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Chemoprevention Strategies (chemoprevention + strategy)
Selected AbstractsFinasteride treatment alters MMP-2 and -9 gene expression and activity in the rat ventral prostateINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2010Flávia K. Delella Summary The safety of using finasteride as a prevention of prostate cancer is still under debate. In this study, we investigated the effects of finasteride on the location, gene expression and activities of matrix metalloproteinases -2 and -9, which are involved in the degradation of extracellular matrix components during tissue remodelling and prostate cancer progression, invasion and metastasis. Ventral prostates (VP) from Wistar rats treated with finasteride (25 mg/kg/day) for 7 and 30 days and age-matched controls were evaluated using histology, immunohistochemistry, semi-quantitative RT-PCR and gelatin zymography. Finasteride treatment reduced the epithelial immunostaining of MMP-2 but increased MMP-9 immunostaining in the epithelial cells and in the stroma. The mRNA expression of both MMP-2 and MMP-9 were significantly increased on day 7 of finasteride treatment, mainly for MMP-9 and returned to the control levels by day 30. However, gelatin zymography showed that MMP-9 activity was significantly increased on day 7 of finasteride treatment and remained elevated on day 30 (p < 0.05), while MMP-2 activity was reduced after 30 days of treatment. Finasteride increases MMP-9 and reduces MMP-2 activities in the prostate, which may affect negatively and positively both normal and tumoural prostatic cell behaviour during the treatment. Studies on expression of MMPs in the prostate during different androgen manipulation or cancer chemoprevention strategies can contribute to understand the tissue's overall response and clinical data. [source] Systematic review: the application of molecular pathogenesis to prevention and treatment of oesophageal adenocarcinomaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2007C. J. PETERS Summary Background Oesophageal adenocarcinoma is an increasingly common cancer with a poor prognosis. It develops in a stepwise progression from Barrett's metaplasia to dysplasia, and then adenocarcinoma followed by metastasis. Aim To outline the key molecular changes in oesophageal adenocarcinoma and to summarize the chemopreventative and therapeutic strategies proposed. Methods A literature search was performed to identify appropriate research papers in the field. Search terms included: Barrett's (o)esophagus, intestinal metaplasia, (o)esophageal adenocarcinoma, molecular changes, genetic changes, pathogenesis, chemoprevention, therapeutic strategies and treatment. The search was restricted to English language articles. Results A large number of molecular changes have been identified in the progression from Barrett's oesophagus to oesophageal adenocarcinoma although there does not appear to be an obligate order of events. Potential chemoprevention strategies include acid suppression, anti-inflammatory agents and antioxidants. In established adenocarcinoma, targeted treatments under evaluation include receptor tyrosine kinase inhibitors of EGFR and cyclin-dependent kinase inhibitors, which may benefit a subgroup of patients. Conclusions Advances in molecular methodology have led to a greater understanding of the oesophageal adenocarcinoma pathways, which provides opportunities for chemoprevention and therapeutic strategies with a mechanistic basis. More work is required to assess both the safety and efficacy of these new treatments. [source] Impact of concurrent proliferative high-risk lesions on the risk of ipsilateral breast carcinoma recurrence and contralateral breast carcinoma development in patients with ductal carcinoma in situ treated with breast-conserving therapy,CANCER, Issue 1 2006Linda J. Adepoju M.D. Abstract BACKGROUND The purpose of the study was to determine the risk of ipsilateral breast carcinoma recurrence (IBCR) and contralateral breast carcinoma (CBC) development in patients with a concurrent diagnosis of ductal carcinoma in situ (DCIS) with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). METHODS Records of all 307 patients with DCIS treated with breast-conserving treatment (BCT) from 1968 to 1998 were analyzed. Initial pathology reports and all slides available were re-reviewed for evidence of ADH, ALH, or LCIS. Actuarial local recurrence rates were calculated. RESULTS Fifty-five cases of DCIS were associated with ADH, 11 with ALH or LCIS, and 14 with both ADH and ALH or LCIS. Overall, IBCR occurred in 14% and no significant difference in the IBCR rate was identified for patients with proliferative lesions compared with patients without these lesions (P = 0.38). Development of CBC in patients with concurrent DCIS and ADH was 4.4 times (95% confidence interval [CI], 1.44,13.63) that in patients with DCIS alone (P < 0.01). The 15-year cumulative rate of CBC development was 22.7% in patients with ALH or LCIS compared with 6.5% in patients without these lesions (P = 0.30) and 19% in patients with ADH compared with 4.1% in patients with DCIS alone (P < 0.01). CONCLUSION The risk of CBC development is higher with concurrent ADH than in patients with DCIS alone, and these patients may therefore be appropriate candidates for additional chemoprevention strategies. Concurrent ADH, ALH, or LCIS with DCIS is not a contraindication to BCT. Cancer 2006. © 2005 American Cancer Society. [source] Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras -transformed human breast epithelial cellsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Hye-Jung Kang Abstract Efforts have been made to develop a chemoprevention strategy that selectively triggers apoptosis in malignant cancer cells. Previous studies showed that capsaicin, the major pungent ingredient of red pepper, had differential effect between normal and transformed cells. As an approach to unveil the molecular mechanism by which capsaicin selectively induces apoptosis in transformed cells, we investigated the effect of capsaicin in nontransformed and ras -transformed cells of a common origin: parental (MCF10A) and H- ras -transformed (H- ras MCF10A) human breast epithelial cells. Here, we show that capsaicin selectively induces apoptosis in H- ras -transformed cells but not in their normal cell counterparts. The capsaicin-induced apoptosis, which is dependent on ras transformation, involves the activity of DEVDase (caspase-3 like). In H - ras MCF10A cells, capsaicin treatment markedly activated c-Jun N-terminal protein kinase (JNK)-1 and p38 matigen-activated protein kinase (MAPK) while it deactivated extracellular signal-regulated protein kinases (ERKs). The use of kinase inhibitors and overexpression of dominant-negative forms of MAPKs demonstrated a role of JNK-1 and p38, but not that of ERKs, in apoptosis induced by capsaicin in H- ras -transformed MCF10A cells. Based on the present study, we propose that capsaicin selectively induces apoptosis through modulation of ras -downstream signaling molecules in ras -activated MCF10A cells. Taken in conjunction with the fact that uncontrolled ras activation is probably the most common genetic defect in human cancer cells, our finding may be critical to the chemopreventive potential of capsaicin and for developing a strategy to induce tumor cell-specific apoptosis. © 2002 Wiley-Liss, Inc. [source] Sulforaphane and its analogues inhibit CYP1A1 and CYP1A2 activity induced by benzo[a]pyreneJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2009Katarzyna Skupinska Abstract CYP1A1 and CYP1A2 enzymes metabolize polycyclic aromatic hydrocarbons (PAHs) to the reactive oxyderivatives. PAHs can induce the activity of both enzymes, which increases its conversion and enhances risk of carcinogenesis. Thus, the inhibition of CYP enzymes is recognized as a cancer chemoprevention strategy. A well-known group of chemopreventive agents is isothiocyanates, which occur naturally in Brassica vegetables. In this paper, a naturally occurring sulforaphane and its two synthetic analogues isothiocyanate-2-oxohexyl and alyssin were investigated. The aim of the study was to determine whether the differences in the isothiocyanate structure change its ability to inhibit CYP1A1 and CYP1A2 activity induced by benzo[a]pyrene in HepG2 and Mcf7 cells. Also a mechanistic study was performed including isothiocyanates' influence on CYP1A1 and CYP1A2 catalytic activity, enzymatic protein level, and AhR translocation. It was shown that both enzymes were significantly induced by benzo[a]pyrene, and isothiocyanates were capable of decreasing the induced activity. The inhibitory properties depend on the types of isothiocyanate and enzyme. In general, CYP1A2 was altered in the more meaningful way than CYP1A1 by isothiocyanates. Sulforaphane exhibited weak inhibitory properties, whereas both analogues were capable of inhibiting BaP-induced activity with the similar efficacy. The mechanistic study revealed that analogues decreased the CYP1A2 activity via the protein-level reduction and CYP1A1 directly. The results indicate that isothiocyanates can be considered as potent chemopreventive substances and the change in the sulforaphane structure increases its chemopreventive potency. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:18,28, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20259 [source] | ||||||||||