Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.     

Transcutaneous Electrical Acustimulation Ameliorates Motion Sickness Induced by Rotary Chair in Healthy Subjects: A Prospective Randomized Crossover Study

ObjectivesMotion sickness (MS) is a common physiological response to real or virtual motion. The purpose of this study was to investigate the effects of transcutaneous electrical acustimulation (TEA) on MS and the underlying mechanisms in healthy subjects.Materials and MethodsA total of 50 healthy participants were recruited and randomly assigned into two groups to complete two separate sessions in a crossover study. A Coriolis rotary chair was used as a model to provoke severe MS. The total tolerable rotation time and Graybiel scoring scale were recorded. Gastric slow waves were detected by electrogastrogram. The autonomic nervous function, including the vagal activity, was evaluated by the analysis of heart rate variability derived from the electrocardiogram recording. The serum levels of arginine vasopressin (AVP) and norepinephrine (NE) were examined.ResultsOf note, 22 participants in TEA and only 11 participants in the sham-TEA session completed the entire five-rotation MS stimuli (p = 0.019). TEA significantly prolonged the total tolerable rotation time of MS stimuli (220.4 ± 11.59 vs 173.6 ± 12.3 seconds, p < 0.001) and lowered MS symptom scores (12.56 ± 2.03 vs 22.06 ± 3.0, p < 0.001). TEA improved the percentage of normal gastric slow waves, compared with sham-TEA (56.0 ± 2.1% vs 51.6 ± 2.0%, p = 0.033). TEA also significantly enhanced vagal activity compared with sham-TEA (0.41 ± 0.02 vs 0.31 ± 0.02, p < 0.001). In addition, the increased serum levels of AVP and NE on MS stimulation were markedly suppressed by TEA treatment, compared with sham-TEA (AVP, 56.791 ± 4.057 vs 79.312 ± 10.036 ng/mL, p = 0.033; NE, 0.388 ± 0.037 vs 0.501 ± 0.055 ng/mL, p = 0.021).ConclusionsNeedleless TEA is a potent therapeutic approach for severe MS, as it increases participants' tolerance and ameliorates MS symptoms, which may be attributed to the integrative effects of TEA on autonomic functions and neuroendocrine balance.     

Cytohistology of papillary carcinoid and emerging concept of pulmonary neuroendocrine neoplasms

This timely review starts by reporting the clinical, cytologic and histologic features of a morphologic variant of pulmonary carcinoid tumor forming exclusively of papillae. This growth pattern is so rare that it was not included in 2014 WHO classification of pulmonary neuroendocrine neoplasms. The current concept is reviewed, and example of spindle cell carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma are illustrated with fine needle aspiration cytology, surgical and clinical follow‐up. Finally, the new findings in cell biology and molecular biology that led to the emerging concept that carcinoids and high‐grade neuroendocrine lung carcinomas are separate biological entities are reviewed and summarized in a tumorigenic module. Diagn. Cytopathol. 2016;44:52–60. © 2015 Wiley Periodicals, Inc.     

Small cell carcinoma of the prostate presenting with Cushing Syndrome. A narrative review of an uncommon condition

Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting with CS. The origin of these neoplasms is still unclear. It may be suspected when laboratory features appear in patients diagnosed with prostatic adenocarcinoma which becomes resistant to specific therapy. SCC usually occurs after the 6th decade. Patients suffering SCC of the prostate presenting with CS usually present symptoms such as hypertension, hyperglycemia, alkalosis or hypokalemia; cushingoid phenotype is less frequent. Cortisol and ACTH levels are often high. Prostatic-specific antigen levels are usually normal. CT scan is the preferred imaging test to localize the lesion, but its performance may be improved by adding other tests, such as FDG-PET scan. All patients have metastatic disease at the time of diagnosis. Lymph nodes, liver and bone are the most frequent metastases sites. Surgery and Ketokonazole are the preferred treatments for CS. The prognosis is very poor: 2- and 5-year survival rates are 27.5 and 14.3%, respectively.

• Key messages

• When a patient presents with ectopic Cushing Syndrome but lungs are normal, an atypical localization should be suspected.

• We should suspect a prostatic origin if Cushing Syndrome is accompanied by obstructive inferior urinary tract symptoms or in the setting of a prostatic adenocarcinoma with rapid clinical and radiological progression with relatively low PSA levels.

• Although no imaging test is preferred to localize these tumors, FDG-PET-TC can be very useful. Hormone marker scintigraphy (e.g. somatostatin) could be used too.

• As Cushing Syndrome is a paraneoplastic phenomenon, treatment of the underlying disease may help control hypercortisolism manifestations.

• These tumors are usually metastatic by the time of diagnosis. They have very poor prognosis.

     

Neuroendocrine neoplasms of the sinonasal region

Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small‐cell and large‐cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high‐grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E2259–E2266, 2016     

穿心莲内酯对前列腺癌细胞的增殖及神经内分泌分化的抑制作用

目的 探讨穿心莲内酯(Andro)对前列腺神经内分泌癌细胞增殖及神经内分泌分化的影响.方法 Andro处理前列腺癌细胞(PC3),用MTT法检测48 h时Andro作用的最大效应浓度及对PC3细胞增殖的时间依赖性;进一步提取细胞蛋白,通过Western blotting检测神经内分泌分化标志物(NSE、CgA)表达情况.结果 Andro作用48 h时7.5 μmol/L达到最大效应浓度,且随着时间的延长Andro抑制PC3细胞增殖的作用越显著;Andro能明显抑制PC3细胞的增殖,并具有浓度和时间依赖性.Western blotting检测结果显示,NSE、CgA是PC3细胞中神经内分泌的标志物,Andro能显著抑制NSE、CgA的表达.结论 Andro可抑制PC3细胞增殖及神经内分泌分化.