BCL6 degradation caused by the interaction with the C-terminus of pro-HB-EGF induces cyclin D2 expression in gastric cancers

BCL6 is a transcriptional repressor that has important functions in lymphocyte differentiation and lymphomagenesis, but there have been no reports of BCL6 expression in gastric cancers. In the present study, we investigated the BCL6 function in gastric cancers. Treatment with TPA resulted in BCL6 degradation and cyclin D2 upregulation. This phenomenon was inhibited by the suppression of the nuclear translocation of HB-EGF-CTF (C-terminal fragment of pro-HB-EGF). The HB-EGF-CTF nuclear translocation leads to the interaction of BCL6 with HB-EGF-CTF and the nuclear export of BCL6, and after that BCL6 degradation was mediated by ubiquitin/proteasome pathway. Real-time RT–PCR and siRNA targeting BCL6 revealed that BCL6 suppresses cyclin D2 expression. Our data indicate that BCL6 interacts with nuclear-translocated HB-EGF-CTF and that the nuclear export and degradation of BCL6 induces cyclin D2 upregulation. We performed immunohistochemical analyses of BCL6, HB-EGF and cyclin D2 in human gastric cancers. The inverse correlation between BCL6 and cyclin D2 was also found in HB-EGF-positive human gastric cancers. BCL6 degradation caused by the HB-EGF-CTF also might induce cyclin D2 expression in human gastric cancers. Inhibition of HB-EGF-CTF nuclear translocation and maintenance of BCL6 function are important for the regulation of gastric cancer progression

MiR-339-5p inhibits breast cancer cell migration and invasion in vitro and may be a potential biomarker for breast cancer prognosis

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) play an important role in the regulation of cell growth, differentiation, apoptosis, and carcinogenesis. Detection of their expression may lead to identifying novel markers for breast cancer.</p> <p>Methods</p> <p>We profiled miRNA expression in three breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-468) and then focused on one miRNA, miR-339-5p, for its role in regulation of tumor cell growth, migration, and invasion and target gene expression. We then analyzed miR-339-5p expression in benign and cancerous breast tissue specimens.</p> <p>Results</p> <p>A number of miRNAs were differentially expressed in these cancer cell lines. Real-time PCR indicated that miR-339-5p expression was downregulated in the aggressive cell lines MDA-MB-468 and MDA-MB-231 and in breast cancer tissues compared with benign tissues. Transfection of miR-339-5p oligonucleotides reduced cancer cell growth only slightly but significantly decreased tumor cell migration and invasion capacity compared with controls. Real-time PCR analysis showed that BCL-6, a potential target gene of miR-339-5p, was downregulated in MDA-MB-231 cells by miR-339-5p transfection. Furthermore, the reduced miR-339-5p expression was associated with an increase in metastasis to lymph nodes and with high clinical stages. Kaplan-Meier analyses found that the patients with miR-339-5p expression had better overall and relapse-free survivals compared with those without miR-339-5p expression. Cox proportional hazards analyses showed that miR-339-5p expression was an independent prognostic factor for breast cancer patients.</p> <p>Conclusions</p> <p>MiR-339-5p may play an important role in breast cancer progression, suggesting that miR-339-5p should be further evaluated as a biomarker for predicting the survival of breast cancer patients.</p

BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation

Appropriately timed proliferation, differentiation and apoptosis are essential to the normal functions of the mammary epithelium. Here, we report that the transcription factor BCL-6 is expressed in mammary epithelium in nonpregnant animals as well as during early pregnancy. When overexpressed in the nontransformed EpH4 mammary epithelial cell line, BCL-6 prevents the STAT-driven expression of the milk protein beta-casein and duct formation, and prevents apoptosis. Consistent with an antiapoptotic function, we demonstrate that BCL-6 is expressed in 68% of histologically high-grade ductal breast carcinomas, which are clinically the most aggressive. BCL-6 has previously been characterized as a regulator of B lymphocyte growth and development, but our work identifies a novel role for it in mammary epithelial differentiation, which may also implicate it in carcinogenesis

Regional Anesthetic Use in Trans-Hiatal Esophagectomy. Are They Worth Consideration? A Case Series

William Mitchell,1,&ast; Thomas Roser,1,&ast; Jessica Heard,2 Shankar Logarajah,2 John Ok,1,2 John Jay,2 Houssam Osman,1,2 D Rohan Jeyarajah1,2 1Burnett School of Medicine at Texas Christian University, Fort Worth, TX, USA; 2Methodist Richardson Medical Center, Richardson, TX, USA&ast;These authors contributed equally to this workCorrespondence: D Rohan Jeyarajah, Tel +1 972 619 3500, Email [email protected]: Esophagectomy traditionally has high levels of perioperative morbidity and mortality due to surgical techniques and case complexity. While thoracic epidural analgesia (TEA) is considered first-line for postoperative analgesia after esophagectomy, complications can arise related to its sympathectomy and mobility impairment. Additionally, it has been shown that postoperative outcomes are improved with early extubation following esophagectomy. Our aim is to describe the impact of transversus abdominis plane (TAP) blocks on extubation rates following esophagectomy when uncoupled from TEA.Methods: This is a case series of 42 patients who underwent trans-hiatal esophagectomy between 2019 and 2022 who received a TAP block without TEA. The primary outcomes of interest were the rates of extubation within the operating room (OR) and reintubation. Secondary outcomes included: intensive care unit (ICU) and hospital length of stay (LOS), opioid pain medication use, post-operative hypotension, fluid administration, postoperative pain scores, development of anastomotic leak, and 30-day readmission.Results: The mean age at operation was 63 years and 97.6% of patients were represented by American Society of Anesthesia (ASA) physical status class III or IV. Thirty-four (81%) patients immediately extubated postoperatively. Nine patients (21.4%) underwent reintubation during their hospital course. Only seven patients (16.7%) required vasopressors postoperatively. The median LOS was five days in the ICU and 10 days in the hospital. TAP block alone was found to be equivalent to TAP with additional regional blocks (TAP+) on the basis of immediate extubation, reintubation, ICU and hospital LOS, and reported postoperative pain.Conclusion: The results of this study demonstrated immediate extubation is possible using TAP blocks while limiting post-operative hypotension and fluid administration. This was shown despite the elevated comorbidity burden of this study’s population. Overall, this study supports the use of TAP blocks as a possible alternative for primary analgesia in patients undergoing trans-hiatal esophagectomy.Trial Registration: This study includes participants who were retrospectively registered. IRB&num; 037.HPB.2018.R.Keywords: trans-hiatal, esophagectomy, transversus abdominis plane, TAP, quadratus lumborum, QL, block, epidural, ERAS, analgesi