Somatostatin receptors: from basic science to clinical approach

Mosca, Alessandra; Dogliotti, Luigi; Berruti, Alfredo; Lamberts, Steven W. J.; Hofland, Leo J.

doi:10.1016/j.dld.2003.11.021

Cited by 7 publications

(7 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among those, SSTR2‐specific SST analogs octreotide and lanreotide have attracted significant attention in the past several years. They have been used as new diagnostic and treatment methods for various endocrine disorders and as adjunctive treatment for various benign and malignant tumours [12–16]. The antiproliferative and antiangiogenic properties of octreotide have been exploited in several clinical trials [17,18].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression of somatostatin receptor subtypes in prostate tissue from cystoprostatectomies with incidental prostate cancer

et al. 2010

View full text Add to dashboard Cite

OBJECTIVE To examine immunohistochemically the expression of the five somatostatin receptors (SSTRs) in cystoprostatectomies (CyPs) with incidental prostate cancer. MATERIALS AND METHODS The five SSTRs (SSTR1–5) were evaluated in ‘normal‐looking’ epithelium (NEp), high‐grade prostatic intraepithelial neoplasia (HGPIN) and pT2a Gleason score 6 adenocarcinoma in 20 CyP specimens with incidental prostate cancer and 20 radical prostatectomy (RP) specimens with clinically detected prostate cancer. RESULTS For cytoplasm expression, the mean percentage of positive secretory cells with strong cytoplasmic staining increased from NEp to HGPIN and prostate cancer, being slightly lower in the CyP than in the RP specimens. Both in the CyP and RP specimens SSTR4 was found in the highest percentage of cells. There was membrane staining in the secretory cells for SSTR3 and SSTR4. There was nuclear staining in the secretory cells for SSTR4 and SSTR5. For SSTR1 and SSTR3 the mean proportions of positive basal cells were higher than for the other three subtypes, and greater in NEp than in HGPIN. There were positive smooth muscle and endothelial cells for all five SSTR subtypes, the highest proportions being SSTR1 and the lowest SSTR5. CONCLUSIONS This immunohistochemical study expands our knowledge of the expression and localization of SSTRs in the various tissue components in the prostate with incidental cancer, compared with clinically detected cancer. Such information might be useful in developing further non‐invasive strategies for the prevention and treatment of pre‐neoplastic and neoplastic lesions of the prostate.

show abstract

Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression of somatostatin receptor subtypes in prostate tissue from cystoprostatectomies with incidental prostate cancer

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Somatostatins may have a role in the progression of prostate cancer and in the degree of neuroendocrine differentiation of the disease. 22,25,27 The effect is likely to be mediated via specific somatostatin receptors, and expression levels of these receptors might be used in selection of patients for somatostatin treatment. Serum chromogranin A levels and tissue expression may be of value in the detection of the neuroendocrine phenotype, which is often androgen independent and associated with expression of high levels of somatostatin receptors, probably SR 1 and SR 4 in human prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The neuroendocrine phenotype and hormone-refractory prostate cancer are also characterized by high circulating chromogranin A levels, 26 which are known to be decreased by somatostatin analogue treatment. 27 However, the chromogranin B might be an even better marker for the number of neuroendocrine (NE) cells in prostate cancer. 25 These somatostatin effects are mediated through ligand binding to their cognate membrane receptors, which are found in a majority of human tumors including prostatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Phase I Trial on sms‐D70 Somatostatin Analogue in Advanced Prostate and Renal Cell Cancer

Joensuu

Nilsson

Holmberg

et al. 2004

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Plasma concentrations and tolerability of a novel somatostatin analogue sms-D70 were studied in patients with metastatic hormone-resistant prostate cancer (HRPC) or metastatic renal cell cancer. To overcome the limitations of the octapeptides having affinity only to somatostatin receptor subtypes 2 and 5, HRPC expressing mainly somatostatin receptors 1 and 4, a somatostatin derivative based on the natural somatostatin having affinity to all five somatostatin receptor subtypes, was developed. The in vivo stability of this dextran-conjugated derivative, somatostatin-D70, was confirmed previously in animal studies, and the nanomolar "panaffinity" has been shown in in vitro receptor binding studies on cell lines transfected with the somatostatin receptor genes. Sms-D70 was given with subcutaneous injection once a week at dose levels of 5, 10, 20, 35, and 50 mg. For pharmacokinetic studies, sms-D70 was labeled with 131I. Fourteen patients were treated, of whom 10 had prostate and 4 renal cell cancer. The kinetic data revealed high stability with a long half-life in the blood. The drug was well tolerated, and no grade 4 (WHO) toxicity was observed. The maximal tolerated dose could not be established due to the lack of dose-limiting toxicities. Objective PSA responses were not recorded in these heavily treated patients, but subjective stabilization of pain was observed and urinary symptoms were alleviated in four patients. Three patients with metastatic HRPC received 5-10-mg intravenous injections of sms-D70 once weekly for 4-14 months on a compassionate use basis. In all cases, serum PSA values decreased more than 50% from the pretreatment level, but these results are difficult to interpret due to concomitant treatments given to these patients. In conclusion, sms-D70 was well tolerated in the treatment of metastatic prostate and renal cell cancer, but no responses were found in these heavily treated patients.

show abstract

“…The differences in the expression of SSTRs between primary and AIPC are likely to be related to the changes in the neuroendocrine phenotype during androgen deprivation. Circulating chromogranin A is only marginally affected by hormones or chemotherapy but suppressed by SST analogs [8] . Finally, an interesting mechanism is related to the observation that LHRH receptors are expressed in prostate cancer after exposure to an LHRH agonist [43] .…”

Section: Combination Therapymentioning

confidence: 99%

“…The AIPC, though resistant to castration, is still sensitive to secondary hormonal manipulations among which somatostatins (SSTs) are of interest. SSTs are a family of regulatory peptides which can act as hormones and can exert a paracrine or autocrine regulation or function as a monotransmitter, but mainly they inhibit cell secretion and proliferation [8] . In suppressing growth hormone (GH) secretion, SSTs interfere with the production of insulin-like growth factor-1 (IGF-1), which may stimulate prostate cancer cells.…”

mentioning

confidence: 99%

Growth Hormone Inhibitors in Prostate Cancer: A Systematic Analysis

2008

View full text Add to dashboard Cite

Objective: Despite initial therapeutic success through androgen ablation in patients with advanced prostate cancer, the vast majority progress to androgen independence. Somatostatin (SST) analogs are a viable therapeutic modality before resorting to chemotherapy or immunotherapy. Their mechanism of action is related to a reduction in the IGF-1 (survival factor, reaction on neuroendocrine cells) appearing incrementally after long-term androgen deprivation and a possible suppression of GnRH receptors in prostate cancer following exposure to LHRH agonists. Methods: The computerized databases Medline, NCBI and OMIM were searched for the terms, somatostatin and prostate cancer, in parallel with printed bibliographic references. Forty-two studies were included and 267 patients with androgen-independent prostate cancer (AIPC) who were treated with SST analogs alone or in combination with other medications, e.g. dexamethasone, were analyzed. Results: In 42 studies with 267 AIPC patients, SST analogs were found to be effective, particularly when combined with estrogens or corticosteroids. The side effects are mild and related to the gastrointestinal tract. Conclusions: It would be interesting to study SST analogs in randomized trials including patients with well-defined AIPC. Whether SST analogs could be given earlier during sequential hormonal therapy remains to be studied.

show abstract

Somatostatin receptors: from basic science to clinical approach

Cited by 7 publications

References 63 publications

Immunohistochemical expression of somatostatin receptor subtypes in prostate tissue from cystoprostatectomies with incidental prostate cancer

Immunohistochemical expression of somatostatin receptor subtypes in prostate tissue from cystoprostatectomies with incidental prostate cancer

Phase I Trial on sms‐D70 Somatostatin Analogue in Advanced Prostate and Renal Cell Cancer

Growth Hormone Inhibitors in Prostate Cancer: A Systematic Analysis

Contact Info

Product

Resources

About