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https://www.readbyqxmd.com/read/29433109/pathogenesis-of-aortic-wall-complications-in-marfan-syndrome
#1
Nimrat Grewal, Adriana C Gittenberger-de Groot
BACKGROUND: Patients with Marfan (MFS) syndrome and patients with a bicuspid aortic valve (BAV) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common as well as distinct pathways of clinical relevance, we compared the histopathological substrates of aortic pathology. PATIENT AND METHODS: Ascending aortic wall specimen were divided in five groups: BAV (n=36) and TAV (n=23) without and with dilation and non-dilated MFS (n=8)...
February 2, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29420582/ethyl-pyruvate-ameliorates-hepatic-injury-following-blunt-chest-trauma-and-hemorrhagic-shock-by-reducing-local-inflammation-nf-kappab-activation-and-hmgb1-release
#2
Nils Wagner, Scott Dieteren, Niklas Franz, Kernt Köhler, Katharina Mörs, Luka Nicin, Julia Schmidt, Mario Perl, Ingo Marzi, Borna Relja
BACKGROUND: The treatment of patients with multiple trauma including blunt chest/thoracic trauma (TxT) and hemorrhagic shock (H) is still challenging. Numerous studies show detrimental consequences of TxT and HS resulting in strong inflammatory changes, organ injury and mortality. Additionally, the reperfusion (R) phase plays a key role in triggering inflammation and worsening outcome. Ethyl pyruvate (EP), a stable lipophilic ester, has anti-inflammatory properties. Here, the influence of EP on the inflammatory reaction and liver injury in a double hit model of TxT and H/R in rats was explored...
2018: PloS One
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
#3
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
#4
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/29399573/de-novo-cd5-positive-primary-gastric-diffuse-large-b-cell-lymphoma-coexpressing-myc-and-bcl6-towards-a-proper-subset-of-double-hit-triple-hit-and-maybe-quadruple-hit-b-cell-lymphomas
#5
EDITORIAL
https://www.readbyqxmd.com/read/29386360/therapeutic-synergy-between-tigecycline-and-venetoclax-in-a-preclinical-model-of-myc-bcl2-double-hit-b-cell-lymphoma
#6
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/29383130/gsk-3%C3%AE-inhibitor-9-ing-41-reduces-cell-viability-and-halts-proliferation-of-b-cell-lymphoma-cell-lines-as-a-single-agent-and-in-combination-with-novel-agents
#7
Reem Karmali, Vineela Chukkapalli, Leo I Gordon, Jeffrey A Borgia, Andrey Ugolkov, Andrew P Mazar, Francis J Giles
The complexities of GSK-3β function and interactions with PI3K/AKT/mTOR signaling, cell cycling, and apoptotic pathways are poorly understood in the context of lymphomagenesis and cancer therapeutics. In this study, we explored the anti-tumor effects of the GSK-3β inhibitor, 9-ING-41, in lymphoma cell lines as a single agent and in combination with novel agents comprising BCL-2 inhibitor (Venetoclax), CDK-9 inhibitor (BAY-1143572) and p110δ-PI3K inhibitor (Idelalisib). Treatment of Daudi, SUDHL-4, Karpas 422, KPUM-UH1, and TMD8 lymphoma cell lines with 1 μM 9-ING-41 reduced cell viability by 40-70% (p<0...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29383095/polo-like-kinase-1-plk-1-and-c-myc-inhibition-with-the-dual-kinase-bromodomain-inhibitor-volasertib-in-aggressive-lymphomas
#8
Carlos Murga-Zamalloa, Avery Polk, Walter Hanel, Pinki Chowdhury, Noah Brown, Alexandra C Hristov, Nathanael G Bailey, Tianjiao Wang, Tycel Phillips, Sumana Devata, Pradeep Poonnen, Juan Gomez-Gelvez, Kedar V Inamdar, Ryan A Wilcox
Survival following anthracycline-based chemotherapy remains poor among patients with most T-cell lymphoproliferative disorders. This may be attributed, at least in part, to cell-autonomous mechanisms of chemotherapy resistance observed in these lymphomas, including the loss of important tumor suppressors and the activation of signaling cascades that culminate in the expression and activation of transcription factors promoting cell growth and survival. Therefore, the identification of novel therapeutic targets is needed...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29368541/double-hit-lymphoma-do-we-need-a-double-hit-of-intensive-therapy
#9
Diego Villa, Laurie H Sehn
No abstract text is available yet for this article.
January 25, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29364511/-18-f-ge180-positron-emission-tomographic-imaging-indicates-a-potential-double-hit-insult-in-the-intrahippocampal-kainate-mouse-model-of-temporal-lobe-epilepsy
#10
Mirjam Brackhan, Pablo Bascuñana, Tobias L Ross, Frank M Bengel, Jens P Bankstahl, Marion Bankstahl
OBJECTIVE: Accumulating evidence suggests that brain inflammation, elicited by epileptogenic insults, is involved in epilepsy development. Noninvasive nuclear imaging of brain inflammation in animal models of epileptogenesis represents a diagnostic in vivo approach with potential for direct translation into the clinic. Here, we investigated up-regulation of the translocator protein (TSPO) indicative of microglial activation by serial [18 F]GE180 positron emission tomographic (PET) imaging in a mouse model of temporal lobe epilepsy...
January 24, 2018: Epilepsia
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
#11
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...
January 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29352717/should-we-use-cell-of-origin-and-dual-protein-expression-in-treating-dlbcl
#12
REVIEW
Peter A Riedell, Sonali M Smith
Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy is highly variable and dependent on a number of clinical, biologic, and genetic features. The identification of molecular heterogeneity via gene expression profiling dichotomizes patients based on the cell of origin (COO) model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subsets, with ABC-DLBCL having a worse outcome...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29339272/an-old-friend-is-trouble-for-double-expressor-and-double-hit-lymphoma
#13
Michael Scordo
No abstract text is available yet for this article.
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29332092/early-life-stress-activates-glial-cells-in-the-hippocampus-but-attenuates-cytokine-secretion-in-response-to-an-immune-challenge-in-rat-pups
#14
Luis Miguel Saavedra, Bertha Fenton Navarro, Luz Torner
OBJECTIVE: Early life stress (ELS) increases the vulnerability to developing psychopathological disorders in adulthood that are accompanied by brain inflammatory processes. However, it is not known how a combined double hit (stress and immune) at an early age affects the response of the neuroimmune system. Here we investigated the effect of periodic maternal separation (MS) followed by administration of lipopolysaccharide (LPS) on glial cells in the CA3 region and hilus of the hippocampus and on cytokine release on postnatal day (PN) 15...
January 13, 2018: Neuroimmunomodulation
https://www.readbyqxmd.com/read/29326077/mechanism-of-nanoparticle-induced-hypersensitivity-in-pigs-complement-or-not-complement
#15
János Szebeni
A recent study on nanoparticle-induced hypersensitivity reactions in pigs showed robust pulmonary intravascular macrophage clearance of Polybead® carboxylate microspheres in mediating the adverse cardiopulmonary distress, irrespective of the ability of these particles to activate the Complement (C) system in vitro. Focusing on this observation, this article highlights the controversies in projecting in vitro C assay data to in vivo conditions and applying data on polystyrene particles to therapeutic nanopharmaceuticals...
January 8, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29325248/-survival-of-patients-with-primary-central-nervous-system-diffuse-large-b-cell-lymphoma-impact-of-gene-aberrations-and-protein-overexpression-of-bcl-2-and-c-myc-and-selection-of-chemotherapy-regimens
#16
W J Yin, X Zhu, H Y Yang, W Y Sun, M J Wu
Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER)...
January 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
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
#17
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
https://www.readbyqxmd.com/read/29234922/pharmacokinetically-targeted-dosed-everolimus-maintenance-therapy-in-lymphoma-patients
#18
L K Schoch, A Asiama, M Zahurak, S Shanbhag, J Hurtt, K Sawyer, L J Swinnen, N Wagner-Johnston, R J Jones, R F Ambinder, Douglas E Gladstone
BACKGROUND: Everolimus, an mTOR inhibitor, is active in refractory lymphomas. However, toxicity with flat dosing limits its usage. Speculatively, pharmacokinetically-targeted dosing could improve tolerability. Therefore, we studied serum-trough dosing with rituximab as maintenance after high-dose cyclophosphamide (HDC) consolidation in lymphoma patients. PATIENTS/METHODS: After HDC, everolimus was dosed to serum trough levels (goal 3-15 ng/mL), with quarterly rituximab infusions for 1 year while maintaining < grade II non-hematologic and < grade III hematologic toxicities...
December 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29225339/early-speech-development-in-koolen-de-vries-syndrome-limited-by-oral-praxis-and-hypotonia
#19
Angela T Morgan, Leenke van Haaften, Karen van Hulst, Carol Edley, Cristina Mei, Tiong Yang Tan, David Amor, Simon E Fisher, David A Koolen
Communication disorder is common in Koolen de Vries syndrome (KdVS), yet its specific symptomatology has not been examined, limiting prognostic counselling and application of targeted therapies. Here we examine the communication phenotype associated with KdVS. Twenty-nine participants (12 males, 4 with KANSL1 variants, 25 with 17q21.31 microdeletion), aged 1.0-27.0 years were assessed for oral-motor, speech, language, literacy, and social functioning. Early history included hypotonia and feeding difficulties...
December 11, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29222269/current-treatment-of-double-hit-and-double-expressor-lymphoma
#20
REVIEW
Patrick M Reagan, Andrew Davies
A 60-year-old female presented with abdominal pain and distension. Following computed tomography scans of the abdomen and pelvis, she was taken urgently to the operating room, with the belief that she had appendicitis with perforation. At laparotomy, the findings were consistent with an ovarian carcinoma; there was extensive infiltration of the ovary, bowel, and omental deposits. Cytoreductive surgery was performed including total abdominal hysterectomy and bilateral salpingo-oophorectomy. The final pathology, however, revealed infiltration with medium-sized atypical lymphoid cells positive for CD20, CD10, MYC, BLC2, and BCL6 by immunohistochemistry...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
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