Study of endocrine disruptor effects in AVP and OT mediated behavioral and reproductive processes in female rat models.

Environmental exposures may have endocrine disruptor (ED) effects, e.g., a role for halogenated hydrocarbon chlorobenzenes in increasing vasopressin (AVP), oxytocin (OT) secretion and, in association, anxiety and aggression in male rats has been shown. Our aim is to investigate whether 1,2,4-trichlorobenzenehexachlorobenzene= 1:1 (mClB) treatment of female rats also shows ED effects and reproductive biology differences, and whether AVP may have a mediator role in this? Female Wistar rats were treated (0.1; 1.0; 10.0 µg/bwkg/day) with mClB (by gastrictube) and then 30; 60; 90 days after treatment anxiety (open field test) and aggressive (resident intruder test) behaviors AVP, OT concentrations from blood plasma samples were detected by radioimmunoassay on 30; 60; 90 days. Treated female rats were mated with untreated males. Mating success, number of newborn and maternal aggression on the neonates were monitored. Results showed that AVP, OT levels; and anxiety, aggressive behaviors; and mothers' aggression towards their offspring increased significantly in relation to the duration and the dose of mClB treatment. But mating propensity and number of offspring decreased. Patterns of AVP, OT release and anxiety, aggression behaviors, and reproductive-related behaviors were correlated. Consistent with the literature, our studies confirmed the role of AVP and OT in different behavioral effects.

[Alectinib and mixed large cell neuroendocrine carcinoma of the lung.] / Az alectinib és a tüdo kevert nagysejtes neuroendokrin carcinomája.

The treatment of mixed large cell neuroendocrine carcinoma is less studied due to its low incidence. However, the presence of anaplastic lymphoma kinase (ALK) fusion gene is rare in such tumours, ALK inhibitors may represent a promising therapeutic option instead of cytostatic therapy. Routine chest X-ray and then computed tomography (CT) examination revealed a pulmonary tumour in a 52-year-old asymptomatic woman. The neoplasm was removed by lobectomy. Histological examination confirmed papillary predominant lung adenocarcinoma. The patient was treated with postoperative chemotherapy and irradiation. 3 years later, neurologic symptoms were observed, therefore, brain CT was performed. The evaluation confirmed brain metastases which were removed. Histological examination identified metastasis of large cell neuroendocrine carcinoma. Revision and molecular examination of the metastasis and lung specimen revealed pulmonary mixed large cell neuroendocrine carcinoma with ALK-rearrangement. Alectinib (Alecensa) treatment was initiated resulting in regression of the previously observed liver metastases. Progression has not occurred in the last 3 years since the start of treatment. Detection of ALK fusion genes and research of ALK inhibitor therapy focus primarily on lung adenocarcinomas. Our case report would like to draw attention to the evaluation of driver mutations in pulmonary mixed neuroendocrine carcinoma with adenocarcinoma component because targeted treatment may be an effective alternative. Orv Hetil. 2023; 164(14): 548-554.

Architectural Grade Combined With Spread Through Air Spaces (STAS) Predicts Recurrence and is Suitable for Stratifying Patients Who Might Be Eligible for Lung Sparing Surgery for Stage I Adenocarcinomas.

The spread through air spaces (STAS) has a main role in local recurrence of stage I lung adenocarcinomas (LAs), therefore its presence might question sublobar resection as a therapeutic option. The aim of our study was to evaluate the distribution of STAS in stage I LAs, to stratify patients according to local recurrence and to identify a group of patients who might be suitable for sublobar surgery. Patients resected with LA were included. The presence of STAS was recorded on hematoxylin eosin stained slides and clinicopathological data were obtained from medical charts. Overall survival (OS) and disease-free survival (DFS) were registered. Statistical methods included Kruskal-Wallis tests, Kaplan-Meier analyses, log-rank tests and Cox-regressions. 292 patients were included. STAS was identified in 38.7% and 95.7% of micropapillary carcinomas showed STAS. Significant correlation was found between STAS and high-grade patterns. Significant differences were found between OS and DFS estimates of STAS0 and STAS1 cases (5-y-OS: 80.0% vs. 68.4%; 5-y-DFS: 71.1% vs. 57.1%). The presence of STAS was associated with unfavorable prognosis in low and intermediate architectural grades, but not in high-grade. Multivariate analysis revealed that architectural grade (HR(OS):2.09; HR(DFS):1.52) and STAS (HR(OS):1.51; HR(DFS):1.48) were independent prognostic markers in stage I LA. Architectural grade combined with STAS was superior to other prognostic grades. The combination of architectural grade and STAS proved to be a prognostic factor that is superior to previously introduced grading systems. Patients having low and intermediate grade LAs without STAS might be eligible for sublobar resection.

[Large-cell neuroendocrine carcinoma of the lung - challenges of diagnosis and treatment]. / Nagysejtes neuroendocrin carcinoma ­ a kórisme és a kezelés nehézségei.

Small-cell lung carcinoma (SCLC) and the rare large-cell neuroendocrine carcinoma belong to the high grade pulmonary neuroendocrine carcinomas. Making the correct diagnosis and selection of treatment modalities require multidisciplinary meetings due to the morphological overlaps, aggressive behaviour and debated therapeutic guidelines of these entities. A 52-year-old woman was admitted to the hospital because of headache, nausea and tenebrous vision. The CT revealed metastatic tumour mass in the occipital lobe and in the cerebellum. Both tumours were removed and resulted in histological diagnosis of metastatic neuroendocrine carcinoma. Chest X-ray established contrast-enhancing lesion in the left lung. Bronchoscopy was performed and histological examination revealed large-cell neuroendocrine carcinoma. Postoperative skull irradiation and small-cell lung cancer chemotherapy protocol were utilized. Due to atelectasis and progression, chest irradiation was initiated, which was interrupted because of novel brain metastases. Further chemotherapy followed the non-small-cell lung cancer protocol. After 3 months, thoracic progression, brain and disseminated bone metastases were diagnosed. After a 14-month-long therapy, the patient deceased. Large-cell neuroendocrine carcinoma has a poor prognosis, the incidence of brain metastasis is 25-50%. In early stage large-cell neuroendocrine carcinoma, lobectomy is the standard treatment and adjuvant chemotherapy should also be considered. Although the non-small-cell lung cancer chemotherapy protocol is approved widely in the treatment of large-cell neuroendocrine carcinoma, the utility of SCLC scheme has also been suggested. Orv Hetil. 2020; 161(8): 313-319.

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.

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 10 µg/b.w. (body weight)kg of 1,2,4- trichlorobenzene and hexachlorobenzene (ClB) mix via gastric tube for 30, 60 or 90 days. 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.

Acute oesophageal toxicity related to paclitaxel-based concurrent chemoradiotherapy for non-small cell lung cancer.

BACKGROUND: Dosimetric data and acute oesophageal toxicity (AET) during chemoradiotherapy (CRT) were evaluated in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty patients were treated with paclitaxel-based conformal CRT with a mean ± SD dose of 60.7 ± 9.8 Gy. The oesophageal toxicity was prospectively registered and evaluated in relation to the maximal dose (Dmax), mean dose (D(mean)), length and volume of oesophagus irradiated with 35-60 Gy (V(35-60Gy)), and according to the seriousness of AET. RESULTS: Dmax and D(mean) to the oesophagus were 57.0 ± 10.8 Gy and 24.9 ± 9.0 Gy, respectively. AET of grade 1, 2 and 3 developed in 16 (32%), 14 (28%) and three (6%) cases, respectively. The Dmax, D(mean), length and the V(35-60Gy) were all related to dysphagia (p<0.001). V(45Gy) was the most reliable predictor of AET of grade 2 or more. CONCLUSION: Our results indicate that keeping oesophageal V(45Gy) below 32.5% can prevent severe AET during CRT of NSCLC.

Pulmonary epithelioid haemangioendothelioma studies in vitro and in vivo: new diagnostic and treatment methods.

BACKGROUND: Pulmonary epithelioid haemangioendothelioma is a rare endothelial tumour without standard treatment. For this reason, our aim is to present contemporary research outlining new therapeutic possibilities; thus in vitro and in vivo methods were combined. PATIENTS AND METHODS: Pulmonary epithelioid haemangioendothelioma was diagnosed in a 49-year-old female patient. A bronchial excision was obtained from a parenchymal lesion, and the excised sample was manipulated with in vitro-standardized experiments to support the diagnostic and therapeutic procedures. RESULTS: according to in vitro examination of tumour pulmonum and metastases from bone, carboplatin, docetaxel and pharmarubicin was the most effecient treatment modality. CONCLUSION: Currently, pulmonary epithelioid haemangioendothelioma does not have any standard treatment; the most efficient therapeutic regimen was gradually developed by combining in vitro and in vivo methods, which proved to be an efficient therapeutic modality hitherto.

[Primary pulmonary epitheloid haemangioendothelioma]. / Primer pulmonalis epitheloid haemangioendothelioma.

A 49-year-old female patient was admitted in July 2009 because of cough, weight loss and effort dyspnoe. Chest X-ray and CT showed multiple bilateral nodules which have been identified earlier and these nodules were unchanged. However, there was a new parenchymal lesion in the right upper lobe, and new right hilar and mediastinal lymphadenomegaly was also found. Sample was taken by bronchoscope and the pathological diagnosis was pulmonary epitheloid haemangioendothelioma. This rare endothelial tumor usually affects middle-aged patients with a female predominance and it presents with chest pain, effort dyspnoe, cough, sputum, or it may remain asymptomatic. Multiple bilateral nodules are usually detected by radiologic examination. The diagnosis of this tumor is often challenging and, because of its rarity, it does not have any standard therapeutic regimen. Treatment can be surgery, chemo-, radio-, hormone- or immunotherapy. In order to find the most effective anticancer treatment, authors performed in vitro studies. On the basis of the results, chemotherapy was initiated which resulted in a partial regression.

Roles of BCL-2 and MDR1 expression in the efficacy of paclitaxel-based lung cancer chemoradiation.

BACKGROUND: The associations between B-cell lymphoma 2 (BCL-2) and multi-drug resistance associated P-glycoprotein (MDR1) expressions and chemoradiotherapy outcome of patients with non-small cell lung cancer (NSCLC) were analysed. PATIENTS AND METHODS: Thirty-two NSCLC patients were treated with paclitaxel-based chemoradiotherapy. The tumour expressions of BCL-2 and MDR1 were analysed by means of immunohistochemistry with regard to the clinical response and survival data. RESULTS: Partial remission and stable disease were achieved in 19 (59%) and 10 (31%) cases, respectively. Significant differences in progression-free survival were observed between responders and non-responders (13.7 vs. 6.0 months, p=0.028), and between patients with or without a gross tumour volume (GTV) shrinkage (GTV(>50) 13.7 vs. 6.0 months, p=0.009). Overexpression of BCL-2 and of MDR1 was observed in 6 (21.4%) cases each. Overexpression of both markers together was associated with poor response (GTV reduction: p=0.005; RECIST: p=0.023) and lower progression-free survival (overexpression of both, low expression of both, mixed: 3.1, 13.4, 4.1 months, respectively, p<0.001). CONCLUSION: BCL-2 and MDR1 overexpression may predict the inefficacy of paclitaxel-based chemoradiotherapy.