The Effects of Hypokalaemia on the Hormone Exocytosis in Adenohypophysis and Prolactinoma Cell Culture Model Systems

The extracellular ion milieu determines the exocytosis mechanism that is coupled to spontaneous electrical activity. The K+ ion plays crucial role in this mechanism: as the potassium current is associated with membrane hyperpolarization and hormone release through protein cascade activation. The primary aim of this study was to investigate the response mechanisms of normal adenohypophysis and adenohypophyseal prolactinoma cell populations at different extracellular K+ levels with an otherwise isoionic milieu of all other essential ions. We focused on prolactin (PRL) and adrenocorticotrophic hormone (ACTH) release.In our experimental study, female Wistar rats (n=20) were treated with estrone-acetate (150 mug/kg b.w./week) for 6 months to induce prolactinomas in the adenohypophysis. Primary, monolayer cell cultures were prepared by enzymatic and mechanical digestion. PRL and ACTH hormone presence was measured by radioimmunoassay or immuno-chemiluminescence assay. Immunocytochemistry was used to assess the apoptotic cells.Differences between the effects of hypokalaemia on normal adenohypophysis cultures and prolactinoma cell populations were investigated. Significant alteration (p<0.001, n=10) in hormone exocytosis was detected in K+ treated adenohypophyseal and prolactinoma cell cultures compared to untreated groups. Immunocyto-chemistry showed that Bcl-2 expression was reduced under hypokalaemic conditions.The decrease in hormone exocytosis was tightly correlated to the extracellular K+ in both cell types, leading to the conclusion that external K+ may be the major factor for the inhibition of hormone release. The significant increase in hormone content in supernatant media suggests that hypokalaemia may play important role in apoptosis

The more the micropapillary pattern in stage I lung adenocarcinoma, the worse the prognosis: a retrospective study on digitalized slides

Although the majority of lung adenocarcinomas show mixed pattern, only the predominant component is taken into account according to the novel classification. We evaluated the proportion of different patterns and their impact on overall survival (OS) and disease-free survival (DFS). Patterns were recorded according to predominance and their proportions were rated and calculated by objective area measuring on digitalized, annotated slides of resected stage I lung adenocarcinomas. Spearman’s rank correlation, Kaplan-Meier models and the log rank test were used for statistical evaluation. Two hundred forty-three stage I adenocarcinoma were included. Lepidic pattern is more frequent in tumours without recurrence (20 vs. 8%), and lepidic predominant tumours have favourable prognosis (OS 90.5%, DFS 89.4%), but proportions above 25% are not associated with improving outcome. Solid and micropapillary patterns are more frequent in patients with recurrence (48 vs. 5% and 13 vs. 4%) and predominance of each one is associated with unfavourable prognosis (OS 64.1%, DFS 56.3% and OS 28.1%, DFS 28.1%, respectively). Above 25%, a growing proportion of solid or micropapillary pattern is not associated with worsening prognosis. In contrast, tumours having micropapillary pattern as secondly predominant form a different intermediate group (OS 51.1%, DFS 57.8%). Our study was based on measured area of each growth pattern on all available slides digitalized. This is the most precise way of determining the size of each component from the material available. We propose using predominant and secondly predominant patterns for prognostic purposes, particularly in tumours having solid or micropapillary patterns. © 2018 Springer-Verlag GmbH Germany, part of Springer Natur

Az alectinib és a tüdő kevert nagysejtes neuroendokrin carcinomája : Egy sikeres eset bemutatása [Alectinib and mixed large cell neuroendocrine carcinoma of the lung : Report of a successfully treated patient]

A kevert nagysejtes neuroendokrin carcinoma ritka, nem kissejtes morfológiájú tüdőrák, melynek kezelésére kevés kutatás fókuszál. Ezen esetek patogenezisében az anaplasticus lymphoma kináz (ALK) fúziós gén szerepe ritkaság, ugyanakkor a mutáció jelenléte esetén az ALK -inhibitorok ígéretes terápiás lehetőséget jelentenek a citosztatikumok helyett. Az 52 éves, tünetmentes nőnél rutin mellkasröntgenvizsgálat során térfoglaló folyamat merült fel, melyet a mellkasi komputertomográfiás vizsgálat megerősített. A tumort lobectomia révén eltávolították. A szövettani vizsgálat papillaris predomináns tüdő adenocarcinomát igazolt, melyet posztoperatív kemoterápia és besugárzás követett. 3 évvel később központi idegrendszeri tünetek miatt koponya képalkotó vizsgálat történt, melynek során áttét igazolódott. Az agyi metasztázisok eltávolításra kerültek. A szövettani vizsgálat nagysejtes neuroendokrin carcinoma áttétét igazolta. Az áttét és a kimetszett tüdőrészlet metszeteinek újbóli elemzése, illetve a molekuláris vizsgálat alapján ALK -transzlokált, kevert, nagysejtes neuroendokrin carcinomát kórisméztünk. Alectinib (Alecensa)-kezelés indult, melynek hatására az időközben megjelent májáttétek regressziót mutattak. A kontroll radiológiai vizsgálatok a kezelés kezdete óta eltelt 3 évben progressziót nem igazoltak. Az ALK -transzlokáció kimutatása, illetve az ALK -inhibitorok alkalmazásának kutatása elsősorban a tüdő adenocarcinomákra helyezi a hangsúlyt. Esetismertetésünkkel arra szeretnénk felhívni a figyelmet, hogy a kevert, adenocarcinoma-komponenst is tartalmazó, neuroendokrin tumorok esetén is érdemes a ’driver’ mutációk vizsgálata, mivel a célzott kezelés eredményes alternatívát jelenthet. Orv Hetil. 2023; 164(14): 548–554

Effects of chronic and subtoxic chlorobenzenes on adrenocorticotrophic hormone release

Many environmental chemicals and pesticides have been found to alter neuroendocrine communication in exposed biological objects. The environmental loads have primary and secondary effects that can alter the homeostatic regulation potential. Since it is difficult to avoid human exposition, a potentially important area of research to develop in vivo and in vitro experimental models. In this context, the primary aim of this study was to demonstrate the effects of chlorobenzenes on adrenocorticotrophic hormone (ACTH) release. In our experimental study, male Wistar rats were exposed to 0.1, 1.0 and 10mug/b.w. (body weight)kg of 1,2,4- trichlorobenzene and hexachlorobenzene (ClB) mix via gastric tube for 30, 60 or 90days. At the endpoints of the experiment blood samples were taken and animals were decapitated. Primary, monolayer adenohypophysis cell cultures were prepared by enzymatic and mechanical digestion. The ACTH hormone content in serum and supernatant media was measured by immuno-chemiluminescence assay. The Mg(2+)-dependent ATPase activity was determined by modified method of Martin and Dotty. Significant differences were detected in the hormone release between the control and treated groups. The hormone release was enhanced characteristically in exposed groups depending upon the dose and duration of exposure. The Mg(2+)-ATPase activity enhanced after chronic and subtoxic ClB exposition. Light microscopy revealed that the adenohypophysis seemed to be more abundant. Results indicate that Wistar rats exposed to subtoxic ClB have direct and indirect effects on hypothalamus-hypophysis-adrenal axis