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https://www.readbyqxmd.com/read/29681711/diagnostic-hysterolaparoscopy-for-evaluation-of-infertility-our-experience-in-a-tertiary-care-hospital
#1
Sairem Mangolnganbi Chanu, Gouri Sankar Rudra Pal, Subrat Panda, A S Santa Singh
Objective: The objective of this study is to analyze the role of diagnostic hysterolaparoscopy (DHL) for evaluation of infertility in a tertiary care hospital. Materials and Methods: This retrospective study was conducted from July 2014 to June 2016. Results: Out of 151 patients, 58.28% and 41.72% had primary and secondary infertility, respectively. In primary infertility group 37.5% and in secondary infertility group 49.2% had abnormal findings...
January 2018: Journal of Human Reproductive Sciences
https://www.readbyqxmd.com/read/29649047/preliminary-outcomes-report-for-co2-laser-assisted-electric-acoustic-cochlear-implantation
#2
Shawn M Stevens, Andrew Redmann, Kayla Whitaker, Alyson Ruotanen, Lisa Houston, Theresa Hammer, Ravi N Samy
OBJECTIVE: Report on the safety/efficacy of a novel, carbon dioxide (CO2) laser-assisted protocol for hearing-preservation cochlear implantation (HPCI) and electric-acoustic stimulation (EAS). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Adult patients meeting established criteria for HPCI and EAS. INTERVENTION: Therapeutic/rehabilitative. A standardized protocol used CO2 laser to achieve meticulous hemostasis and perform cochleostomy was evaluated...
April 11, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29629947/identification-of-double-hit-lymphomas-using-updated-who-criteria-insights-from-routine-myc-immunohistochemistry-in-272-consecutive-cases-of-aggressive-b-cell-lymphomas
#3
Hany Sakr, James R Cook
Aggressive lymphomas with MYC and BCL2 and/or BCL6 translocations ("double hit" lymphomas, DHL) represent a distinct diagnostic category in the updated World Health Organization (WHO) classification. The diagnostic yield of MYC immunohistochemistry (IHC) for the identification of DHL is currently uncertain. MYC IHC was performed in 272 consecutive cases of aggressive B-cell lymphoma, and results correlated with fluorescence in situ hybridization (FISH) for MYC translocations. Among 156 patients with IHC and FISH data, MYC IHC identified MYC translocations with 89% sensitivity, 38% specificity, 92% negative predictive value, and 29% positive predictive value...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29627725/proteolysis-targeting-chimeras-protacs-of-anaplastic-lymphoma-kinase-alk
#4
Chengwei Zhang, Xiao-Ran Han, Xiaobao Yang, Biao Jiang, Jing Liu, Yue Xiong, Jian Jin
Anaplastic lymphoma kinase (ALK) activation has been associated with many types of human cancer. Significant efforts have been devoted to the development of ALK inhibitors to antagonize the kinase activity of ALK. Four ALK inhibitors have been approved by the FDA to date for treating patients with ALK-positive non-small cell lung cancers (NSCLC). However, drug resistance has been observed in the majority of patients treated with these inhibitors. New therapeutic strategies (e.g., compounds with novel mechanisms of action) are needed to overcome the drug resistance issue...
March 27, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29601991/discovery-of-novel-quinazolinone-derivatives-as-high-potent-and-selective-pi3k%C3%AE-and-pi3k%C3%AE-%C3%AE-inhibitors
#5
Chen-Chen Ma, Cheng-Mei Zhang, Long-Qian Tang, Zhao-Peng Liu
PI3Kδ and PI3Kγ regulate immune cell signaling. Selective PI3Kδ or PI3Kγ inhibitors and dual PI3Kδ/γ inhibitors have the potential for the treatment of immune cell-mediated diseases and hematological malignancies. Based on the quinazolinone pharmacophore, we used a pyrazolo[3,4-d]pyrimidin-4-amine portion as the hinge region binding moiety, an aromatic or a heteroaromatic substituent at the 3-position of the pyrazolo[3,4-d]pyrimidine core as the affinity element, and designed novel 2-tolyl and 2,6-dimethylphenyl quinazolinone derivatives as potential PI3Kδ inhibitors...
March 23, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29593718/secretion-of-the-phosphorylated-form-of-s100a9-from-neutrophils-is-essential-for-the-proinflammatory-functions-of-extracellular-s100a8-a9
#6
Véronique Schenten, Sébastien Plançon, Nicolas Jung, Justine Hann, Jean-Luc Bueb, Sabrina Bréchard, Eric J Tschirhart, Fabrice Tolle
S100A8 and S100A9 are members of the S100 family of cytoplasmic EF-hand Ca2+ -binding proteins and are abundantly expressed in the cytosol of neutrophils. In addition to their intracellular roles, S100A8/A9 can be secreted in the extracellular environment and are considered as alarmins able to amplify the inflammatory response. The intracellular activity of S100A8/A9 was shown to be regulated by S100A9 phosphorylation, but the importance of this phosphorylation on the extracellular activity of S100A8/A9 has not yet been extensively studied...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29536777/introduction-of-pyrrolidineoxy-or-piperidineamino-group-at-the-4-position-of-quinazoline-leading-to-novel-quinazoline-based-phosphoinositide-3-kinase-delta-pi3k%C3%AE-inhibitors
#7
Minhang Xin, Weiming Duan, Yifan Feng, Yuan-Yuan Hei, Hao Zhang, Ying Shen, Hong-Yi Zhao, Shuai Mao, San-Qi Zhang
Phosphoinositide 3-kinase Delta (PI3Kδ) plays a key role in B-cell signal transduction and inhibition of PI3Kδ was confirmed to have clinical benefit in certain types of activation of B-cell malignancies. Herein, we reported a novel series of 4-pyrrolidineoxy or 4-piperidineamino substituted quinazolines, showing potent PI3Kδ inhibitory activities. Among these compounds, 12d, 14b and 14c demonstrated higher potency against PI3Kδ with the half maximal inhibitory concentration (IC50 ) values of 4.5, 3.0, and 3...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29534936/novel-6-aryl-substituted-4-pyrrolidineaminoquinazoline-derivatives-as-potent-phosphoinositide-3-kinase-delta-pi3k%C3%AE-inhibitors
#8
Minhang Xin, Weiming Duan, Yifan Feng, Yuan-Yuan Hei, Hao Zhang, Ying Shen, Hong-Yi Zhao, Shuai Mao, San-Qi Zhang
In this study, a novel series of 6-aryl substituted 4-pyrrolidineaminoquinazoline derivatives were designed and evaluated as potent PI3Kδ inhibitors. The preliminary SAR was established, and compounds 12d, 20a and 20c displayed leading potent PI3Kδ inhibition, with IC50 values of 4.5, 2.7 and 3.1 nM, respectively, that were comparable to idelalisib (IC50  = 2.7 nM). Moreover, these three compounds showed favorable PI3Kδ isoform selectivity over PI3Kα, PI3Kβ, and PI3Kγ, and showed distinct anti-proliferation profiles against four human B cell lines of Ramos, Raji, RPMI-8226 and SU-DHL-6...
March 2, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29510342/uric-acid-disrupts-hypochlorous-acid-production-and-the-bactericidal-activity-of-hl-60-cells
#9
Larissa A C Carvalho, João P P B Lopes, Gilberto H Kaihami, Railmara P Silva, Alexandre Bruni-Cardoso, Regina L Baldini, Flavia C Meotti
Uric acid is the end product of purine metabolism in humans and is an alternative physiological substrate for myeloperoxidase. Oxidation of uric acid by this enzyme generates uric acid free radical and urate hydroperoxide, a strong oxidant and potentially bactericide agent. In this study, we investigated whether the oxidation of uric acid and production of urate hydroperoxide would affect the killing activity of HL-60 cells differentiated into neutrophil-like cells (dHL-60) against a highly virulent strain (PA14) of the opportunistic pathogen Pseudomonas aeruginosa...
June 2018: Redox Biology
https://www.readbyqxmd.com/read/29500147/a-retrospective-study-of-double-hit-lymphomas-in-elderly-patients-aged-70-years-overall-outcomes
#10
Christie Hancock, Phillip Knouse, Imad Almanaseer, Jacob Bitran
BACKGROUND: Double-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advanced disease at presentation and typically responds poorly to standard therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). More intensive treatment regimens have been studied; however, few data are available on the outcomes in elderly patients (aged > 70 years) treated with these therapies...
April 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29445868/induction-of-systemic-resistance-in-tomato-against-botrytis-cinerea-by-n-decanoyl-homoserine-lactone-via-jasmonic-acid-signaling
#11
Zhangjian Hu, Shujun Shao, Chenfei Zheng, Zenghui Sun, Junying Shi, Jingquan Yu, Zhenyu Qi, Kai Shi
N-decanoyl-homoserine lactone activates plant systemic resistance against Botrytis cinerea in tomato plants, which is largely dependent on jasmonic acid biosynthesis and signal transduction pathways. Rhizosphere bacteria secrete N-acylated-homoserine lactones (AHLs), a type of specialized quorum-sensing signal molecule, to coordinate their population density during communication with their eukaryotic hosts. AHLs behave as low molecular weight ligands that are sensed by plants and promote the host's resistance against foliar pathogens...
February 14, 2018: Planta
https://www.readbyqxmd.com/read/29427012/-blood-pressure-targets-the-lower-the-better-does-not-suit-all
#12
REVIEW
U Hoffmann
BACKGROUND: The systolic blood pressure intervention trial (SPRINT) published in 2015 has opened up new discussions on whether a lower blood pressure target as recommended by the current guidelines would be better for some patient groups. OBJECTIVES: To review patient groups in which lower blood pressure targets would not be better. MATERIALS AND METHODS: The results of SPRINT, its post-hoc and subgroup analyses, other studies and newer studies, as well as metaanalyses on the topic of blood pressure targets are reviewed and discussed...
February 9, 2018: Der Internist
https://www.readbyqxmd.com/read/29419530/challenges-and-opportunities-for-high-grade-b-cell-lymphoma-with-myc-and-bcl2-and-or-bcl6-rearrangement-double-hit-lymphoma
#13
Dongfeng Zeng, Aakash Desai, Fangfang Yan, Tiejun Gong, Haige Ye, Makhdum Ahmed, Krystle Nomie, Jorge Romaguera, Richard Champlin, Shaoying Li, Michael Wang
The most common subtype of non-Hodgkin lymphoma, diffuse large B-cell lymphoma, is cured in approximately two thirds of patients after initial therapy. The remaining one-third of patients who suffer relapse or become refractory have very poor survival outcomes despite salvage chemotherapy with or without stem cell transplantation. A considerable proportion of relapsed or refractory large B cells belong to the WHO subtype known as high-grade B-cell lymphoma with rearrangement of MYC and BCL2 and/or BCL6, also known as double-hit lymphoma (DHL)...
February 6, 2018: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29416618/preclinical-efficacy-and-biological-effects-of-the-oral-proteasome-inhibitor-ixazomib-in-diffuse-large-b-cell-lymphoma
#14
Wei Liu, Juan Chen, Archito T Tamayo, Changgeng Ruan, Li Li, Shouhao Zhou, Chan Shen, Ken H Young, Jason Westin, Richard E Davis, Shimin Hu, Leonard J Medeiros, Richard J Ford, Lan V Pham
Despite advances in deciphering the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL), patients with relapsed/refractory disease, particularly those with adverse genetic features (e.g., mutated p53 or double hit lymphoma (DHL)) have very poor prognoses, and effective therapies are lacking. In this study we examined the preclinical efficacy and associated biological effects of the first oral proteasome inhibitor, ixazomib, in DLBCL in vitro and in vivo models. We demonstrated that ixazomib exhibited anti-tumor activities in 28 representative DLBCL cell lines, 10 primary DLBCL samples, and a DHL xenotransplant mouse model, at clinically achievable drug concentrations...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29392398/generation-and-characterisation-of-decellularised-human-corneal-limbus
#15
Kristina Spaniol, Joana Witt, Sonja Mertsch, Maria Borrelli, Gerd Geerling, Stefan Schrader
PURPOSE: Limbal epithelial stem cells (LESC) reside in a niche in the corneo-scleral transition zone. Deficiency leads to pain, corneal opacity, and eventually blindness. LESC transplantation of ex-vivo expanded human LESC on a carrier such as human amniotic membrane is a current treatment option. We evaluated decellularised human limbus (DHL) as a potential carrier matrix for the transplantation of LESC. METHODS: Human corneas were obtained from the local eye bank...
February 1, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/29386360/therapeutic-synergy-between-tigecycline-and-venetoclax-in-a-preclinical-model-of-myc-bcl2-double-hit-b-cell-lymphoma
#16
Micol Ravà, Aleco D'Andrea, Paola Nicoli, Ilaria Gritti, Giulio Donati, Mirko Doni, Marco Giorgio, Daniela Olivero, Bruno Amati
High-grade B cell lymphomas with concurrent activation of the MYC and BCL2 oncogenes, also known as double-hit lymphomas (DHL), show dismal prognosis with current therapies. MYC activation sensitizes cells to inhibition of mitochondrial translation by the antibiotic tigecycline, and treatment with this compound provides a therapeutic window in a mouse model of MYC -driven lymphoma. We now addressed the utility of this antibiotic for treatment of DHL. BCL2 activation in mouse Eμ- myc lymphomas antagonized tigecycline-induced cell death, which was specifically restored by combined treatment with the BCL2 inhibitor venetoclax...
January 31, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29380901/the-influence-of-agents-differentiating-hl-60-cells-toward-granulocyte-like-cells-on-their-ability-to-release-neutrophil-extracellular-traps
#17
Aneta Manda-Handzlik, Weronika Bystrzycka, Małgorzata Wachowska, Sandra Sieczkowska, Anna Stelmaszczyk-Emmel, Urszula Demkow, Olga Ciepiela
Studies on neutrophil extracellular traps (NETs) are challenging as neutrophils live shortly and easily become activated. Thus, availability of a cell line model closely resembling the functions of peripheral blood neutrophils would be advantageous. Our purpose was to find a compound that most effectively differentiates human promyelocytic leukemia (HL-60) cells toward granulocyte-like cells able to release NETs. HL-60 cells were differentiated with all-trans retinoic acid (ATRA), dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) and stimulated with phorbol 12-myristate 13-acetate (PMA) or calcium ionophore A23187 (CI)...
April 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29353886/the-bet-bromodomain-inhibitor-cpi203-overcomes-resistance-to-abt-199-venetoclax-by-downregulation-of-bfl-1-a1-in-in-vitro-and-in-vivo-models-of-myc-bcl2-double-hit-lymphoma
#18
A Esteve-Arenys, J G Valero, A Chamorro-Jorganes, D Gonzalez, V Rodriguez, I Dlouhy, I Salaverria, E Campo, D Colomer, A Martinez, G Rymkiewicz, P Pérez-Galán, A Lopez-Guillermo, G Roué
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, mostly known as double-hit lymphoma (DHL), is a rare entity characterized by morphologic and molecular features between Burkitt lymphoma and the clinically manageable diffuse large B-cell lymphoma (DLBCL). DHL patients usually undergo a rapidly progressing clinical course associated with resistance to standard chemo-immunotherapy. As a consequence, the prognosis of this entity is particularly poor with a median overall survival inferior to 1 year...
April 2018: Oncogene
https://www.readbyqxmd.com/read/29338562/targeted-microbubbles-with-ultrasound-irradiation-and-pd-1-inhibitor-to-increase-antitumor-activity-in-b-cell-lymphoma
#19
Shiya Zheng, Dan Song, Xiaoxiao Jin, Haijun Zhang, Mohanad Aldarouish, Yan Chen, Cailian Wang
AIM: Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro-environment become main obstacles for the effective treatment of B-cell lymphoma. In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs) were designed for exploring a combination approach of targeted microbubbles with ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned above. METHODS: In vivo studies were performed on SU-DHL-4 cell-grafted mice and ex vivo studies were performed on CD20+ human SU-DHL-4 cells and human T cells...
February 2018: Nanomedicine
https://www.readbyqxmd.com/read/29310838/a-leukemic-double-hit-follicular-lymphoma-associated-with-a-complex-variant-translocation-t-8-14-18-q24-q32-q21-involving-bcl2-myc-and-igh
#20
Daisuke Minakata, Kazuya Sato, Takashi Ikeda, Yumiko Toda, Shoko Ito, Kiyomi Mashima, Kento Umino, Hirofumi Nakano, Ryoko Yamasaki, Kaoru Morita, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Iekuni Oh, Shin-Ichiro Fujiwara, Ken Ohmine, Hirotoshi Kawata, Kazuo Muroi, Ikuo Miura, Yoshinobu Kanda
Double-hit lymphoma (DHL) is defined as lymphoma with concurrent BCL2 and MYC translocations. While the most common histological subtype of DHL is diffuse large B-cell lymphoma, the present patient had leukemic follicular lymphoma (FL). A 52-year-old man was admitted to our hospital due to general fatigue and cervical and inguinal lymph node swelling. The patient was leukemic and the pathological diagnosis of the inguinal lymph node was FL grade 1. Chromosomal analysis revealed a complex karyotype including a rare three-way translocation t(8;14;18)(q24;q32;q21) involving the BCL2, MYC, and IGH genes...
January 2018: Cancer Genetics
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