Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bombesin-like peptides such as gastrin-releasing peptide (GRP) have been shown to play a role in cancer as autocrine growth factors that stimulate tumor growth through specific receptors. To search for potential clinical indications for GRP analogues, it is important to identify human tumor types expressing sufficient amounts of the respective receptors. In the present study, we have evaluated the expression of GRP receptors in human nonneoplastic and neoplastic prostate tissues using in vitro receptor autoradiography on tissue sections with 125I-Tyr4-bombesin as radio-ligand. GRP receptors were detected, often in high density, in 30 of 30 invasive prostatic carcinomas and also in 26 of 26 cases of prostatic intraepithelial proliferative lesions, corresponding mostly to prostatic intraepithelial neoplasias. Well-differentiated carcinomas had a higher receptor density than poorly differentiated ones. Bone metastases of androgen-independent prostate cancers were GRP receptor-positive in 4 of 7 cases. Conversely, GRP receptors were identified in only a few hyperplastic prostates and were localized in very low density in glandular tissue and, focally, in some stromal tissue. In all of the cases, the receptors corresponded to the GRP receptor subtype of bombesin receptors, having high affinity for GRP and bombesin and lower affinity for neuromedin B. These data demonstrate a massive GRP receptor overexpression in prostate tissues that are neoplastically transformed or, like prostatic intraepithelial neoplasias, are in the process of malignant transformation. GRP receptors may be markers for early molecular events in prostate carcinogenesis and useful in differentiating prostate hyperplasia from prostate neoplasia Such data may not only be of biological significance but may also provide a molecular basis for potential clinical applications such as GRP-receptor scintigraphy for early tumor diagnosis, radiotherapy with radiolabeled bombesin-like peptide analogues, and chemotherapy with cytotoxic bombesin analogues.
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PMID:Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. 1007 Sep 77

Prostate cancer (PCa) is the fourth most common cancer worldwide in terms of incidence and third among male, but is becoming the most common cancer in developed countries. In many patients the disease will progress despite of castration levels of testosterone, to become castration-resistant PCa (CRPC). Nearly all patients with CRPC show bone metastases. The treatment of patients with bony metastases has dramatically changed during the past three years because of new therapeutic approaches addressed to obtain pain control, reduced skeletal morbidity, and most importantly, increased survival rate. A possible therapy can be based also on the use of radiopharmaceuticals systemically administered to slow or reverse the bone metastatic progression. In facts bone-homing radiopharmaceuticals are taken up in areas of high bone turnover, including areas with high osteoblastic activity. Recently, a bone targeting radiopharmaceutical, Radium-223 dichloride was added to this group of drugs clearly representing a new generation of radiopharmaceutical in bone therapy. Clinical trials had shown that the treatment with Ra-223 allowed the reduction of the risk of death respect to placebo. No other radiometabolic treatment achieved such result, evidentiating the disease-modifying properties of this bone-homing radiopharmaceutical. In an effort to treat patients with disseminated PCa, who became resistant to hormonal therapy, molecular targets have been recently identified. Prostate specific membrane antigen (PSMA) is one attractive target for diagnosis and therapy of metastasized PCa since its expression levels are directly correlated to androgen independence, metastasis, and progression. Gastrin-releasing peptide receptors (GRPr) are also highly overexpressed in PCa. Numerous studies suggest the possibility of a high PCa-specific signal with radiolabeled bombesin analogs targeting GRPr. Low molecular weight peptides directed against these molecular targets have been radiolabeled with positron emitting radionuclides such as 68Ga in order to improve sensitivity and specificity for detecting primary, metastatic, and recurrent PCa by PET/CT over conventional imaging techniques. Although peptide radionuclide ligand therapy studies have just initiated, the diagnostic relevance of 68Ga labeled specific tracers has already been established its clinical utility and represents a valid tool against this common and deadly cancer.
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PMID:New radiopharmaceutical agents for the treatment of castration-resistant prostate cancer. 2622 74

Although postoperative recurrence or prostate cancer metastasis is usually accompanied by high prostate-specific antigen (PSA)levels, it may occur even if PSA level is within the normal range. Neuroendocrine differentiation(NED), which is one of such cases, causes rapid disease progression. A man in his 70s underwent total prostatectomy for prostate cancer with high PSA levels. Twenty-two months later, liver, lung, and bone metastases appeared even though the PSA levels were normal. The levels of both neuron-specific enolase and pro-gastrin-releasing peptide were elevated and the patient was clinically diagnosed with NED. Although systemic chemotherapy was administered, the outcome was progressive disease. Transcatheter arterial chemoembolization(TACE)was opted because liver metastases were one of the prognostic factors. Four types of chemotherapy drugs(cisplatin 20 mg, docetaxel 20 mg, 5-FU 250 mg, and bevacizumab 100 mg)were infused through the right and left hepatic arteries, followed by embolization with HepaSphereTM. The liver tumors were remarkably reduced in size and the levels of tumor markers were reduced in 5 sessions. This treatment would avoid the lethal liver trouble; however, the patient died 7 months after the first session of TACE.
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PMID:[Transcatheter Arterial Chemoembolization with HepaSphereTM for Diffuse Liver Metastases from Prostatic Cancer without Elevation of the Serum Prostate-Specific Antigen Level-A Case Report]. 3238 63