Wenhai Huang, Shu Wang, Zhimin Zhang, Chixiao Zhang, Shenxin Zeng, Meihao Liang, Zhengrong Shen, Xingguo Liu
Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec kinases family and is essential for B cell receptor (BCR) mediated signaling. BTK inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies. Here we disclose a potent, selective, and covalent BTK inhibitor, HZ-A-005, currently in preclinical development. HZ-A-005 demonstrated dose-dependent activity in two xenograft models of lymphoma in vivo. It showed highly favourable safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles in preclinical studies...
October 13, 2020: Bioorganic Chemistry
Fei Lu, Yanan Zhao, Yihua Pang, Min Ji, Yanping Sun, Hongchun Wang, Jie Zou, Yan Wang, Guosheng Li, Tao Sun, Jingxin Li, Daoxin Ma, Jingjing Ye, Chunyan Ji
The NLRP3 inflammasome plays a pro-tumorigenic role in various malignancies. However, its potential role in lymphomagenesis remains unclear. In this study, we identified an immunosuppressive state in patients with diffuse large B cell lymphoma (DLBCL), which was characterized by markedly elevated interleukin (IL)-18 levels in lymphoma tissues and positive correlation with programmed death ligand 1 (PD-L1) expression. Furthermore, NLRP3 inflammasome activation in DLBCL cell lines upregulated PD-L1 and reduced the proportion of cytotoxic T cells...
October 19, 2020: Cancer Letters
Joana A S Marques, Fátima Ferreira, Daniel P Melo, Margarida Santos, Ricardo P Vaz
Head and neck lymphomas can present with a wide range of symptoms. Timely and accurate diagnosis is often challenging. The blastoid variant of mantle cell lymphoma (MCL) accounts for less than one-third of all MCL cases. Isolated primary presentation on the palatine tonsils is rare, and prognosis and outcome are seemingly unfavorable. An 81-year-old man presented with persistent odynophagia, dysphagia, and obstructive hypertrophic palatine tonsils with purulent exudate. The signs and symptoms were non-responsive to antibiotic therapy, and the tonsils were biopsied...
October 22, 2020: Head and Neck Pathology
Lingaraj Nayak, Hasmukh Jain, Avinash Bonda, Sridhar Epari, Siddhartha Laskar, Anant Gokarn, Tanuja Shet, Sumeet Gujral, Nehal Khanna, Bhausaheb Bagal, Sachin Punatar, Jayant Goda, Jayashree Thorat, Karthik Rengaraj, Manju Sengar
Purpose: There is lack of consensus on management of adolescent and young adult (AYA) Hodgkin lymphoma with respect to chemotherapy approach (adult or pediatric). Hence we sought to evaluate the efficacy and safety of Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy in AYA Hodgkin lymphoma. Patients and Methods: It is a retrospective, observational, single-center study. From January 2013 to December 2016, all consecutive patients with AYA (15-25 years, all stages) were analyzed. The primary endpoint of the study was event-free survival (EFS)...
October 22, 2020: Journal of Adolescent and Young Adult Oncology
Vincenzo L'Imperio, Mattia Rossi, Afu Abdul, Satyen R Mehta, Aaron C Shaver, Agnes B Fogo
Lymphomatous infiltration of kidney parenchyma is a frequent complication of systemic hematologic malignancies and often shows subtle clinical presentation. Diffuse large B-cell lymphoma represents the most frequent form involving the kidney, with advanced stage at diagnosis, poor outcome, and risk for central nervous system relapse if not adequately treated. Kidney biopsy can provide specific and early detection of these cases, helping in the differential diagnosis with more frequent entities. Finally, further hematologic workup (bone marrow biopsy, complete blood cell count, and positron emission tomography) can distinguish secondary involvement of the kidney from the rarer kidney-limited forms, especially in patients without a previous diagnosis of lymphoma...
September 2020: Kidney medicine
Pengxuan Zhao, Yuebao Zhang, Wenqing Li, Christopher Jeanty, Guangya Xiang, Yizhou Dong
Antibody drug conjugates (ADCs) normally compose of a humanized antibody and small molecular drug via a chemical linker. After decades of preclinical and clinical studies, a series of ADCs have been widely used for treating specific tumor types in the clinic such as brentuximab vedotin (Adcetris®) for relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, gemtuzumab ozogamicin (Mylotarg®) for acute myeloid leukemia, ado-trastuzumab emtansine (Kadcyla®) for HER2-positive metastatic breast cancer, inotuzumab ozogamicin (Besponsa®) and most recently polatuzumab vedotin-piiq (Polivy®) for B cell malignancies...
September 2020: Acta Pharmaceutica Sinica. B
Naomi Yoshida, Gen Sugiyama, Suzuna Sugi, Koki Satake, Daisuke Wakasugi, Satoshi Yamasaki, Yutaro Mihara, Kotaro Matsuda, Hiroaki Ida, Koichi Ohshima, Rin Yamaguchi, Munetoshi Nakashima
A 70-year-old woman was hospitalised due to jaundice and fever. She was diagnosed with rheumatoid arthritis (RA) at 54 years of age. Treatment with methotrexate (MTX) was successful, and her RA was in remission. Five weeks before the hospitalisation, she was diagnosed with optic neuritis due to a decline in the visual acuity of the right eye. She was treated with methylprednisolone pulse therapy, followed by prednisolone (PSL), before the hospitalisation, which were not effective. Blood tests showed increased C-reactive protein (CRP) levels, liver injury, and thrombocytopenia...
July 2020: Modern rheumatology case reports
Hilma J van der Horst, Inger S Nijhof, Tuna Mutis, Martine E D Chamuleau
Monoclonal antibody (mAb) therapy has rapidly changed the field of cancer therapy. In 1997, the CD20-targeting mAb rituximab was the first mAb to be approved by the U.S. Food and Drug Administration (FDA) for treatment of cancer. Within two decades, dozens of mAbs entered the clinic for treatment of several hematological cancers and solid tumors, and numerous more are under clinical investigation. The success of mAbs as cancer therapeutics lies in their ability to induce various cytotoxic machineries against specific targets...
October 19, 2020: Cancers
Andrea Di Pietro
During the past decade, the rapid development of high-throughput next-generation sequencing technologies has significantly reinforced our understanding of the role of epigenetics in health and disease. Altered functions of epigenetic modifiers lead to the disruption of the host epigenome, ultimately inducing carcinogenesis and disease progression. Epstein-Barr virus (EBV) is an endemic herpesvirus that is associated with several malignant tumours, including B-cell related lymphomas. In EBV-infected cells, the epigenomic landscape is extensively reshaped by viral oncoproteins, which directly interact with epigenetic modifiers and modulate their function...
October 19, 2020: Cancers
Hui Boon Tay, Stanley Angkodjojo, Zhi En Amos Tay, Puay Hoon Tan, Yan Denise Tan
New-onset systemic lupus erythematosus (SLE) is uncommon in elderly patients. We report the case of a 71-year-old woman who was diagnosed with SLE based on clinical manifestations of fever, alopecia, bicytopenia, hepatomegaly, lymphadenopathy, glomerulonephritis, positive antinuclear antibody (ANA) and anti-double stranded DNA (anti-dsDNA) antibody. Renal biopsy was consistent with lupus nephritis and excision biopsy of a right inguinal lymph node was initially reported as having features of reactive hyperplasia...
2020: European Journal of Case Reports in Internal Medicine
S A Touré, M Seck, A B Diallo, E H D Niang, M Keita, M F Dabo, B F Faye, S Diop
Angioimmunoblastic T-cell lymphoma (AITL) is a rare hematologic malignancy recognized in the WHO 2016 classification as a clinical and histological entity. It is a very poorly described disease in Africa due to its rarity and diagnostic difficulties, particularly differential diagnosis with tuberculosis. Here, we report a 57-year-old man who presented with fever, weight loss, and lymphadenopathies. The diagnosis of tuberculosis was carried out based on lymph node fine needle aspiration showing the image of tuberculous adenitis and CT images in favor of necrotic lymphadenopathies...
2020: Case Reports in Hematology
Lisa Johnson, Kathryn Lowry, John Scheel, Brian Mau, Steven J Rockoff
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of T-cell lymphoma that arises in the setting of textured breast implants. In this case report, a 69-year-old woman with a remote history of right-sided invasive lobular carcinoma status post right mastectomy and bilateral breast reconstruction presents with spontaneous right breast swelling and pain, suspicious for implant rupture. Diagnostic MRI revealed a peri-implant fluid collection in the right breast and focal nonmass enhancement in the left breast...
December 2020: Radiology Case Reports
Wiebke Wesemüller, Christian Taverna
Tumor lysis syndrome (TLS) is a hemato-oncological emergency characterized by metabolic and electrolyte imbalances which are associated with disintegrating tumor cells. The syndrome is frequently observed when starting cytotoxic treatment of hematological malignancies, while the incidence of spontaneous tumor lysis prior to the start of tumor therapy is rare. Here, we present a case of spontaneous TLS in a male patient who was referred with unspecific symptoms and suspected metastatic malignancy. He developed acute renal failure before the diagnosis of a high-grade B-cell lymphoma (double hit lymphoma) and start of therapy...
September 2020: Case Reports in Oncology
Takafumi Hamada, Toshinari Kaku, Sumitaka Mitsu, Yoshinori Morita, Nobuhito Ohno, Hironori Yamaguchi
Lactic acidosis is pathophysiologically classified into type A and type B. The latter is a rare but potentially life-threatening emergency, mainly described in hematological malignancies. The association between Type B lactic acidosis and malignancy is known as the Warburg effect. Patients with the Warburg effect have a very poor prognosis. Herein, we report a case of gastric diffuse large B-cell lymphoma (DLBCL) with severe lactic acidosis and hypoglycemia owing to the Warburg effect that were effectively treated by prompt introduction of chemotherapy...
May 2020: Case Reports in Oncology
Yun Liu, Baohuan Cai, Yating Chong, Hualei Zhang, Chesley-Anne Kemp, Sumin Lu, Chang-Sheng Chang, Mingqiang Ren, John K Cowell, Tianxiang Hu
Resistance to molecular therapies frequently occur due to genetic changes affecting the targeted pathway. In myeloid and lymphoid leukemias/lymphomas resulting from constitutive activation of FGFR1 kinases, resistance has been shown to be due either to mutations in FGFR1 or deletions of PTEN. RNA-Seq analysis of the resistant clones demonstrates expression changes in cell death pathways centering on the p53 upregulated modulator of apoptosis (Puma) protein. Treatment with different tyrosine kinase inhibitors (TKIs) revealed that, in both FGFR1 mutation and Pten deletion-mediated resistance, sustained Akt activation in resistant cells leads to compromised Puma activation, resulting in suppression of TKI-induced apoptosis...
October 20, 2020: Cell Death & Disease
Gabrielle McDonald, Victor Chubukov, John Coco, Kevin Truskowski, Rohini Narayanaswamy, Sung Choe, Mya Steadman, Erin Artin, Anil K Padyana, Lei Jin, Sebastien Ronseaux, Charles Locuson, Zi Peng Fan, Tabea Erdmann, Alan Mann, Sebastian Hayes, Mark Fletcher, Kavitha Nellore, Siva Sanjeeva Rao, Hosahalli Subramanya, Satish Reddy Kunnam, Sunil Kumar Panigrahi, Thomas Anthony, Sreevalsam Gopinath, Zhihua Sui, Nelamangala Nagaraja, Lenny Dang, Georg Lenz, Jonathan Hurov, Scott A Biller, Josh Murtie, Kevin M Marks, Danielle B Ulanet
Agents targeting metabolic pathways form the backbone of standard oncology treatments, though a better understanding of differential metabolic dependencies could instruct more rationale-based therapeutic approaches. We performed a chemical biology screen that revealed a strong enrichment in sensitivity to a novel dihydroorotate dehydrogenase (DHODH) inhibitor, AG-636, in cancer cell lines of hematologic versus solid tumor origin. Differential AG-636 activity translated to the in vivo setting, with complete tumor regression observed in a lymphoma model...
October 20, 2020: Molecular Cancer Therapeutics
Beata Wolska-Kusnierz, Agata Pastorczak, Wojciech Fendler, Anna Wakulinska, Bozena Dembowska-Baginska, Edyta Heropolitanska-Pliszka, Barbara Piatosa, Barbara Pietrucha, Krzysztof Kalwak, Marek Ussowicz, Anna Pieczonka, Katarzyna Drabko, Monika Lejman, Sylwia Koltan, Jolanta Gozdzik, Jan Styczynski, Alina Fedorova, Natalia Miakova, Elena Deripapa, Larysa Kostyuchenko, Zdenka Krenova, Eva Hlavackova, Andrew Gennery, Karl-Walter Sykora, Sujal Ghosh, Michael H Albert, Dmitry Balashov, Mary Eapen, Peter Svec, Markus G Seidel, Sara Sebnem Kilic, Agnieszka Tomaszewska, Ewa Wiesik-Szewczyk, Alexandra Kreins, Johann Greil, Jochen Buechner, Bendik Lund, Hanna Gregorek, Krystyna Chrzanowska, Wojciech Mlynarski
PURPOSE: Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematological malignancies. EXPERIMENTAL DESIGN: We describe the natural history of NBS, including cancer incidence, risk of death and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency. RESULTS: Among two hundred forty-one (n=241) patients with NBS enrolled in the study from 11 countries, 151 (63...
October 20, 2020: Clinical Cancer Research
Giuliana Amato, Federica Vita, Paolina Quattrocchi, Paola Lucia Minciullo, Giovanni Pioggia, Sebastiano Gangemi
BACKGROUND AND OBJECTIVES: Common variable immunodeficiency (CVID) is the most prevalent antibody impairment. It is characterized by failure in immunoglobulin and protective antibody generation and defined by an increased tendency toward bacterial infections, autoimmunity, and malignancy. Most CVID diagnoses do not follow a classical Mendelian pattern of inheritance. In recent years, CVID has been considered an epigenetic phenomenon in the majority of cases, overtaking previous monogenetic and/or polygenetic theories...
October 16, 2020: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jisoo Lee, Kyeoungseo Park, Kyoung Ha Kim, Hae In Bang, Seug Yun Yoon, In Ho Choi
INTRODUCTION: Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of mature T cell lymphomas which do not correspond to any specific subtype of mature T-cell lymphoma in current classifications. Some researchers have suggested that PTCL with low Ki-67 labeling index should be classified as indolent PTCL PATIENT CONCERNS:: A 58-year old man diagnosed with alcoholic fatty liver 3 months prior complained of tenesmus and abdominal distension. Colonoscopy of the small and large intestines revealed multiple polyps, which were histologically diagnosed as lymphoid hyperplasia...
October 16, 2020: Medicine (Baltimore)
Monish Ram Makena, Thinh H Nguyen, Balakrishna Koneru, Ashly Hindle, Wan-Hsi Chen, Dattesh U Verlekar, Min H Kang, C Patrick Reynolds
T-cell lymphoid malignancies (TCLMs) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitors and the synthetic cytotoxic retinoid fenretinide have achieved durable clinical responses in T-cell lymphomas as single agents, and patients who failed prior HDAC inhibitor treatment have responded to fenretinide. We have previously shown fenretinide synergized with the class I HDAC inhibitor romidepsin in preclinical models of TCLMs. There exist some key differences between HDAC inhibitors...
October 19, 2020: Anti-cancer Drugs
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