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

Garlic has been used throughout the world to treat coughs, toothache, earache, dandruff, hypertension, hysteria, diarrhoea, dysentery, diptheria, vaginitis and many other conditions. Garlic contains a complex mixture of oil and water-soluble organosulfur compounds. Diallyl disulfide (DADS), an oil-soluble constituent of garlic seems to be effective in reducing tumour cells originating from colon, lung and skin. Hence our present study focuses on the dose-dependent effect of DADS on an androgen-dependent prostate cancer cell line. Various concentrations of DADS ranging from 25 to 100 microM were given to LNCaP cells and the activity of lactate dehydrogenase (LDH) prostatic acid phosphatase (PAcP) and the level of prostate specific antigen were studied. DADS reduced the secretory activity of LNCaP cells with the gradual increase in dosage. DADS was found to act as a good antiproliferative agent, which was confirmed by proliferation assay. DADS also induced apoptosis and nuclear segmentation in the higher doses.
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PMID:Antiproliferative effect of diallyl disulfide (DADS) on prostate cancer cell line LNCaP. 1614 93

In this study we report late bladder, gastrointestinal and sexual dysfunctions in 23 patients following radical radiotherapy (66Gy-70Gy/33-35fx, 5 fx/week) for prostate cancer. We interviewed the subjects by telephone and compared the results with those of 45 healthy population controls. In general, the patients' bladder function was well preserved. However, compared with the population controls, significantly more patients reported dysuria and hematuria. Twenty-six percent of the patients reported moderate distress from the gastrointestinal tract. Fecal urgency, incontinence and the use of sanitary pads, as well as diarrhoea, and blood and mucous were significantly more common among the patients. Thirty-nine percent of the patients reported moderate or worse distress upon sexual activity, and significantly more patients suffered from erectile impotence.
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PMID:[Late effects following curative radiotherapy for prostate cancer]. 1615 60

(1) The standard treatment for metastatic prostate cancer is hormone therapy, based on medical castration (with an LH-RH agonist) or surgical castration (pulpectomy), possibly combined with an androgen antagonist. For patients with hormone-resistant disease the only cytotoxic agents approved in France, estramustine and mitoxantrone, have no proven impact on survival. (2) Docetaxel is now approved in Europe for the treatment of hormone-resistant metastatic prostate cancer, in combination with a steroid. (3) In an open-label comparative trial involving 1006 patients, docetaxel infusion at a dose of 75 mg/m2 every 3 weeks, in combination with prednisone (or prednisolone), significantly extended the median survival time by about 2.5 months as compared with a mitoxantrone-prednisone combination (18.9 versus 16.5 months). In another open-label comparative trial involving 674 patients, a combination of docetaxel + estramustine was significantly more effective than a mitoxantrone + prednisone combination in extending median survival time (17.5 versus 15.6 months). (4) The adverse effects of docetaxel + prednisone were the same as those seen with other indications (hair loss, nausea and vomiting, diarrhea, neutropenia, nail disorders, neuropathies), and were severe in 25% of patients. (5) In France the cost of docetaxel therapy for hormone-resistant metastatic prostate cancer is more than 1000 euros every three weeks. (6) In practice, docetaxel is the first cytotoxic agent shown to prolong survival in men with hormone-resistant metastatic prostate cancer. The benefit is limited, however, especially given the potentially severe adverse effects of docetaxel, which must be disclosed to patients.
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PMID:Doxetaxel: new indication. Prostate cancer: a few more weeks. 1654 96

Epothilones are cytotoxic macrolides with a similar mechanism of action to paclitaxel but with the potential advantage of activity in taxane-resistant settings in preclinical models. The epothilones ixabepilone, patupilone, BMS-310705, KOS-862 and ZK-EPO are in early clinical trials for cancer treatment. Phase I studies have shown that dose-limiting toxicities of epothilones are generally neurotoxicity and neutropoenia although initial studies with patupilone indicated that diarrhoea was dose limiting. Neuropathy induced by ixabepilone may be schedule dependent. Over 20 Phase II studies of epothilones in cancer treatment have been reported, and significant activity in taxane-sensitive tumour types (such as breast, lung and prostate cancers) has been noted. Response rates in taxane-refractory metastatic breast cancer are relatively modest, but ixabepilone and patupilone have shown promising efficacy in hormone-refractory metastatic prostate cancer and in taxane-refractory ovarian cancer.
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PMID:Epothilones in the treatment of cancer. 1673 19

A 65-year-old man underwent a radical retropubic prostatectomy for prostate cancer, and 5 days later fecaluria and serous diarrhea appeared suddenly. Cystourethrography domonstrated the flow of contrast material into the rectum through the fistula, so we diagnosed a rectourethral fistula. We first attempted conservative management, but the fistula did not close spontaneously. So we performed the transanal repair of rectourethral fistula about 2 months after surgery. This repair was effective, and the patient was alive without fistula recurrence at about 2 years after the repair surgery. This approach is simple and does not require a new incision, but it is only useful for low rectourethral
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PMID:[Transanal repair of rectourethral fistula after radical retropubic prostatectomy: a case report]. 1675 30

The effects of two modalities of dose-escalated radiotherapy on health-related quality of life (HRQOL) were compared. Forty-one consecutive patients were treated with a 3-D conformal (3-DC) boost to 74 Gy, and 43 with high-dose rate (HDR) brachytherapy boost (2x9 Gy), following 3-D conformal treatment to 46 Gy. Median age was 70 years in both groups, median initial PSA was 7.9 microg/l in 3-DC boost patients and 8.1 microg/l in HDR boost patients. Stage was <or=T2 in 66% and 67% and Gleason score was >or=7 in 52% and 47%, respectively. HRQOL was assessed cross-sectionally using EORTC QLQ-C30 and organ-specific PR25 modules 3--32 (median 19) and 4--25 (median 14) months after treatment, respectively. Questionnaires were completed by 93% and 97% of patients, respectively. Diarrhea and insomnia scores were significantly increased in both groups. In the PR25 module, scores of 3-DC boost and HDR boost patients for urinary, bowel and treatment-related symptoms were similar. Among responders, 34% of 3-DC boost patients and 86% of HDR boost patients had severe erectile problems. Dose escalation in prostate cancer by either 3-DC boost to 74 Gy or HDR brachytherapy boost appears to result in similar HRQOL profiles.
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PMID:3-D conformal treatment of prostate cancer to 74 Gy vs. high-dose-rate brachytherapy boost: a cross-sectional quality-of-life survey. 1693 14

Biochemical markers of bone metabolism are strongly associated with skeletal complications in metastatic bone disease. The bisphosphonate clodronate reduces skeletal morbidity by inhibiting bone resorption. This study investigated the use of bone markers to assess the efficacy of oral clodronate across a range of clinically relevant doses. There were 125 patients with metastatic bone disease randomized to daily oral clodronate (800, 1,600, 2,400 and 3,200 mg) or placebo in a double-blind, multicenter study. Urinary N-terminal telopeptide of type I collagen (U-NTX), serum C-terminal telopeptide of type I collagen (S-CTX), urinary calcium (U-Ca), and bone alkaline phosphatase were measured weekly for a 6-week treatment period. Doses of >or=1,600 mg clodronate produced mean reductions of >40% in U-NTX, S-CTX and U-Ca, all significantly different from placebo (P=0.0015, 0.001, 0.0036, respectively), after 6 weeks. Evaluation of least significant changes in markers suggested that the commonly used 1,600 mg dose was most appropriate for breast cancer patients. However, this dose was suboptimal for other (mainly prostate cancer) patients, who showed better response to 2,400 mg. The number of adverse events in the treatment arms was not significantly different from that in placebo, but a higher number of patients had diarrhea in the 3,200 mg arm and withdrew from the study. This trial is the first to explore the dose-response relationship of clodronate in oncology using specific markers of bone turnover. It has confirmed that the 1,600 mg dose is safe and effective for breast cancer patients but may be suboptimal for the other tumors studied.
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PMID:The use of bone markers in a 6-week study to assess the efficacy of oral clodronate in patients with metastatic bone disease. 1787 31

The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m(-2) of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1-3, 8-10, 15-17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1-9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44-72) and median duration of PSA response was 8.0 months (95% CI: 6.9-9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel.
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PMID:Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study. 1795 53

There are few treatment options for prostate cancer once it becomes hormone refractory, with a mean life expectancy of 9-12 months. During the period 1997-2002, a product known as PC-Spes, containing a mixture of extracts from eight herbs based on the principles of traditional Chinese medicine, was reported to inhibit prostate cancer cell growth in vitro and reduce PSA in patients with hormone refractory prostate cancer (HRPC). This product was withdrawn from the market in 2002 due to concerns over quality control and reported contamination with traces of warfarin, indomethacin and diethylstilbesterol. PC-spes2, manufactured by Active Botanicals Ltd. (UK) with strict, independently-conducted quality control, has demonstrated no contaminants by high pressure liquid chromatography and liquid chromatography/mass spectroscopy. This compound was investigated in a single-centre, prospective, open pilot study. Eighteen patients with HRPC, mean age 72, median Gleason sum 8 (range 4-9) and median PSA 110 (range 4-2870) with three consecutive monthly increases in PSA were studied. Ten patients withdrew during the study period with significant diarrhoea (8 out of the first 10 patients at one month and only 2 out of the last 8 due to an improved dosing schedule). At one month, 7 out of 10 patients had a drop in their PSA doubling time or PSA velocity, which was still apparent in 4 out of 5 patients still on trial at three months and all three patients still on trial at six months. No serious adverse events or derangement of coagulation were observed. PC-Spes2 offers renewed hope and a safe alternative treatment option for patients with advanced HRPC. Further investigation with phase II trials is warranted.
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PMID:Phase I trial of PC-Spes2 in advanced hormone refractory prostate cancer. 1828 23

PURPOSE Studies on quality of life (QOL) among women with endometrial cancer have shown that patients who undergo pelvic radiotherapy report lower role functioning and more diarrhea and fatigue. In the Post Operative Radiation Therapy in Endometrial Cancer (PORTEC) trial, patients with endometrial carcinoma were randomly assigned to receive external-beam radiotherapy (EBRT) or vaginal brachytherapy (VBT). QOL was evaluated by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and subscales from the prostate cancer module, PR-25, and the ovarian cancer module, OV-28. PATIENTS AND METHODS PORTEC-2 accrued 427 patients between 2002 and 2006, of whom 214 were randomly assigned to EBRT, and 213 were randomly assigned to VBT. Three-hundred forty-eight patients (81%) were evaluable for QOL. QOL outcomes were analyzed at a median follow-up of 2 years. Results At baseline after surgery, patient functioning was at the lowest level, and it increased during and after radiotherapy to reach a plateau after 12 months. Patients in the VBT group reported better social functioning (P < .002) and lower symptom scores for diarrhea, fecal leakage, the need to stay close to the toilet, and limitation in daily activities because of bowel symptoms (P < .001). At baseline, 15% of patients were sexually active; this increased significantly to 39% during the first year (P < .001). Sexual functioning and symptoms did not differ between the treatment groups. CONCLUSION Patients who received EBRT reported significantly higher levels of diarrhea and bowel symptoms. This resulted in a higher need to remain close to a toilet and, as a consequence, more limitation of daily activities because of bowel symptoms and decreased social functioning. Vaginal brachytherapy provides a better QOL, and should be the preferred treatment from a QOL perspective.
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PMID:Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized PORTEC-2 trial. 1954 4


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