The Hippo Pathway Effectors YAP/TAZ-TEAD Oncoproteins as Emerging Therapeutic Targets in the Tumor Microenvironment.

Various cancer cell-associated intrinsic and extrinsic inputs act on YAP/TAZ proteins to mediate the hyperactivation of the TEAD transcription factor-based transcriptome. This YAP/TAZ-TEAD activity can override the growth-limiting Hippo tumor-suppressor pathway that maintains normal tissue homeostasis. Herein, we provide an integrated summary of the contrasting roles of YAP/TAZ during normal tissue homeostasis versus tumor initiation and progression. In addition to upstream factors that regulate YAP/TAZ in the TME, critical insights on the emerging functions of YAP/TAZ in immune suppression and abnormal vasculature development during tumorigenesis are illustrated. Lastly, we discuss the current methods that intervene with the YAP/TAZ-TEAD oncogenic signaling pathway and the emerging applications of combination therapies, gut microbiota, and epigenetic plasticity that could potentiate the efficacy of chemo/immunotherapy as improved cancer therapeutic strategies.

The effects of curcumin on hepatic T2*MRI and liver enzymes in patients with ß-thalassemia major: a double-blind randomized controlled clinical trial.

Background: Curcumin present in turmeric has been considered due to its cancer-preventive features, antioxidant and anti-inflammatory properties. This double-blind, randomized, controlled clinical trial with a reasonable sample size and longer intervention period was conducted to investigate how oral curcumin affected cardiac and hepatic T2*MRI and liver enzymes in patients with ß-thalassemia major. Method: This clinical trial study was conducted on 171 patients over 5 years old. The subjects were randomly divided into a curcumin-treatment group and a placebo group to receive either curcumin capsules twice daily or placebo for 6 months. Patients were examined once a month for 6 months to receive capsules and measure the levels of alanine aminotransferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), direct and total bilirubin, ferritin and cardiac and hepatic T2*MRI. Result: There was a significant decrease in levels of AST, ALT, ALP, and bilirubin (direct and total) in the curcumin group compared with the placebo group by the end of the study (p < 0.05). The levels of serum ferritin remained unchanged in both groups at the end of the follow-up period (p > 0.05). No significant differences were observed between the curcumin and placebo groups at baseline values or at the end of the study of cardiac and hepatic T2*MRI and serum magnesium. Conclusion: Administration of curcumin has some beneficial effects on liver function by reducing liver enzymes in patients with beta-thalassemia major.

Anti-inflammatory activity of a natural herbal-marine drug (MS14 - SANT and SUSP) compared to sodium salicylate or methylprednisolone in a rat model for multiple sclerosis.

A natural compound of marine herbal origin has been used in Persian Traditional Medicine to relieve some symptoms of multiple sclerosis. The present study investigated the anti-inflammatory effects of a patented extracts of the traditional receipt (MS14). In this preliminary experiment, we used seven groups of six rats: the control group received vehicle, the two positive control groups were treated with either sodium salicylate (300 mg/kg) intraperitoneal (i.p.) or methyl prednisolon (MPN 10 mg/kg) i.p., while the test groups were treated with a solution centrifuged MS14 (SANT 100 mg/kg) and suspension of MS14 (SUSP 100, 150, 300 mg/kg) i.p. After thirty minutes, paw volume was measured by plethysmometer and immediately formalin solution was injected subcutaneously into the hind paw and after an hour, inflamed paw volume was measured. In days 2-8, the inflamed paw volume was measured and immediately drugs were injected i.p. The anti-inflammatory effect of MPN was significant only on days 5 and 6. The anti-inflammatory effect of SS was significant only on the 6th day, while the anti-inflammatory effect of SANT MS14 (100 mg/kg) was also significant only on the 6th day. SUSP MS14 (150 mg/kg) significantly reduced edema from second to 6th day. Intra-peritoneal injection of SUSP MS14 with 300 mg/kg was toxic, so excluded from the study. This research indicates that the MS14 possesses an anti-inflammatory effect after intra-peritoneal administration. Comparative anti-inflammatory effects of MS14 with Glucocorticoids in this study, may justify a possible mechanism for its action in multiple sclerosis, if further studies will provid strong statistically confirmatory effects in animals and safety human trials.

Brain mucormycosis in a child with acute lymphoblastic leukemia.

This article reports a rare case of Brain Mucormycosis in a 12 year-old girl who presented with relapse Acute Lymphoblastic Leukemia (ALL). On the 12th day of chemotherapy, although there was no CNS symptoms, the second Lumbar Puncture (LP) revealedmthe CNS relapse which developed to Into brain abscess presenting with right side hemiparesis. The brain magnetic resonance imaging (MRI) and the brain biopsy revealed small, multifocal necrosis and acute inflammation with septal fungal hyphae branching, which was proven to be caued by Mucormycosis according to Polymerase Chain Reaction (PCR). The patient responded to treatment with intravenous liposomal Amohotericin B and Caspofungin after two months, suggesting that Brain Mucormycosis in ALL cases can be managed with sequential therapy by antifungals.

The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy.

Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Despite innovative and notable advances in immunotherapy, challenges associated with variable patient response rates and efficacy on select tumors minimize the overall effectiveness of immunotherapy. Variations observed in response rates to immunotherapy are due to multiple factors, including adaptative resistance, competency, and a diversity of individual immune systems, including cancer stem cells in the tumor microenvironment, composition of the gut microbiota, and broad limitations of current immunotherapeutic approaches. New approaches are positioned to improve the immune response and increase the efficacy of immunotherapies, highlighting the challenges that the current global COVID-19 pandemic places on the present state of immunotherapy.

Are serial hematocrit measurements sensitive enough to predict intra-abdominal injuries in blunt abdominal trama?

OBJECTIVE: Routine serial hematocrit measurements are a component of the trauma evaluation for patients without serious injury identified on initial evaluation. We sought to determine whether serial hematocrit testing was useful in predicting the probable injuries in blunt abdominal trauma. MATERIALS AND METHOD: We performed a prospective study of trauma patients admitted in our observation unit over a 12-month period. Patients routinely underwent serial hematocrit testing in 6-hour intervals (two hematocrit levels). We compared trauma patients with a hematocrit drop of 5 and 10 points or more to those without a significant hematocrit drop. RESULTS: Five hundred forty-two isolated blunt abdominal trauma patients were admitted to observation unit, and 468 patients (86.35%) had serial hematocrit during their 6-hour stay. Of these patients, 36.11% had a hematocrit drop of 5 or more and 12.61% a drop of 10 or more. Of patients with the hematocrit drop >10, 50.8% have had diagnostic manifestations of intra-abdominal injury in both ultrasonographic and computed tomography scanning (P<0.001). There was no significant correlation between hematocrit drop >5 and positive imaging. CONCLUSION: Although serial hematocrit testing may be useful in specific situations, routine use of serial hematocrit testing in trauma patients at a level I trauma center's observation unit did not significantly aid in the prediction of occult injuries.

Preliminary report of hepatitis B virus genotype prevalence in Iran.

AIM: To determine the prevalence of hepatitis B virus (HBV) genotypes in Iranian hepatitis B surface antigen (HBsAg) carriers, chronic hepatitis B and cirrhotic patients. METHODS: A total of 109 HBsAg-positive patients were included in this study. HBV genotypes were determined by using INNO-LiPA methodology which is based on the reverse hybridization principle. RESULTS: The distribution of patients with different stages of liver disease was as follows: 95(86.4%) chronic hepatitis, 11(10%) liver cirrhosis, and 3(2.7%) inactive carrier. Of the chronic hepatitis and liver cirrhosis patients, 26.4% were HBeAg-positive while 70% were HBeAg-negative. Genotype D was the only detected type found in all patients. CONCLUSION: Classifying HBV into genotypes has to be cost-effective and clinically relevant. Our study indicates that HBV genotype D prevails in the Mediterranean area, Near and Middle East, and South Asia. Continued efforts for understanding HBV genotype through international co-operation will reveal further virological differences of the genotypes and their clinical relevance.