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

Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor that typically occurs in elderly, immunosuppressed patients. Infection with Merkel cell virus (MCV) and immunosuppression play an important role in the development of MCC. Different staging systems make it difficult to compare the existing clinical data. Furthermore, there predominantly exist single case reports and case series, but no randomized controlled trials. However, it is necessary to develop further therapy options because MCC tends to grow rapidly and metastasizes early. In the metastatic disease, therapeutic attempts were made with various chemotherapeutic combination regimens. Because of the high toxicity of these combinations, especially those established in SCLC, and regarding the unsatisfying results, the challenge is to balance the pros and cons of chemotherapy individually and carefully. Up to now, emerging new therapy options as molecular-targeted agents, for example, pazopanib, imatinib, or somatostatin analogues as well as immunologicals, for example, imiquimod and interferons, also showed less success concerning the disease-free response rates. According to the literature, neither chemotherapy nor molecular-targeted agents or immunotherapeutic strategies have shown promising effects in the therapy of the metastatic disease of MCC so far. There is a great demand for randomized controlled studies and a need for an MCC registry and multicenter clinical trials due to the tumors curiosity.
 ...
PMID:Merkel cell carcinoma: chemotherapy and emerging new therapeutic options. 2347 82

Small cell lung cancer (SCLC) represents approximately 13% of all newly diagnosed lung cancers. SCLC is a very aggressive disease characterized by early locoregional and distant metastases. The median survival is 14-16 months for patients with limited disease and 8-11 months for those with extensive disease, with 20-40% of patients with limited disease and 5% of patients with extensive disease alive at 2 years. This report discusses the case of a long-term SCLC survivor treated with radiotherapy, several lines of chemotherapy and long-acting somatostatin analogs who is alive 7 years after diagnosis, with no evidence of further relapse. In the near future, better identification of prognostic and predictive factors based on models that integrate clinical data and multiple gene expression profiles and the use of novel treatments could increase the number of long-term SCLC survivors.
 ...
PMID:Long-term survival in small cell lung cancer: a case report and review of the literature. 2475 83

Lung cancer encompasses a diverse spectrum of histologic subtypes. Until recently, the majority of therapeutic advances were limited to the minority of patients with adenocarcinoma. With the advent of comprehensive genomic profiling of squamous and small cell lung cancers, new therapeutic targets have emerged. For squamous tumors, the most promising of these include fibroblast growth factor receptor (FGFR), the phosphatidylinositol 3-kinase (PI3K) pathway, discoidin domain receptor 2 (DDR2), and G1/S checkpoint regulators. In 2014, the antiangiogenic agent ramucirumab was approved for all non-small cell lung cancer (NSCLC) histologies, including squamous tumors. Immunotherapeutic approaches also appear to be promising for these cases. Genomic analysis of small cell lung cancer has revealed a high mutation burden, but relatively few druggable driver oncogenic alterations. Current treatment strategies under investigation are focusing on targeting mitotic, cell cycle, and DNA repair regulation, as well as immunotherapy. Pulmonary neuroendocrine tumors represent a diverse spectrum of diseases that may be treated with somatostatin analogs, cytotoxic agents, and molecularly targeted therapies. Radiolabeled somatostatin analogs and combinations with mammalian target of rapamycin (mTOR) inhibitors also show potential. Large cell neuroendocrine tumors share numerous clinical, pathologic, and molecular features with small cell lung cancer; however, whether they should be treated similarly or according to a NSCLC paradigm remains a matter of debate.
...
PMID:Beyond adenocarcinoma: current treatments and future directions for squamous, small cell, and rare lung cancer histologies. 2599 53

Neuroendocrine cancer cell lines are used to investigate therapeutic targets in neuroendocrine tumors (NET) and have been instrumental in the design of clinical trials targeting the PI3K/AKT/mTOR pathways, VEGF inhibitors, and somatostatin analogues. It remains unknown, however, whether the genomic makeup of NET cell lines reflect that of primary NET since comprehensive unbiased genome sequencing has not been performed on the cell lines. Four bronchopulmonary NET (BP-NET)-NCI-H720, NCI-H727, NCI-H835, and UMC11-and two pancreatic neuroendocrine tumors (panNET)-BON-1 and QGP1-were cultured. DNA was isolated, and exome sequencing was done. GATK and EXCAVATOR were used for bioinformatic analysis. We detected a total of 1,764 nonsynonymous single nucleotide variants at a rate of 8 per Mb in BP-NET and 4.3 per Mb in panNET cell lines, including 52 mutated COSMIC cancer genes in these cell lines, such as TP53, BRCA1, RB1, TSC2, NOTCH1, EP300, GNAS, KDR, STK11, and APC but not ATRX, DAXX, nor MEN1. Our data suggest that mutation rate, the pattern of copy number variations, and the mutational spectra in the BP-NET cell lines are more similar to the changes observed in small cell lung cancer than those found in primary BP-NET. Likewise, mutation rate and pattern including the absence of mutations in ATRX/DAXX, MEN1, and YY1 in the panNET cell lines BON1 and QGP1 suggest that these cell lines do not have the genetic signatures of a primary panNET. These results suggest that results from experiments with BP-NET and panNET cell lines need to be interpreted with caution.
...
PMID:Exome-level comparison of primary well-differentiated neuroendocrine tumors and their cell lines. 2634 99

Ectopic adrenocorticotropic hormone secretion (EAS) is responsible for approximately 10-15% cases of Cushing's syndrome. EAS is associated with various tumors such as small cell lung cancer and well-differentiated bronchial or gastrointestinal neuroendocrine tumors. Hormonal diagnostics include assessments in basic conditions as well as dynamic tests, such as the high-dose dexamethasone suppression test and corticotrophin releasing hormone (CRH) stimulation test. Treatment selection depends on the type of tumor and its extent. In the case of neuroendocrine tumors, the main treatments are surgery and administration of somatostatin analogs that may be additionally radiolabeled for targeted radiotherapy. The tumor histology and the presence and control of hypercortisolemia and metastases are of major importance in prognosis. In this article we presented the principles of modern hormonal and imaging diagnostics techniques as well as the key issues associated with treatment of ACTH-dependent Cushing's syndrome due to EAS.
...
PMID:Ectopic Cushing's syndrome in light of modern diagnostic techniques and treatment options. 2631 84

Despite initial responsiveness to both chemotherapy and radiotherapy, small cell lung cancer (SCLC) commonly relapses within months. Although neuroendocrine characteristics may be difficult to demonstrate in individual cases, a relevant expression of somatostatin receptors (SSTR) on the cell surface has been described. We aimed to evaluate the prognostic value of SSTR-expression in advanced SCLC. We further examined pre-requisites for successful peptide receptor radionuclide therapy (PRRT). 21 patients with extensive stage SCLC were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) with 68Ga-DOTATATE to select patients for SSTR-directed therapy. PET scans were visually and semi-quantitatively assessed and compared to SSTR2a and SSTR5 expression in biopsy samples. Peak standardized uptake values (SUVpeak) of tumors as well as tumor-to-liver ratios were correlated to progression-free (PFS) and overall survival (OS). In 4/21 patients all SCLC lesions were PET-positive. 6/21 subjects were rated "intermediate" with the majority of lesions positive, the remaining 11/21 patients were PET-negative. PET-positivity correlated well with histologic SSTR2a, but not with SSTR5 expression. Neither PET-positivity nor SUVpeak were predictors of PFS or OS. In 4 patients with intensive SSTR2a-receptor expression, PRRT was performed with one partial response and one stable disease, respectively. SSTR-expression as detected by 68Ga-DOTATATE-PET and/or histology is not predictive of PFS or OS in patients with advanced SCLC. However, in patients exhibiting sufficient tracer uptake, PRRT might be a treatment option given its low toxicity and the absence of effective alternatives.
...
PMID:Somatostatin receptor expression in small cell lung cancer as a prognostic marker and a target for peptide receptor radionuclide therapy. 2693 94

Chemotherapy represents the cornerstone of treatment for patients with small cell lung cancer (SCLC); however, standard therapy has reached a plateau in improving patient survival with overall disappointing results. The demonstration that SCLC expresses neuroendocrine markers, such as somatostatin (SST) receptors, has led to use SST analogs or radiolabeled SST analogs in the treatment of SCLC patients. In the current review, we would focus on the possible role of SST analogs in SCLC.
...
PMID:Somatostatin Analog Therapy in Small Cell Lung Cancer. 2706 4

Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are currently classified as grade (G) 1, G2 and G3, in accordance with the 2010 WHO classification. G1 and G2 are named neuroendocrine tumors (NETs) whereas G3 neuroendocrine carcinomas (NECs). While advanced G1 and G2 are usually treated with several different therapies, including somatostatin analogs, chemotherapy, interferon, molecular targeted agents, peptide receptor radionuclide therapy (PRRT) and liver-directed treatments, advanced G3 NECs are usually treated with a platinum-etoposide chemotherapy, trusting their clinical homogeneity is similar to that of small cell lung cancer. However, over the last years a number of reports suggested that 2010 WHO G3 GEP NECs are more heterogeneous than expected. Therefore, we critically reviewed the literature about this topic and reported pathological and clinical considerations on 2010 WHO G3 GEP NEC category proposing new sub-categories. Over the last five years, six studies specifically investigating large series of G3 GEP NECs have been published, including around 800 patients. Tumor morphology and Ki-67 Labeling Index (that will be mentioned as Ki-67 in this manuscript) combination has been reported as a tool to define two or even three subgroups of this category with different prognosis and potentially different therapeutic approach. Prospective trials are warranted to investigate if several types of therapy other than the platinum/etoposide chemotherapy can be effective in well differentiated GEP NEN with 21-55% Ki-67 and alkylating-based chemotherapy in poorly differentiated GEP NEN with 21-55% Ki-67.
 ...
PMID:Heterogeneity of grade 3 gastroenteropancreatic neuroendocrine carcinomas: New insights and treatment implications. 2763 9

Neuroendocrine tumors (NETs) of the lung are divided into 4 major types: small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), atypical carcinoid (AC) or typical carcinoid (TC). Each classification has distinctly different treatment paradigms, making an accurate initial diagnosis essential. The inconsistent clinical presentation of this disease, however, makes this difficult. The objective of this manuscript is to detail the diagnosis and management of the well differentiated pulmonary carcinoid (PC) tumors. A multidisciplinary approach to work up and treatment should be utilized for each patient. A multimodal radiological work-up is used for diagnosis, with contrast enhanced CT predominantly utilized and functional imaging techniques. A definitive diagnosis is based on tissue findings. Surgical management remains the mainstay of therapy and can be curative. In those with advanced disease, medical treatments consist of somatostatin analog (SSA) therapy, targeted therapy, chemotherapy or peptide receptor radionuclide therapy. SSAs are the standard of care in those with metastatic NETs, using either Octreotide long acting repeatable (LAR) or lanreotide as reasonable options, despite a scarcity of prospective data in PCs. Targeted therapies consist of everolimus which is approved for use in PCs, with various studies showing mixed results with other targeted agents. Additionally, radionuclide therapy may be used and has been shown to increase survival and to reduce symptoms in some studies. Prospective trials are needed to determine other strategies that may be beneficial in PCs as well as sequencing of therapy. Successful diagnosis and optimal treatment relies on a multidisciplinary approach in patients with lung NETs. Clinical trials should be used in appropriate patients.
 ...
PMID:Management of pulmonary neuroendocrine tumors. 2886 78

Small cell lung cancer (SCLC) is a malignant human cancer and patients have very limited benefit from traditional anticancer treatments, with a poor five-year survival rate being 10% less. In present study, we observed that Notch signalling activation induced SCLC cell growth suppression via overexpressing Notch active fragments (ICN1, ICN2, ICN3 and ICN4), implying its tumor suppressive role. The histone deacetylase (HDAC) inhibitors also displayed their suppressive effects. Valproic acid (VPA) as a HDAC inhibitor was found to suppress SCLC cell growth and cell cycle arrest at phase G1, and observed to decrease HDAC4 and increase acetylation of histone H4 (AcH4) while activating Notch signalling with an increase of Notch1, Notch target gene HES1 and p21. Meanwhile, we also observed that VPA greatly stimulated the expression of somatostatin receptor type II (SSTR2) that is usually overexpressed in many cancer cells and is used as a target for anticancer drug development, providing a combination therapy with VPA and the SSTR2-targeting cytotoxins. Thus, VPA was investigated in combination with SSTR2-targeted cytotoxins captothecine-somatostatin conjugate (CPT-SST) and colchicine-somatostatin conjugate (COL-SST). Our assays showed that these combination treatments strongly led to a greater suppression as compared to each alone. In conclusion, we found that VPA suppressed SCLC cell growth and increased the expression of SSTR2. These may provide a novel clinical opportunity for enhanced anticancer therapy using the combination strategy of Notch signalling regulator and SSTR2-targeting cytotoxins in SCLC treatments.
 ...
PMID:HDAC inhibitors suppressed small cell lung cancer cell growth and enhanced the suppressive effects of receptor-targeting cytotoxins via upregulating somatostatin receptor II. 2951 49


<< Previous 1 2 3 4 5 6 7 Next >>