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)

GnRH plays a pivotal role in the reproductive system, and GnRH analogs have wide therapeutic applications ranging from the treatment of prostatic cancer to infertility. Determination of the predicted structure of the GnRH receptor (GnRHR) would illuminate the mechanisms of receptor activation and regulation and allow directed design of improved GnRH analogs. We report the cloning of a cDNA representing the mouse GnRHR and confirm its identity using Xenopus oocyte expression. Injection of sense RNA transcript leads to the expression of a functional, high affinity GnRHR. Expression of the GnRHR using gonadotrope cell line RNA, however, is blocked by an antisense oligonucleotide. In situ hybridization in the rat anterior pituitary reveals a characteristic GnRHR distribution. The nucleotide sequence encodes a 327-amino acid protein which has the seven putative transmembrane domains characteristic of G protein-coupled receptors, but which lacks a typical intracellular C-terminus. The unusual structure and novel potential regulatory domain of the GnRHR may explain unique aspects of its signal transduction and regulation.
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PMID:Cloning and functional expression of a mouse gonadotropin-releasing hormone receptor. 132 22

This updated literature review on heterosteroids and drug research has information on chemical structure, pharmacology, and effects. It first discusses the anti-inflammatory heterosteroids, such as mometasone furoate and cortivazol. It also covers heterosteroidal antimineralocorticoids and anabolic hetero derivatives. The review discusses at length the 19-norsteroid, mifepristone (RU-486), which exhibits antiprogestational activity and is being used for fertility control in women. It also has antiglucocorticoid activity and shows promise as a treatment of diseases characterized by muscle atrophy. In vitro studies indicate that mifepristone inhibits growth of breast cancer cell lines and of endometrial cancer cell lines. It has already exhibited growth inhibitory effects in some breast cancer patients. Discussions of mifepristone's pharmacokinetics and structural modifications of mifepristone follow. Danazol is an antigonadotropin and is used to treat endometriosis, benign breast disease, precocious puberty, hereditary angioneurotic edema, menorrhagia, some types of infertility, and gynecomastia. Danazol effects considerable changes in lipid metabolism. Other hormonal, antihormonal, and/or antifertility heterosteroids and/or aspects include androgen antagonists (e.g., cyproterone acetate), estrogen activity, antiestrogens, STS-557, and oximinosteroids. Heterosteroidal inhibitors of steroid hormone biosynthesis discussed are aromatase inhibitors, 5 alpha-reductase inhibitors, and 3 beta-hydroxysteroid dehydrogenase inhibitors (trilostane, epostane, and azastene). Heterosteroids affect the cardiovascular system, including the cardiac glycosides, antiarrhythmic agents, and antilipemic agents. Some heterosteroids affect central nervous system activity (e.g., RU-5135 causes convulsions in rodents). Pancuronium analogues and chandonium and analogues are neuromuscular blocking azasteroids. In addition to danazol and RU-486, several other antineoplastic heterosteroids exist (e.g., estramustine phosphate sodium, a prostate cancer drug).
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PMID:Heterosteroids and drug research. 184 48

Most interest in transrectal ultrasound (US) of the prostate has concentrated on its role in the diagnosis and management of prostatic cancer. The increasingly detailed investigation of male patients with infertility has recently led to interest in the use of US in investigating the structure and function of the ejaculatory ducts and seminal vesicles. The anatomy and pathology of the ejaculatory ducts and seminal vesicles as demonstrated by transrectal US are discussed and illustrated.
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PMID:Transrectal ultrasound of the ejaculatory apparatus. 195

Endorectal prostate ultrasound has become a clinically useful application. This paper describes the necessary understanding of the newer concepts of anatomy, origins of disease and indications for prostate ultrasound. These indications include: (1) an abnormal digital rectal examination, (2) biopsy guidance, (3) evaluation of the patient with known prostate cancer, (4) follow-up of patients with prostate cancer, (5) certain cases of infertility, (6) prostatic inflammation, (7) voiding studies, and (8) evaluation of prostate in selected patients without previously suspected pathology.
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PMID:Ultrasound of the prostate--applications and indications. 202 4

The gonadotrophin releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); gonadorelin] agonist buserelin is a promising new agent in the treatment of a variety of disorders in gynaecology and andrology, paediatrics and oncology. While a single dose of buserelin stimulates the release of pituitary gonadotrophins, multiple doses produce reversible pituitary desensitisation, and this specific blockade of gonadotrophin support to the gonads provides the basis for the drug's efficacy in conditions dependent on sex hormone secretion. Thus, buserelin provides comparable efficacy to orchidectomy or high dose estrogens in the treatment of hormone-sensitive prostate cancer and exhibits a lower incidence of adverse effects. During the early phase of treatment it may be particularly useful in combination with antiandrogens. Buserelin also appears promising in hormone-sensitive premenopausal breast cancer. Extensive studies have proven the value of buserelin in endometriosis, where it produces a transient remission with gradual recurrence of the disease on cessation of treatment. Surgical intervention is necessary in severe disease after buserelin-induced involution of the lesions. In patients with uterine leiomyoma, preliminary data suggest that buserelin may be beneficial in rendering surgery more conservative by reducing fibroid size, although it appears unlikely to preclude surgical intervention. The use of buserelin to induce a state of reversible hypogonadotrophism before administration of exogenous gonadotrophins is a promising strategy in the treatment of infertility associated with polycystic ovary syndrome and other conditions of infertility with underlying ovarian dysfunction; such a strategy also clearly enhances the efficiency of in vitro fertilisation programmes. Initial studies suggest its potential usefulness as a female contraceptive when administered intermittently in conjunction with a progestogen. Buserelin represents a first-line treatment of central precocious puberty. In endometriosis the adverse effect profile of buserelin is generally favourable, with hypoestrogenic effects such as hot flushes and vaginal dryness, and decreased libido, predominating. There is no apparent detrimental effect on lipid metabolism. The potential for adverse hypoestrogenic effects on bone mineral content with long term administration remains to be clarified. Thus, the GnRH agonist buserelin represents an advance in the treatment of a variety of gynaecological and andrological as well as paediatric and oncological conditions, infertility and other sex-hormone dependent conditions, with a low incidence of adverse treatment effects.
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PMID:Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile. 210 79

Initial investigation demonstrated antibodies to sperm (ASA) in patients with benign prostatic hypertrophy (BPH) and prostate cancer (PCa). The occurrence of ASA under a variety of normal and pathological circumstances indicated the need for confirmation and extension, including delineation of their possible disease-associated specificity and implications. As countercurrent immunoelectrophoresis (CIEP) employing sonicated allogeneic sperm (Sp) extracts appeared most efficient from initial studies of ASA, CIEP was employed for the present further study of 200 serum specimens from patients with and without prostatic disease. While ubiquitous, the continuing presence of ASA in BPH and PCa, with a combined incidence in this study of 57 (52%) of 109 vs. 9 (10%) of 91 in the absence of prostatic disease remains provocative in view of the hypothesized role of Sp in the development of BPH and PCa. The presence, however, of ASA in patients with genitourinary neoplasms other than prostate, raises doubt as to their disease specificity. Implications of ASA, other than in their more commonly related role in infertility, including their cross-reactivity with foetal antigens and lymphocytes and higher incidence in association with tumours and the presence of tumour-associated immunity are considered. However, pending further investigation, the present data may most appropriately be viewed as being reflective of a host response (marker?) to aberrant genitourinary cellular alterations.
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PMID:Antibodies to sperm in benign and malignant diseases of the prostate in man: incidence, disease-associated specificity, and implications. 245 22

With the advent of effective treatment for urologic cancer, the preservation of sexual function and fertility has become an important goal. Some cancer treatments damage the physiological systems involved in reproduction. All have a psychological impact on sexuality. For men with prostate cancer, current issues in sexual rehabilitation include the debate on nerve-sparing radical prostatectomy, the role of vascular damage in causing erectile dysfunction after radiotherapy, and the need for a better understanding of hormonal effects on central and peripheral mechanisms of sexual function. In the treatment of men and women with bladder cancer, the sexual function morbidity of radical cystectomy is described in data from prospective interview studies. Sexual desire and orgasm remain normal after surgery despite disruption of the genital vasocongestion accompanying sexual arousal. Long-term follow-up studies of testicular cancer patients suggest that some increase in sexual dysfunction does occur. Infertility remains a concern for a subgroup of younger, childless men. Attempts to modify or eliminate retroperitoneal lymphadenectomy are discussed, as is recovery of spermatogenesis after chemotherapy and radiotherapy. Sexual function in patients with penile, urethral, or renal cell carcinoma is briefly reviewed.
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PMID:Sexuality and fertility in urologic cancer patients. 303 34

Deoxyribonucleic acid (DNA) flow cytometry of testicular tissue has been demonstrated to be a quantitative means of assessing spermatogenesis. This study evaluates testes aspirates and DNA flow cytometry in the evaluation of the infertile male. Testicular tissue obtained from 12 men who underwent bilateral orchiectomy for prostate cancer (group 1) were examined by both flow cytometry and standard histologic technique to assess the correlation between these two modalities. Thirteen men evaluated for infertility (group 2) and requiring histologic evaluation of spermatogenesis underwent both open biopsy and fine needle aspiration of their testes. Histology was independently examined and grouped according to standard nomenclature. Flow cytometric analysis revealed characteristic patterns in the relative numbers of haploid (1C), diploid (2C), and tetraploid (4C) cells. These patterns correlated reproducibly with the histologic diagnoses. DNA flow cytometry of testicular aspirates provides a rapid and reliable quantitative means of assessing spermatogenesis.
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PMID:Aspiration flow cytometry of the testes in the evaluation of spermatogenesis in the infertile male. 360 40

Obesity is a product of welfare. About 1/3 of our population has got excessive weight, 6 to 8% is truly obese and in 0.1% we may speak of pathologic obesity. Obesity is not only an esthetic problem, but is goes together with higher morbidity and mortality. In men with a body mass index (BMI = W (kg)/L2 (m)) of more than 35, the glucose metabolism was disturbed in 70%, the lipid spectrum had a clearly atherogenic profile, the average (free) testosterone level was significantly diminished and there was also a certain degree of hypogonadism. A short term treatment (4 to 6 weeks) based on a hypocaloric diet (400) and rich in proteins normalized the glucose metabolism in a very great number of patients, while the insulinemia fell with 40% and the lipidogram always became normal, but for the HDL-C, which showed a slight drop, while the testosterone levels became normal with a strong rise of the sex hormone binding globulin. And yet, at that very moment the patients were still definitely obese: this suggests that the metabolic disturbances are not the consequence of obesity in itself, but may be related to the dietary habits of the patients. Concerning the mechanism of hypogonadism, the cause of its disturbance seems to be situated in the hypothalamo-hypophyseal area and be characterized by a lower amplitude of LH-pulses, which are correlated with the testosterone levels. This hypothalamic disorder is however not limited to the LH-secretion, but the amplitude of growth hormone- and of ACTH-pulses is also reduced. Our study suggests that not obesity itself, but dietary factors might be responsible for the detected abnormalities. This might have important implications. Indeed, it is well known that in population groups, whose diet contains fewer calories and less fat--such as the Chinese and the Japanese--sex hormone binding globulin exists in far higher concentrations whereas free testosterone is found in a lower concentration. In these populations the prevalence of clinically obvious prostate cancer--which is androgen-sensitive--is much lower than in Western countries: it seems obvious to look for a correlation between both observations. Another remarkable phenomenon is the difference in testosterone metabolism between the Eastern and Western people; this leads us to the remarkable findings that in Asian people the same amount of androgens nearly always produces azoospermia and infertility, whereas this appears in only 2/3 of the cases among Western people.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Metabolic effects of obesity in men]. 812 79

The human genome project will result in many new diagnostic techniques applicable to assisted reproduction. These may be directed both at infertile patients as well as at patients who seek ART because they carry a deleterious genetic disease. There are many potential advantages to the use of preprocedural testing as a means of obtaining additional preliminary information that might allow patients to make a more informed choice, either when deciding between ART and adoption or when comparing the benefits of various ART procedures. The cost of testing is relatively low when compared with the cost of additional IVF or ICSI cycles. In the case of genetic screening protocols, the results may be useful not only to the patient but also to the next generation. Genetic counseling should be made available in concert with expanded opportunities, both for diagnosing infertility and for making preimplantation genetic diagnoses. Already some of the genetic screening that has occurred because of discoveries made during the human genome initiative has become a regulatory concern with regard to insurance availability and other issues. When counseling patients, it is important to point out that certain tests hold far more prognostic value and/or serious health implications than others. A test to diagnose breast cancer susceptibility, for example, holds more serious ramifications than the less predictive test that detects the phenotype for Klinefelter's syndrome. Presymptomatic prognostic screening systems, such as the tests currently used to detect genetic mutations related to breast and prostate cancer and cystic fibrosis, provide diagnostic clues but also have serious societal implications. We are on a rather slippery slope when we attempt to determine which tests actually might prove beneficial to patients, both individually and collectively. Therefore, as part of patient counseling, cost-benefit ratios, in addition to clinical and preventive implications, should be weighed.
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PMID:Panel One: marketing strategies and informing the patient/consumer. Infertility diagnostic techniques: the rush to market. 920 65


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