A New Concept for Cancer Chemoprevention

    PubMed Central

    Shahani, Komal; Swaminathan, Suresh Kumar; Freeman, Diana; Blum, Angela; Ma, Linan; Panyam, Jayanth

    2010-01-01

    Poor oral bioavailability limits the use of curcumin and other dietary polyphenols in the prevention and treatment of cancer. Minimally invasive strategies that can provide effective and sustained tissue concentrations of these agents will be highly valuable tools in the fight against cancer. The objective of this study was to investigate the use of an injectable sustained release microparticle formulation of curcumin as a novel approach to breast cancer chemoprevention. A biodegradable and biocompatible polymer, poly(D,L-lactide-co-glycolide) (PLGA), was used to fabricate curcumin microparticles. When injected subcutaneously in mice, a single dose of microparticles sustained curcumin levels in the blood and other tissues for nearly a month. Curcumin levels in the lungs and brain, frequent sites of breast cancer metastases, were 10-30-fold higher than that in the blood. Further, curcumin microparticles showed marked anticancer efficacy in nude mice bearing MDA-MB-231 xenografts compared to other controls. Repeated systemic injections of curcumin were not effective in inhibiting tumor growth. Treatment with curcumin microparticles resulted in diminished VEGF expression and poorly developed tumor microvessels, indicating a significant effect on tumor angiogenesis. These results suggest that sustained delivery of chemopreventives such as curcumin using polymeric microparticles is a promising new approach to cancer chemoprevention and therapy. PMID:20460537

  2. The Prostate Cancer Biorepository Network (PCBN)

    DTIC Science & Technology

    2016-10-01

    embedded material and tissue microarrays (TMAs)), prostate cancer patient derived xenografts (PDX) and derived specimens ( DNA and RNA) from prostate...derived RNA and DNA where required. Specimens were made available to prostate cancer researchers through the PCBN. 15. SUBJECT TERMS Biorepository...and derived specimens ( DNA and RNA) from prostate cancer patients; these specimens are linked to clinical and outcome data and supported by an

  3. A review of animal model studies of tomato carotenoids, lycopene, and cancer chemoprevention.

    PubMed

    Cohen, Leonard A

    2002-11-01

    There are relatively few reports on the cancer chemopreventive effects of lycopene or tomato carotenoids in animal models. The majority, but not all, of these studies indicate a protective effect. Inhibitory effects were reported in two studies using aberrant crypt foci, an intermediate lesion leading to colon cancer, as an end point and in two mammary tumor studies, one using the dimethylbenz(a)anthracene model, and the other the spontaneous mouse model. Inhibitory effects were also reported in mouse lung and rat hepatocarcinoma and bladder cancer models. However, a report from the author's laboratory found no effect in the N-nitrosomethylurea-induced mammary tumor model when crystalline lycopene or a lycopene-rich tomato carotenoid oleoresin was administered in the diet. Unfortunately, because of differences in routes of administration (gavage, intraperitoneal injection, intra-rectal instillation, drinking water, and diet supplementation), species and strain differences, form of lycopene (pure crystalline, beadlet, mixed carotenoid suspension), varying diets (grain-based, casein based) and dose ranges (0.5-500 ppm), no two studies are comparable. It is clear that the majority of ingested lycopene is excreted in the feces and that 1000-fold more lycopene is absorbed and stored in the liver than accumulates in other target organs. Nonetheless, physiologically significant (nanogram) levels of lycopene are assimilated by key organs such as breast, prostate, lung, and colon, and there is a rough dose-response relationship between lycopene intake and blood levels. Pure lycopene was absorbed less efficiently than the lycopene-rich tomato carotenoid oleoresin and blood levels of lycopene in rats fed a grain-based diet were consistently lower than those in rats fed lycopene in a casein-based diet. The latter suggests that the matrix in which lycopene is incorporated is an important determinant of lycopene uptake. A number of issues remain to be resolved before any

  4. Metastatic Prostate Cancer of Hand

    PubMed Central

    Oshima, Koji; Ishimaru, Daichi; Nishimoto, Yutaka; Ohno, Yoshiyuki; Hirakawa, Akihiro; Miyazaki, Tatsuhiko; Akiyama, Haruhiko

    2016-01-01

    Soft tissue metastases of prostate cancer to other sites are extremely rare, and, to our best knowledge, there have been no reports of metastasis to soft tissue of the hand. A 63-year-old man was diagnosed with prostatic cancer. During treatment, bone and soft tissue metastases to the right hand, appearing in the first web space, were observed. The tumor was resected, along with both the first and second metacarpal bones. The thumb was reconstructed by pollicization of the remaining index finger, enabling the patient to use the pollicized thumb for activities of daily living. This is the first case report of prostate cancer metastasizing to the soft tissue in hand. After wide resection, pollicization was able to reconstruct a functional hand and thumb. PMID:27843661

  5. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2014-05-01

    institutions. A major project in the lab is targeted therapy of prostate cancer using PSMA-guided aptamers. Prabhat Goswami, PhD; Professor...derived dendritic cell (DC) and T cell functional deficiencies. Long-term goals are to develop novel, immune-based therapies for advanced solid tumors...and radiolabeling of peptides and small molecules for small molecule cancer therapy , molecular imaging, and radionuclide therapy for cancer. He

  6. The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer

    PubMed Central

    Loeb, Stacy; Sanda, Martin G.; Broyles, Dennis L.; Shin, Sanghyuk S.; Bangma, Chris H.; Wei, John T.; Partin, Alan W.; Klee, George G.; Slawin, Kevin M.; Marks, Leonard S.; van Schaik, Ron H. N.; Chan, Daniel W.; Sokoll, Lori J.; Cruz, Amabelle B.; Mizrahi, Isaac A.; Catalona, William J.

    2015-01-01

    Purpose The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. Materials and Methods From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, [-2]proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. Results The Prostate Health Index was significantly higher in men with Gleason 7 or greater and “Epstein significant” cancer. On receiver operating characteristic analysis phi had the highest AUC for overall cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, [-2]proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) and significant cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, [-2]proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. Conclusions The new phi test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis. PMID:25463993

  7. Statins in the chemoprevention of colorectal cancer in established animal models of sporadic and colitis-associated cancer.

    PubMed

    Pikoulis, Emmanouil; Margonis, Georgios A; Angelou, Anastasios; Zografos, George C; Antoniou, Efstathios

    2016-03-01

    Despite the availability of effective surveillance for colorectal cancer with colonoscopy, chemoprevention might be an acceptable alternative. Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins have been found to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. This systematic review aimed to gather information on the possible chemopreventive role of statins in preventing carcinogenesis and tumor promotion by a diverse array of mechanisms in both sporadic and colitis-associated cancer in animal models. The MEDLINE database was thoroughly searched using the following keywords: 'statin, HMG-CoA reductase inhibitor, colon cancer, mice, rats, chemoprevention, colitis-associated cancer'. Additional articles were gathered and evaluated. There are a lot of clinical studies and meta-analyses, as well as a plethora of basic research studies implementing cancer cell lines and animal models, on the chemopreventive role of statins in colorectal cancer (CRC). However, data derived from clinical studies are inconclusive, yet they show a tendency toward a beneficial role of statins against CRC pathogenesis. Thus, more research on the molecular pathways of CRC tumorigenesis as related to statins is warranted to uncover new mechanisms and compare the effect of statins on both sporadic and colitis-associated cancer in animal models. Basic science results could fuel exclusive colitis-associated cancer clinical trials to study the chemopreventive effects of statins and to differentiate between their effects on the two types of CRCs in humans.

  8. In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis

    DTIC Science & Technology

    2005-03-01

    selenium, finasteride , DNA damage, animal model 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18. NUMBER 19a. NAME OF RESPONSIBLE PERSON OF ABSTRACT...treatment with the 5-alpha reductase inhibitor finasteride (with or without selenium) induces prostatic atrophy without significantly reducing the...the prostate (using the 5ot-reductase inhibitor finasteride ) significantly influences the response of the aging prostate to selenium supplementation

  9. Linking obesogenic dysregulation to prostate cancer progression

    PubMed Central

    Taylor, Renea A; Lo, Jennifer; Ascui, Natasha; Watt, Matthew J

    2015-01-01

    The global epidemic of obesity is closely linked to the development of serious co-morbidities, including many forms of cancer. Epidemiological evidence consistently shows that obesity is associated with a similar or mildly increased incidence of prostate cancer but, more prominently, an increased risk for aggressive prostate cancer and prostate cancer-specific mortality. Studies in mice demonstrate that obesity induced by high-fat feeding increases prostate cancer progression; however, the mechanisms underpinning this relationship remain incompletely understood. Adipose tissue expansion in obesity leads to local tissue dysfunction and is associated with low-grade inflammation, alterations in endocrine function and changes in lipolysis that result in increased delivery of fatty acids to tissues of the body. The human prostate gland is covered anteriorly by the prominent peri-prostatic adipose tissue and laterally by smaller adipose tissue depots that lie directly adjacent to the prostatic surface. We discuss how the close association between dysfunctional adipose tissue and prostate epithelial cells might result in bi-directional communication to cause increased prostate cancer aggressiveness and progression. However, the literature indicates that several ‘mainstream’ hypotheses regarding obesity-related drivers of prostate cancer progression are not yet supported by a solid evidence base and, in particular, are not supported by experiments using human tissue. Understanding the links between obesity and prostate cancer will have major implications for the health policy for men with prostate cancer and the development of new therapeutic or preventative strategies. PMID:26581226

  10. Prostate cancer immunotherapy: beyond immunity to curability.

    PubMed

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials.

  11. [Markers of prostate cancer stem cells: research advances].

    PubMed

    Wang, Shun-Qi; Huang, Sheng-Song

    2013-12-01

    Prostate cancer is one of the most seriously malignant diseases threatening men's health, and the mechanisms of its initiation and progression are not yet completely understood. Recent years have witnessed distinct advances in researches on prostate cancer stem cells in many aspects using different sources of materials, such as human prostate cancer tissues, human prostate cancer cell lines, and mouse models of prostate cancer. Prostate cancer stem cell study offers a new insight into the mechanisms of the initiation and progression of prostate cancer and contributes positively to its treatment. This article presents an overview on the prostate cancer stem cell markers utilized in the isolation and identification of prostate cancer stem cells.

  12. Hormonal therapy of prostate cancer.

    PubMed

    Labrie, Fernand

    2010-01-01

    Of all cancers, prostate cancer is the most sensitive to hormones: it is thus very important to take advantage of this unique property and to always use optimal androgen blockade when hormone therapy is the appropriate treatment. A fundamental observation is that the serum testosterone concentration only reflects the amount of testosterone of testicular origin which is released in the blood from which it reaches all tissues. Recent data show, however, that an approximately equal amount of testosterone is made from dehydroepiandrosterone (DHEA) directly in the peripheral tissues, including the prostate, and does not appear in the blood. Consequently, after castration, the 95-97% fall in serum testosterone does not reflect the 40-50% testosterone (testo) and dihydrotestosterone (DHT) made locally in the prostate from DHEA of adrenal origin. In fact, while elimination of testicular androgens by castration alone has never been shown to prolong life in metastatic prostate cancer, combination of castration (surgical or medical with a gonadotropin-releasing hormone (GnRH) agonist) with a pure anti-androgen has been the first treatment shown to prolong life. Most importantly, when applied at the localized stage, the same combined androgen blockade (CAB) can provide long-term control or cure of the disease in more than 90% of cases. Obviously, since prostate cancer usually grows and metastasizes without signs or symptoms, screening with prostate-specific antigen (PSA) is absolutely needed to diagnose prostate cancer at an 'early' stage before metastasis occurs and the cancer becomes non-curable. While the role of androgens was believed to have become non-significant in cancer progressing under any form of androgen blockade, recent data have shown increased expression of the androgen receptor (AR) in treatment-resistant disease with a benefit of further androgen blockade. Since the available anti-androgens have low affinity for AR and cannot block androgen action completely

  13. Ethanolic extract of Brazilian green propolis sensitizes prostate cancer cells to TRAIL-induced apoptosis.

    PubMed

    Szliszka, Ewelina; Zydowicz, Grzegorz; Janoszka, Beata; Dobosz, Cezary; Kowalczyk-Ziomek, Grazyna; Krol, Wojciech

    2011-04-01

    Prostate cancer represents an ideal disease for chemopreventive intervention. Propolis possesses immuno-modulatory, anti-tumour and chemopreventive properties. The tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is an important endogenous anti-cancer agent that induces apoptosis selectively in tumour cells. However, some cancer cells are resistant to TRAIL-mediated apoptosis. Naturally occurring phenolic and polyphenolic compounds sensitize TRAIL-resistant cancer cells and augment the apoptotic activity of TRAIL. The ethanolic extract of Brazilian green propolis (EEP) is rich in phenolic components. Our in vitro results indicate the potential targets in the TRAIL-induced apoptotic pathway for the cancer chemopreventive activity of Brazilian propolis. We examined the cytotoxic and apoptotic effects of Brazilian EEP and its bioactive components in combination with TRAIL on LNCaP prostate cancer cells. The chemical composition of Brazilian green propolis was determined by high performance liquid chromatography-diode array detection. The cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl-tetrazolium and lactate dehydrogenase assays. Apoptosis was detected using annexin V-FITC by flow cytometry and fluorescence microscopy. The mitochondrial membrane potential (∆Ψm) was evaluated using DePsipher staining by fluorescence microscopy. Flow cytometry was used to analyse death receptor (TRAIL-R1 and TRAIL-R2) expression in LNCaP cells. The inhibition of nuclear factor-κB (NF-κB) (p65) activation in cancer cells was confirmed by the ELISA-based TransAM NF-κB kit. The LNCaP cells were shown to be resistant to TRAIL-induced apoptosis. Our study demonstrates that EEP sensitizes TRAIL-resistant prostate cancer cells. The main phenolic components detected in Brazilian green propolis are artepillin C, quercetin, kaempferol and p-coumaric acid. Brazilian propolis and its bioactive components markedly augmented TRAIL-mediated apoptosis and

  14. Chemoprevention with phytonutrients and microalgae products in chronic inflammation and colon cancer.

    PubMed

    Talero, Elena; Ávila-Roman, Javier; Motilva, Virginia

    2012-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder caused by deregulated immune responses in a genetically predisposed individual. This is a complex process mediated by cytokines, chemokines, adhesion molecules, cytoplasm nuclear receptors, among others. Recent data support a participation of the endoplasmic reticulum (ER) stress and mitochondrial dysfunctions in IBD. Moreover, now it is evident that chronic degenerative pathologies, including IBD, share comparable disease mechanisms at the cellular level with alteration of the autophagy mechanisms. Mounting evidence suggests that the risk of developing colorectal cancer (CRC) is dramatically increased in patients with chronic inflammatory disease. Chronic inflammation in IBD exposes these patients to a number of signals known to have tumorigenic effects including nuclear factor kappa B (NF-κB) activation, proinflammatory cytokines and prostaglandins release and reactive oxygen species (ROS) production. Chemoprevention consists in the use of drugs, vitamins, or nutritional supplements to reduce the risk of developing, or having a recurrence of cancer. Numerous in vitro and animal studies have established the potential colon cancer chemopreventive properties of phytochemicals derived from both plants (curcumin, resveratrol, epigallocatechin gallate, quercetin or genistein) and substances from marine environment, including microalgae species and their products. This review summarizes the mechanisms by which these naturally occurring compounds may mediate chemopreventive effects on cancer. These actions include induction of cell cycle arrest and apoptosis, inhibition of cell proliferation, stimulation of antimetastatic and antiangiogenic responses and increased antioxidant and anti-inflammatory activity.

  15. Obesity and prostate enlargement in men with localized prostate cancer.

    PubMed

    Kopp, Ryan P; Han, Misop; Partin, Alan W; Humphreys, Elizabeth; Freedland, Stephen J; Parsons, J Kellogg

    2011-12-01

    What's known on the subject? and What does the study add? Obesity is associated with prostate enlargement in men without prostate cancer. This study demonstrates an association between obesity and prostate enlargement in men with prostate cancer, and leads to possible implications for prostate cancer screening and diagnosis. • To determine if obesity is associated with prostate size in men with prostate cancer. • We examined preoperative body mass index (BMI) and whole prostate weight in a cohort of 16,325 patients undergoing radical prostatectomy for localized prostate cancer from 1975 to 2008 at a single institution. • We used multivariable regression modelling adjusting for age, year of surgery, preoperative serum prostate-specific antigen (PSA), pathological stage and Gleason grade. • Of the entire cohort, 13,343 (82%) patients had a prostate weight of at least 40 g. These men were older (P < 0.001), had a higher preoperative BMI (P < 0.002), higher preoperative PSA (P < 0.001), and were more likely to have pT2 disease (P < 0.001). • In multivariable regression, preoperative BMI was associated with increased prostate weight: for each 1 kg/m(2) increase in BMI, prostate weight increased by 0.45 g (95% CI 0.35-0.55, P-trend < 0.001). • Compared with men with BMI < 25 kg/m(2) , men with a BMI ≥35 kg/m(2) had a 40% (odds ratio 1.40, 95% CI 1.01-1.95) increased risk of prostate weight of at least 40 g and a 70% (odds ratio 1.70, 95% CI 1.32-2.20) increased risk of prostate weight of at least 50 g. • In men with localized prostate cancer, obesity is associated with an increased risk of prostate enlargement. • These data validate other observations linking obesity with prostate enlargement and may have important ramifications for prostate cancer diagnosis in obese men. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  16. Disease Subtype-Independent Biomarkers of Breast Cancer Chemoprevention by the Ayurvedic Medicine Phytochemical Withaferin A.

    PubMed

    Samanta, Suman K; Sehrawat, Anuradha; Kim, Su-Hyeong; Hahm, Eun-Ryeong; Shuai, Yongli; Roy, Ruchi; Pore, Subrata K; Singh, Krishna B; Christner, Susan M; Beumer, Jan H; Davidson, Nancy E; Singh, Shivendra V

    2017-06-01

    A nontoxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. The present study was undertaken to determine the efficacy of an Ayurvedic medicine phytochemical (Withaferin A, [WA]) for chemoprevention of breast cancer and to elucidate its mode of action. Chemopreventive efficacy of WA (4 and 8 mg/kg body weight) was determined using a rat model of breast cancer induced by N-methyl-N-nitrosourea (MNU; n = 14 for control group, n = 15 for 4 mg/kg group, and n = 18 for 8 mg/kg group). The mechanisms underlying breast cancer chemoprevention by WA were elucidated by immunoblotting, biochemical assays, immunohistochemistry, and cytokine profiling using plasma and tumors from the MNU-rat (n = 8-12 for control group, n = 7-11 for 4 mg/kg group, and n = 8-12 for 8 mg/kg group) and/or mouse mammary tumor virus-neu (MMTV-neu) models (n = 4-11 for control group and n = 4-21 for 4 mg/kg group). Inhibitory effect of WA on exit from mitosis and leptin-induced oncogenic signaling was determined using MCF-7 and/or MDA-MB-231 cells. All statistical tests were two-sided. Incidence, multiplicity, and burden of breast cancer in rats were decreased by WA administration. For example, the tumor weight in the 8 mg/kg group was lower by about 68% compared with controls (8 mg/kg vs control, mean = 2.76 vs 8.59, difference = -5.83, 95% confidence interval of difference = -9.89 to -1.76, P = .004). Mitotic arrest and apoptosis induction were some common determinants of breast cancer chemoprevention by WA in the MNU-rat and MMTV-neu models. Cytokine profiling showed suppression of plasma leptin levels by WA in rats. WA inhibited leptin-induced oncogenic signaling in cultured breast cancer cells. WA is a promising chemopreventative phytochemical with the ability to inhibit at least two different subtypes of breast cancer. © The Author 2016. Published by Oxford University Press

  17. Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.

    PubMed

    Aviello, Gabriella; Romano, Barbara; Borrelli, Francesca; Capasso, Raffaele; Gallo, Laura; Piscitelli, Fabiana; Di Marzo, Vincenzo; Izzo, Angelo A

    2012-08-01

    Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. Thus, we investigated its possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice. AOM treatment was associated with aberrant crypt foci (ACF, preneoplastic lesions), polyps, and tumour formation, up-regulation of phospho-Akt, iNOS and COX-2 and down-regulation of caspase-3. Cannabidiol-reduced ACF, polyps and tumours and counteracted AOM-induced phospho-Akt and caspase-3 changes. In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB(1)-, TRPV1- and PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.

  18. Evaluation of resveratrol and N-acetylcysteine for cancer chemoprevention in a Fanconi anemia murine model.

    PubMed

    Zhang, Qing-Shuo; Marquez-Loza, Laura; Sheehan, Andrea M; Watanabe-Smith, Kevin; Eaton, Laura; Benedetti, Eric; Major, Angela; Schubert, Kathryn; Deater, Matthew; Joseph, Eric; Grompe, Markus

    2014-04-01

    Fanconi anemia (FA) patients suffer from progressive bone marrow failure and often develop cancers. Previous studies showed that antioxidants tempol and resveratrol (RV) delayed tumor onset and reduced hematologic defects in FA murine models, respectively. Here we tested whether antioxidants N-acetylcysteine (NAC) or RV could delay cancer in tumor prone Fancd2(-/-) /Trp53(+/-) mice. Unlike tempol, neither compound had any significant chemopreventive effect in this model. We conclude that not all anti-oxidants are chemopreventive in FA. In addition, when given to Fancd2(-/-) mice, NAC helped maintain Fancd2(-/-) KSL cells in quiescence while tempol did not. The mechanisms behind the different actions of these antioxidants await further investigation.

  19. Reconstructing the Prostate Cancer Transcriptional Regulatory Network

    DTIC Science & Technology

    2010-09-01

    TITLE: Reconstructing the prostate cancer transcriptional regulatory network PRINCIPAL INVESTIGATOR: Keyan Salari...2009 – 30 Sep 2010 5a. CONTRACT NUMBER W81XWH-09-1-0414 4. TITLE AND SUBTITLE Reconstructing the prostate cancer transcriptional regulatory...to novel diagnostic, prognostic, and therapeutic strategies in the future. The overall objective of this study was to reconstruct the prostate

  20. [CCAFU Recommendations 2013: Prostate cancer].

    PubMed

    Salomon, L; Bastide, C; Beuzeboc, P; Cormier, L; Fromont, G; Hennequin, C; Mongiat-Artus, P; Peyromaure, M; Ploussard, G; Renard-Penna, R; Rozet, F; Azria, D; Coloby, P; Molinié, V; Ravery, V; Rebillard, X; Richaud, P; Villers, A; Soulié, M

    2013-11-01

    The sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer. Guidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation. Pathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways. From 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. Infections and inflammation in prostate cancer

    PubMed Central

    Sfanos, Karen S; Isaacs, William B; Marzo, Angelo M De

    2013-01-01

    The frequent observation of both acute and chronic inflammation of unknown stimulus in the adult prostate has motivated a large body of research aimed at identifying potential infectious agents that may elicit prostatic inflammation. The overarching hypothesis is that infection-induced inflammation may be associated with prostate cancer development or progression, as inflammation is known to serve as an “enabling characteristic” of cancer. With recent advances in molecular techniques for microorganism identification, a panoply of microorganisms has been scrutinized in prostate tissues and in relation to prostate carcinogenesis. The aim of this review is to summarize the current literature on the evidence for infectious agents as a contributing factor to prostatic inflammation and prostate cancer, and to highlight recent literature suggesting an infectious etiology to the biogenesis of prostatic corpora amylacea and on the development of mouse models of prostatic infections. PMID:25110720

  2. Infections and inflammation in prostate cancer.

    PubMed

    Sfanos, Karen S; Isaacs, William B; De Marzo, Angelo M

    2013-12-25

    The frequent observation of both acute and chronic inflammation of unknown stimulus in the adult prostate has motivated a large body of research aimed at identifying potential infectious agents that may elicit prostatic inflammation. The overarching hypothesis is that infection-induced inflammation may be associated with prostate cancer development or progression, as inflammation is known to serve as an "enabling characteristic" of cancer. With recent advances in molecular techniques for microorganism identification, a panoply of microorganisms has been scrutinized in prostate tissues and in relation to prostate carcinogenesis. The aim of this review is to summarize the current literature on the evidence for infectious agents as a contributing factor to prostatic inflammation and prostate cancer, and to highlight recent literature suggesting an infectious etiology to the biogenesis of prostatic corpora amylacea and on the development of mouse models of prostatic infections.

  3. Novel applications of COX-2 inhibitors, metformin, and statins for the primary chemoprevention of breast cancer

    PubMed Central

    Micallef, Darren; Micallef, Sarah; Schembri-Wismayer, Pierre; Calleja-Agius, Jean

    2016-01-01

    Recent evidence shows that commonly prescribed drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), metformin, and statins, may have beneficial roles in the primary chemoprevention of breast cancer. Therefore, these drugs could potentially be used in addition to the hormonal drugs currently used for this purpose (namely, selective estrogen receptor modulators and aromatase inhibitors) due to their alternative mechanisms of action. PMID:27990091

  4. Chemopreventive effects of honokiol on UVB-induced skin cancer development.

    PubMed

    Chilampalli, Shivani; Zhang, Xiaoying; Fahmy, Hesham; Kaushik, Radhey S; Zeman, David; Hildreth, Michael B; Dwivedi, Chandradhar

    2010-03-01

    Skin cancer is the most prevalent of all cancer types and its incidence is expected to increase substantially. Chemoprevention involves the administration of chemical agents to prevent initiation, promotion and/or progression that occurs during neoplastic development. Honokiol, a plant lignan isolated from bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on chemically induced skin cancer development. The objective of this investigation was to study the chemopreventive effects of honokiol on UVB-induced skin tumor development in SKH-1 mice, a model relevant to humans, and to elucidate the possible role of apoptotic proteins involved in the prevention of skin tumor development. Female SKH-1 mice were divided into two groups. Group 1 received acetone (0.2 ml, topical) and Group 2 received honokiol (30 microg in 0.2 ml acetone, topical) one hour before UVB treatment. Tumor initiation and promotion were carried out by UVB radiation (30 mJ/cm(2)/day), 5 days a week for 30 weeks. Tumor counts and mouse weights were taken weekly. The honokiol-pretreated group exhibited a 45% reduction in tumor multiplicity as compared to the control group. Mechanistic studies showed the possible involvement of caspase-3, caspase-8, caspase-9, poly (ADP-ribose) polymerase (PARP) and p53 activation (p<0.05) leading to the induction of DNA fragmentation and apoptosis. Pretreatment with honokiol, at concentrations in micrograms per application compared with milligram applications of other potential chemopreventive agents, prevents UVB-induced skin cancer development, possibly by activating proapoptotic proteins through both intrinsic and extrinsic pathways.

  5. Silymarin and epithelial cancer chemoprevention: How close we are to bedside?

    SciTech Connect

    Kaur, Manjinder; Agarwal, Rajesh

    2007-11-01

    Failure and high systemic toxicity of conventional cancer therapies have accelerated the focus on the search for newer agents, which could prevent and/or slow-down cancer growth and have more human acceptability by being less or non-toxic. Silymarin is one such agent, which has been extensively used since ages for the treatment of liver conditions, and thus has possibly the greatest patient acceptability. In recent years, increasing body of evidence has underscored the cancer preventive efficacy of silymarin in both in vitro and in vivo animal models of various epithelial cancers. Apart from chemopreventive effects, other noteworthy aspects of silymarin and its active constituent silibinin in cancer treatment include their capability to potentiate the efficacy of known chemotherapeutic drugs, as an inhibitor of multidrug resistance-associated proteins and as an adjunct to the cancer therapeutic drugs due to their organ-protective efficacy specifically liver, and immunostimulatory effects. Widespread use of silymarin for liver health in humans and commercial availability of its formulations with increased bioavailability, further underscore the necessity of carrying out controlled clinical trials with these agents in cancer patients. In this review, we will briefly discuss the outcomes of clinical trials being conducted by us and others in cancer patients to provide insight into the clinical relevance of the observed chemopreventive effects of these agents in various epithelial cancer models.

  6. Silymarin and Epithelial Cancer Chemoprevention: How close we are to bedside?

    PubMed Central

    Kaur, Manjinder; Agarwal, Rajesh

    2009-01-01

    Failure and high systemic toxicity of conventional cancer therapies have accelerated the focus on the search for newer agents, which could prevent and/or slow-down cancer growth and have more human acceptability by being less or non-toxic. Silymarin is one such agent, which has been extensively used since ages for the treatment of liver conditions, and thus has possibly the greatest patient acceptability. In recent years, increasing body of evidence has underscored the cancer preventive efficacy of silymarin in both in vitro and in vivo animal models of various epithelial cancers. Apart from chemopreventive effects, other noteworthy aspects of silymarin and its active constituent silibinin in cancer treatment include their capability to potentiate the efficacy of known chemotherapeutic drugs, as an inhibitor of multidrug resistance associated proteins, and as an adjunct to the cancer therapeutic drugs due to their organ-protective efficacy specifically liver, and immunostimulatory effects. Widespread use of silymarin for liver health in humans and commercial availability of its formulations with increased bioavailability, further underscore the necessity of carrying out controlled clinical trials with these agents in cancer patients. In this review, we will briefly discuss the outcomes of clinical trials being conducted by us and others in cancer patients to provide insight into the clinical relevance of the observed chemopreventive effects of these agents in various epithelial cancer models. PMID:17184801

  7. Stages of Prostate Cancer

    MedlinePlus

    ... tissues to make echoes that form a sonogram (computer picture) of the prostate. Transrectal magnetic resonance imaging ( ... uses a strong magnet, radio waves , and a computer to make a series of detailed pictures of ...

  8. Chemopreventive Agent Development Clinical Trials | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  9. Chemopreventive Agent Development Funding Opportunities | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  10. Active Chemopreventive Agent Development Grants | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  11. Chemopreventive Agent Development Staff | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  12. Screening spectroscopy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Yermolenko, S. B.; Voloshynskyy, D. I.; Fedoruk, O. S.

    2015-11-01

    The aim of the study was to establish objective parameters of the field of laser and incoherent radiation of different spectral ranges (UV, visible, IR) as a non-invasive optical method of interaction with different samples of biological tissues and fluids of patients to determine the state of prostate cancer and choosing the best personal treatment. The objects of study were selected venous blood plasma of patient with prostate cancer, histological sections of rat prostate gland in the postoperative period. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5-25 microns) dry residue of plasma by spectral diagnostic technique of thin histological sections of biological tissues.

  13. Cancer Chemoprevention by Resveratrol: The p53 Tumor Suppressor Protein as a Promising Molecular Target.

    PubMed

    Ferraz da Costa, Danielly C; Fialho, Eliane; Silva, Jerson L

    2017-06-18

    Increasing epidemiological and experimental evidence has demonstrated an inverse relationship between the consumption of plant foods and the incidence of chronic diseases, including cancer. Microcomponents that are naturally present in such foods, especially polyphenols, are responsible for the benefits to human health. Resveratrol is a diet-derived cancer chemopreventive agent with high therapeutic potential, as demonstrated by different authors. The aim of this review is to collect and present recent evidence from the literature regarding resveratrol and its effects on cancer prevention, molecular signaling (especially regarding the involvement of p53 protein), and therapeutic perspectives with an emphasis on clinical trial results to date.

  14. Antiangiogenic activity of selenium in cancer chemoprevention: metabolite-specific effects.

    PubMed

    Lu, J; Jiang, C

    2001-01-01

    We review recent data that support a potential antiangiogenic effect of selenium (Se) in the chemoprevention of cancer and data that contrast two pools of Se metabolites, namely, methylselenol vs. hydrogen selenide, that differentially affect proteins and cellular processes crucial to tumor angiogenesis regulation. With regard to tumor angiogenesis, the chemopreventive effect of increased Se intake on chemically induced mammary carcinogenesis has been associated with reduced intratumoral microvessel density and an inhibition of the expression of vascular endothelial growth factor. The in vitro data show that monomethyl Se potently inhibits cell cycle progression of vascular endothelial cells to the S phase, endothelial expression of matrix metalloproteinase-2, and cancer epithelial expression of vascular endothelial growth factor with concentrations giving half-maximal inhibition that are within the plasma range of Se in US adults. The methyl Se-specific activities may therefore be physiologically pertinent for angiogenic switch regulation in early lesions in vivo in the context of cancer chemoprevention, which aims at retarding and blocking the growth and progression of early lesions. We argue for the antiangiogenic action of Se, especially the methyl Se pool of metabolites, as a primary mechanism for preventing avascular lesion growth. Contrary to the currently held paradigm, we speculate that there is a potential role for selenoproteins in regulating the growth and fate of transformed epithelial cells.

  15. Selection of topically applied non-steroidal anti-inflammatory drugs for oral cancer chemoprevention.

    PubMed

    Sood, Sandeep; Shiff, Steven J; Yang, Chung S; Chen, Xiaoxin

    2005-07-01

    Topical delivery of non-steroidal anti-inflammatory drugs through the oral mucosa has been used for oral cancer chemoprevention. Local permeation of these agents has been one of the major concerns. Here we propose an approach to predict the permeability of topically applied agents for oral cancer chemoprevention. In theory, the total flux through the oral mucosa (Jmax) can be estimated by adding the transcellular flux (JTC) and the paracellular flux (JPC). To target the Cox-2 enzyme in oral epithelial cells, it is desirable to maximize the theoretical activity index, the ratio of JTC and IC50 of a Cox-2 inhibitor (JTC/IC50-Cox-2). Among the 12 commonly used NSAIDs, celecoxib, nimesulide and ibuprofen had the highest values and may be the agents of choice to target Cox-2 in oral epithelial cells through topical application. Based on these calculations, a long-term chemopreventive experiment using celecoxib (3% or 6%) through topical application was performed in a DMBA induced hamster oral cancer model. Both 3% and 6% reduced the incidence of squamous cell carcinoma at the post-initiation stage.

  16. Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage and Cell Proliferation.

    PubMed

    Pedro, Dalila F N; Ramos, Alice A; Lima, Cristovao F; Baltazar, Fatima; Pereira-Wilson, Cristina

    2016-02-01

    Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2 O2 -induced and azoxymethane-induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption.

  17. Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention.

    PubMed

    Cheung, Ka Lung; Kong, Ah-Ng

    2010-03-01

    Development of cancer is a long-term and multistep process which comprises initiation, progression, and promotion stages of carcinogenesis. Conceivably, it can be targeted and interrupted along these different stages. In this context, many naturally occurring dietary compounds from our daily consumption of fruits and vegetables have been shown to possess cancer preventive effects. Phenethyl isothiocyanate (PEITC) and sulforaphane (SFN) are two of the most widely investigated isothiocyanates from the crucifers. Both have been found to be very potent chemopreventive agents in numerous animal carcinogenesis models as well as cell culture models. They exert their chemopreventive effects through regulation of diverse molecular mechanisms. In this review, we will discuss the molecular targets of PEITC and SFN potentially involved in cancer chemoprevention. These include the regulation of drug-metabolizing enzymes phase I cytochrome P450s and phase II metabolizing enzymes. In addition, the signaling pathways including Nrf2-Keap 1, anti-inflammatory NFkappaB, apoptosis, and cell cycle arrest as well as some receptors will also be discussed. Furthermore, we will also discuss the similarities and their potential differences in the regulation of these molecular targets by PEITC and SFN.

  18. Prostate cancer and inflammation: the evidence

    PubMed Central

    Sfanos, Karen S; De Marzo, Angelo M

    2014-01-01

    Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

  19. Prevalence of chemopreventive agent use among hospitalised women at high risk for breast cancer: a cross-sectional study

    PubMed Central

    Khaliq, Waseem; Jelovac, Danijela; Wright, Scott M

    2016-01-01

    Objective To characterise the current usage of chemoprevention agents among hospitalised women who are at higher risk for breast cancer. Study design A cross-sectional study. Setting Academic hospital at Baltimore. Participants A bedside survey of 250 women aged 50–75 years was conducted who were cancer-free at the time of study enrolment and hospitalised to a general medicine service. Reproductive history, family history for breast cancer, chemopreventive agents use and medical comorbidities data was collected for all patients. χ2 and t-tests were used to analyse population characteristics. Primary outcome measures Prevalence of women at high risk for developing breast cancer (5-year Gail risk score ≥1.7) and their chemopreventive agent use. Results Mean age for the study population was 61.5 years (SD 7.5), and mean 5-year Gail risk score was 1.67 (SD 0.88). A third of study population was at high risk for breast cancer. None of the high-risk women (0%) were taking chemoprevention for breast cancer risk reduction, and 23% were at very high risk with 5-year Gail score ≥3%. These women were not recognised as being high risk by their hospital providers and none were referred to the high-risk breast cancer clinics following discharge. Conclusions Many hospitalised women are at high risk for breast cancer and we could not identify even a single woman who was using chemoprevention for risk reduction. Current chemoprevention guidelines may be falling short in their dissemination and implementation. Since women at high risk for breast cancer may only interface with the healthcare system at select points, all healthcare providers must be willing and able to do risk assessment. For those identified to be at high risk, providers must then either engage in chemopreventive counselling or refer patients to providers who are more comfortable working with patients on this critical decision. PMID:27852714

  20. Potential efficacy of some african plants in benign prostatic hyperplasia and prostate cancer.

    PubMed

    Russo, Giorgio I; Cimino, Sebastiano; Salamone, Costanza; Madonia, Massimo; Favilla, Vincenzo; Castelli, Tommaso; Morgia, Giuseppe

    2013-10-01

    Traditional medicine is very popular in Africa and it is considered as an alternative form of health care. Plants and vegetables used in folk and traditional medicine have gained wide acceptance as one of the main sources of prophylactic and chemopreventive drug discovery and this is due to the evidence of particular biological and biochemical characteristics of each plants extracts. The role of these compounds in urological field may be explained by the antiinflammatory effect through interference with prostaglandin metabolism, alteration of lipid peroxidation, direct inhibition of prostate growth and moreover through an antiandrogenic or antiestrogenic effect and a decrease of the availability of sex hormone-binding globulin. Since Benign Prostatic Hyperplasia and Prostate Cancer are two of the most diffuse diseases of aging male and considering that standard medical therapy is accompanied with different side effects, the emerging use of African plants may be justified. This review takes a look at some African plants extracts properties and their relative urological application. Different biomolecular mechanisms of action are promising, suggesting a real application in reducing prostate cells proliferation.

  1. Biological/chemopreventive activity of stilbenes and their effect on colon cancer.

    PubMed

    Rimando, Agnes M; Suh, Nanjoo

    2008-10-01

    Colon cancer is one of the leading causes of cancer death in men and women in Western countries. Epidemiological studies have linked the consumption of fruits and vegetables to a reduced risk of colon cancer, and small fruits are particularly rich sources of many active phytochemical stilbenes, such as resveratrol and pterostilbene. Recent advances in the prevention of colon cancer have stimulated an interest in diet and lifestyle as an effective means of intervention. As constituents of small fruits such as grapes, berries and their products, stilbenes are under intense investigation as cancer chemopreventive agents. One of the best-characterized stilbenes, resveratrol, has been known as an antioxidant and an anti-aging compound as well as an anti-inflammatory agent. Stilbenes have diverse pharmacological activities, which include cancer prevention, a cholesterol-lowering effect, enhanced insulin sensitivity, and increased lifespan. This review summarizes results related to the potential use of various stilbenes as cancer chemopreventive agents, their mechanisms of action, as well as their pharmacokinetics and efficacy for the prevention of colon cancer in animals and humans.

  2. Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the human papillomavirus (HPV) vaccine.

    PubMed

    Tsai, Horng-Jyh

    2015-04-01

    Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV) vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population), and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer.

  3. Vaccine Immunotherapy for Prostate Cancer

    DTIC Science & Technology

    2010-05-01

    Center IRB, and the I owa City VA Medical Center Research and Development Committee. During the second and t hird years we have been recruiting pa...American Urologic Association (AUA). (3) Talks to prostate cancer survivor support groups in at the University of I owa , Mercy Medical Center in Cedar

  4. Particle radiotherapy for prostate cancer.

    PubMed

    Shioyama, Yoshiyuki; Tsuji, Hiroshi; Suefuji, Hiroaki; Sinoto, Makoto; Matsunobu, Akira; Toyama, Shingo; Nakamura, Katsumasa; Kudo, Sho

    2015-01-01

    Recent advances in external beam radiotherapy have allowed us to deliver higher doses to the tumors while decreasing doses to the surrounding tissues. Dose escalation using high-precision radiotherapy has improved the treatment outcomes of prostate cancer. Intensity-modulated radiation therapy has been widely used throughout the world as the most advanced form of photon radiotherapy. In contrast, particle radiotherapy has also been under development, and has been used as an effective and non-invasive radiation modality for prostate and other cancers. Among the particles used in such treatments, protons and carbon ions have the physical advantage that the dose can be focused on the tumor with only minimal exposure of the surrounding normal tissues. Furthermore, carbon ions also have radiobiological advantages that include higher killing effects on intrinsic radio-resistant tumors, hypoxic tumor cells and tumor cells in the G0 or S phase. However, the degree of clinical benefit derived from these theoretical advantages in the treatment of prostate cancer has not been adequately determined. The present article reviews the available literature on the use of particle radiotherapy for prostate cancer as well as the literature on the physical and radiobiological properties of this treatment, and discusses the role and the relative merits of particle radiotherapy compared with current photon-based radiotherapy, with a focus on proton beam therapy and carbon ion radiotherapy.

  5. Post-study aspirin intake and factors motivating participation in a colorectal cancer chemoprevention trial.

    PubMed

    Sample, Dory A; Sinicrope, Pamela S; Wargovich, Michael J; Sinicrope, Frank A

    2002-03-01

    We conducted an exploratory, cross-sectional study examining motivators for study participation and post-study aspirin intake in a chemoprevention trial. The parent clinical trial aimed to determine the optimal aspirin dose for colorectal cancer chemoprevention using prostaglandin E(2) as a mucosal biomarker. This trial was randomized and double-blinded in 60 subjects with prior sporadic colorectal adenoma(s) and evaluated three aspirin doses or placebo taken once daily for 4 weeks. A cross-section of 55 evaluable participants who completed the chemoprevention trial were mailed a 16-item, self-administered questionnaire evaluating subject demographics, motivational factors, and health-related behaviors within the framework of Pender's Health Promotion Model (HPM). Forty-three (78%) of 55 participants returned the questionnaire. The most important motivators for study participation were altruistic, i.e., a desire to help future generations at risk of colorectal cancer and personal factors including a desire to reduce one's own risk. Nineteen (44%) of 43 respondents reported that they chose to take daily aspirin post-study without knowledge of study results. At a mean follow-up of 17.3 months, 18 of these 19 subjects continued to take aspirin regularly. Regular use of vitamin supplements pre-study was found to correlate with post-study aspirin use (Mann-Whitney U test, U = 154.0; P = 0.04). We demonstrate, for the first time, that participation in a chemoprevention study can influence the decision to continue the study drug, if available, to reduce perceived cancer risk. Continued post-study aspirin intake indicates an impact of study participation on a health-related behavior and underscores the importance of patient education to guide such decision-making.

  6. Boron intake and prostate cancer risk.

    PubMed

    Gonzalez, Alejandro; Peters, Ulrike; Lampe, Johanna W; White, Emily

    2007-12-01

    Experimental studies suggest that boron may prevent prostate cancer. Only one small epidemiological study has been conducted of boron, which found that those in the highest quartile of boron intake had less than half the risk of prostate cancer versus those in the lowest quartile. We evaluated the association between boron intake and prostate cancer within the VITamins And Lifestyle (VITAL) cohort. A total of 35,244 men completed the baseline supplement and food frequency questionnaire (FFQ) in 2000-2002. A boron database was constructed from published sources to estimate boron intake from the FFQ and from multivitamins. A total of 832 men developed prostate cancer from baseline to 31 December 2004. Dietary boron intake and total boron intake from diet plus multivitamins were not associated with prostate cancer risk. The hazard ratio of prostate cancer for those in the highest versus lowest quartile of total boron intake was 1.17 (95% CI 0.85, 1.61). This risk did not vary by prostate cancer stage or Gleason score. Furthermore, none of the foods high in boron content was associated with a decreased risk of prostate cancer. This cohort study provides no evidence for a preventive role of boron intake on prostate cancer. Since few studies exist on this topic, future research is needed to better elucidate any role that boron may play in the prevention of prostate cancer.

  7. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2014-04-01

    Oncology Departments at the University of Iowa and other institutions. A major project in the lab is targeted therapy of prostate cancer using PSMA...develop novel, immune-based therapies for advanced solid tumors, using the knowledge we gain from our pre-clinical studies. Because her goal is to...in the molecular design, organic synthesis, characterization, and radiolabeling of peptides and small molecules for small molecule cancer therapy

  8. Targeting prostate cancer stem cells.

    PubMed

    Crea, Francesco; Mathews, Lesley A; Farrar, William L; Hurt, Elaine M

    2009-12-01

    Cancer stem cells are the sub-population of cells present within tumors responsible for tumorigenesis. These cells have unique biological properties including self-renewal and the ability to differentiate. Furthermore, it is thought that these cells are more resistant to conventional chemotherapy and, as a result, are responsible for patient relapse. We will discuss the identification of prostate cancer stem cells, their unique properties and how these cells may be targeted for more efficacious therapies.

  9. Early Detection of Prostate Cancer

    DTIC Science & Technology

    2007-01-01

    effective marker for diagnosis and detection of prostate cancer. Low concentrations of PSA would be detected using acoustic wave sensors because of...associated electrical field. For biological sensors, binding of a substance onto the resonating membrane surface causes a decrease in the acoustic...of diverse conditions and diseases including those that affect the thyroid, HIV, diabetes , pregnancy, and several types of cancer. In clinical

  10. The Gordon Wilson Lecture. Natural history and treatment of early stage prostate cancer.

    PubMed Central

    Scardino, P. T.

    2000-01-01

    Prostate cancer poses a challenge to society and to physicians. It is a remarkably prevalent tumor, perhaps the most common cancer in the world in its histologic manifestation. In its clinically apparent form, it is notably heterogeneous. Some patients live out their lives with a prostate cancer that remains stable for decades without treatment. In other cases, the cancer grows aggressively, responds poorly to therapy, and causes death within a few years. The median loss-of-life expectancy for men diagnosed with prostate cancer has been estimated at 9 years. Important advances have been made in the past two decades in the treatment of prostate cancer. Further progress will require more accurate characterization of the primary tumor in each individual patient to tailor treatment--whether conservative or aggressive, surgery or radiation--more accurately to the nature of the individual cancer. Imaging studies in particular must be improved if we are to have better, noninvasive ways to identify the presence of a cancer and to define its volume, location, and extent. Substantial progress against this disease will require major breakthroughs in our understanding of the etiology of prostate cancer, the development of effective chemopreventive agents, more accurate ways to assess the biological potential of the tumor, and more effective systemic agents to treat metastatic cancer. Images Fig. 1 PMID:10881343

  11. Ethanolic Extract of Propolis Augments TRAIL-Induced Apoptotic Death in Prostate Cancer Cells

    PubMed Central

    Szliszka, Ewelina; Czuba, Zenon P.; Bronikowska, Joanna; Mertas, Anna; Paradysz, Andrzej; Krol, Wojciech

    2011-01-01

    Prostate cancer is a commonly diagnosed cancer in men. The ethanolic extract of propolis (EEP) and its phenolic compounds possess immunomodulatory, chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effects of EEP and phenolic compounds isolated from propolis in combination with TRAIL on two prostate cancer cell lines, hormone-sensitivity LNCaP and hormone-refractory DU145. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC/propidium iodide. The prostate cancer cell lines were proved to be resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL-induced death in prostate cancer cells. The percentage of the apoptotic cells after cotreatment with 50 μg mL−1 EEP and 100 ng mL−1 TRAIL increased to 74.9 ± 0.7% for LNCaP and 57.4 ± 0.7% for DU145 cells. The strongest cytotoxic effect on LNCaP cells was exhibited by apigenin, kaempferid, galangin and caffeic acid phenylethyl ester (CAPE) in combination with TRAIL (53.51 ± 0.68–66.06 ± 0.62% death cells). In this work, we showed that EEP markedly augmented TRAIL-mediated apoptosis in prostate cancer cells and suggested the significant role of propolis in chemoprevention of prostate cancer. PMID:19892808

  12. Ethanolic Extract of Propolis Augments TRAIL-Induced Apoptotic Death in Prostate Cancer Cells.

    PubMed

    Szliszka, Ewelina; Czuba, Zenon P; Bronikowska, Joanna; Mertas, Anna; Paradysz, Andrzej; Krol, Wojciech

    2011-01-01

    Prostate cancer is a commonly diagnosed cancer in men. The ethanolic extract of propolis (EEP) and its phenolic compounds possess immunomodulatory, chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effects of EEP and phenolic compounds isolated from propolis in combination with TRAIL on two prostate cancer cell lines, hormone-sensitivity LNCaP and hormone-refractory DU145. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC/propidium iodide. The prostate cancer cell lines were proved to be resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL-induced death in prostate cancer cells. The percentage of the apoptotic cells after cotreatment with 50 μg mL(-1) EEP and 100 ng mL(-1) TRAIL increased to 74.9 ± 0.7% for LNCaP and 57.4 ± 0.7% for DU145 cells. The strongest cytotoxic effect on LNCaP cells was exhibited by apigenin, kaempferid, galangin and caffeic acid phenylethyl ester (CAPE) in combination with TRAIL (53.51 ± 0.68-66.06 ± 0.62% death cells). In this work, we showed that EEP markedly augmented TRAIL-mediated apoptosis in prostate cancer cells and suggested the significant role of propolis in chemoprevention of prostate cancer.

  13. Ginger phytochemicals exhibit synergy to inhibit prostate cancer cell proliferation

    PubMed Central

    Brahmbhatt, Meera; Gundala, Sushma R.; Asif, Ghazia; Shamsi, Shahab A; Aneja, Ritu

    2014-01-01

    Dietary phytochemicals offer non-toxic therapeutic management as well as chemopreventive intervention for slow-growing prostate cancers. However, the limited success of several single-agent clinical trials suggest a paradigm shift that the health benefits of fruits and vegetables are not ascribable due to individual phytochemicals rather may be ascribed to but to synergistic interactions among them. We recently reported growth-inhibiting and apoptosis-inducing properties of ginger extract (GE) in in vitro and in vivo prostate cancer models. Nevertheless, the nature of interactions among the constituent ginger biophenolics, viz. 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogoal, remains elusive. Here we show antiproliferative efficacy of the most-active GE biophenolics as single-agents and in binary combinations, and investigate the nature of their interactions using the Chou-Talalay combination-index (CI) method. Our data demonstrate that binary combinations of ginger phytochemicals synergistically inhibit proliferation of PC-3 cells with CI values ranging from 0.03-0.88. To appreciate synergy among phytochemicals present in GE, the natural abundance of ginger biophenolics was quantitated using LC-UV/MS. Interestingly, combining GE with its constituents (in particular, 6-gingerol) resulted in significant augmentation of GE’s antiproliferative activity. These data generate compelling grounds for further preclinical evaluation of GE alone and in combination with individual ginger biophenols for prostate cancer management. PMID:23441614

  14. Benefits of whole ginger extract in prostate cancer

    PubMed Central

    Karna, Prasanthi; Chagani, Sharmeen; Gundala, Sushma R.; Rida, Padmashree C. G.; Asif, Ghazia; Sharma, Vibhuti; Gupta, Meenakshi V.; Aneja, Ritu

    2012-01-01

    It is appreciated far and wide that increased and regular consumption of fruits and vegetables is linked with noteworthy anticancer benefits. Extensively consumed as a spice in foods and beverages worldwide, ginger (Zingiber officinale Roscoe) is an excellent source of several bioactive phenolics, including non-volatile pungent compounds such as gingerols, paradols, shogaols and gingerones. Ginger has been known to display anti-inflammatory, antioxidant and antiproliferative activities, indicating its promising role as a chemopreventive agent. Here, we show that whole ginger extract (GE) exerts significant growth-inhibitory and death-inductory effects in a spectrum of prostate cancer cells. Comprehensive studies have confirmed that GE perturbed cell-cycle progression, impaired reproductive capacity, modulated cell-cycle and apoptosis regulatory molecules and induced a caspase-driven, mitochondrially mediated apoptosis in human prostate cancer cells. Remarkably, daily oral feeding of 100 mg/kg body weight of GE inhibited growth and progression of PC-3 xenografts by approximately 56 % in nude mice, as shown by measurements of tumour volume. Tumour tissue from GE-treated mice showed reduced proliferation index and widespread apoptosis compared with controls, as determined by immunoblotting and immunohistochemical methods. Most importantly, GE did not exert any detectable toxicity in normal, rapidly dividing tissues such as gut and bone marrow. To the best of our knowledge, this is the first report to demonstrate the in vitro and in vivo anticancer activity of whole GE for the management of prostate cancer. PMID:21849094

  15. Progress Against Prostate Cancer | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Prostate Cancer Progress Against Prostate Cancer Past Issues / Winter 2010 Table of Contents Click ... This can narrow the urethra, decreasing urine flow. Prostate cancer is made up of cells the body does ...

  16. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

    SciTech Connect

    Meeran, Syed M.; Katiyar, Suchitra; Katiyar, Santosh K.

    2008-05-15

    Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-1E). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygen species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.

  17. Cancer chemopreventive activity and metabolism of isoliquiritigenin, a compound found in licorice

    PubMed Central

    Cuendet, Muriel; Guo, Jian; Luo, Yan; Chen, Shaonong; Oteham, Carol P.; Moon, Richard C.; van Breemen, Richard B.; Marler, Laura E.; Pezzuto, John M.

    2009-01-01

    Isoliquiritigenin (2′,4′,4-trihydroxychalcone, ILG), a chalcone found in licorice root and many other plants, has shown potential chemoprevention activity through induction of phase II enzymes such as quinone reductase-1 in murine hepatoma cells. In this study, the in vivo metabolism of ILG was investigated in rats. In addition, ILG glucuronides and ILG-glutathione adducts were observed in human hepatocytes and in livers from rats treated with ILG. ILG glucuronides were detected in both plasma and rat liver tissues. Also, in a full-term cancer chemoprevention study conducted with 7,12-dimethylbenz(a)anthracene (DMBA)-treated female Sprague-Dawley rats, dietary administration of ILG slightly increased tumor latency but had a negative effect on the incidence of mammary tumors starting at approximately 65 days post DMBA. Further, no significant induction of phase II enzymes was found in mammary glands, which is consistent with the low level of ILG observed in these tissues. However, ILG significantly induced quinone reductase-1 activity in the colon, and glutathione as well as glutathione S-transferase in the liver. Analysis of mRNA expression in tissues of rats treated with ILG supported these findings. These results suggest ILG should be tested for chemopreventive efficacy in non-mammary models of cancer. PMID:20068129

  18. Metabolic imbalance and prostate cancer progression

    PubMed Central

    Burton, Anya J; Tilling, Kate M; Holly, Jeff M; Hamdy, Freddie C; Rowlands, Mari-Anne E; Donovan, Jenny L; Martin, Richard M

    2010-01-01

    There is substantial evidence implicating environmental factors in the progression of prostate cancer. The metabolic consequences of a western lifestyle, such as obesity, insulin resistance and abnormal hormone production have been linked to prostate carcinogenesis through multiple overlapping pathways. Insulin resistance results in raised levels of the mitogens insulin and insulin-like growth factor-1, both of which may affect prostate cancer directly, or through their effect on other metabolic regulators. Obesity is associated with abnormal levels of adipocyte-derived peptides (adipokines), sex hormones and inflammatory cytokines. Adipokines have been shown to influence prostate cancer in both cell culture studies and observational, population level studies. Testosterone appears to have a complex relationship with prostate carcinogenesis, and it has been suggested that the lower levels associated with obesity may select for more aggressive androgen independent prostate cancer cells. Prostatic inflammation, caused by infection, urinary reflux or dietary toxins, frequently occurs prior to cancer development and may influence progression to advanced disease. High levels of ω-6 fatty acids in the diet may lead to the production of further inflammatory molecules that may influence prostate cancer. Increased fatty acid metabolism occurs within tumour cells, providing a potential target for prostate cancer therapies. Aberrations in amino acid metabolism have also been identified in prostate cancer tissue, particularly in metastatic cancer. This evidence indicates lifestyle interventions may be effective in reducing the incidence of clinical disease. However, much more research is needed before recommendations are made. PMID:21532839

  19. Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence.

    PubMed

    Kotecha, Ritesh; Takami, Akiyoshi; Espinoza, J Luis

    2016-08-09

    Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations.

  20. Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence

    PubMed Central

    Kotecha, Ritesh; Takami, Akiyoshi; Espinoza, J. Luis

    2016-01-01

    Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations. PMID:27232756

  1. Identification of Prostate Cancer-Related Genes Using Inhibition of NMD in Prostate Cancer Cell Lines

    DTIC Science & Technology

    2005-01-01

    TITLE AND SUBTITLE 5. FUNDING NUMBERS Identification of Prostate Cancer -Related Genes Using W81XWH-04- 1 -0045 Inhibition of NMD in Prostate Cancer Cell...analytical filter to the prostate cancer cell lines 22RV- 1 and DU-145. Ten genes for each cell line have been selected for sequencing analysis.(Table...list of candidate genes for sequencing analysis from the LNCaP, PC3, 22RV- 1 and DU- 145 prostate cancer cell lines has been produced REPORTABLE

  2. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer.

    PubMed

    Białek, Waldemar; Rudzki, Sławomir; Iberszer, Paweł; Wronecki, Lech

    2016-12-01

    Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin.

  3. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer

    PubMed Central

    Rudzki, Sławomir; Iberszer, Paweł; Wronecki, Lech

    2016-01-01

    Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin. PMID:28138411

  4. Mechanism of Selenium Chemoprevention and Therapy in Prostate Cancer

    DTIC Science & Technology

    2010-11-01

    active methylselenol (12). The effect of physiologic concen- trations of methylseleninic acid on cultured cells has been documented in several studies (11...apoptosis and cell-cycle G1 arrest by selenium metabolite methylselenol . Mol Carcinog 2002;34:113–20. 13. Zu K, Ip C. Synergy between selenium and vitamin E

  5. Mechanism of Selenium Chemoprevention and Therapy in Prostate Cancer

    DTIC Science & Technology

    2006-11-01

    NUMBER E-Mail: allen.gao@roswellpark.org 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION...Epidemiol Biomarkers Prev 2000;9:883–7. 7. Yoshizawa K, Willett WC, Morris SJ, et al. Study of prediagnostic selenium level in toenails and the risk of

  6. Cancer chemoprevention and mitochondria: targeting apoptosis in transformed cells via the disruption of mitochondrial bioenergetics/redox state.

    PubMed

    Hail, Numsen; Lotan, Reuben

    2009-01-01

    Cancer chemoprevention employs agents that block, hinder, or reverse tumorigenesis to prevent malignancy. Several putative cancer chemopreventive agents promote apoptosis in transformed cells initiated in animal carcinogenesis models or identified in human subjects, and/or in tumor cells cultured in vitro. Consequently, apoptosis induction is increasingly valued as a biologically significant anticancer mechanism in the arena of chemoprevention. In vitro studies suggest that the permeabilization of mitochondrial membranes is an important mechanistic determinant associated with the apoptosis induced by these agents. Mitochondrial membrane permeabilization (MMP) may occur via the control of proapoptotic Bcl-2 family members, and/or by the induction of the mitochondrial permeability transition. Both of these cell death-inducing regulatory mechanisms are ultimately responsive to the bioenergetic status/redox state of mitochondria. Interestingly, in addition to inducing MMP, various chemopreventive agents can directly modulate mitochondrial bioenergetics and/or redox tone in transformed cells. This review will examine prospective mechanisms associated with the disruption of mitochondrial function by chemopreventive agents that affect MMP and apoptosis. In doing so, we will construct a paradigm supporting the notion that the bioenergetic and/or redox characteristics of the mitochondria in transformed cells are important targets in the chemoprevention of cancer.

  7. Imaging for Prostate Cancer Recurrence.

    PubMed

    Maurer, Tobias; Eiber, Matthias; Fanti, Stefano; Budäus, Lars; Panebianco, Valeria

    2016-06-01

    Correct identification of metastatic sites in recurrent prostate cancer (PCa) is of crucial importance because it leads to further treatment decisions. To provide an overview on current imaging procedures and their performance in recurrent PCa. Medline search via PubMed was performed with the keywords imaging, recurrent, and prostate cancer as well as more detailed searches including the keywords bone scan, bone scintigraphy, computed tomography, magnetic resonance imaging, positron emission tomography, PET, choline, FDG, prostate-specific membrane antigen, and PSMA, with emphasis on recent literature from 2010 to the present. Non-English published literature was excluded. Abstracts and full-text articles were reviewed and assessed for relevant content. In diagnostic imaging and particularly with newer technologies like positron emission tomography (PET), a profound lack of prospectively designed studies in recurrent PCa has to be noted. In most studies histologic validation has only been performed in a subset of patient cohorts. Heterogeneity of included patient cohorts, lack of standardized assessment, as well as diverging end points, hamper systematic comparison of different image modalities. Thus evidence for currently used imaging in recurrent PCa is only presented descriptively. Computed tomography and magnetic resonance imaging (MRI) as well as bone scintigraphy still represent the standard imaging for recurrent PCa; however, particularly for detection of local recurrence, multiparametric MRI is a valuable imaging modality. PET using choline and particularly tracers against prostate-specific membrane antigen might improve visualization of metastatic lesions. These findings need to be validated in prospective trials. Imaging of recurrent prostate cancer (PCa) is important to guide further treatment. Computed tomography, magnetic resonance imaging, and bone scintigraphy represent the current standard. Positron emission tomography, especially with cancer

  8. Magnetic Resonance Spectroscopy (MRS) of Prostatic Fluids for Early Detection of Prostate Cancer

    DTIC Science & Technology

    2005-10-01

    most widely used marker of prostate cancer - and prostate cancer risk. Moreover, benign prostatic hyperplasia (BPH), which is also strongly associated...Vigneron, D.B., Konety, B., Nelson, S.J., Narayan, P., and Hricak, H. Citrate as in vivo marker to discriminate prostate cancer from benign prostatic hyperplasia and

  9. Benzo(a)pyrene induced lung cancer: Role of dietary phytochemicals in chemoprevention.

    PubMed

    Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Barua, Chandana C; Sriram, Chandra Shekhar; Gogoi, Ranadeep

    2015-10-01

    Lung cancer is the major cause of overall cancer deaths, and chemoprevention is a promising strategy to control this disease. Benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is one among the principal constituents of tobacco smoke that plays a key role in lung carcinogenesis. The B(a)P induced lung cancer in mice offers a relevant model to study the effect of natural products and has been widely used by many researchers and found considerable success in ameliorating the pathophysiological changes of lung cancer. Currently available synthetic drugs that constitute the pharmacological armamentarium are themselves effective in managing the condition but not without setbacks. These hunches have accelerated the requisite for natural products, which may be used as dietary supplement to prevent the progress of lung cancer. Besides, these agents also supplement the conventional treatment and offer better management of the condition with less side effects. In the context of soaring interest toward dietary phytochemicals as newer pharmacological interventions for lung cancer, in the present review, we are attempting to give a silhouette of mechanisms of B(a)P induced lung carcinogenesis and the role of dietary phytochemicals in chemoprevention.

  10. Steroidal pyrazolines evaluated as aromatase and quinone reductase-2 inhibitors for chemoprevention of cancer.

    PubMed

    Abdalla, Mohamed M; Al-Omar, Mohamed A; Bhat, Mashooq A; Amr, Abdel-Galil E; Al-Mohizea, Abdullah M

    2012-05-01

    The aromatase and quinone reductase-2 inhibition of synthesized heterocyclic pyrazole derivatives fused with steroidal structure for chemoprevention of cancer is reported herein. All compounds were interestingly less toxic than the reference drug (Cyproterone(®)). The aromatase inhibitory activities of these compounds were much more potent than the lead compound resveratrol, which has an IC(50) of 80 μM. In addition, all the compounds displayed potent quinone reductase-2 inhibition. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). The aromatase and quinone reductase-2 inhibitors resulting from this study have potential value in the treatment and prevention of cancer.

  11. Polyphenols from the mangosteen (Garcinia mangostana) fruit for breast and prostate cancer

    PubMed Central

    Li, Gongbo; Thomas, Stacey; Johnson, Jeremy J.

    2013-01-01

    The mangosteen (Garcinia mangostana) is a tropical fruit native to Southeast Asia and has long been reported to contain multiple health promoting properties. This fruit is an abundant source of xanthones, a class of polyphenolic compounds with a distinctive tricyclic aromatic ring system and is largely responsible for its biological activities including anti-cancer activity. Herein we describe the anti-cancer activity and mechanisms of mangosteen polyphenolic xanthones including α-Mangostin against breast cancer and prostate cancer. So far, extracts and individual xanthones have been found to induce apoptosis and inhibit proliferation on cancer cells in vitro and in vivo. Based on the reported findings there is clear evidence that these polyphenols target multiple signaling pathways involved in cell cycle modulation and apoptosis. Further work is required to understand its potential for health promotion and potential drug discovery for prostate and breast cancer chemoprevention. PMID:23805102

  12. [Prostate cancer brachytherapy].

    PubMed

    Pommier, P; Guérif, S; Peiffert, D; Créhange, G; Hannoun-Lévi, J-M; de Crevoisier, R

    2016-09-01

    Prostate brachytherapy techniques are described, concerning both Iodine 125 high dose rate brachytherapy. The following parts are presented: brachytherapy indications, technical description, immediate postoperative management and post-treatment evaluation, and 4 to 6 weeks as well as long-term follow-up. Copyright © 2016. Published by Elsevier SAS.

  13. The Early Prostate Cancer program: bicalutamide in nonmetastatic prostate cancer.

    PubMed

    Iversen, Peter; Roder, Martin Andreas

    2008-03-01

    The Early Prostate Cancer program is investigating the addition of bicalutamide 150 mg to standard care for localized or locally advanced, nonmetastatic prostate cancer. The third program analysis, at 7.4 years' median follow-up, has shown that bicalutamide 150 mg does not benefit patients with localized disease, but does confer significant progression-free survival benefits in patients with locally advanced disease, irrespective of standard care received. In patients receiving radiotherapy for locally advanced disease, bicalutamide 150 mg significantly reduced the risk of death by 35%; the magnitude of this benefit compares favorably with that of adjuvant luteinizing hormone-releasing hormone agonist therapy in a similar population. Bicalutamide 150 mg represents an alternative to castration for patients with locally advanced disease who wish to avoid the side effects associated with castration.

  14. Targeting Prostate Cancer with Multifunctional Nanoparticles

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0487 TITLE: Targeting Prostate Cancer with Multifunctional Nanoparticles PRINCIPAL INVESTIGATOR: Darryl Martin...Targeting Prostate Cancer with Multifunctional Nanoparticles 5b. GRANT NUMBER W81XWH-14-1-0487 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Darryl...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer cells were transfected with claudin siRNA

  15. Prostate Cancer Presenting with Parietal Bone Metastasis

    PubMed Central

    Pare, Abdoul Karim; Abubakar, Babagana Mustapha; Kabore, Moussa

    2017-01-01

    Bone metastases from prostate cancer are very common. They are usually located on the axial skeleton. However, cranial bone metastases especially to the parietal bone are rare. We report a case of metastatic prostate cancer presenting with left parietal bone metastasis in a patient with no urological symptoms or signs. We should consider prostate cancer in any man above 60 years presenting unusual bone lesions.

  16. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    al. Plasma antibodies against Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiology Biomarkers and Prevention 2006;15...infectious agents with respect to prostate cancer: T vaginalis , the most common non-viral sexually transmitted infection, and the recently identified...To characterize the role of the infectious protozoa T. vaginalis in prostate carcinogenesis and progression. The current study is nested within the

  17. Targeting TMPRSS2 ERG in Prostate Cancer

    DTIC Science & Technology

    2016-09-01

    molecules in prostate cancer cells for perturbations that would modulate the ERG signature. These results will provide new insights into ERG function...prostate cancer, however, the exact role of TMPRSS2-ERG in tumorigenesis is unclear, making it difficult to design assays to target its function...essential for TMPRSS2-ERG activity in prostate cancer cells (months 1-28) 1a. Generate and titer lentiviruses expressing shRNAs targeting

  18. Molecular Imaging of Prostate Cancer: PET Radiotracers

    PubMed Central

    Jadvar, Hossein

    2012-01-01

    OBJECTIVE Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer. PMID:22826388

  19. Roles of Eicosanoids in Prostate Cancer

    PubMed Central

    Nithipatikom, Kasem; Campbell, William B.

    2012-01-01

    Summary Eicosanoids, the metabolites of arachidonic acid, have diverse functions in the regulation of cancer including prostate cancer. This review will provide an overview of the roles of eicosanoids and endocannabinoids and their potential as therapeutic targets for prostate cancer treatment. PMID:24563660

  20. Vitamin D, Sunlight and Prostate Cancer Risk

    PubMed Central

    Donkena, Krishna Vanaja; Young, Charles Y. F.

    2011-01-01

    Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR), and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention. PMID:21991434

  1. Prostate and Urologic Cancer | Division of Cancer Prevention

    Cancer.gov

    [[{"fid":"183","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Prostate and Urologic Cancer Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Prostate and Urologic Cancer Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Prostate and Urologic Cancer Research Group Homepage Logo","title":"Prostate and Urologic Cancer Research Group Homepage Logo","height":"266","width":"400","clas | Conducts and supports research on the prevention and early detection of prostate, bladder, and skin cancers.

  2. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2010-03-01

    progression; 2-) To characterize the role of the infectious protozoa T. vaginalis in prostate carcinogenesis and progression. The current study is...understanding of the infectious pathogenesis of prostate cancer. Aim II. To characterize the role of the infectious protozoa T. vaginalis in prostate

  3. Personalizing Aspirin Use for Targeted Breast Cancer Chemoprevention Among Postmenopausal Women

    PubMed Central

    Bardia, Aditya; Keenan, Tanya E.; Ebbert, Jon O.; Lazovich, DeAnn; Wang, Alice H.; Vierkant, Robert A.; Olson, Janet E.; Vachon, Celine M.; Limburg, Paul J.; Anderson, Kristin E.; Cerhan, James R.

    2016-01-01

    Objective To better understand the potential risk/benefit ratio for targeted chemoprevention, we evaluated the association of aspirin and other NSAIDs with incidence of postmenopausal breast cancer for risk subgroups defined by selected non-modifiable or difficult-to-modify breast cancer risk factors. Patients and Methods Postmenopausal women with no history of cancer on July 1, 1992 (N=26,580) were prospectively followed through December 31, 2005 for breast cancer incidence (N=1581). Risk subgroups were defined on family history of breast cancer, age at menarche, age at menopause, parity/age at first live birth, history of benign breast disease, and body mass index (BMI). Hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for other breast cancer risk factors were estimated using Cox models. Results Aspirin use was associated with a lower incidence of breast cancer for women with family history of breast cancer (HR=0.62 for 6+ per week vs. never use; 95%CI 0.41-0.93) and personal history of benign breast disease (HR=0.69; 95%CI 0.50-0.95), but not for women in higher risk subgroups for age at menarche, age at menopause, parity/age at first live birth or BMI. In contrast, inverse associations with aspirin use were observed in all lower risk subgroups. NSAID use had no association with breast cancer incidence. Conclusion Based on their increased risk of breast cancer, postmenopausal women with a family history of breast cancer or a history of benign breast disease could potentially be targeted for aspirin chemoprevention studies. Future studies are needed to confirm these findings. PMID:26678006

  4. Cancer chemopreventive properties of orally bioavailable flavonoids -methylated versus unmethylated flavones

    PubMed Central

    Walle, Thomas; Ta, Nga; Kawamori, Toshihiko; Wen, Xia; Tsuji, Petra A.; Walle, U. Kristina

    2007-01-01

    Poor oral bioavailability has been a major limitation for the successful use of dietary flavonoids as cancer chemopreventive agents. In this study, we examined fully methylated flavones as promising improved agents. In the humanoral SCC-9 cancer cells, 5,7-dimethoxyflavone and 5,7,4’-trimethoxyflavone were both ten times more potent inhibitors of cell proliferation (IC50 values 5-8 μM) than the corresponding unmethylated analogs chrysin and apigenin. Flow cytometry indicated that both methylated flavones arrested the SCC-9 cells in the G1 phase with a concomitant decrease in the S phase, dramatically different from the unmethylated analogs, which promoted G2/M phase arrest. Both methylated compounds inhibited the proliferation of two other cancer cell lines with very little effect on two immortalized normal cell lines. Examination of additional flavone structures indicated that methylated flavones in general have antiproliferative properties. Finally, we demonstrated that 5,7-dimethoxyflavone, in contrast to its unmethylated analog chrysin, was well absorbed and had high oral bioavailability as well as tissue accumulation in vivo in the rat. Thus, fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents, in particular in oral cancer. PMID:17250812

  5. Cancer chemopreventive properties of orally bioavailable flavonoids--methylated versus unmethylated flavones.

    PubMed

    Walle, Thomas; Ta, Nga; Kawamori, Toshihiko; Wen, Xia; Tsuji, Petra A; Walle, U Kristina

    2007-05-01

    Poor oral bioavailability has been a major limitation for the successful use of dietary flavonoids as cancer chemopreventive agents. In this study, we examined fully methylated flavones as promising improved agents. In the human oral SCC-9 cancer cells, 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone were both 10 times more potent inhibitors of cell proliferation (IC(50) values 5-8 microM) than the corresponding unmethylated analogs chrysin and apigenin. Flow cytometry indicated that both methylated flavones arrested the SCC-9 cells in the G1 phase with a concomitant decrease in the S phase, dramatically different from the unmethylated analogs, which promoted G2/M phase arrest. Both methylated compounds inhibited the proliferation of two other cancer cell lines with very little effect on two immortalized normal cell lines. Examination of additional flavone structures indicated that methylated flavones in general have antiproliferative properties. Finally, we demonstrated that 5,7-dimethoxyflavone, in contrast to its unmethylated analog chrysin, was well absorbed and had high oral bioavailability as well as tissue accumulation in vivo in the rat. Thus, fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents, in particular in oral cancer.

  6. Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong remodeling of our epigenomes.

    PubMed

    Vanden Berghe, Wim

    2012-06-01

    Cancer, as one of the non-communicable diseases, remains one of the leading causes of death around the world. Recently, epigenetic changes in DNA methylation patterns at CpG sites (epimutations) or deregulated chromatin states of tumor promoting genes and noncoding RNAs emerged as major governing factors in tumor progression and cancer drug sensitivity. Furthermore, various environmental factors such as nutrition, behavior, stress, and toxins remodel our epigenomes lifelong in a beneficial or detrimental way. Since epigenetic marks (epimutations) are reversible in contrast to genetic defects, chemopreventive nutritional polyphenols (soy, genistein, resveratrol, catechin, curcumin) are currently evaluated for their ability to reverse adverse epigenetic marks in cancer (stem) cells to attenuate tumorigenesis-progression, prevent metastasis or sensitize for drug sensitivity. Although polyphenols in fruit and vegetables may help to reduce the risk of cancer, few protective effects have been firmly established, presumably because of inappropriate timing or dosing of diet exposure or due to confounding factors such as smoking and alcohol. In this review will discuss the possible epigenetic contributions of dietary polyphenols in cancer chemoprevention. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. The rainbow trout liver cancer model: response to environmental chemicals and studies on promotion and chemoprevention.

    PubMed

    Williams, David E

    2012-01-01

    Rainbow trout (Oncorhynchus mykiss) are an outstanding model of liver cancer induction by environmental chemicals and development of strategies for chemoprevention. Trout have critical and unique advantages allowing for cancer studies with 40,000 animals to determine dose-response at levels orders of magnitude lower than possible in rodents. Examples of two promoters in this model, the dietary supplement dehydroepiandrosterone (DHEA) and industrial chemical perfluorooctanoic acid (PFOA), are presented. In addition, indole-3-carbinol (I3C) and chlorophyllin (CHL) inhibit initiation following exposure to potent human chemical carcinogens (e.g., aflatoxin B(1) (AFB(1))). Two "ED(001)" cancer studies have been conducted, utilizing approximately 40,000 trout, by dietary exposure to AFB(1) and dibenzo[d,e,f,p]chrysene (DBC). These studies represent the two largest cancer studies ever performed and expand the dose-response dataset generated by the 25,000 mouse "ED(01)" study over an order of magnitude. With DBC, the liver tumor response fell well below the LED(10) line, often used for risk assessment, even though the biomarker (liver DBC-DNA adducts) remained linear. Conversely, the response with AFB(1) remained relatively linear throughout the entire dose range. These contributions to elucidation of mechanisms of liver cancer, induced by environmental chemicals and the remarkable datasets generated with ED(001) studies, make important contributions to carcinogenesis and chemoprevention. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Microsatellite instability in prostate cancer

    SciTech Connect

    Shan, A.L.; Wick, M.J.; Persons, D.L.

    1994-09-01

    Microsatellite instability (MIN) has been documented in hereditary nonpolyposis colorectal cancer (HNPCC) as well as in sporadic forms of human cancers. Two of the genes which appear to be responsible for this particular tumor phenotype, hMSH2 and hMLH1, have now been identified. To determine the potential role of these mutator genes in prostate cancer, we have examined 95 prostate adenocarcinomas (40 paraffin embedded and 55 fresh frozen) for the presence of genetic instability at four microsatellite markers. The markers are localized to chromosome arms 5q(APC-CA1), 8p(Mfd 210Z), 15q(635/636), and 17q(p53-CA). Patients from whom paraffin embedded material was obtained were divided into short term (<3 years, n=18), and long term (>3 years, n=22) survivors. Of the 95 tumors examined, only four tumors (4%) demonstrated MIN: two tumors demonstrated MIN at 3 loci (p53-CA, APC-CA1, 635/636), one tumor demonstrated MIN at 2 loci (APC-CA1 and 635/636), and one tumor demonstrated instability at 635/636 only. All tumors exhibiting MIN had Gleason scores of {ge} 4+4. A correlation between MIN and survival was not observed. Information on family history was limited. However, of the two patients demonstrating MIN at three loci, one patient was diagnosed with a second malignancy (TCC of the ureter), but otherwise had a negative family history, while the second patient had one first degree relative with esophageal cancer. The patient demonstrating MIN at two loci had a negative family history, while the remaining patient had two first degree relatives with cancer (prostate and stomach). These results suggest that hMSH2 and hMLH1 (as reflected by the small percentage of tumors displaying MIN) do not play a prominent role in the process of prostate tumorigenesis.

  9. Simulated prostate biopsy: prostate cancer distribution and clinical correlation

    NASA Astrophysics Data System (ADS)

    Bauer, John J.; Zeng, Jianchao; Zhang, Wei; Sesterhenn, Isabell A.; Dean, Robert; Moul, Judd W.; Mun, Seong K.

    2000-04-01

    Our group has recently obtained data based upon whole- mounted step-sectioned radical prostatectomy specimens using a 3D computer assisted prostate biopsy simulator that suggests an increased detection rate is possible using laterally placed biopsies. A new 10-core biopsy pattern was demonstrated to be superior to the traditional sextant biopsy. This patter includes the traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland. The objective of this study is to confirm the higher prostate cancer defection rate obtained using our simulated 10-core biopsy pattern in a small clinical trial. We retrospectively reviewed 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent of patients were diagnosed solely with the laterally placed biopsies. Our results suggest that biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern.

  10. Biochemical and molecular mechanisms underlying the chemopreventive efficacy of rosmarinic acid in a rat colon cancer.

    PubMed

    Venkatachalam, Karthikkumar; Gunasekaran, Sivagami; Namasivayam, Nalini

    2016-11-15

    To shed light on colon cancer chemoprevention, natural phytochemicals attract researchers by virtue of their beneficial biological effects. The chemopreventive potential of rosmarinic acid (RA) was tested by using the colon carcinogen, 1,2-dimethylhydrazine (DMH) by evaluating the Aberrant crypt foci (ACF), tumour incidence, lipid peroxidative byproducts, phase I & II drug metabolizing enzymes, cell proliferative and apoptotic proteins. Rats were divided into six groups and received modified pellet diet. Group 1 served as control rats, group 2 rats received RA (5mg/kg b.w. p.o.), rats in groups 3-6 received DMH (20mg/kg b.w., s.c.) for the first fifteen weeks. In addition to DMH, groups 4-6 received RA at the dose of 5mg/kg b.w. during initiation, post initiation stages and also for the entire study period. DMH treated rats showed an increase in the development of ACF, tumour formation and multiplicity and decrease in lipid peroxidative byproducts. Moreover, it modulates xenobiotic enzymes and reduces the expressions of proapoptotic proteins; increases expressions of anti apoptotic proteins at the end of the study. Supplementation with RA to carcinogen treated rats protected them from the above deleterious effects caused by DMH and thus RA may be used as a potent chemopreventive agent.

  11. Clove (Syzygium aromaticum L.), a potential chemopreventive agent for lung cancer.

    PubMed

    Banerjee, Sarmistha; Panda, Chinmay Kr; Das, Sukta

    2006-08-01

    Spices and flavoring plants part rich in supposedly health-promoting phytochemicals are currently receiving much attention as a possible source of cancer chemopreventive compounds. Clove, the sun-dried unopened flower bud from the plant Syzygium aromaticum L. is a commonly used spice and food flavor. In the present work we assess the chemopreventive potential of aqueous infusion of clove during benzo[a]pyrene (BP)-induced lung carcinogenesis in strain A mice. Incidence of hyperplasia, dysplasia and carcinoma in situ evident in the carcinogen control group on the 8th, 17th and 26th weeks, respectively, were effectively reduced after treatment with clove infusion. Significant reduction in the number of proliferating cells and an increased number of apoptotic cells was also noted in these BP-induced lung lesions following clove treatment. Western blotting analysis revealed that clove infusion upregulates the expression of pro-apoptotic proteins p53 and Bax, and downregulates the expression of anti-apoptotic protein Bcl-2 in the precancerous stages. Expression of caspase 3 and its activation by clove infusion were evident from a very early stage of carcinogenesis (eighth week). Clove infusion was also found to downregulate the expression of some growth-promoting proteins, viz, COX-2, cMyc, Hras. The observations signify the chemopreventive potential of clove in view of its apoptogenic and anti-proliferative properties.

  12. Mitochondria, prostate cancer, and biopsy sampling error.

    PubMed

    Parr, Ryan L; Mills, John; Harbottle, Andrew; Creed, Jennifer M; Crewdson, Gregory; Reguly, Brian; Guimont, François S

    2013-04-01

    Mitochondria and their associated genome are emerging as sophisticated indicators of prostate cancer biology. Alterations in the mitochondrial genome (mtgenome) have been implicated in cell proliferation, metastatic behavior, androgen independence, as a signal for apoptosis, and as a predictor of biochemical recurrence. Somatic mutation patterns in complete mtgenomes are associated with prostate specific antigen levels (PSA) in prostate cancer patients and a large-scale mtgenome deletion (3.4 kb) is consistent with a prostate "cancerization" field effect. This review will focus on the biological characteristics of mitochondria and their direct clinical application to prostate cancer. Mitochondrial science is currently influencing clinical prostate cancer diagnostics and the rapid progress in this area indicates future, break-through contributions in the general field of oncology.

  13. WITHDRAWN: Can the conventional sextant prostate biopsy reliably diagnose unilateral prostate cancer in low-risk, localized, prostate cancer?

    PubMed

    Mayes, J M; Mouraviev, V; Sun, L; Madden, J F; Polascik, T J

    2008-05-13

    The authors hereby retract the e-publication dated 13 May 2008 and entitled, 'Can the conventional sextant prostate biopsy reliably diagnose unilateral prostate cancer in low-risk, localized, prostate cancer?' The authors are submitting a revised version with the same title. This article's statistics were performed for predicting bilateral prostate cancer outcomes. The article was written to help predict unilateral prostate cancer. Although the statistical numbers are correct, they are backwards. We apologize that the statistics indicate a contrary outcome (eg predicting bilateral cancer instead of unilateral disease).

  14. Chemoprevention of chemical-induced skin cancer by Panax ginseng root extract

    PubMed Central

    Sharma, Jyoti; Goyal, Pradeep K.

    2015-01-01

    Background Cancer has emerged as a major health problem globally as a consequence to the increased longevity of the population, changing the environment and life style. Chemoprevention is a new and promising strategy for reducing cancer burden. Recently, some natural products have been identified for their chemopreventive activity to reduce the cancer incidence. Ginseng is known for its potential to treat various ailments in human beings. The present study was designed to explore the anticancer and antioxidative potential of Panax ginseng against chemical-induced skin carcinogenesis in mammals. Methods Skin tumors were induced in Swiss albino mice by a single topical application of 7,12-dimethylbenz(a)anthracene (100 μg/100 μL acetone) and, 2 wks later, promoted by repeated applications of croton oil (thrice in a wk in 1% acetone) till the end of the experiment (i.e., 16 wk). Hydroalcoholic ginseng root extract at a dose of 25 mg/kg body weight/d was orally administered at the peri-initiation, postinitiation, and peri–post-initiation stages. Results Ginseng root extract treatment caused a significant reduction in tumor incidence, cumulative number of tumors, tumor yield, and tumor burden, as compared to the 7,12-dimethylbenz(a)anthracene–croton oil-treated control group. Further, biochemical assays revealed a significant enhancement in the levels of reduced glutathione, superoxide dismutase, catalase, vitamin C, and total proteins but a significant reduction in lipid peroxidation levels in both the liver and skin with ginseng root extract treatment, as compared to carcinogen-treated control group. Conclusion These results suggest that P. ginseng has the potential to become a pivotal chemopreventive agent that can reduce cancer in mammals. PMID:26199559

  15. Weaknesses and Pitfalls of Using Mice and Rats in Cancer Chemoprevention Studies

    PubMed Central

    Ma, Yukui; Jia, Yuping; Chen, Lichan; Ezeogu, Lewis; Yu, Baofa; Xu, Ningzhi; Liao, D. Joshua

    2015-01-01

    Many studies, using different chemical agents, have shown excellent cancer prevention efficacy in mice and rats. However, equivalent tests of cancer prevention in humans require decades of intake of the agents while the rodents' short lifespans cannot give us information of the long-term safety. Therefore, animals with a much longer lifespan should be used to bridge the lifespan gap between the rodents and humans. There are many transgenic mouse models of carcinogenesis available, in which DNA promoters are used to activate transgenes. One promoter may activate the transgene in multiple cell types while different promoters are activated at different ages of the mice. These spatial and temporal aspects of transgenes are often neglected and may be pitfalls or weaknesses in chemoprevention studies. The variation in the copy number of the transgene may widen data variation and requires use of more animals. Models of chemically-induced carcinogenesis do not have these transgene-related defects, but chemical carcinogens usually damage metabolic organs or tissues, thus affecting the metabolism of the chemopreventive agents. Moreover, many genetically edited and some chemically-induced carcinogenesis models produce tumors that exhibit cancerous histology but are not cancers because the tumor cells are still mortal, inducer-dependent, and unable to metastasize, and thus should be used with caution in chemoprevention studies. Lastly, since mice prefer an ambient temperature of 30-32°C, it should be debated whether future mouse studies should be performed at this temperature, but not at 21-23°C that cold-stresses the animals. PMID:26366220

  16. Functional Angiogenic Mediators in Prostate Cancer

    DTIC Science & Technology

    2000-08-01

    FUNDING NUMBERS Functional Angiogenic Mediators in Prostate Cancer DAMD17-99- 1 -9521 6. AUTHOR(S) Jennifer A. Doll, Ph.D. 7. PERFORMING ORGANIZATION NAME...transition in the prostate by 1 ) identifying the key angiogenic mediators , 2) investigating the clinical significance of mediator levels in prostatic fluid...our proposal, we set out to 1 ) identify such mediators in the prostate, 2) assess the clinical usefulness of measuring angiogenic mediator levels in

  17. [Active surveillance of prostate cancer].

    PubMed

    Ploussard, G; Hennequin, C; Rozet, F

    2017-10-01

    Several prospective studies have demonstrated the safety of active surveillance as a first treatment of prostate cancer. It spares many patients of a useless treatment, with its potential sequelae. Patients with a low-risk cancer are all candidates for this approach, as recommended by the American Society of Clinical Oncology (ASCO). Some patients with an intermediate risk could be also concerned by active surveillance, but this is still being discussed. Currently, the presence of grade 4 lesions on biopsy is a contra-indication. Modalities included a repeated prostate specific antigen test and systematic rebiopsy during the first year after diagnosis. MRI is now proposed to better select patients at inclusion and also during surveillance. No life style changes or drugs are significantly associated with a longer duration of surveillance. Copyright © 2017. Published by Elsevier SAS.

  18. [Medical treatment of prostate cancer].

    PubMed

    Lobel, B; Cipolla, B; Labrador, J

    1994-03-01

    Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment.

  19. Anticancer and Cancer Chemopreventive Potential of Grape Seed Extract and Other Grape-Based Products1–3

    PubMed Central

    Kaur, Manjinder; Agarwal, Chapla; Agarwal, Rajesh

    2009-01-01

    With emerging trends in the incidence of cancer of various organ sites, additional approaches are needed to control human malignancies. Intervention or prevention of cancer by dietary constituents, a strategy defined as chemoprevention, holds great promise in our conquest to control cancer, because it can be implemented on a broader population base with less economic burden. Consistent with this, several epidemiological studies have shown that populations that consume diets rich in fruits and vegetables have an overall lower cancer incidence. Based on these encouraging observations, research efforts from across the globe have focused on identifying, characterizing, and providing scientific basis to the efficacy of various phytonutrients in an effort to develop effective strategy to control various human malignancies. Cancer induction, growth, and progression are multi-step events and numerous studies have demonstrated that various dietary agents interfere with these stages of cancer, thus blocking malignancy. Fruits and vegetables represent untapped reservoir of various nutritive and nonnutritive phytochemicals with potential cancer chemopreventive activity. Grapes and grape-based products are one such class of dietary products that have shown cancer chemopreventive potential and are also known to improve overall human health. This review focuses on recent advancements in cancer chemopreventive and anticancer efficacy of grape seed extract and other grape-based products. Overall, completed studies from various scientific groups conclude that both grapes and grape-based products are excellent sources of various anticancer agents and their regular consumption should thus be beneficial to the general population. PMID:19640973

  20. Vaccine Immunotherapy for Prostate Cancer

    DTIC Science & Technology

    2006-07-01

    opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position...Vaccine Immunotherapy for Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-05-1-0462 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ...NAME( S ) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER University of Iowa Iowa City, IA 52242 9. SPONSORING

  1. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2007-02-01

    award. Validation of these findings in animal models is currently in progress. 15. SUBJECT TERMS Selenium, methylselenol , prostate cancer...Pharmacologic inhibitors were used to manipulate caspases and c-Jun-N-terminal kinases (JNK). Results: The methylselenol precursor methylseleninic acid...Email: jlu@hi.umn.edu Methylselenol has been implicated as an active metabolite for the anticancer effect of selenium in part through the induction of

  2. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2011-05-01

    this laboratory concentrates on the area of tumor immunology with an emphasis on immunotherapy. We have constructed microbial vaccines to be used...to the transgene product induced by the vaccine are underway. Additionally, we are carrying our "translational" research in the form of clinical...trials of our adenovirus vaccine in men with prostate cancer. Important in these trials is the safety of the vaccine and its ability to induce anti

  3. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2012-05-01

    i mmunology with an emphasis on immunotherapy. We ha ve constructed microbial vaccines to be used for the investigation of gene and immunotherapy... vaccine are underway. Additionally, we are carrying our "translational" research in the fo rm of clinical trials of our adenovirus vaccine in men with...prostate cancer. Important in thes e trials is the safety of the vaccine and its ability to in duce anti-tumor immunity. We have recently completed

  4. Utility of ADC measurement on diffusion-weighted MRI in differentiation of prostate cancer, normal prostate and prostatitis.

    PubMed

    Esen, Meltem; Onur, Mehmet Ruhi; Akpolat, Nusret; Orhan, Irfan; Kocakoc, Ercan

    2013-08-01

    To determine the utility of apparent diffusion coefficient (ADC) values in differentiation of prostate cancer from normal prostate parenchyma and prostatitis we obtained ADC values of 50 patients at b 100, 600 and 1,000 s/mm(2) diffusion gradients. The ADC values of prostate cancer group were significantly lower than normal prostate and prostatitis group at b 600 and 1,000 s/mm(2) gradients. The ADC values at high diffusion gradients may be used in differentiation prostate cancer from normal prostate and prostatitis.

  5. Precision medicine for advanced prostate cancer.

    PubMed

    Mullane, Stephanie A; Van Allen, Eliezer M

    2016-05-01

    Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

  6. Precision medicine for advanced prostate cancer

    PubMed Central

    Mullane, Stephanie A.; Van Allen, Eliezer M.

    2016-01-01

    Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

  7. DNA Vaccines for Prostate Cancer

    PubMed Central

    McNeel, Douglas G.; Becker, Jordan T.; Johnson, Laura E.; Olson, Brian M.

    2013-01-01

    Delivery of plasmid DNA encoding an antigen of interest has been demonstrated to be an effective means of immunization, capable of eliciting antigen-specific T cells. Plasmid DNA vaccines offer advantages over other anti-tumor vaccine approaches in terms of simplicity, manufacturing, and possibly safety. The primary disadvantage is their poor transfection efficiency and subsequent lower immunogenicity relative to other genetic vaccine approaches. However, multiple preclinical models demonstrate anti-tumor efficacy, and many efforts are underway to improve the immunogenicity and anti-tumor effect of these vaccines. Clinical trials using DNA vaccines as treatments for prostate cancer have begun, and to date have demonstrated safety and immunological effect. This review will focus on DNA vaccines as a specific means of antigen delivery, advantages and disadvantages of this type of immunization, previous experience in preclinical models and human trials specifically conducted for the treatment of prostate cancer, and future directions for the application of DNA vaccines to prostate cancer immunotherapy. PMID:24587772

  8. A potential role of PUFAs and COXIBs in cancer chemoprevention.

    PubMed

    Vara-Messler, Marianela; Buccellati, Carola; Pustina, Linda; Folco, Giancarlo; Rovati, G Enrico; Hoxha, Malvina

    2015-07-01

    Polyunsaturated fatty acids (PUFAs), particularly the ω-3 PUFAs and COXIBs have been associated with decreased inflammation and the prevention of tumorigenesis. ω-3 PUFAs have shown to display multiple antitumour actions, while ω-6 PUFAs and its derived eicosanoids promote the effects in cancer cell growth, angiogenesis, and invasion. ω-3 PUFAs may act by suppressing the metabolism of arachidonic acid to form proinflammatory mediators or as a precursors of novel lipid mediators with pro-resolving activity, while COXIBs are able to modulate inflammatory response by inhibiting cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase overexpressed in several human cancers. As recently has been postulated, the anti-inflammation and pro-resolution processes are not equivalent. A family of lipid mediators from ω-3 PUFAs can act as agonist promoting resolution, while antinflammatory agents such as COXIBs may act as antagonists limiting the inflammatory response. The present paper reviews the current knowledge about the role of PUFAs and its derivatives (metabolites), as well as the COXIBs activity in cancer process as a sinergic therapeutic alternative for cancer treatment.

  9. Cancer chemopreventive potential of apples, apple juice, and apple components.

    PubMed

    Gerhauser, Clarissa

    2008-10-01

    Apples ( MALUS sp., Rosaceae) are a rich source of nutrient as well as non-nutrient components and contain high levels of polyphenols and other phytochemicals. Main structural classes of apple constituents include hydroxycinnamic acids, dihydrochalcones, flavonols (quercetin glycosides), catechins and oligomeric procyanidins, as well as triterpenoids in apple peel and anthocyanins in red apples. Several lines of evidence suggest that apples and apple products possess a wide range of biological activities which may contribute to health beneficial effects against cardiovascular disease, asthma and pulmonary dysfunction, diabetes, obesity, and cancer (reviewed by Boyer and Liu, Nutr J 2004). The present review will summarize the current knowledge on potential cancer preventive effects of apples, apple juice and apple extracts (jointly designated as apple products). In brief, apple extracts and components, especially oligomeric procyanidins, have been shown to influence multiple mechanisms relevant for cancer prevention in IN VITRO studies. These include antimutagenic activity, modulation of carcinogen metabolism, antioxidant activity, anti-inflammatory mechanisms, modulation of signal transduction pathways, antiproliferative and apoptosis-inducing activity, as well as novel mechanisms on epigenetic events and innate immunity. Apple products have been shown to prevent skin, mammary and colon carcinogenesis in animal models. Epidemiological observations indicate that regular consumption of one or more apples a day may reduce the risk for lung and colon cancer.

  10. Pharmacogenetics, pharmacogenomics and epigenetics of Nrf2-regulated xenobiotic-metabolizing enzymes and transporters by dietary phytochemical and cancer chemoprevention.

    PubMed

    Wu, Tien-Yuan; Khor, Tin Oo; Lee, Jong Hun; Cheung, Ka Lung; Shu, Limin; Chen, Chi; Kong, Ah-Ng

    2013-07-01

    Cancer chemopreventive activities of various phytochemicals have been attributed to the modulation of xenobiotic disposition, which includes absorption, distribution, metabolism, and excretion. The interaction between xenobiotics and xenobiotic-metabolizing enzymes (XMEs) is bidirectional. XMEs are responsible for the biotransformation of xenobiotics such as bioactivation and detoxification. Conversely, xenobiotics affect XMEs through transcriptional regulation (induction or suppression) and post-translational interactions (inhibition or activation). Similar relationships also exist between xenobiotics and their transporters. Studies conducted over the past decade have demonstrated that the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), plays a critical role in the regulation of detoxifying enzymes and transporters through a signaling system that senses and responds to redox imbalance. The role of Nrf2 in the interaction between chemopreventive phytochemicals and detoxifying enzymes/transporters has become an important topic in cancer chemoprevention. In this review, the genetic and epigenetic factors that contribute to Nrf2-mediated regulation of detoxifying XMEs and transporters are discussed in the context of cancer chemoprevention. Phytochemicals may modulate the genome as well as epigenome, altering the regulation of XMEs and transporters, which may be critical for both cancer chemoprevention and the prevention of other oxidative stress- and inflammatory-related diseases, including cardiovascular, metabolic and neurological pathologies. The pharmacogenomic expression of XMEs and transporters, with an emphasis on both genomics and epigenetics, will also be discussed.

  11. Linking Estrogens, Prostatitis and Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    provide the first direct evidence linking phy siologic estr ogen up- regulation an d pr ostate ma lignancy via inflammation. Ellem, Stuart J...inflammation and malignancy in the prostate. The identification of estr ogen as a cause of prostatitis, as well as a fac tor in the development of

  12. Recruitment strategies for a lung cancer chemoprevention trial involving ex-smokers.

    PubMed

    Kye, Steve H; Tashkin, Donald P; Roth, Michael D; Adams, Bradley; Nie, Wen-Xian; Mao, Jenny T

    2009-09-01

    The ability to recruit qualified subjects who are willing to adhere to the study protocol in clinical trials is an essential component of translational research. Such tasks can be particularly challenging for chemoprevention studies when the targeted study population is healthy, at risk individuals who do not have signs or symptoms of the disease, and the study participation involves complex scheduling and invasive procedures such as bronchoscopy. In this report, we describe the recruitment process and evaluated the effectiveness of various recruitment strategies utilized in our National Cancer Institute sponsored lung cancer chemoprevention study with celecoxib. Heavy ex-smokers were recruited into the study through various methods such as radio advertisements, print media, mass mailings, flyers, internet postings and others. The number of inquiries, on-site screenees and randomization generated by each method determined the efficacy of that recruitment strategy. We prescreened 4470 individuals, invited 323 people for on-site screening and randomized 137 subjects. Radio advertisements (ads) generated the most inquiries (71.1%), followed by internet posting (11.8%), print media (6.0%), posted and racked flyers (4.4%), mass mailings (2.7%) and other strategies such as referrals from friends or family members or health care providers (2.3%). Radio ads, although costly, yielded the most subjects for on-site screening and randomization. Moreover, among the various types of radio stations, news radio stations were by far the most successful. Our results suggest that advertising on news radio is a highly effective recruitment method for successful accrual of ex-smokers into lung cancer chemoprevention trials.

  13. Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer.

    PubMed

    El-Ashmawy, Nahla E; Khedr, Eman G; El-Bahrawy, Hoda A; Al-Tantawy, Samar M

    2017-02-01

    Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as

  14. Esophageal cancer: The latest on chemoprevention and state of the art therapies.

    PubMed

    Le Bras, Gregoire F; Farooq, Muhammad H; Falk, Gary W; Andl, Claudia D

    2016-11-01

    Esophageal cancer is currently the 8th most common cancer worldwide and the 6th leading cause of cancer-related mortality. Despite remarkable advances, the mortality for those suffering from esophageal cancer remains high, with 5-year survival rates of less than 20%. In part, because most patients present with late-stage disease, long-term survival even after resection and therapy is disappointingly low. As we will discuss in this review, multiple characteristics specific to the disease stage and patient must be considered when choosing a treatment plan. This article will summarize current standard therapies, potential application of chemoprevention drugs and the promise and partial failure of personalized medicine, as well as novel treatments addressing this disease.

  15. Arachidonic acid metabolism in human prostate cancer

    PubMed Central

    YANG, PEIYING; CARTWRIGHT, CARRIE A.; LI, JIN; WEN, SIJIN; PROKHOROVA, INA N.; SHUREIQI, IMAD; TRONCOSO, PATRICIA; NAVONE, NORA M.; NEWMAN, ROBERT A.; KIM, JERI

    2012-01-01

    The arachidonic acid pathway is important in the development and progression of numerous malignant diseases, including prostate cancer. To more fully evaluate the role of individual cyclooxygenases (COXs), lipoxygenases (LOXs) and their metabolites in prostate cancer, we measured mRNA and protein levels of COXs and LOXs and their arachidonate metabolites in androgen-dependent (LNCaP) and androgen-independent (PC-3 and DU145) prostate cancer cell lines, bone metastasis-derived MDA PCa 2a and MDA PCa 2b cell lines and their corresponding xenograft models, as well as core biopsy specimens of primary prostate cancer and nonneoplastic prostate tissue taken ex vivo after prostatectomy. Relatively high levels of COX-2 mRNA and its product PGE2 were observed only in PC-3 cells and their xenografts. By contrast, levels of the exogenous 12-LOX product 12-HETE were consistently higher in MDA PCa 2b and PC-3 cells and their corresponding xenograft tissues than were those in LNCaP cells. More strikingly, the mean endogenous level of 12-HETE was significantly higher in the primary prostate cancers than in the nonneoplastic prostate tissue (0.094 vs. 0.010 ng/mg protein, respectively; p=0.019). Our results suggest that LOX metabolites such as 12-HETE are critical in prostate cancer progression and that the LOX pathway may be a target for treating and preventing prostate cancer. PMID:22895552

  16. Caveolin-1 and prostate cancer progression.

    PubMed

    Freeman, Michael R; Yang, Wei; Di Vizio, Dolores

    2012-01-01

    Caveolin-1 was identified in the 1990s as a marker of aggressive prostate cancer. The caveolin-1 protein localizes to vesicular structures called caveolae and has been shown to bind and regulate many signaling proteins involved in oncogenesis. Caveolin-1 also has lipid binding properties and mediates aspects of cholesterol and fatty acid metabolism and can elicit biological responses in a paracrine manner when secreted. Caveolin-1 is also present in the serum of prostate cancer patients and circulating levels correlate with extent of disease. Current evidence indicates that increased expression of caveolin-1 in prostate adenocarcinoma cells and commensurate downregulation of the protein in prostate stroma, mediate progression to the castration-resistant phase of prostate cancer through diverse pathways. This chapter summarizes the current state of our understanding of the cellular and physiologic mechanisms in which caveolin-1 participates in the evolution of prostate cancer cell phenotypes.

  17. Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

    PubMed Central

    Nicastro, Holly L.; Dunn, Barbara K.

    2013-01-01

    The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention. PMID:23552052

  18. Vietnam military service history and prostate cancer

    PubMed Central

    Justine, Leavy; Gina, Ambrosini; Lin, Fritschi

    2006-01-01

    Background Three decades after US and Australian forces withdrew from Vietnam, there has been much public interest in the health consequences of service in Vietnam. One controversial question is whether the risk of prostate cancer amongst Vietnam veterans is increased. This paper examines relationships between military history, family history and risk of prostate cancer in a population-based case control study. Methods Cases were selected from the Cancer Registry of Western Australia as incident cases of histologically-confirmed prostate cancer, and controls were age-matched and selected from the Western Australian electoral roll. Study participants were asked to report any military service history and details about that service. Results Between January 2001 and September 2002, 606 cases and 471 controls aged between 40–75 years were recruited. An increased prostate cancer risk was observed in men reporting they were deployed in Vietnam although this was not statistically significant (OR = 2.12; 95% CI 0.88–5.06). An increased risk was also observed in men reporting prostate cancer in fathers (OR = 1.90; 95% CI 1.20–3.00) or brothers (OR = 2.05; 95% CI 1.20–3.50) diagnosed with prostate cancer. Conclusion These findings support a positive association between prostate cancer and military service history in the Vietnam war and a first degree relative family history of prostate cancer. PMID:16556325

  19. Prevention and Early Detection of Prostate Cancer

    PubMed Central

    Cuzick, Jack; Thorat, Mangesh A.; Andriole, Gerald; Brawley, Otis W.; Brown, Powel H.; Culig, Zoran; Eeles, Rosalind A.; Ford, Leslie G.; Hamdy, Freddie C.; Holmberg, Lars; Ilic, Dragan; Key, Timothy J.; La Vecchia, Carlo; Lilja, Hans; Marberger, Michael; Meyskens, Frank L.; Minasian, Lori M.; Parker, Chris; Parnes, Howard L.; Perner, Sven; Rittenhouse, Harry; Schalken, Jack; Schmid, Hans-Peter; Schmitz-Dräger, Bernd J.; Schröder, Fritz H.; Stenzl, Arnulf; Tombal, Bertrand; Wilt, Timothy J.; Wolk, Alicja

    2014-01-01

    Prostate cancer is one of the most common cancers in men and the global burden of this disease is rising. Lifestyle modifications like smoking cessation, exercise and weight control offer opportunities to decrease the risk of developing prostate cancer. Early detection of prostate cancer by PSA screening remains controversial; yet, changes in PSA threshold, frequency of screening, and addition of other biomarkers have potential to minimise overdiagnosis associated with PSA screening. Several new biomarkers appear promising in individuals with elevated PSA levels or those diagnosed with prostate cancer, these are likely to guide in separating individuals who can be spared of aggressive treatment from those who need it. Several pharmacological agents like 5α-reductase inhibitors, aspirin etc. have a potential to prevent development of prostate cancer. In this review, we discuss the current evidence and research questions regarding prevention, early detection of prostate cancer and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer. PMID:25281467

  20. Dietary Antioxidants and Prostate Cancer: A Review

    PubMed Central

    Vance, Terrence M.; Su, Joseph; Fontham, Elizabeth T. H.; Koo, Sung I.; Chun, Ock K.

    2013-01-01

    Prostate cancer is the most common non-cutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, while lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms. PMID:23909722

  1. Functional Imaging for Prostate Cancer: Therapeutic Implications

    PubMed Central

    Aparici, Carina Mari; Seo, Youngho

    2012-01-01

    Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities CT or MRI (SPECT/CT, PET/CT, and PET/MRI) are promising tools for the management of prostate cancer particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection, to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regards to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, while the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects. PMID:22840598

  2. Chemoprevention Against Breast Cancer with Genistein and Resveratrol

    DTIC Science & Technology

    2007-03-01

    genistein and resveratrol suppress the development of chemically-induced mammary cancer in rats , we proposed to investigate the potential of...Figure 1. Rats treated ± genistein (250mg/kg diet) were sacrificed at 50 days postpartum. Mammary glands were dissected and assayed for protein...significant effect on uterine to body weight ratios, although genistein -treated rats displayed a 34% increase compared to the control group. This would fit

  3. A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression

    PubMed Central

    Simons, Brian W; Durham, Nicholas M; Bruno, Tullia C; Grosso, Joseph F; Schaeffer, Anthony J; Ross, Ashley E; Hurley, Paula J; Berman, David M; Drake, Charles G; Thumbikat, Praveen; Schaeffer, Edward M

    2015-01-01

    Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate-derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1-infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. PMID:25348195

  4. Prostate Cancer: How Young is too Young?

    PubMed Central

    Gupta, Sahil; Gupta, Arjun; Saini, Ashish K.; Majumder, Kaustav; Sinha, Kalpana; Chahal, Anurag

    2017-01-01

    Prostate cancer is the most common non-cutaneous malignancy in men. It is generally considered a cancer of the elderly, and the median age of presentation is 68 years. However 10% of new diagnoses in the USA occur in men aged ≤ 55 years. This may be due to more prevalent screening nowadays, and may also reflect the diagnosis of an increasingly recognized but underappreciated entity, i.e. early-onset prostate cancer. Patients with early onset prostate cancer pose unique challenges. Current data suggest that early-onset prostate cancer is a distinct phenotype—from both an etiological and clinical perspective— that deserves further attention. We present a case of a 28-year-old man who presented with lower urinary tract symptoms and was diagnosed with advanced stage prostate cancer. PMID:28413383

  5. Genetic variation: effect on prostate cancer

    PubMed Central

    Sissung, Tristan M.; Price, Douglas K.; Del Re, Marzia; Ley, Ariel M.; Giovannetti, Elisa; Danesi, Romano

    2014-01-01

    Summary The crucial role of androgens in the development of prostate cancer is well established. The aim of this review is to examine the role of constitutional (germline) and tumor-specific (somatic) polymorphisms within important regulatory genes of prostate cancer. These include genes encoding enzymes of the androgen biosynthetic pathway, the androgen receptor gene, genes that encode proteins of the signal transduction pathways that may have a role in disease progression and survival, and genes involved in prostate cancer angiogenesis. Characterization of deregulated pathways critical to cancer cell growth have lead to the development of new treatments, including the CYP17 inhibitor abiraterone and clinical trials using novel drugs that are ongoing or recently completed [1]. The pharmacogenetics of the drugs used to treat prostate cancer will also be addressed. This review will define how germline polymorphisms are known affect a multitude of pathways, and therefore phenotypes, in prostate cancer etiology, progression, and treatment. PMID:25199985

  6. Review of selenium and prostate cancer prevention.

    PubMed

    Yang, Lei; Pascal, Mouracade; Wu, Xiao-Hou

    2013-01-01

    Prostate cancer is the most common malignancy in men in the United States. Surgery or radiation are sometimes unsatisfactory treatments because of the complications such as incontinence or erectile dysfunction. Selenium was found to be effective to prevent prostate cancer in the Nutritional Prevention of Cancer Trial (NPC), which motivated two other clinical trials: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and a Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia. However, these two trials failed to confirm the results of the NPC trial and indicated that the selenium may not be preventive of prostate cancer. In this article we review the three clinical trials and discuss some different points which might be potential factors underlying variation in results obtained.

  7. Mechanistic perspectives on cancer chemoprevention/chemotherapeutic effects of thymoquinone.

    PubMed

    Kundu, Juthika; Chun, Kyung-Soo; Aruoma, Okezie I; Kundu, Joydeb Kumar

    2014-10-01

    The bioactive natural products (plant secondary metabolites) are widely known to possess therapeutic value for the prevention and treatment of various chronic diseases including cancer. Thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone; TQ), a monoterpene present in black cumin seeds, exhibits pleiotropic pharmacological activities including antioxidant, anti-inflammatory, antidiabetic and antitumor effects. TQ inhibits experimental carcinogenesis in a wide range of animal models and has been shown to arrest the growth of various cancer cells in culture as well as xenograft tumors in vivo. The mechanistic basis of anticancer effects of TQ includes the inhibition of carcinogen metabolizing enzyme activity and oxidative damage of cellular macromolecules, attenuation of inflammation, induction of cell cycle arrest and apoptosis in tumor cells, blockade of tumor angiogenesis, and suppression of migration, invasion and metastasis of cancer cells. TQ shows synergistic and/or potentiating anticancer effects when combined with clinically used chemotherapeutic agents. At the molecular level, TQ targets various components of intracellular signaling pathways, particularly a variety of upstream kinases and transcription factors, which are aberrantly activated during the course of tumorigenesis.

  8. Functional Angiogenic Mediators in Prostate Cancer

    DTIC Science & Technology

    2001-08-01

    Prostate DAMD17-99- 1 -9521 Cancer 6. AUTHOR(S) Jennifer A. Doll, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING...determine the efficacy of the natural inhibitor thrombospondin- 1 (TSP- 1 ) in treating prostate cancer in model systems. Prostate cells secrete many molecules...17-39 3 Annual Summary Report P.I. Jennifer A. Doll Award #DAMD17-99- 1 -9521 Introduction Prostate cancer is a heterogeneous disease (Cheng et al.,

  9. Overview of Dietary Supplements in Prostate Cancer.

    PubMed

    Yacoubian, Aline; Dargham, Rana Abu; Khauli, Raja B; Bachir, Bassel G

    2016-11-01

    Prostate cancer is a key health concern for men with its etiology still under investigation. Recently, the role of dietary supplements has been noted to have a major inhibitory effect on prostate cancer and numerous studies have been conducted in this regard. This review provides a summary on numerous recent studies conducted in this field. Some of the studies reviewed revealed a protective role for supplements, and others showed no correlation while some even had an adverse effect. The mechanism of how these supplements act on the prostate is still not clear. Further studies are warranted especially for supplements that have been shown to have a potential inhibitory role in prostate cancer.

  10. Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate.

    PubMed

    Heo, M Y; Sohn, S J; Au, W W

    2001-05-01

    Flavonoids are polyphenolic compounds that are present in plants. They have been shown to possess a variety of biological activities at non-toxic concentrations in organisms. Galangin, a member of the flavonol class of flavonoid, is present in high concentrations in medicinal plants (e.g. Alpinia officinarum) and propolis, a natural beehive product. Results from in vitro and in vivo studies indicate that galangin with anti-oxidative and free radical scavenging activities is capable of modulating enzyme activities and suppressing the genotoxicity of chemicals. These activities will be discussed in this review. Based on our review, galangin may be a promising candidate for cancer chemoprevention.

  11. Natural products as a source of potential cancer chemotherapeutic and chemopreventive agents.

    PubMed

    Cassady, J M; Baird, W M; Chang, C J

    1990-01-01

    Recent advances in the chemistry of novel bioactive natural products are reported. This research is directed to the exploration of plants with confirmed activity in bioassays designed to detect potential cancer chemotherapeutic and chemopreventive agents. Structural work and chemical studies are reported for several cytotoxic agents from the plants Annona densicoma, Annona reticulata, Claopodium crispifolium, Polytrichum obioense, and Psorospermum febrifugum. Studies are also reported based on development of a mammalian cell culture benzo[a]pyrene metabolism assay for the detection of potential anticarcinogenic agents from natural products. In this study a number of isoflavonoids and flavonoids with antimutagenic activity have been discovered.

  12. Metformin Use and Risk of Prostate Cancer: Results from the REDUCE Study

    PubMed Central

    Feng, Tom; Sun, Xizi; Howard, Lauren E.; Vidal, Adriana C.; Gaines, Alexis R.; Moreira, Daniel M.; Castro-Santamaria, Ramiro; Andriole, Gerald L.; Freedland, Stephen J.

    2015-01-01

    The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other anti-diabetic medications, vs. no anti-diabetic medication use and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4–6, high-grade Gleason 7–10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any anti-diabetic medications, 141 (26%) reported use of at least one anti-diabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR=1.19, p=0.50), low- (OR=1.01, p=0.96), or high-grade (OR=1.83, p=0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin anti-diabetic medications and prostate cancer risk in both crude (OR=1.02, p=0.95) and multivariable analysis (OR=0.85, p=0.56). Furthermore, the interactions between anti-diabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all p>0.05). Among diabetic men with a negative pre-study biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis. PMID:26353947

  13. Metformin use and risk of prostate cancer: results from the REDUCE study.

    PubMed

    Feng, Tom; Sun, Xizi; Howard, Lauren E; Vidal, Adriana C; Gaines, Alexis R; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

    2015-11-01

    The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4-6 and high-grade Gleason 7-10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any antidiabetic medications, 141 (26%) reported use of at least one antidiabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR, 1.19; P = 0.50), low- (OR, 1.01; P = 0.96), or high-grade (OR, 1.83; P = 0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin antidiabetic medications and prostate cancer risk in both crude (OR, 1.02; P = 0.95) and multivariable analysis (OR, 0.85; P = 0.56). Furthermore, the interactions between antidiabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all P > 0.05). Among diabetic men with a negative prestudy biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis.

  14. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  15. Regulation of the Prostate Cancer Tumor Microenvironment

    DTIC Science & Technology

    2013-04-01

    epithelium , stroma, as well as immune system, and the fixed nature of the prostate model with expression of the large T antigen, which may have limited...cancer glandular architecture formed (Figure 8). Figure 8. Subcutanous TRAMP Model to Recapitulate Prostate Cancer. TRAMP C2 cells with and...model to be able to alter the aggressiveness of the tumor and specifically modulate the TLR signaling pathway in prostate epithelium , stroma, and immune

  16. Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-fluorouracil: a preliminary study.

    PubMed

    Shakeel, Faiyaz; Haq, Nazrul; Al-Dhfyan, Abdullah; Alanazi, Fars K; Alsarra, Ibrahim A

    2015-01-01

    Oral delivery of 5-fluorouracil (5-FU) is difficult due to its serious adverse effects and extremely low bioavailability. Therefore, the aim of present investigation was to develop and evaluate low HLB surfactant nanoemulsion of 5-FU for topical chemoprevention of skin cancer. Low HLB surfactant nanoemulsions were prepared by oil phase titration method. Thermodynamically stable nanoemulsions were characterized in terms of droplet size distribution, zeta potential, viscosity and refractive index. Selected formulations and control were subjected to in vitro skin permeation studies through rat skin using Franz diffusion cells. Optimized formulation F9 was subjected to stability and in vitro cytotoxic studies on melanoma cell lines. Enhancement ratio was found to be 22.33 in formulation F9 compared with control and other formulations. The values of steady state flux and permeability coefficient for formulation F9 were found to be 206.40 ± 14.56 µg cm(-2) h(-1) and 2.064 × 10(-2) ± 0.050 × 10(-2 )cm h(-1), respectively. Optimized formulation F9 was found to be physical stable. In vitro cytotoxicity studies on SK-MEL-5 cancer cells indicated that 5-FU in optimized nanoemulsion is much more efficacious than free 5-FU. From these results, it can be concluded that the developed nanoemulsion might be a promising vehicle for chemoprevention of skin cancer.

  17. The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review

    PubMed Central

    Capurso, Cristiano; Vendemiale, Gianluigi

    2017-01-01

    Prostate cancer is the second most common cancer in the world among men, and is the fifth most common cause of cancer death among men. The aim of our review was to analyze observational and case–control studies to point out the effects of overweight and diets components on the cancer risk, particularly on risk of prostate cancer, and the effect of the Mediterranean diet (MD) on the reduction of risk and mortality of prostate cancer. It is known that incidence and progression of cancer is multifactorial. Cancer of the large bowel, breast, endometrium, and prostate are due also to a high body mass index and to high consumption of high carcinogenic dietary factors, as red and processed meat or saturated fats rich foods, and to a low consumption of vegetables and fruits. Previous meta-analysis suggested that high adherence to diet model based on the traditional MD pattern gives a significant protection from incidence and mortality of cancer of all types. The main component of the MD is olive oil, consumed in high amount by Mediterranean basin populations. In addition, phenolic compounds exert some strong chemo-preventive effects, which are due to several mechanisms, including both antioxidant effects and actions on cancer cell signaling and cell cycle progression and proliferation. The protective effect of the MD against the prostate cancer is also due to the high consumption of tomato sauce. Lycopene is the most relevant functional component in tomatoes; after activating by the cooking of tomato sauce, it exerts antioxidant properties by acting in the modulation of downregulation mechanisms of the inflammatory response. MD, therefore, represents a healthy dietary pattern in the context of a healthy lifestyle habits. In conclusion, our narrative review allows us to reaffirm how nutritional factors play an important role in cancer initiation and development, and how a healthy dietary pattern represented by MD and its components, especially olive oil, could exert a

  18. [Second cancer after starting treatment for prostate cancer].

    PubMed

    Mikata, Noriharu; Imao, Sadao; Fukasawa, Ritu

    2002-08-01

    The subjects for the present study were 270 patients with prostate cancer who underwent initial treatment at our hospital over the 14 years from 1986 to 1999. They were investigated to assess the relationship between their treatment and metachronous tumors. Sixteen patients (5.9%) developed cancer of other organs after starting treatment for prostate cancer. These metachronous tumors included gastric cancer in six patients as well as lung cancer, esophageal cancer, colorectal cancer, liver cancer, renal cancer, bladder cancer, skin cancer, leukemia, and mediastinal adenocarcinoma. Treatment for prostate cancer other than surgery included radiotherapy in eight patients, administration of estramustine phosphate sodium in nine patients, and LH-RH analogues in six patients. The chi-square test showed no significant difference in the incidence of metachronous cancer in relation to the presence/absence of these three therapies. The present study therefore ruled out the possible induction of other tumors by treatment for prostate cancer.

  19. Apoptosis by dietary agents for prevention and treatment of prostate cancer

    PubMed Central

    Khan, Naghma; Adhami, Vaqar Mustafa; Mukhtar, Hasan

    2010-01-01

    Accumulating data clearly indicate that induction of apoptosis is an important event for chemoprevention of cancer by naturally occurring dietary agents. In mammalian cells, apoptosis has been divided into two major pathways: the extrinsic pathway, activated by pro-apoptotic receptor signals at the cellular surface; and the intrinsic pathway, which involves the disruption of mitochondrial membrane integrity. This process is strictly controlled in response to integrity of pro-death signaling and plays critical roles in development, maintenance of homeostasis, and host defense in multicellular organisms. For chemoprevention studies, prostate cancer (PCa) represents an ideal disease due to its long latency, its high incidence, tumor marker availability, and identifiable preneoplastic lesions and risk groups. In this article, we highlight the studies of various apoptosis-inducing dietary compounds for prevention of PCa in vitro in cell culture, in preclinical studies in animals, and in human clinical trials. PMID:19926708

  20. Prostate Cancer Genetics in African Americans

    DTIC Science & Technology

    2015-11-01

    AWARD NUMBER: W81XWH-11-1-0566 TITLE: Prostate Cancer Genetics in African Americans PRINCIPAL INVESTIGATOR: Henry T. Lynch, MD CONTRACTING...W81XWH-11-1-0566 November 2015 Final 15Aug2011 - 14Aug2015 Prostate Cancer Genetics in African Americans Henry T. Lynch Nothing listed 36