Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma.

Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program and SSs are sensitive to the small molecule SAE1/2 inhibitor, TAK-981.

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma.

Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein. and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis.

Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification.

The possible anticancer activity of combination (M + E + F) of metformin (M), efavirenz (E), and fluoxetine (F) was investigated in normal HDF cells and HCT116 human colon cancer cells. Metformin increased cellular FOXO3a, p-FOXO3a, AMPK, p-AMPK, and MnSOD levels in HDFs but not in HCT116 cells. Cellular ATP level was decreased only in HDFs by metformin.

Exploitation of Sulfated Glycosaminoglycan Status for Precision Medicine of Triplatin in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking targetable biomarkers. TNBC is known to be most aggressive and when metastatic is often drug-resistant and uncurable. Biomarkers predicting response to therapy improve treatment decisions and allow personalized approaches for patients with TNBC.

Pharmaceutical Interference of the EWS-FLI1-driven Transcriptome By Cotargeting H3K27ac and RNA Polymerase Activity in Ewing Sarcoma.

The translocation is the hallmark genomic alteration of Ewing sarcoma, a malignancy of the bone and surrounding tissue, predominantly affecting children and adolescents. Although significant progress has been made for the treatment of localized disease, patients with metastasis or who relapse after chemotherapy have less than a 30% five-year survival rate. EWS-FLI1 is currently not clinically druggable, driving the need for more effective targeted therapies.

Transoral endoscopic repair of Zenker diverticulum by a thoracic surgical service.

Objective: Zenker diverticulum (ZD), a pulsion diverticulum of the esophagus, has been traditionally managed with an open surgical approach, but endoscopic transoral stapling has been reported with increasing frequency. The objective of this study was to evaluate the results of endoscopic repair of ZD by a thoracic surgery service.

Methods: We conducted a retrospective review of patients who underwent transoral stapling repair of ZD at our institution by the thoracic surgery service.

-Amplified Neuroblastoma Is Addicted to Iron and Vulnerable to Inhibition of the System Xc-/Glutathione Axis.

is amplified in 20% to 25% of neuroblastoma, and -amplified neuroblastoma contributes to a large percent of pediatric cancer-related deaths. Therapy improvements for this subtype of cancer are a high priority. Here we uncover a MYCN-dependent therapeutic vulnerability in neuroblastoma.

The modulatory role of β‑amyloid in the regulation of nociception in mice.

β-amyloid is an important factor in the pathophysiology of Alzheimer's disease. This study investigates β-amyloid's role in the regulation of nociception in mice. Pretreated once, 2 weeks prior to testing with β-amyloid, male ICR mice were examined on various nociceptive tests.

Robot-assisted bronchoscopy for pulmonary lesion diagnosis: results from the initial multicenter experience.

Background: The Robotic Endoscopic System (Auris Health, Inc., Redwood City, CA) has the potential to overcome several limitations of contemporary guided-bronchoscopic technologies for the diagnosis of lung lesions. Our objective is to report on the initial post-marketing feasibility, safety and diagnostic yield of this technology.

Castleman Disease Presenting with Pseudotumour Cerebri and Myasthenia Gravis: A Case Report and Literature Review.

Castleman disease (CD) is a rare lymphoproliferative disorder that may present with various autoimmune, inflammatory, or neurologic syndromes. This is a case of a 21-year-old woman who presented with signs and symptoms of pseudotumour cerebri (PTC) who subsequently developed myasthenia gravis (MG), and was incidentally found to have a large mass in the posterior mediastinum. Upon resection, the mass was classified as unicentric CD involved with follicular dendritic cell sarcoma.

Oxidative stress and its impact on mitochondrial DNA in pulmonary tuberculosis patients- a pilot study.

Background: Pulmonary tuberculosis (PTB) remains a major cause of morbidity and mortality all around the world. Recent studies have pointed out increased oxidative stress and also DNA damage in peripheral blood in PTB. Till date, to the best of our knowledge, no study has so far been conducted to show the mitochondrial DNA (mtDNA) deletions mapping in PTB patients.

Chromosomal Aberrations in Couples with Pregnancy Loss: A Retrospective Study.

Background: Recurrent pregnancy loss is a challenging reproductive problem, and chromosomal anomalies approximately affect 2%-8% of couples with recurrent pregnancy loss. The chromosomal abnormality, especially balanced translocation rearrangement in either parent, is the important cause of recurrent spontaneous abortion.

Aims: The aim of this study was to investigate the role and prevalence of chromosomal anomalies in recurrent miscarriages.

SXP-RAL Family Filarial Protein, rWbL2, Prevents Development of DSS-Induced Acute Ulcerative Colitis.

Helminthic infections lead to the release of various molecules which play an important role in modulation of the host immune system. Such filarial proteins with immunomodulatory potential can be used for therapeutic purpose in inflammatory and immune mediated diseases. In the present study, we have explored the prophylactic effect of filarial SXP-RAL family protein of i.

Histomorphometric demonstration of the effect of chronic use of nonsteroidal anti-inflammatory drugs-ibuprofen on mucosa of small intestine.

The purpose of this study was to ascertain change in structure of mucosa of small intestine, if any, in small intestine of Swiss albino mice as an effect of chronic use of nonsteroidal anti-inflammatory drugs-Ibuprofen. Longitudinal study conducted on 46 adult Swiss albino mice, 23 as experimental and 23 as control. Ibuprofen was given at a dose of 40 µg/g body weight per day for 6 weeks by intragastric route in experimental group of mice while control group of mice received same volume of distilled water.

Immunomodulatory potential of recombinant filarial protein, rWbL2, and its therapeutic implication in experimental ulcerative colitis in mouse.

Objective: Immunomodulation by helminth proteins has potential therapeutic implications in inflammatory bowel disease. In the present study, we have explored the therapeutic effect of a RAL family protein of filarial parasite Wuchereria bancrofti i.e.

Human filarial proteins attenuate chronic colitis in an experimental mouse model.

Encouraged by our earlier results of promising therapeutic effect of filarial recombinant proteins BmALT2, BmCys and WbL2 individually in the mouse model of acute ulcerative colitis, in this study, these proteins have been explored individually and in different combinations for their therapeutic potential in dextran sulphate sodium (DSS)-induced chronic colitis mice. These mice, treated with filarial proteins, showed reduced disease parameters including body weight loss, disease activity index, macroscopic and histopathological scores of colon and myeloperoxidase activity in colonic mucosa. Among various treatment schemes, rBmALT2 + rBmCys which showed most pronounced therapeutic implication was found to downregulate the mRNA expressions of IFN-γ and TNF-α and upregulate IL-10 and TGF-β expression in the splenocytes.

Mesh cruroplasty in laparoscopic repair of paraesophageal hernias is not associated with better long-term outcomes compared to primary repair.

Background: Equipoise still exists regarding routine mesh cruroplasty during laparoscopic paraesophageal hernia (PEH). We aimed to determine whether selective mesh cruroplasty is associated with differences in recurrence and patient-reported outcomes.

Methods: We compared symptom outcomes (n = 688) and radiographic recurrences (n = 101; at least 10% [or 2 cm] of stomach above hiatus) for 795 non-emergent PEH repair with fundoplication (n = 106 with mesh).

Computed Tomographic Estimation of Relationship between Renal Volume and Body Weight of an Individual.

Introduction: Knowledge of normal range of size and volume of abdominal organs plays a vital role in clinical practices as various medical conditions affects the abdominal organs causing alteration in their dimensions.

Aim: The present retrospective study was done to establish the normal range of renal volume in study population and to see the correlation between renal volume and body weight of an individual.

Materials And Methods: Computed tomographic evaluations of kidneys were performed on 140 kidneys of 70 individuals who had undergone abdominal CT scan for indications other than renal disease.

Prospective study of quality of life after lung cancer resection.

Background: Surgical resection with curative-intent remains the gold standard for clinically operable early-stage non-small cell lung cancer (NSCLC). This goal can be accomplished using a minimally invasive option, e.g.

Large Scale 7436-bp Deletions in Human Sperm Mitochondrial DNA with Spermatozoa Dysfunction and Male Infertility.

Introduction: Mitochondria and mitochondrial DNA are essential to sperm motility and fertility. It controls growth, development and differentiation through oxidation energy supply. Mitochondrial (mtDNA) deletions or mutation are frequently attributed to defects of sperm motility and finally these deletions lead to sperm dysfunction and causes infertility in male.

Cancer Recurrence After Esophagectomy: Impact of Postoperative Infection in Propensity-Matched Cohorts.

Background: Postoperative infection increases cancer recurrence and worsens survival in colorectal cancer, but the relationship for esophagogastric adenocarcinoma after esophagectomy is not well defined. We aimed to determine whether recurrence and survival after minimally invasive esophagectomy for esophagogastric adenocarcinoma were influenced by postoperative infection using propensity-matched analysis.

Methods: We abstracted data for 810 patients (1997-2010) and defined exposure as at least 1 in-hospital or 30-day infectious complication (n = 206 [25%]).

Non-Elective Paraesophageal Hernia Repair Portends Worse Outcomes in Comparable Patients: a Propensity-Adjusted Analysis.

Introduction: Patients undergoing non-elective paraesophageal hernia repair (PEHR) have worse perioperative outcomes. Because they are usually older and sicker, however, these patients may be more prone to adverse events, independent of surgical urgency. Our study aimed to determine whether non-elective PEHR is associated with differential postoperative outcome compared to elective repair, using propensity-score weighting.

Teratogenic effects of insulin: an experimental study on developing chick embryo.

Objective: The objective was to observe the effect of insulin on chick embryos with reference to their growth and developmental defects.

Materials And Methods: An experimental study was performed to assess any abnormal growth pattern caused by insulin. For this, two batches of 100 fertilized eggs were utilized.