Cancer prostate

The prostate is both a blessing and a curse. This small walnut-shaped organ surrounds the urethra (the tube through which urine passes) and is situated at the base of the bladder. It is the source of seminal fluid and is thus intimately involved in maintenance of sexual performance and libido. But to many men over the age of 40 (and to just about all over the age of 70), it is a source of annoyance and discomfort. With advancing age, the prostate grows and begins to constrict the urethra, reducing urine flow - a condition known as prostatic hyperplasia. 

The situation improved with the arrival of the anti-androgens like cypro-terone acetate and flutamide, which function like tamoxifen and deny access of testosterone to its receptors in cancer cells. In addition, mimics of the gonadotropin hormone releasing hormone, like leuprolide and goserelin, were discovered, and these act upon the pituitary to switch off the production of LH. This in turn leads to a diminished production of testosterone by the testes. None of these new drugs could effect a cure, although they did cause tumour regression, and where metastasis had led to spread of the tumour to the bones (a frequent problem with this cancer), they provided pain relief. In 

Two recently developed classes of drug show promise, and these act by inhibiting the production of testosterone from cholesterol or its metabolism by the enzyme 5-cc-reductase. Attempts to control benign prostatic hyperplasia provided the incentive for the development of 5-a-reductase inhibitors. It has been known for some time that there is a genetic condition that is manifested by a deficiency of this enzyme. Men who have this gene defect have normal external genitalia but only a very small prostate and additionally, they do not develop acne or exhibit the typical male pattern of hair loss. All of these processes are under the control of 5- -reductase, which controls the conversion of testosterone to another steroid, dihydrotestosterone, and it is an imbalance in the ratio of these two steroids that leads to acne, male-pattern baldness, prostatic hyperplasia and probably prostatic cancer. Several 

PSA cannot predict reliably whether a man has a cancer that will progress to cause ill health or death...and routine testing of men to detect prostate cancer should be discouraged. 

Clearly, the money spent on costly screening procedures and (possibly) unnecessary surgery and chemotherapy could be better spent on research to discover better drugs to treat this major disease. 

Prostate cancer is the most common cancer in U.S. males, and there is evidence that dietary fat, soy proteins, vitamin E, and selenium affect risk for this disease. Furthermore, it has been shown that consumption of lycopene and lycopene-containing foods (tomato and tomato paste) is associated with reduced risk of prostate cancer. 

Prostate cancer is a malignant neoplasm that arises from the prostate gland. Prostate cancer has an indolent course localized prostate cancer is curable by surgery or radiation therapy but advanced prostate cancer is not yet curable. 

The normal prostate is composed of acinar secretory cells that are altered when invaded by cancer. The major pathologic cell type is adenocarcinoma (more than 95% of cases). 

Locally invasive prostate cancer is associated with ureteral dysfunction or impingement, such as alterations in micturition (e.g., urinary frequency, hesitancy, dribbling). 

Patients with advanced disease commonly present with back pain and stiffness due to osseous metastases. Untreated spinal cord lesions can lead to cord compression. Lower extremity edema can occur as a result of lymphatic obstruction. Anemia and weight loss are nonspecific signs of advanced disease. 

The risk of prostate cancer was reduced 25% in patients taking finasteride for treatment of BPH. 

Similar to cancer at other sites, there are strong correlations between per capitut fat intake and prostate cancer deaths in international comparative studies (Kolonel, 2001 Kushi and Giovannucci, 2002). Early case-control studies often showed positive associations between prostate cancer risk and total, animal, and saturated fat intake. However, in later studies in which energy intake was adjusted, only two of five found an increased risk for total fat intake, whereas two of eight found an increase in the risk of prostate cancer with animal fat intake (Kolonel, 2001). 

There have been a number of prospective studies in which the relationship between fat intake and risk of prostate cancer was examined. Only four of these studies adjusted for energy intake. In these studies, there were no statistically significant associations between total fat, fat type or individual fatty acids and the risk of prostate cancer. An exception was a positive association with a-linolenic acid in the Health Professionals Follow-up Study (Kolonel, 2001). 

Unlike colon and breast cancer, there is a lack of suitable animal models for mechanistic and dietary studies on prostate cancer. Studies that have investigated dietary fat intake and the role of individual fatty acids on prostate cancer risk have produced inconsistent results. 

Evidence from well-conducted epidemiological studies does not support any meaningful associations between the intake of total fat, fat type or individual fatty acids and the risk of colon, breast or prostate cancer. Final proof of a null effect should come from randomized clinical trials. However, such trials seem unlikely because initiation of tumors may occur early in life, whereas the clinical symptoms arise late in life. The cost of appropriate trials would be prohibitive. Further advances, however, may come from improved dietary assessment and a better understanding of, and adjustment for, confounding factors in epidemiological studies. 

A different approach to diagnosis involved searching for individual markers. In one study, three potential markers were detected in PC but none in 12 controls. The 15.9 kDa marker appeared in 9/11 PC but was absent in 12 patients with BPH. The 15.2 kDa marker appeared in 9/11 PC and 4/12 BPH patients. The intensities of the 17.5 kDa marker were essentially the same in the PC and BPH groups. Because the 15.9 kDa protein was present in 82% of PC but was absent in all BPH, it was concluded that this protein may be a putative marker to differentiate PC from BPH [90]. 

In another study, a 50.8 kDa protein was detected in 96% of cancer patients ( = 56) but not in 70-80% of subjects with various benign prostate diseases (n = 22) 

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Prosta.te Ca.ncer, Estrogen has an inhibitory effect on the prostate in addition to its suppression of gonadotropin secretion by the pituitary. The three- and five-year survival rates in prostate cancer patients with metastatic disease improved when treated with DES (7) alone or along with castration. However, DES does not improve the survival rates in patients whose carcinoma is confined to the prostate. Small doses of DES (1 mg/d) appear to retard prostate cancer growth and could reduce the cardiovascular complications associated with larger doses (5 mg/d) (135) (see... 

The incidence of prostate cancer also appears to have risen in many countries. "... 

Prostate Cancer. Evidence that phytoestrogens can influence the incidence of male-speciflc diseases is restricted to prostate cancer, and is largely of an observational nature. In the UK, prostate cancer is the most common hormone-related cancer in men. However, like breast cancer in women, it is comparatively rare as a clinically evident disease in men living in Asian countries. 

Several studies have investigated the role of dietary factors in prostate cancer risk, but results appear inconsistent. Significant effects have not been detected for dietary soya products certain vegetables, beans, fruit, rice and seaweed appear to be protective in some studies, while another has shown no protective effect from seaweed or vegetable consumption. In addition, a number of other risk factors have been shown to be associated with an increased risk of this cancer, including meat and dairy products and carotenoids. 

The majority of promising drug candidates emerging from marine natural products research to date are potential cancer treatments. Six anti-cancer compounds that are either marine natural products or synthetic analogs of marine natural products have made it to clinical trials. The first of these compounds to enter clinical trials was didemnin B (43), one of a family of cyclic depsipetides isolated from the Caribbean tunicate Trididemnum solidum Didemnin B was advanced to Phase II clinical trials for treatment of small cell lung cancer, myeloma, prostate cancer, and melanoma. Unfortunately, no favorable responses were found so the compound has been withdrawn. Crude extracts of another Caribbean tunicate, Ecteinascidia turbinata, showed extremely... 

Interest contmues in prodrugs of 5-fluorouracil (5-FU) Doxifluridine (8) was recently mtroduced and appears to be more potent and less toxic than 5 FU [10 Flutamide (9) and nilutamide (/O) are both available for the treatment of prostatic cancer [//, 12]... 

Therapeutic Function Estrogen used in hormone therapy for prostate cancer Chemical Name 4,4 -(1,2-Diethyl-1,1-ethenediyl)bisphenol-bis(dihydrogen phosphate) Common Name Fosfestrol Structural Formula ... 

Leuprolide is a synthetic nonapeptide used to treat both endometriosis in women and prostate cancer in men. 

Glucocorticoids have inhibitory (apoptotic) effects on lymphocyte proliferation and are used to treat leukemias and lymphomas. Estrogens (fosfestrol) are used to block the effect of androgens in prostate cancer. Progestogens (megestrol, medroxyprogesteroneacetate) have been useful for treating endometrial carcinoma, renal tumors, and breast cancer. 

Gonadotropin releasing hormone analogs (goserelin, buserelin, leuprorelin, triptorelin) inhibit gonadotropin release and thus lower testosterone or estrogen levels. They are used to treat breast cancer and prostate cancer. 

Hormone antagonists (tamoxifen and toremifen bind to the estradiol receptor, flutamide binds to the androgen receptor) are used for treating breast and prostate cancer. 

Cancer Neuroblastoma, leukemia, brain tumors and prostate cancer (A) ... 

In malignant prostate epithelial cells, auto- and paracrine release of ET-1 is a critical factor in ETA receptor-mediated proliferation [5]. In addition, the ET-1/ETa receptor axis has emerged as a potential target in prostate cancer bone metastasis... 

As endothelins mediate potent vasoconstrictor effects, ECE inhibitors and endothelin receptor antagonists were developed for the treatment of cardiovascular diseases, such as acute and chronic heart failure, pulmonary hypertension and subarachnoid haemorrhage. As ETa recqrtors have potent mitogenic responses and may promote progression of ovarian and prostate cancer and bone metastases ETA receptors are also considered as a potential targets for anti-tumour activity. 

ABT-627 (Atrasentan) Abbott Laboratories, USA ETA receptor Hormone-refractory prostate cancer, stage IV (phase III)... 

PA S1 S01.251 Prostase Proposed for use in vaccine strategies against prostate cancer... 

Acid- and alkaline phosphatases act on a variety of mono- and multiple phosphate carrying low molecular mass molecules. In addition, they hydrolyze many, but not all, phosphoproteins. They are in use for decades to easily screen for diseases, however, somewhat unspe-cifially. For instance, acid phosphatase is used as biomarker for prostate cancer, and alkaline phosphatase to monitor bone (de-) mineralization and liver tumors. 

In clinical use are pure and partial agonists and antagonists (see individual SHR) as contraceptives, treatment for hormonal ablation in breast and prostate cancer, and HRT in osteoporosis. 

TRPV5 and TRPV6, also known as the epithelial Ca2+ channel or ECaC (TRPV5) and Ca2+transporter 1 or Ca2+ transporter-like (TRPV6), are the only two Ca2+-selective TRP channels identified so far. They may function in vitamin D-dependent transcellular transport of Ca2+in kidney, intestine and placenta. TRPV6 is also expressed in pancreatic acinar cells, and in prostate cancer, but not in healthy prostate or in benign prostate hyperplasia. 

Older men treated with the steroids are at increased risk for prostate enlargement and prostate cancer. 

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