M.G. Muni Reddy
Other affiliations: University College of Engineering
Bio: M.G. Muni Reddy is an academic researcher from Andhra University. The author has contributed to research in topics: Cement & Mortar. The author has an hindex of 4, co-authored 9 publications receiving 219 citations. Previous affiliations of M.G. Muni Reddy include University College of Engineering.
TL;DR: These results provide proof-of-concept of the clinical actionability of RET alterations, and identify selective RET inhibition by LOXO-292 as a promising treatment in heavily pretreated, multikinase inhibitor-experienced patients with diverse RET-altered tumors.
Abstract: Background Alterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed to inhibit diverse RET fusions, activating mutations and acquired resistance mutations. Patients and methods Potent anti-RET activity, high selectivity, and central nervous system coverage were confirmed preclinically using a variety of in vitro and in vivo RET-dependent tumor models. Due to clinical urgency, two patients with RET-altered, MKI-resistant cancers were treated with LOXO-292, utilizing rapid dose-titration guided by real-time pharmacokinetic assessments to achieve meaningful clinical exposures safely and rapidly. Results LOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations; cells engineered to express a KIF5B-RET fusion protein −/+ the RET V804M gatekeeper resistance mutation or the common RET activating mutation M918T; and RET-altered human cancer cell line and patient-derived xenografts, including a patient-derived RET fusion-positive xenograft injected orthotopically into the brain. A patient with RET M918T-mutant medullary thyroid cancer metastatic to the liver and an acquired RET V804M gatekeeper resistance mutation, previously treated with six MKI regimens, experienced rapid reductions in tumor calcitonin, CEA and cell-free DNA, resolution of painful hepatomegaly and tumor-related diarrhea and a confirmed tumor response. A second patient with KIF5B-RET fusion-positive lung cancer, acquired resistance to alectinib and symptomatic brain metastases experienced a dramatic response in the brain, and her symptoms resolved. Conclusions These results provide proof-of-concept of the clinical actionability of RET alterations, and identify selective RET inhibition by LOXO-292 as a promising treatment in heavily pretreated, multikinase inhibitor-experienced patients with diverse RET-altered tumors.
TL;DR: In this paper, it was proved that desired workability, gain in strength, reduction in permeability, resistance to thermal and electrical conductivity are observed in sugarcane bagasse ash replaced concrete when compared with conventional concrete.
Abstract: Cement is a non-replaceable, versatile component of concrete which is highly used in world in all construction works. Demand for cement has been increasing day by day where emission of CO2, over-use of natural resources like lime stone, shale has become environmental problems. To balance this, supplementary cementitious materials are encouraged which involves less use of cement in concrete. Agricultural wastes like bagasse ash, rice husk ash, palm oil ash have been tested for their performance in concrete with partial replacements of cement. Countries like Brazil, India are largest producers of sugarcane, faces scarcity of land due to dumping of raw bagasse. Processing of sugarcane bagasse collected from factory scrap by cleaning and incinerating alters the morphological characters of sugarcane bagasse ash making it fit for using as pozzolanic admixture. It is proved that desired workability, gain in strength, reduction in permeability, resistance to thermal and electrical conductivity are observed in sugarcane bagasse ash replaced concrete when compared with conventional concrete.
TL;DR: Wave forces on a vertical cylinder defensed by a perforated vertical and inclined barriers with 45° angle of inclination were experimentally investigated and the force ratios were found reducing with increase of wave steepness.
Abstract: Wave forces on a vertical cylinder defensed by a perforated vertical and inclined barriers with 45° angle of inclination were experimentally investigated. The relative wave height, (H i /d) varied from 0.114 to 0.429 and the porosity was kept constant with 12%. The force ratios were found reducing with increase of H i /d. It is estimated that on an average, the reduction of force on the vertical cylinder is about 35% due to perforated vertical barrier and is about 30% due to sloped barrier. Incident wave steepness, (H i /L) varied from 0.007 to 0. 080 and the force ratios were also found reducing with increase of wave steepness. The force ratios are less sensitive for the scattering parameter (ka).
TL;DR: In this article, 32 cases of hydatid disease in children were reported and the most common sites involved were liver, lung and spleen and unusual sites brain, mesentery and subdural space.
Abstract: 32 cases of hydatid disease in children were reported. The youngest child was of 4 years. A detailed post mortem examination was done in 2 cases. The usual sites involved were liver, lung and spleen and unusual sites brain, mesentery and subdural space. Casoni's test was positive in 24 cases.
TL;DR: In this article, a bisphenol-A diglycidyl ether-based thermosetting polymer mortars containing an epoxy resin, Fly ash and Rock sand are presented.
Abstract: Fusion and characterization of bisphenol-A diglycidyl ether based thermosetting polymer mortars containing an epoxy resin, Fly ash and Rock sand are presented here for the Experimental study. The specimens have been prepared by means of an innovative process, in mild conditions, of commercial epoxy resin, Fly ash and Rock sand based paste. In this way, thermosetting based hybrid mortars characterized by a different content of normalized Fly ash and Rock sand by a homogeneous dispersion of the resin have been obtained. Once hardened, these new composite materials show improved compressive strength and toughness in respect to both the Fly ash and the Rock sand pastes since the Resin provides a more cohesive microstructure, with a reduced amount of micro cracks. The micro structural characterization allows pointing out the presence of an Interfacial Transition Zone similar to that observed in cement based mortars. A correlation between micro-structural features and mechanical properties of the mortar has also been studied.
TL;DR: Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy; Department of Head and Neck Oncology, Gustave Roussy, Villejuif; Université Paris Saclay, Villeroy-sur-Sierre, France; and Department of Nuclear Medicine and Endocrine Oncological Sciences and Public Health, University of Brescia.
Abstract: Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy; Department of Head and Neck Oncology, Gustave Roussy, Villejuif; Université Paris Saclay, Villejuif; Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Villejuif, France; Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London, UK; Department of Pathology, University of Turin, Turin; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology Unit, University of Brescia, ASST Spedali Civili, Brescia, Italy
Cornell University1, Harvard University2, The Chinese University of Hong Kong3, Sarah Cannon Research Institute4, University of California, San Francisco5, University of Bern6, Institut Gustave Roussy7, Yonsei University8, Ben-Gurion University of the Negev9, University of North Carolina at Chapel Hill10, Seoul National University11, Japanese Foundation for Cancer Research12, Sungkyunkwan University13, University of Chicago14, Tottori University15, Ohio State University16, University of California, San Diego17, New York University18, Okayama University19, University of Milan20, City of Hope National Medical Center21, Roswell Park Cancer Institute22, University of Cologne23, Peter MacCallum Cancer Centre24, University of Texas MD Anderson Cancer Center25
TL;DR: Selpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated.
Abstract: Background RET fusions are oncogenic drivers in 1 to 2% of non–small-cell lung cancers (NSCLCs). In patients with RET fusion–positive NSCLC, the efficacy and safety of selective RET inhibi...
TL;DR: Cohen et al. as mentioned in this paper reviewed the remarkable progress made over the past 20 years in improving the potency and specificity of small-molecule inhibitors of protein and lipid kinases, resulting in the approval of more than 70 new drugs since imatinib was approved in 2001.
Abstract: Protein kinases regulate nearly all aspects of cell life, and alterations in their expression, or mutations in their genes, cause cancer and other diseases. Here, we review the remarkable progress made over the past 20 years in improving the potency and specificity of small-molecule inhibitors of protein and lipid kinases, resulting in the approval of more than 70 new drugs since imatinib was approved in 2001. These compounds have had a significant impact on the way in which we now treat cancers and non-cancerous conditions. We discuss how the challenge of drug resistance to kinase inhibitors is being met and the future of kinase drug discovery. Twenty years have passed since the first small-molecule protein kinase inhibitor, imatinib, gained FDA approval. Here, Cohen et al. review advances in improving the potency and specificity of small-molecule protein kinase inhibitors and assess approaches to overcome the challenge of drug resistance. Applications of these compounds in cancers and other disorders, as well as future directions in the field, are discussed.
TL;DR: Department of Medical Oncology, Thoracic Group, Gustave-Roussy Villejuif, France; Royal Marsden Hospital, London; Aberdeen Royal Infirmary, Aberdeen University Medical School, Aberdeen, UK; Department of Oncologists, University of Turin, San Luigi Hospital, Orbassano, Italy.
Abstract: Department of Medical Oncology, Thoracic Group, Gustave-Roussy Villejuif, France; Royal Marsden Hospital, London; Aberdeen Royal Infirmary, Aberdeen University Medical School, Aberdeen, UK; Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Italy; Thoracic Oncology Service, Netherlands Cancer Institute, Amsterdam, The Netherlands; Division of Cancer Sciences, University of Manchester, Manchester, UK; Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China; LungenClinic Airway Research Center North (ARCN), German Center for Lung Research, Grosshansdorf, Germany; Department of Thoracic and Vascular Surgery, Antwerp University Hospital and Antwerp University, Antwerp, Belgium; Weill Cornell Medical College, New York, USA; Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
TL;DR: A significant enrichment for fusions in DNAseq driver–negative samples with low TMB is observed, supporting the prioritization of such cases for additional RNAseq.
Abstract: Purpose: Targeted next-generation sequencing of DNA has become more widely used in the management of patients with lung adenocarcinoma; however, no clear mitogenic driver alteration is found in some cases. We evaluated the incremental benefit of targeted RNA sequencing (RNAseq) in the identification of gene fusions and MET exon 14 (METex14) alterations in DNA sequencing (DNAseq) driver–negative lung cancers. Experimental Design: Lung cancers driver negative by MSK-IMPACT underwent further analysis using a custom RNAseq panel (MSK-Fusion). Tumor mutation burden (TMB) was assessed as a potential prioritization criterion for targeted RNAseq. Results: As part of prospective clinical genomic testing, we profiled 2,522 lung adenocarcinomas using MSK-IMPACT, which identified 195 (7.7%) fusions and 119 (4.7%) METex14 alterations. Among 275 driver-negative cases with available tissue, 254 (92%) had sufficient material for RNAseq. A previously undetected alteration was identified in 14% (36/254) of cases, 33 of which were actionable (27 in-frame fusions, 6 METex14). Of these 33 patients, 10 then received matched targeted therapy, which achieved clinical benefit in 8 (80%). In the 32% (81/254) of DNAseq driver–negative cases with low TMB [0–5 mutations/Megabase (mut/Mb)], 25 (31%) were positive for previously undetected gene fusions on RNAseq, whereas, in 151 cases with TMB >5 mut/Mb, only 7% were positive for fusions (P Conclusions: Targeted RNAseq assays should be used in all cases that appear driver negative by DNAseq assays to ensure comprehensive detection of actionable gene rearrangements. Furthermore, we observed a significant enrichment for fusions in DNAseq driver–negative samples with low TMB, supporting the prioritization of such cases for additional RNAseq. See related commentary by Davies and Aisner, p. 4586