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

The mitomycins are antitumor antibiotics that are under investigation now for more than 30 years. Mitomycin C (MMC) is the best investigated subtype. It serves as a prototype for drugs with bioreductive alkylation, which is a unique feature of this class. MMC is mainly active under anaerobic circumstances. The pharmacokinetics are linear in a two-compartment model. The main toxicities of MMC are thrombocytopenia and leucocytopenia. Rare but severe side effects are a hemolytic uremic syndrome, pneumonitis and cardiac failure. MMC has a wide clinical antitumor spectrum with efficacy in various tumor types such as gastric cancer, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. Still, the above mentioned side effects prevent a more widespread use. The most important features of the drug will be reviewed.
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PMID:Mitomycin C: mechanism of action, usefulness and limitations. 213 Oct 38

In most western countries, carcinoma of the prostate is the second most frequent cause of cancer death following carcinoma of the lung. In the pathogenesis of clinical carcinoma of the prostate, several mutational steps can be distinguished which correlate with subclinical and clinical situations. Focal carcinoma is identified in autopsy series at least 500-1,000 times more than is appreciated on clinical grounds alone. Still, focal carcinoma must be considered the precursor of all clinical disease. At least three mutational steps must be involved in the pathogenesis: the development of focal carcinoma from normal cells, the progression to hormone-dependent clinical carcinoma, and the progression to hormone-independent carcinoma. The geographic variation of these events suggests that exogenous factors play an important role in the pathogenesis of prostatic cancer. Focal, noninvasive carcinoma is found in the clinical situation incidentally upon treatment of obstruction in 8-12% of cases with benign prostatic hyperplasia. This lesion is usually not treated aggressively. The incidence of clinical prostatic carcinoma is strictly age-related. Because the tumor largely occurs after age 50, and competing causes of death play an important role, only about 50% of all patients with clinical prostatic carcinoma are likely to die of this disease. Prostatic carcinoma is most frequently diagnosed in the metastatic state (40-50%). The remainder are locally confined with an incidence of lymph node metastases of roughly 35%. Tumors diagnosed in the metastatic state have a distinctly poorer prognosis than tumors diagnosed as potentially curable lesions. Metastatic prostatic carcinoma is usually managed by means of androgen suppression. Hormone-dependent human tumor lines in nude mice suggest that endocrine-dependent cells are not killed by androgen withdrawal, but remain dormant and can be restimulated to grow. In the same sense, management of prostatic carcinoma appears to be palliative. Patients die of prostatic carcinoma because hormone-independent cell populations develop and cannot be influenced by hormonal management. Still-open questions concerning endocrine management are the timing of androgen withdrawal (early versus delayed) and the degree of androgen withdrawal (total versus subtotal). Luteinizing hormone-releasing hormone (LHRH) agonists and antiandrogens allow endocrine management with minimal side effects. Prolongation of life and cure can only be expected from simultaneous effective treatment of hormone-independent tumor cell populations.
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PMID:Current concepts in the management of prostatic cancer. 338 35

About 42 million couples worldwide, most of whom live in developing countries, have chosen vasectomy as their family planning (FP) method. There has been considerable research on the short and longterm safety of vasectomy. In the 1970s, research on rhesus monkeys indicated an increased risk of atherosclerosis, possible due to an increased level of antisperm antibodies. Later research on vasectomized men in developed and developing countries did not support these animal studies. Epidemiological studies in the US and Scotland showed an increased risk of testicular cancer in vasectomized men. A WHO meeting reviewed these studies and found no logical mechanism for this association. Later research found that vasectomy does not cause testicular tumors or accelerate the development of existing neoplasms. 2 studies in the US in 1990 suggested that vasectomy increases the risk of prostate cancer many years after the procedure. No studies since then have substantiated these findings. Besides, no known biological mechanism or hypothesis can explain the association. Vasectomy and prostate cancer specialists at a meeting of the US National Institutes of Health in March, 1993, agreed that physicians should continue to perform vasectomies and need not change clinical practice. Extrapolation of the US results to other countries is not logical, particularly to countries where prostate cancer is rare. Nevertheless, these recent reports will probably affect FP programs and acceptance of vasectomy in countries where vasectomy is common. Still, the evidence does not justify changes pertaining to vasectomy in national FP programs. Research on the longterm safety of vasectomy should be conducted. In conclusion, vasectomy is still a simple, safe, and very effective FP method.
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PMID:The safety of vasectomy: recent concerns. 832 61

Each year in the United States, approximately 100,000 men are found to have prostate cancer. Of these, about half show evidence of bony metastases at the time of presentation. Each year, too, some 30,000 American men die of prostate cancer. Conceptually, the treatment of metastatic prostate cancer has changed little in the 50 years since Charles B. Huggins and Clarence V. Hodges discovered the hormone-dependent nature of prostate cancer cells. Still, as the years have passed, several therapeutic options have become available. For the most advanced cases, treatment centers on relief of urinary obstruction and amelioration of the pain of bony metastases, along with vigilance for the potentially disastrous sequelae of acute neurologic change due to spinal fractures. In Part I of this article, which appeared in the April 15 issue of Hospital Practice, we discussed the assessment and management of localized carcinoma of the prostate. In this part, the focus shifts to disseminated disease (Figure 1). We again present two cases representing distinctly different points on the spectrum of disease and discuss how management would proceed in each case. This strategy affords an opportunity to review the various available treatment options, with their advantages and drawbacks.
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PMID:Managing prostate cancer. Part II: Disseminated disease. 847 66

Prostate cancer is a common cancer and a leading cause of cancer death in men. It is potentially detectable at early, possibly curative stages through various combinations of testing, including DRE, PSA, and TRUS of the prostate. Still unproven is the effectiveness of prostate cancer treatment, and because of that lack of proof, the optimal screening strategies are also elusive. It is possible that what is known as prostate cancer today may be, in fact, multiple entities with different natural histories, different treatment needs, and, consequently, different screening strategies. The role of informed consent has been suggested as a means to involve patients in the decision process, especially because the literature presents an environment of intense controversy. It is hoped that the PIVOT trial or similar efforts and further research into the basic mechanisms of the disease will provide clearer answers in the future.
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PMID:Prostate cancer screening. 856 2

The combination of radiation therapy and total androgen suppression shows potential for improving the outcome in patients with locally advanced prostate cancer. Both radiation and androgen ablation induce apoptosis through different mechanisms, and a synergistic interaction has been reported between the two modalities in vitro. Studies of neoadjuvant hormonal therapy before radical prostatectomy have shown considerable tumor shrinkage, a change that would greatly facilitate subsequent radiotherapy. A recent randomized trial involving patients with bulky disease has shown that the use of androgen ablation therapy before and during radiation therapy substantially improved local control and decreased the time to biochemical failure. Still another randomized trial performed in patients with locally advanced disease has shown that the positive biopsy rate was strikingly lower in patients who received neoadjuvant hormonal therapy before radiation than in those who underwent radiotherapy alone, and was even lower in patients who were treated with both neoadjuvant and adjuvant total androgen suppression. The combination of hormonal therapy and radiation has not yet been proven to prolong survival. Nevertheless, given the limitations of conventional radiotherapy, it is recommended that patients at high risk for failure be entered into one of the ongoing Radiation Therapy Oncology Group (RTOG) trials. These trials are attempting to clarify such questions as the role of adjuvant therapy following neoadjuvant therapy and radiation, the optimal timing of hormonal therapy, and the role of whole pelvic irradiation.
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PMID:Neoadjuvant total androgen suppression and radiotherapy in the management of locally advanced prostate cancer. 872 89

Cooked-food mutagens formed when frying meat have been suggested to contribute to the etiology of colon, breast and prostate cancer. The most prevalent of these mutagens is 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which after absorption is bioactivated by both phase I and phase II enzymes. Although available data suggest absorption of PhIP in humans, the extent and mechanism of absorption are unknown. In the present study we examined the transport of [(3)H]PhIP through the human Caco-2 intestinal epithelial cell monolayer, a well-accepted model of human intestinal absorption. The influx, or absorption, was extensive and linear for 2 h and up to a PhIP concentration of 5 microM. Still, the basolateral to apical efflux [apparent permeability coefficient (P(app)) 54.2 +/- 0.7x10(-6) cm/s, mean +/- SEM, n = 24] was 3.6 times greater than the apical to basolateral influx (P(app) 15.1 +/- 0.6x10(-6) cm/s, n = 21, P < 0.0001). Equilibrium exchange experiments demonstrated the efflux to be a true active process. Preincubations with verapamil, an inhibitor of P-glycoprotein-mediated transport, or MK-571, an inhibitor of multidrug resistance-associated protein-mediated transport, stimulated influx and reduced efflux of PhIP, suggesting that PhIP is a substrate for both of these transporters. These findings should be considered when determining exposure to the cooked food mutagens.
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PMID:Transport of the cooked-food mutagen 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) across the human intestinal Caco-2 cell monolayer: role of efflux pumps. 1054 19

Prostate cancer is a major cause of male cancer death. In vitro and in vivo data support a role for 1 alpha,25 Dihydroxyvitamin D(3) (1 alpha,25(OH)(2)D(3)) in regulating the growth and differentiation of the normal prostate gland yet prostate cancer cells appear significantly less sensitive to this action. Vitamin D(3) receptor (VDR) content or mutational status do not correlate clearly with the antiproliferative effects of 1 alpha,25(OH)(2)D(3) and therefore it is unclear why prostate cancer cell lines are significantly less sensitive to this action. We hypothesized that the antiproliferative responses of prostate cancer cells to 1 alpha,25(OH)(2)D(3) are suppressed by a process involving histone deacetylation. Sodium butyrate (NaB) and trichostatin A (TSA) are inhibitors of histone deacetylase (HDAC) activity. Low doses of NaB or TSA (300 microM and 15 nM respectively), which alone were relatively inactive, synergized with 1 alpha,25(OH)(2)D(3) in liquid and semi-solid agar to inhibit the growth of LNCaP, PC-3 and DU-145 prostate cancer cells. Still greater synergy was observed between vitamin D(3) hexafluoride analogs and either NaB or TSA. The mechanism appeared to involve neither the cyclin-dependent kinase inhibitor, p21((waf1/cip1)) nor cell cycle arrest, but rather induction of apoptosis. These data suggest that cells dysregulate the normal pro-apoptotic signals of 1 alpha,25(OH)(2)D(3) during prostate cancer development by a mechanism involving histone deacetylation. Combination therapy with potent vitamin D(3) analogs and clinically approved HDAC inhibitors may overcome this lesion and improve the treatment of both androgen-dependent and independent prostate cancer.
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PMID:Synergistic growth inhibition of prostate cancer cells by 1 alpha,25 Dihydroxyvitamin D(3) and its 19-nor-hexafluoride analogs in combination with either sodium butyrate or trichostatin A. 1131 34

Urology is a specialty with many branches, including urological oncology with 25% of all cancers. Development in certain areas been very rapid, for instance with the introduction of minimally and non-invasive methods such as ESWL and phosphodiesterase inhibitors, innovations which have brought obvious improvements and have been promptly adopted in clinical practice. In other areas such as chronic abacterial prostatitis and renal cancer, progress has been very limited. Still other areas have seen useful but less spectacular improvements for which it has taken time, clinical experience and a multitude of clinical studies before they have been embraced in daily clinical practice. Examples of these more gradual developments are hyperthermia for the treatment of benign prostatic hyperplasia and transrectal ultrasound in prostate cancer.
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PMID:[Both major breakthroughs and stagnation in urology. Industry, together with clinicians, are responsible for most innovations]. 1143 74

Prostate cancer is perceived to be a disease of older men often diagnosed with widespread metastases that respond to hormonal ablation but for which there are few additional treatment options. Fortunately this perception is rapidly changing as newer combination chemotherapy trials demonstrate improved prostate-specific antigen and measurable response rates and enhanced quality of life. Still, treatment of prostate cancer lags behind treatment of other malignancies. Work remains in understanding the natural history of disease, refining our grouping of patients by stage into clinical trials, and adhering to new response criteria recently developed. Applying the newer active chemotherapy regimens to patients with earlier stage disease should lead to improvements in overall survival.
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PMID:Can chemotherapy alter the course of prostate cancer? 1156 89


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