Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The function of the pituitary-gonadal axis in normal (immunocompetent) and nude (immunocompromised) mice, like that of other species, can be suppressed by luteinizing hormone-releasing hormone (LH-RH) agonists and antagonists administered by continuous release systems and, therefore, nude mice provide a valuable model for investigation of the effects of LH-RH analogues on growth of xenografts of human cancers. To extend our findings further, we treated male nude mice bearing xenografts of human prostate adenocarcinoma PC-82, for 42 days, with sustained release formulations (microcapsules or microgranules) of the agonist [D-Trp6]LH-RH, the antagonist [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH- RH (SB-75), or the somatostatin analogue D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160). At necropsy, in mice given microcapsules releasing 25 micrograms/day of [D-Trp6]-LH-RH, tumor weight and volume were significantly decreased, compared with control mice, and weights of testes, ventral prostate, and seminal vesicles were also reduced in this group. In mice which received microgranules liberating 50 micrograms/day of antagonist SB-75, there was a greater decrease in tumor weight and volume than that produced by the agonist and a significant reduction in the weight of the testes and accessory sex organs. Histological parameters also demonstrated significant tumor inhibition, with the best results being obtained by treatment with the antagonist SB-75. The tumor inhibition induced by SB-75 was demonstrated to be due to decreased cellular proliferation, with enhanced cellular death (i.e., apoptosis) of the PC-82 cells. Microcapsules releasing 50 micrograms/day of RC-160 decreased tumor weight and volume by 23% and 28%, respectively, but this reduction was not significant. Serum levels of testosterone were decreased by 90% in mice given the LH-RH agonist and by 94% in response to the antagonist SB-75. Serum levels of prostate-specific antigen were significantly lower in mice treated with LH-RH analogues, with the antagonist SB-75 causing a greater reduction. A ratio of prostate-specific antigen to tumor weight suggests that levels of serum prostate-specific antigen may be correlated with tumor mass. Using sensitive multipoint micromethods, one class of binding sites for LH-RH, with a dissociation constant of 7.8 +/- 1.2 nM and a maximal binding capacity of 126.4 +/- 23.1 fmol/mg protein, was found in the control tumors. Tumors from mice treated with either LH-RH agonist or antagonist, but not somatostatin analogue RC-160, showed a significant reduction in maximal binding capacity for LH-RH, compared to control tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sustained release formulations of luteinizing hormone-releasing hormone antagonist SB-75 inhibit proliferation and enhance apoptotic cell death of human prostate carcinoma (PC-82) in male nude mice. 156 23

Neuroendocrine (NE) differentiation of prostatic adenocarcinomas has received increasing attention in recent years as a result of possible implications on prognosis and therapy. The incidence of NE cells in tumors has been reported from 10% up to 100%. Several studies have shown chromogranin A (CgA) to be the most reliable serum marker of NE differentiation. We have followed 22 patients with prostatic adenocarcinoma over a 2-year period. The patients underwent a palliative transurethral resection of the prostate (TURP) because of urinary outflow obstruction. The prostatic tissue specimens were stained immunohistochemically using antibodies against CgA, chromogranin B (CgB), neuron-specific enolase (NSE), thyroid-stimulating hormone (TSH), serotonin, and somatostatin. In addition, each specimen was stained with hematoxylin & eosin (H & E), and saffran for tumor grading. Blood samples were taken preoperatively and after 1, 3, 6, and 24 months. The serum values of CgA, CgB, pancreastatin (Pst), NSE, and prostate-specific antigen (PSA) were determined from each sample. Carcinomas with groups of CgA-positive cells had higher serum levels of CgA compared to carcinomas with no or only scattered CgA-positive NE cells. During the 2-year period, there were no statistical significant variations in serum levels of CgA, NSE, Pst, and PSA. However, there was a significant increase in serum levels of CgB during the same period, P = 0.002, possibly due to an increase in number of NE cells in tumor or to a relative increase in production of CgB in the NE cells.
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PMID:Use of neuroendocrine serum markers in the follow-up of patients with cancer of the prostate. 914 Jan 24

We evaluated whether the combination of triptorelin, a LHRH analog (LHRH-A), with dexamethasone and lanreotide, a somatostatin analog, can produce objective clinical responses in metastatic androgen ablation-refractory prostate cancer (stage D3) patients who have relapsed, after combined androgen blockade (LHRH-A plus antiandrogen) and antiandrogen withdrawal. Eleven stage D3 patients with diffuse bony metastases, who had progressed despite initial responses (lasting <12 months) to combined androgen blockade therapy and subsequently failed antiandrogen withdrawal, received oral dexamethasone (4 mg daily for the first month, tapered down to 2 mg after the first month and 1 mg after the second month, and continued on 1 mg thereafter) and lanreotide (30 mg im every 14 d) in combination with triptorelin (3.75 mg im every 28 d). Serum prostate-specific antigen, alkaline phosphatase, performance status, and bone pain were assessed monthly during therapy. Fasting blood glucose was measured biweekly, and serum IGF-I, T, and dehydroepiandrosterone sulfate levels were assessed at baseline, at response to the combination therapy, and at relapse from it. Ten of 11 stage D3 patients [90.9% of patients; 95% confidence interval (CI), 58.7-99.8%] had durable objective clinical responses (including > or = 50% prostate-specific antigen decline in 8 patients, 72.7%; 95% CI, 39-94%). All patients reported significant and durable improvement of bone pain (for a median duration of 13 months; 95% CI, 12-14 months; range, 6-22 months) and performance status (median duration, 19 months; 95% CI, 13-25 months; range, 7-22 months) without major treatment-related side effects. The median progression-free survival was 7 months (95% CI, 4-10 months; range, 3-17 months), and the median overall survival was 18 months (95% CI, 16-20 months; range, 7-22 months). Five of six total deaths occurred secondary to disease progression. We observed a statistically significant (P = 0.018) reduction in serum IGF-I levels at response to the combination therapy (60% reduction of baseline IGF-I levels). Dehydroepiandrosterone sulfate levels, although already significantly suppressed at baseline, had an additional significant reduction (P < 0.02) at response to therapy. T levels remained suppressed within castration levels (<3 nmol/liter, at baseline and throughout therapy, including relapse). The combination therapy of LHRH-A with dexamethasone plus somatostatin analog produces objective clinical responses and symptomatic improvement in androgen ablation (LHRH-A) refractory prostate cancer patients.
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PMID:A combination therapy of dexamethasone and somatostatin analog reintroduces objective clinical responses to LHRH analog in androgen ablation-refractory prostate cancer patients. 1173 29

Neuroendocrine cells have been found in all the stages of prostate cancer, but their clinical significance is not completely understood. Neuroendocrine cells are androgen receptor- and prostate-specific antigen-negative, do not proliferate, and secrete many neuropeptides, such as chromogranin A. Neuroendocrine differentiation of prostate cancer correlates with an advancing tumour stage, poor prognosis and tumour progression after androgen deprivation. Furthermore, neuroendocrine phenotype is associated with the increased expression of neo-angiogenesis and vascular endothelial growth factor and with an over-expression of survivin, a new anti-apoptosis protein. Chromogranin A is the quantitatively major secretory protein of the vesicles inside neuroendocrine prostate cells and it is the marker most frequently used to detect neuroendocrine features, both in tissues and in general circulation. Tumours displaying neuroendocrine phenotype tend to be more aggressive and resistant to hormone-therapy. Neuroendocrine differentiation seems to be a dynamic phenomenon: in vitro and in vivo data suggest that it can be induced by androgen suppression. Moreover, the differences in the expression of somatostatin receptors between primary and hormone-refractory prostate cancer are likely to be related to the changes in neuroendocrine phenotype during androgen deprivation. Circulating chromogranin A levels seem to be scarcely affected by endocrine- and chemotherapy, while they significantly decreased after treatment with somatostatin analogs.
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PMID:Somatostatin receptors: from basic science to clinical approach. Unlabeled somatostatin analogues-1: Prostate cancer. 1507 13

Prostate-specific antigen (PSA) is a serine proteases produced by prostatic epithelial cells detectable in male serum and seminal plasma. PSA is also expressed in some female tissues and fluids and is increased in hirsute women showing a positive correlation with androgens. Accordingly, it has been suggested that PSA might be a marker of androgen action in women. The aim of this observational study was to assess serum PSA concentration in acro megalic women with active disease, in remission or during somatostatin analogs therapy. Forty-four acromegalic women, 15 with active disease, 10 in remission and 19 under long-acting somatostatin analogs therapy were enrolled in the study; 273 normal women matched for age, body mass index, with no signs of hirsutism, served as controls. Serum PSA, 3a-androstanediol (3alpha-AG), total testosterone (T), DHEAS, LH, FSH and estradiol were assessed. No patient or control had been given estrogen or antiandrogen drugs; no acromegalic women had hyperprolactinemia or hypopituitarism. Serum PSA concentration was significantly higher in acromegalic patients than in control subjects (p < 0.0001). Patients with active acromegaly or under somatostatin analogs therapy had significant higher serum PSA concentration than controls, while patients in remission after adenomectomy did not differ. Serum PSA was detectable in serum of 75% acromegalic women and 45% of controls. In addition 24% of acromegalic women had serum PSA concentrations higher than the mean +/- 2SD of control subjects. Differences in serum PSA levels did not reach statistical significance in the different acromegalic subgroups possibly because of the small number of subjects, but patients with active acromegaly had higher serum PSA levels than patients under somatostatin analogs therapy or in remission. Acromegalic women had significantly higher serum PSA concentrations than controls both before and after menopause (p < 0.01). 3alpha-AG (p < 0.05) and T (p < 0.01) were higher in acromegalic than in control subjects in pre-menopause (PM) but not in post-menopause (M). A correlation was found in the whole group of acromegalic patients between serum PSA and 3a-AG concentrations (r = 0.3, p < 0.01). In conclusion, acromegalic is associated with an increase in serum PSA concentrations as a group, although this increase is observed, at an individual level, in only 24% of cases. Patients whose disease is controlled by somatostatin analogs or has been cured by pituitary adenomectomy tend to have lower serum PSA levels than patients with active disease. M patients tend to have lower PSA values than PM women, consistent with the main androgen control of PSA production. However, the observation that M women still have higher serum PSA levels than controls suggest that in acromegaly PSA is regulated not only by androgens but also by the GH/IGF-I system itself.
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PMID:Serum prostate-specific antigen concentration is increased in acromegalic women. 1550 87

A 74-yr-old man with prostatic adenocarcinoma underwent magnetic resonance 1H-spectroscopic imaging (1H-MRSI) of the prostate. Based on the results, he was treated with combination therapy using complete androgen blockade (leuprorelin acetate 3.75 mg every 4 wk plus bicalutamide 50 mg daily) and a somatostatin analogue (lanreotide acetate 60 mg every 4 wk). Serum prostate-specific antigen and chromogranin A levels steadily decreased over a 12-mo follow-up period, at which time the patient is alive without disease progression and with a complete objective and symptomatic response.
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PMID:Complete response to the combination therapy with androgen blockade and somatostatin analogue in a patient with advanced prostate cancer: magnetic resonance imaging with 1H-spectroscopy. 1731 66

Almost all patients with hormone-refractory prostate cancer under primary androgen deprivation therapy will develop progression, frequently initially marked by an asymptomatic increase of prostate-specific antigen (PSA). Recent data showed that taxane-based chemotherapy offers significant survival benefit to patients with advanced prostate cancer; however, the toxic side effects frequently exert a significant negative impact on the quality of life. At the androgen-independent stage of the cancer, before becoming hormone refractory, progression might still be delayed by secondary manipulation of either androgen or confounding receptors and their signaling pathways. Secondary hormonal manipulations traditionally included antiandrogen withdrawal, second-line antiandrogens, direct adrenal androgen inhibitors, estrogens, and progestins.We discuss the mode of action and application of somatostatin analogs as an emerging secondary hormonal treatment concept in patients with advanced prostate cancer on the basis of the current literature.
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PMID:[Somatostatin analogs for the treatment of advanced, hormone-refractory prostate cancer: a possibility for secondary hormonal ablation?]. 1856 91

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

Prostate cancer (PC) is usually characterized by an excellent prognosis, largely due to little biological aggressiveness and the power of hormonal deprivation therapy. In spite of these favorable characteristics, however, a significant quota of patients does not respond to androgen deprivation therapy (ADT) and develop a progressive disease. Castration-resistant prostate cancer (CRPC) is defined by disease progression in spite of ADT. This progression may show any combination of a rise in serum prostate-specific antigen (PSA), clinical and radiological progression of pre-existing disease, and appearance of new metastases. This event is a striking change in the clinical scenario, since the power of treatment for CRPC patients with distant metastases is very limited. Somatostatin is a hormone produced by neuroendocrine cells. Its distant effects are mediated by the binding to five specific receptors, which are the most striking parameter for neuroendocrine. Various synthetic somatostatin agonists able to bind to the receptors have been synthesized during the past two decades for diagnostic and therapeutic purposes. Octreotide, the most popular of these, is widely used to treat patients affected by neuroendocrine tumors. A number of researches carried out in the past evaluated the possible neuroendocrine differentiation (NED) of PC cells in the castration resistant phase. If proved, the presence of a specific class of receptor on cell's surfaces should give a potentially biological target to be used for therapy. However, these studies led to contradictory results. Aim of our phase III diagnostic trial was to study "in vivo" the over-expression of somatostatin receptors (SSTRs) in CRPC patients by PET/CT after the administration of the somatostatin analog [(68)Ga-DOTANOC,1-Nal(3)]-octreotide labeled with (68)Ga. Every area of increased uptake corresponding to a metastasis detected with other methods was considered as SSTRs expressing. False positivity to SSTRs expression was considered those localizations with a suspicious uptake not confirmed by other radiologic procedures. On the other hand, metastatic lesions lacking the radiopharmaceutical's uptake were considered not SSTRs expressing metastases. The preliminary results in 6 of the 67 patients scheduled by our phase III trial showed metastases with a variable SSTRs expression in 2 patients.
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PMID:Somatostatin receptors over-expression in castration resistant prostate cancer detected by PET/CT: preliminary report of in six patients. 2620 38

We report on a 62-year-old man with metastatic prostate cancer (cT3b N1) diagnosed in 2011, treated with total androgen blockage with flutamide and goserelin acetate (Zoladex). He presented with left suprascapular swelling and low-back pain after being asymptomatic for 5 years. His prostate-specific antigen was 0.049 ng/mL. F-NaF PET-CT and Ga-PSMA scan were negative, whereas Ga-DOTA NOC scan done after 10 days showed multiple somatostatin-avid hepatic and lymph node metastasis.
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PMID:Molecular Imaging in Neuroendocrine Differentiation of Prostate Cancer: 68Ga-PSMA Versus 68Ga-DOTA NOC PET-CT. 2824 Jun 61


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