Treatment strategies for Zollinger–Ellison syndrome

Background: Zollinger–Ellison syndrome (ZES) is a rare disorder caused by tumor secretion of the hormone gastrin, which results in gastric acid hypersecretion and secondarily complicated peptic ulcer and diarrhea. Until the development of H₂-receptor antagonists and later proton pump inhibitors (PPIs), the disease was virulent, often associated with ulcer-related mortality, and the mainstay of treatment was total gastrectomy. Objective: To evaluate current approaches to diagnosis and therapy, focusing on the role of PPIs. Methods: An extensive literature search through PubMed using the search term ‘Zollinger–Ellison syndrome’ from 1964 to the present was performed. Primary articles were identified, and pertinent articles obtained from the reference lists were also examined. Results/conclusions: The clinical manifestations of ZES are well described, but overlaps with other more common disorders delay diagnosis. The use of abdominal imaging with somatostatin receptor scintigraphy and endoscopic ultrasound has improved tumor staging. PPI therapy is remarkably effective in controlling gastric acid hypersecretion, thereby reducing morbidity and potential mortality of this syndrome. The dose of drug necessary to control symptoms is highly variable but, even when used in high doses for prolonged periods of time, the disease remained controlled with very few drug-related side effects.     

Leading causes of castration-resistant prostate cancer

Prostate cancer (PCa) is the second leading cause of cancer-related death in men. Androgen receptor has a key role in the initiation and progression of PCa. Currently, androgen deprivation therapy is the standard treatment for PCa patients due to its effective suppression of androgen receptor signaling. Even though androgen deprivation therapy shows its initial effectiveness on shrinking tumor size, it eventually fails to cure advanced PCa, which is determined by the occurrence of castration-resistance. In this review, we summarize the widely accepted mechanisms that account for castration-resistant PCa and discuss potential therapeutic targets.     

Characterization of pancreatic islet cell tumors and renal tumors induced by a combined treatment of streptozotocin and nicotinamide in male SD rats

We herein investigated the histopathological features, including proliferative activity and immunoexpression, of pancreatic islet cell tumors (ICTs) in male SD rats induced by streptozotocin (STZ) and nicotinamide (NA), and discussed their relevance to biological behaviors and prognoses. A total of 70 and 43% of rats developed ICTs 37–45 weeks after the treatment with STZ (50 or 75 mg/kg, i.v.) and NA (350 mg/kg, twice, p.o.), respectively. Among the islet tumors observed in the STZ/NA-treated groups, 75% were adenomas, while 25% were carcinomas. Most STZ/NA-induced carcinomas were characterized by well-differentiated tumor cells with/without local invasion into the surrounding tissues, and weak proliferative activity. No outcome such as distance metastasis and death was noted. All of the ICTs strongly expressed insulin, part of which had hormone productivity; however there were no hypoglycemia-related clinical signs such as convulsion in these rats 36 weeks after the treatment. These results suggested that rat ICTs induced STZ/NA have small impact on biological activity or prognosis. STZ/NA treatment significantly increased of focal proliferative lesions in the kidney, liver and adrenal glands other than pancreatic islets. Of the STZ/NA-induced kidney tumors, more than 60% were renal cell adenomas, and many of them were basophilic type. The incidence of eosinophilic or clear cell type of tumors was less than 10%, respectively. Immunohistochemical analyses revealed that many of the STZ/NA-induced basophilic type of renal tumors were derived from proximal tubules, whereas the clear cell and eosinophilic types were derived from collecting tubules.     

Neuropeptides and the Hypothalamic-Pituitary-Adrenocortical (HPA) System: Review of Recent Research Strategies in Depression

Summary: Depressed patients show a variety of alterations in hypothalamic-pituitary-adrenocortical (HPA) system regulation which is reflected by increased pituitary-adrenocortical hormone secretion at baseline and a number of aberrant neuroendocrine function tests. The latter include the combined deamethasone (DEX) suppression/corticotropin-releasing hormone (CRH) challenge test, in which CRH was able to override DEX induced suppression of ACTH and cortisol secretion. Whereas the abnormal HPA activation in these patients improved in parallel with clinical remission, persistent HPA dysregulation was associated with an increased risk of relapse. Moreover, healthy subjects at high genetic risk for depression also showed this phenomenon as a trait marker. In consequence, it has been concluded that HPA alteration and development as well as course of depression may be causally related. As evidenced from clinical and preclinical studies, underlying mechanisms of these abnormalities involve impairment of central corticosteroid receptor function which leads to enhanced activity of hypothalamic neurons synthesising and releasing vasopressin and CRH. These neuropeptides mediate not only neuroendocrine but also behavioural effects. Recent research provided evidence that CRH can induce depression-like symptoms in animals and that these signs are mediated through the CRH1 receptor subtype. Hence, therapeutical application of new compounds acting more specifically on the HPA system such as CRH1 receptor antagonists appear to be a promising approach for future treatment options of depression. In conclusion, research in neuro-endocrinology provided new insights into the underlying pathophysiology of depression and, in consequence, may lead to the development of new therapeutic tools.

This paper was given on the occasion of the Young Investigator Award 1998, presented to Dr Hatzinger by the Swiss Society of Biological Psychiatry (SSBP)