Calcitriol (1alpha,25-dihydroxyvitamin D(3)), the active metabolite of vitamin D, has recently emerged as a promising therapeutic agent in the treatment of prostate cancer, the second most common ...cause of cancer death in American males. In the present study, we have analyzed the effects of calcitriol treatment on the expression and activity of the UDP-glucuronosyltransferase (UGT) 2B15 and 2B17 in prostate cancer LNCaP and 22Rv1 cells. These two enzymes share a crucial role in the inactivation of androgens in the human prostate. We report that calcitriol treatment results in lower glucuronide conjugation of the active androgen dihydrotestosterone and its reduced metabolites androstane-3alpha-diol and androsterone in LNCaP cells. The same treatment also drastically decreased the mRNA and protein levels of UGT2B15 and UGT2B17 in LNCaP and 22Rv1 cells. Using casodex, an androgen receptor (AR) antagonist, and AR-specific small interfering RNA probes, we show that calcitriol requires a functional AR to inhibit the expression of the UGT2B17 gene in LNCaP cells. By contrast, transient transfection and site-directed mutagenesis experiments revealed that calcitriol down-regulates UGT2B15 promoter activity through a responsive region between positions -171 and -113 bp. In conclusion, the present study identifies the vitamin D receptor activator calcitriol as a negative regulator of the UGT2B15- and UGT2B17-dependent inactivation of androgens in prostate cancer LNCaP cells. Androgens promote prostate cancer cell proliferation; thus, the reduction of their inactivation could have a limiting effect of the calcitriol antiproliferative properties in prostate cancer cells.
Plant, animal, forest, aquatic, micro-organism and invertebrate genetic resources are vital to food security, nutrition, livelihoods and the resilience and adaptability of global agricultural ...production systems. Despite increasing efforts in recent years, much remains to be done to improve the management of these resources. Many are at risk of extinction or erosion and many have been overlooked in terms of use and development. There is an urgent need to address these deficiencies, both within the individual sectors of food and agriculture and in terms of how genetic resources management can be better integrated across sectors. These efforts will need to include action to address the multiple knowledge gaps that constrain improvements to management. They will also need to include the creation of policy and institutional frameworks that promote collaboration and stakeholder participation and allow sustainable management strategies to be implemented effectively at appropriate scales.
FOR 10 YEARS NOW the youth-led Otesha Project has fused bicycle tourism, grassroots education and theatrical events to highlight sustainable living and social justice issues. Otesha will collaborate ...with KAIROS Canada (kairoscanada.org) to host theater-based workshops in eight communities along the way, aiming to raise awareness about the history and relationships between Aboriginal and non-Aboriginal communities.
Background It is essential to have the highest level of confidence in axillary staging assessment. Many surgeons and pathologists believe that fewer lymph nodes are present in axillary dissection ...specimens of women treated by neoadjuvant chemotherapy. Consequently, the purpose of this study was to compare the lymph node counts of axillary dissection specimens from patients having received neoadjuvant chemotherapy with those of patients treated with primary operation. Study Design A retrospective analysis of a prospective database from our institution identified 283 women with invasive breast cancer who underwent level I and II axillary lymph node dissections. Women from the neoadjuvant chemotherapy group (n = 107) were compared with those from the primary surgery group (n = 176). The total number of lymph nodes harvested was considered as a continuous variable, but also dichotomized into two categories (< 10 and ≥ 10). Its correlation with the different variables was analyzed. Results The median number of lymph nodes retrieved in the neoadjuvant chemotherapy group was 10.0 (range 0 to 38) compared with 12.5 (range 0 to 30) in the control group (p=0.002). There were also significantly more patients with fewer than 10 lymph nodes recovered in the neoadjuvant group (45 versus 28%, p=0.007). Logistic regression showed that neoadjuvant chemotherapy was the only factor associated with retrieval of fewer than 10 lymph nodes. Conclusions This study suggests that administration of neoadjuvant chemotherapy to breast cancer patients results in a reduced number of lymph nodes retrieved in the axillary dissection specimens.
BANNED ON THE HILL Belanger, Julie
Alternatives journal (Waterloo),
05/2013, Letnik:
39, Številka:
3
Journal Article
Recenzirano
The non-redacted portions of official documents showed that Canada's Department of Foreign Affairs and International Trade intervened to veto a $5,000 grant supporting her tour - an amount previously ...pledged by Nektarina, a Croatian NGO working on climate change education.
In the Pacific garbage patch, plastic items outnumber zooplankton 6:1 Approximately 7% global oil reserves are used to produce plastic bags. 889 million barrels of crude are used every year to make ...plastic. of recycled plastic bags = $55 (not including the cost of recycling) Each year, 1.5 million tonnes of plastic are used for bottling 89 billion litres of water.
...after local passive house advocate Andy Lera discovered the Blest Machine (on YouTube) and convinced other community stakeholders of Its virtues, the city's disposable coffee lids, yogurt ...containers and grocery bags have taken on new value.
Background Regression of breast tumors in response to neoadjuvant chemotherapy is variable. The goal of breast-conservation operation after neoadjuvant chemotherapy is generally to resect any ...residual tumor with negative margins. There are limited data about the success of achieving negative resection margins in these patients. The purpose of this study was to compare surgical margin involvement of breast-conservation resection specimens from patients treated initially with operation with those from patients receiving neoadjuvant chemotherapy. Methods Between January 2003 and June 2006, 478 breast-conservation operations were performed for invasive breast cancer at our institution. Seventy-six patients received neoadjuvant chemotherapy. Data collected included age, tumor size, nodal status, hormonal receptors and Her-2-neu status, lymphovascular invasion, histologic grade and type, use of guidewire, preoperative chemotherapy regimens, and microscopic evaluation of surgical margins. Univariate analyses and a regression model were used to identify factors associated with margin involvement. Results No statistical difference was observed for margin involvement between patients treated with neoadjuvant chemotherapy and those treated initially with operation (21% versus 18%; p = 0.52). Variables associated with positive margins in a logistic regression model were carcinoma type (43% of all lobular carcinomas had positive margins versus 16% in ductal carcinomas; p = 0.002) and hormonal receptor status (margin involvement was present in 20% of tumors that exhibited hormonal receptors versus 10% in negative receptors tumors; p = 0.014). Conclusions Breast conservation after neoadjuvant systemic therapy yields no higher incidence of positive margins than primary surgical treatment. Special consideration should be accorded to lobular carcinoma, because our findings, consistent with previous studies, demonstrate an association with margin involvement.
Public participation for transit projects faces a number of unique challenges compared with many other similar public investments. For example, a smaller subset of the community uses transit on a ...daily basis as compared with highways; moreover, public transit is seen to be limited—both spatially and demographically—in its appeal. Combined, these factors can limit the widespread engagement of the public in the development and evaluation of transit projects. Further, given the lack of direct benefits from transit, it is often more difficult to garner public support for public transport projects. Specific considerations and techniques are demonstrated that can be undertaken by planners and policy makers to actively engage the community beyond those strongly in favor of or opposed to a transit project. Strategies employed in the Region of Waterloo, Ontario, Canada, in the context of public engagement before the introduction of light-rail transit are explored. In light of these strategies and the experiences of planners in Waterloo and in conjunction with evidence from the literature, a number of conclusions are drawn regarding an effective framework for engaging a wide spectrum of community members in transit planning.
Chenodeoxycholic acid (CDCA) is a liver‐formed detergent and plays an important role in the control of cholesterol homeostasis. During cholestasis, toxic bile acids (BA) accumulate in hepatocytes ...causing damage and consequent impairment of their function. Glucuronidation, a conjugation reaction catalyzed by UDP‐glucuronosyltransferase (UGT) enzymes, is considered an important metabolic pathway for hepatic BA. This study identifies the human UGT1A3 enzyme as the major enzyme responsible for the hepatic formation of the acyl CDCA‐24glucuronide (CDCA‐24G). Kinetic analyses revealed that human liver and UGT1A3 catalyze the formation of CDCA‐24G with similar Km values of 10.6 to 18.6 μmol/L, respectively. In addition, electrophoretic mobility shift assays and transient transfection experiments revealed that glucuronidation reduces the ability of CDCA to act as an activator of the nuclear farnesoid X‐receptor (FXR). Finally, we observed that treatment of human hepatocytes with fibrates increases the expression and activity of UGT1A3, whereas CDCA has no effect. In conclusion, UGT1A3 is the main UGT enzyme for the hepatic formation of CDCA‐24G and glucuronidation inhibits the ability of CDCA to act as an FXR activator. In vitro data also suggest that fibrates may favor the formation of bile acid glucuronides in cholestatic patients. (HEPATOLOGY 2006;44:1158–1170.)
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