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)

We have investigated the effects of chronic administration of D-Trp6-LH-RH on the growth of various hormone dependent tumors in rats and mice. Treatment of male Copenhagen F-1 rats bearing the Dunning R-3327H prostate adenocarcinoma with 25 micrograms of D-Trp6-LH-RH bid for 21 days significantly reduced tumor weight and volume as compared to controls. Serum LH, prolactin and testosterone levels in Copenhagen F-1 rats bearing Dunning tumors were significantly decreased after treatment with D-Trp6-LH-RH. Administration of D-Trp6-LH-RH in doses of 25 micrograms/day for 21 days to mice bearing the MXT mammary carcinoma significantly decreased tumor weight and volume. In rats bearing the MT/W9A mammary adenocarcinoma, D-Trp6-LH-RH, at a dose of 25 micrograms bid for 28 days significantly decreased tumor weight and volume. Administration of D-Trp6-LH-RH in a dose of 25 micrograms/day, 3-18 days after inoculation with the tumor, inhibited the growth of the prolactin (PRL) and ACTH-secreting pituitary tumor 7315a in female Buffalo rats. In three experiments D-Trp6-LH-RH (30-60 micrograms/day) decreased tumor weight and/or volume of the Swarm chondrosarcoma. Regression of these hormone-dependent tumors in rats and mice in response to chronic administration of D-Trp6-LH-RH suggests that this compound can be used for treatment of prostate cancer and breast cancer, and also considered for the development of a new endocrine therapy for chondrosarcomas, osteosarcomas, pituitary tumors and other hormone-dependent neoplasias. The demonstration of the successful use of LH-RH agonists for the palliative management of stage C and D prostate cancer has already shown that this treatment could be employed instead of surgical orchiectomy or estrogen therapy. Preliminary clinical trials suggest that agonists of LH-RH might also be of help in the treatment of breast cancer in premenopausal women.
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PMID:Inhibition of the growth of some hormone dependent tumors by D-Trp6-LH-RH. 624 77

Recently, an association between increased blood levels of insulin-like growth factor I (IGF-I) and increased risks of prostate, breast, lung, and colorectal cancers has been suggested. As today adults with GH deficiency are subjected to GH substitution, there is a pressing need for baseline tumor incidence data. The aim of the study was to assess the risk for a second tumor in a cohort of 328 patients with hypopituitarism treated for a pituitary tumor from 1958--1992. The patients were receiving conventional hormone treatment, but without GH substitution. The overall tumor incidence [standardized incidence ratio (SIR)] was lower than expected (0.85), but the 95% confidence interval (CI) did not exclude unity (0.59--1.21). Only two prostate cancers occurred (SIR, 0.34; 95% CI, 0.04--1.24). Two brain tumors (SIR, 1.96; 95% CI, 0.24--7.08) and two endocrine tumors (part of multiple endocrine neoplasm syndromes; SIR, 4.00; 95% CI, 0.48--14.5) had occurred. When excluding brain and endocrine tumors, the overall SIR decreased to 0.77, but did still not differ significantly from unity (0.52--1.13). Thus, a tendency for a decreased overall tumor risk, although not statistically significant, was noted, especially when excluding brain and endocrine tumors. This tendency was more emphasized for prostate cancer, but low numbers hamper a firm conclusion. These results may serve as a baseline for tumor risk among adult patients with pituitary insufficiency supplemented with GH.
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PMID:Incidence of a second tumor in hypopituitary patients operated for pituitary tumors. 1115 27

A 57-year-old man showed high serum cortisol, plasma adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) levels with a large pituitary tumor and a prostatic cancer. High dose dexamethasone did not suppress cortisol secretion and CRH administration did not stimulate cortisol secretion. After surgical removal of the pituitary tumor, plasma CRH, ACTH and serum cortisol levels were normalized. Histological examinations showed pituitary adenoma and prostatic adenocarcinoma, and pituitary adenoma was stained with both anti-CRH and anti-ACTH antibodies, but prostatic cancer was not stained. A CRH-producing pituitary adenoma is a new type of Cushing's syndrome.
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PMID:Cushing's syndrome with a large pituitary adenoma producing both corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH). 1213 23

Pituitary tumor transforming gene (PTTG), also known as securin, is a regulator of cell division that is overexpressed in many tumors. Its expression is cell cycle regulated, although its transcriptional regulation is yet to be determined. The 5' RACE analysis of the human testis mRNA revealed the existence of a previously unreported transcription start site at 317 bp upstream of the translation start site (ATG). This gene is known to be composed of five exons and four introns, which is now changed to six exons and five introns. To map the promoter region, and to understand its regulation, we designed several fusion constructs of the 5' flanking region of PTTG including the sequence from nucleotide -1373 to -3 (relative to the translation start site) to a luciferase reporter gene. Transient transfection of these constructs in prostate cancer cell line (PC-3) and fibroblast cell line (HS27) confirmed the existence of promoter for PTTG between nucleotides -161 and -3 (in relation to translation start site). The 5' and 3' deletion analysis of the PTTG flanking region and electrophoretic mobility shift assays revealed binding of Sp1 and NF-Y transcription factors within nucleotides -540 to -500. Chromatin immunoprecipitation (ChIP) assays of the HS27 and PC-3 cells revealed the binding of Sp1 protein to PTTG promoter sequence in vivo. Site-directed mutagenesis of the Sp1 consensus sequence resulted in approximately 70% reduction of the overall transcriptional activation of the PTTG promoter, whereas mutation of the NF-Y sequence resulted in approximately 25% reduction. Deletion of both Sp1 and NF-Y consensus sequences resulted in 90% loss of PTTG promoter activity. It was further observed, by Western blot analysis, that the levels of Sp1 protein are higher in PC-3 cells when compared to levels in HS27 cells, possibly contributing to a tissue-specific effect. Our studies indicate an important role of Sp1 in transcription regulation of PTTG expression in tumors.
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PMID:Characterization of the role of Sp1 and NF-Y in differential regulation of PTTG/securin expression in tumor cells. 1464 3

Pituitary tumors are common and cause considerable morbidity due to local invasion and altered hormone secretion. Doxazosin (dox), a selective alpha(1)-adrenergic receptor antagonist, used to treat hypertension, also inhibits prostate cancer cell proliferation. We examined the effects of dox on murine and human pituitary tumor cell proliferation in vitro and in vivo. dox treatment inhibited proliferation of murine pituitary tumor cells, induced G(0)-G(1) cell cycle arrest, and reduced phosphorylated retinoblastoma levels. In addition, increased annexin-fluorescein isothiocyanate immunoreactivity and cleaved caspase-3 levels, in keeping with dox-mediated apoptosis, were observed in the human and murine pituitary tumor cells, and dox administration to mice, harboring corticotroph tumors, decreased tumor growth and reduced plasma ACTH levels. dox-mediated antiproliferative and proapoptotic actions were not confined to alpha-adrenergic receptor-expressing pituitary tumor cells and were unaffected by cotreatment with the alpha-adrenergic receptor blocker, phenoxybenzamine. dox treatment led to reduced phosphorylated inhibitory kappaB (IkappaB)-alpha expression, and nuclear factor-kappaB transcription and decreased basal and TNFalpha-induced proopiomelanocortin transcriptional activation. These results demonstrate that the selective alpha(1)-adrenergic receptor antagonist dox inhibits pituitary tumor cell growth in vitro and in vivo by mechanisms that are in part independent of its alpha-adrenergic receptor-blocking actions and involve down-regulation of nuclear factor-kappaB signaling. dox is proposed as a possible novel medical therapy for pituitary tumors.
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PMID:Alpha1-adrenergic receptor antagonists: novel therapy for pituitary adenomas. 1602 Apr 84

Recently, the pituitary tumor transforming gene 1 (PTTG1) has been suggested to be an oncogene. To investigate whether PTTG1 plays a positive role in the pathogenesis of prostate cancer, PTTG1 protein expression was examined in prostate tissue samples by immunohistochemistry. PTTG1 expression was detected in a high percentage of prostate cancer tissues (34/41, 82.9%), but to a much lesser extent in non-malignant tissues (5/14, 35.7%). To further confirm these results, the expression vectors containing either the PTTG1 or antisense-PTTG1 gene were transfected into a prostate cancer cell line, LNCaP, and the cell proliferation rate was studied, as well as tumorigenicity in the LNCaP cells expressing different levels of the PTTG1 protein. Ectopic PTTG1 gene expression promoted prostate cancer cell proliferation and tumorigenesis both in vitro and in nude mice. In contrast, down-regulation of PTTG1 led to suppression of tumor cell growth. These results suggest that PTTG1 may be a potential prognostic marker for prostate cancer and that the down-regulation of PTTG1 may be a therapeutic target in the suppression of prostate cancer growth.
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PMID:Significance of pituitary tumor transforming gene 1 (PTTG1) in prostate cancer. 1661 32

Gonadotropin-releasing hormone (GnRH) agonists have become the treatment of choice for locally advanced and metastatic prostate cancer. We report a case of prostate cancer in which this treatment led to severe symptoms of intracranial hypertension due to the concomitant presence of an asymptomatic functional pituitary adenoma. A 70-year-old white man was initially evaluated for a multifocal adenocarcinoma, Gleason score 6 (3+3) with perineural invasion suggesting an extracapsular extension. A conformational external beam radiation (74 Gy) with a concomitant GnRH agonist (leuprolide) was initiated. Almost 10 days after the administration of leuprolide the patient complained of visual disturbance, diplopia and other symptoms of intracranial hypertension. Magnetic resonance imaging (MRI) of the brain demonstrated a large sella mass lesion. To relieve the patient's symptoms, a transsphenoidal subtotal tumorectomy was necessary. The histopathological examination revealed an invasive gonadotroph pituitary adenoma. Two years later, there is no sign of progression either on his prostatic disease (prostate-specific antigen of 0.21 ng/mL) or on his pituitary disease (FSH, 4.7 UI/L, LH, 3.1 UI/L and total testosterone, 627 ng/dL) with values of the hypothalamic-pituitary axis in the normal range. We advocate that a high index of suspicion of pituitary tumor must be considered in any case of intracranial hypertension following the administration of GnRH agonist. Abarelix could have a place in such cases.
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PMID:Discovery of a pituitary adenoma following a gonadotropin-releasing hormone agonist in a patient with prostate cancer. 1664 33

LHRH analogs have become a promising modality in prostate cancer therapy as an alternative to surgical castration, and the use of these agents is generally considered to be safe. Since now, only few cases of an apoplexy of previously undiagnosed pituitary adenoma (usually gonadotropinoma) at the beginning of therapy have been described in the medical literature. We present a case of a 74 year old patient who was diagnosed of prostate cancer at the age of 68. There was no evidence of metastatic disease. Radical prostatectomy was performed and LHRH analog gosereline (Zoladex 3.6 mg s.c.) was administered. During the first day after gosereline injection the patient developed headaches that became more severe over the next 3 days. Then the patient experienced nausea and vomiting, double vision and eyelid ptosis. On the 5th day the patient temporarily lost consciousness and was admitted to hospital. Imaging (computerized tomography, magnetic resonance imaging) revealed the presence of a pituitary tumor and hemorrhage within the gland. There was no evidence of pituitary dysfunction in hormonal studies. Neurosurgical intervention was postponed for 5 days after admission. Pathological mass with signs of recent hemorrhage was removed via transsphenoidal route. The tumor had negative immunohistochemical GH, ACTH and PRL staining. Neurological impairment resolved within 9 months after the operation. As a result the patient required adrenal and thyroid replacement. During 6 years of follow-up there was no evidence of prostate cancer recurrence.
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PMID:Apoplexy of clinically silent pituitary adenoma during prostate cancer treatment with LHRH analog. 1715 26

The growth of prostate cancer is controlled by several hormones and growth factors. In cases of metastasized prostate cancer, antigonadotropic therapy is currently considered state-of-the-art treatment. Surgical therapies such as adrenalectomy and hypophysectomy are no longer in use. Nevertheless, hypophysectomy has proven efficacy for palliative pain treatment as well as increasing duration of survival. The authors present the case of a 63-year-old man with metastatic prostate cancer who presented with high serum prostate-specific antigen levels (1216 microg/L) and cavernous sinus syndrome. His disease was progressing despite leuprorelin and docetaxel therapy, and he had severe bone pain despite high-dose pain therapy. He was also anemic. Contrast-enhanced MR imaging showed a pituitary lesion as well as metastatic infiltration of the skull base including the cavernous sinus. The patient's serum level of prolactin was mildly elevated, testosterone was below the detection limit, and insulin-like growth factor-I (IGF-I) was in the upper range for a patient of his age (233 microg/L). Because of the elevated prolactin and high-normal IGF-I levels he was offered a hypophysectomy in addition to pituitary tumor removal. Histological examination of the resected lesion confirmed a nonsecreting pituitary adenoma with infiltration of prostate cancer cells. Postoperatively the patient's prostate-specific antigen levels dropped to 876 microg/L, his bone pain resolved, and the cavernous sinus syndrome improved. Nevertheless, he died of septicemia 4 months after surgery. Older publications as well as this case have shown the benefit of hypophysectomy for pain treatment. A reduction of IGF-I levels even in the final stage metastasized prostate cancer may play a major role. Respectively, clinical studies with somatostatin analogs are currently in progress, which may lead to a "new" way of treatment in these otherwise hopeless patients. On the basis of the pain relief seen after hypophysectomy in this case and similar benefits reported in older publications, the authors raise the question whether this treatment should be offered more frequently, and whether additional medical options of hormone treatment may be beneficial in similar cases.
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PMID:Hypophysectomy for prostate cancer: a revival of old knowledge? 1882 67

The identification of a subpopulation of brain tumor cells with potent tumorigenic capacity strengthens the cancer stem cell hypothesis of the origin of the tumors that has recently attracted the attention of many researchers. Reports have been published on the identification of tumor cells with stem cells characteristics in different types of tumors (acute myelogenic leukemia, breast cancer, prostate cancer, bone sarcomas, liver cancer, and melanomas). We and other groups have previously reported the isolation of cancer stem cells from adult glioblastoma multiforme. These cells express stem cell markers, and when differentiated they express glial and neuronal markers. In vivo they give a tumor that recapitulates the characteristics of the tumor in the patient. More recently we have isolated tumor stem-like cells also from benign tumors like pituitary adenomas. Cells derived from pituitary adenomas are able to grow as floating aggregates resembling the neurospheres (typical of normal stem cells) in a medium supplemented by growth factors (EGF and bFGF). The immunocytochemical analysis revealed that pituitary tumor stem-like cells are positives for nestin and, when grown for ten days in differentiation medium they express GFAP, BIII tubulin, and S-100. In vitro tumor stem-like cells derived from a patient with a somatotroph adenoma showed high production of growth hormone and prolactin, while cells derived from the same patient but grown in presence of fetal bovine serum showed no production of hormones.
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PMID:Pituitary adenoma stem cells. 1958 28


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