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https://www.readbyqxmd.com/read/29643063/evaluation-of-prexasertib-a-checkpoint-kinase-1-inhibitor-in-a-phase-ib-study-of-patients-with-squamous-cell-carcinoma
#1
David S Hong, Kathleen N Moore, Manish R Patel, Stefan C Grant, Howard A Burris, William N William, Suzanne Jones, Funda Meric-Bernstam, Jeffrey Infante, Lisa Golden, Wei Zhang, Ricardo Martinez, Sameera R Wijayawardana, Richard P Beckmann, Aimee Bence Lin, Cathy Eng, Johanna C Bendell
PURPOSE: Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent activity in patients with advanced squamous cell carcinoma (SCC) in the dose-escalation portion of a Phase I study (NCT01115790). Monotherapy prexasertib was further evaluated in patients with advanced SCC. EXPERIMENTAL DESIGN: Patients were given prexasertib 105 mg/m2 as a 1-hour infusion on day 1 of a 14-day cycle. Expansion cohorts were defined by tumor and treatment line. Safety, tolerability, efficacy, and exploratory biomarkers were analyzed...
April 11, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29618297/influence-of-a-single-point-mutation-in-the-constant-domain-of-the-bence-jones-protein-bif-on-its-aggregation-properties
#2
M A Timchenko, A A Timchenko
Multiple myeloma nephropathy occurs due to the aggregate formation by monoclonal immunoglobulin light chains (Bence-Jones proteins) in kidneys of patients with multiple myeloma. The mechanism of amyloid deposit formation is still unclear. Earlier, the key role in the fibril formation has been assigned to the variable domains that acquired amyloidogenic properties as a result of somatic mutations. However, fibril formation by the Bence-Jones protein BIF was found to be the function of its constant domain. The substitution of Ser177 by Asn in the constant domain of the BIF protein is most likely an inherited than a somatic mutation...
February 2018: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29466330/the-genomic-history-of-southeastern-europe
#3
Iain Mathieson, Songül Alpaslan-Roodenberg, Cosimo Posth, Anna Szécsényi-Nagy, Nadin Rohland, Swapan Mallick, Iñigo Olalde, Nasreen Broomandkhoshbacht, Francesca Candilio, Olivia Cheronet, Daniel Fernandes, Matthew Ferry, Beatriz Gamarra, Gloria González Fortes, Wolfgang Haak, Eadaoin Harney, Eppie Jones, Denise Keating, Ben Krause-Kyora, Isil Kucukkalipci, Megan Michel, Alissa Mittnik, Kathrin Nägele, Mario Novak, Jonas Oppenheimer, Nick Patterson, Saskia Pfrengle, Kendra Sirak, Kristin Stewardson, Stefania Vai, Stefan Alexandrov, Kurt W Alt, Radian Andreescu, Dragana Antonović, Abigail Ash, Nadezhda Atanassova, Krum Bacvarov, Mende Balázs Gusztáv, Hervé Bocherens, Michael Bolus, Adina Boroneanţ, Yavor Boyadzhiev, Alicja Budnik, Josip Burmaz, Stefan Chohadzhiev, Nicholas J Conard, Richard Cottiaux, Maja Čuka, Christophe Cupillard, Dorothée G Drucker, Nedko Elenski, Michael Francken, Borislava Galabova, Georgi Ganetsovski, Bernard Gély, Tamás Hajdu, Veneta Handzhyiska, Katerina Harvati, Thomas Higham, Stanislav Iliev, Ivor Janković, Ivor Karavanić, Douglas J Kennett, Darko Komšo, Alexandra Kozak, Damian Labuda, Martina Lari, Catalin Lazar, Maleen Leppek, Krassimir Leshtakov, Domenico Lo Vetro, Dženi Los, Ivaylo Lozanov, Maria Malina, Fabio Martini, Kath McSweeney, Harald Meller, Marko Menđušić, Pavel Mirea, Vyacheslav Moiseyev, Vanya Petrova, T Douglas Price, Angela Simalcsik, Luca Sineo, Mario Šlaus, Vladimir Slavchev, Petar Stanev, Andrej Starović, Tamás Szeniczey, Sahra Talamo, Maria Teschler-Nicola, Corinne Thevenet, Ivan Valchev, Frédérique Valentin, Sergey Vasilyev, Fanica Veljanovska, Svetlana Venelinova, Elizaveta Veselovskaya, Bence Viola, Cristian Virag, Joško Zaninović, Steve Zäuner, Philipp W Stockhammer, Giulio Catalano, Raiko Krauß, David Caramelli, Gunita Zariņa, Bisserka Gaydarska, Malcolm Lillie, Alexey G Nikitin, Inna Potekhina, Anastasia Papathanasiou, Dušan Borić, Clive Bonsall, Johannes Krause, Ron Pinhasi, David Reich
Farming was first introduced to Europe in the mid-seventh millennium bc, and was associated with migrants from Anatolia who settled in the southeast before spreading throughout Europe. Here, to understand the dynamics of this process, we analysed genome-wide ancient DNA data from 225 individuals who lived in southeastern Europe and surrounding regions between 12000 and 500 bc. We document a west-east cline of ancestry in indigenous hunter-gatherers and, in eastern Europe, the early stages in the formation of Bronze Age steppe ancestry...
March 8, 2018: Nature
https://www.readbyqxmd.com/read/29454372/a-novel-combination-of-bortezomib-lenalidomide-and-clarithromycin-produced-stringent-complete-response-in-refractory-multiple-myeloma-complicated-with-diabetes-mellitus-clinical-significance-and-possible-mechanisms-a-case-report
#4
Nobuo Takemori, Goro Imai, Kazuo Hoshino, Akishi Ooi, Masaru Kojima
BACKGROUND: In general, dexamethasone is a required component drug in various combination chemotherapies for treating multiple myeloma, and its efficacy has been widely recognized. However, administration of dexamethasone is known to cause various adverse effects including hyperglycemia which requires insulin therapy. During the course of treatment, we developed a novel effective dexamethasone-free combination regimen and evaluated it for its effect in multiple myeloma. CASE PRESENTATION: We report a case of 68-year-old Japanese woman with refractory advanced Bence-Jones-λ type multiple myeloma associated with diabetes mellitus...
February 18, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29431742/transcriptional-regulation-of-macrophage-cholesterol-efflux-and-atherogenesis-by-a-long-noncoding-rna
#5
Tamer Sallam, Marius Jones, Brandon J Thomas, Xiaohui Wu, Thomas Gilliland, Kevin Qian, Ascia Eskin, David Casero, Zhengyi Zhang, Jaspreet Sandhu, David Salisbury, Prashant Rajbhandari, Mete Civelek, Cynthia Hong, Ayaka Ito, Xin Liu, Bence Daniel, Aldons J Lusis, Julian Whitelegge, Laszlo Nagy, Antonio Castrillo, Stephen Smale, Peter Tontonoz
Nuclear receptors regulate gene expression in response to environmental cues, but the molecular events governing the cell type specificity of nuclear receptors remain poorly understood. Here we outline a role for a long noncoding RNA (lncRNA) in modulating the cell type-specific actions of liver X receptors (LXRs), sterol-activated nuclear receptors that regulate the expression of genes involved in cholesterol homeostasis and that have been causally linked to the pathogenesis of atherosclerosis. We identify the lncRNA MeXis as an amplifier of LXR-dependent transcription of the gene Abca1, which is critical for regulation of cholesterol efflux...
March 2018: Nature Medicine
https://www.readbyqxmd.com/read/29250691/nephrotic-syndrome-secondary-to-amyloidosis-in-a-patient-with-monoclonal-gammopathy-with-renal-significance-mgrs
#6
Andrei Niculae, Ileana Peride, Vlad Vinereanu, Daniela Rădulescu, Ovidiu Gabriel Bratu, Bogdan Florin Geavlete, Ionel Alexandru ChecheriŢă
Monoclonal gammopathy with renal significance (MGRS) is a relative new-described entity, diagnosed especially in older patients and deriving from the group with monoclonal gammopathy of undetermined significance (MGUS). Various renal lesions may arise in MGRS, according to the ultrastructural characteristics of the monoclonal immunoglobulin deposition in the kidney, from proliferative glomerulopathies and amyloidosis to light chain proximal tubulopathy and crystal-storing histiocytosis. Although both are considered premalign or non-malignant hematological conditions, kidney involvement in MGRS aggravates the prognosis of the patients and need to be treated aggressively...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/29194778/a-historical-perspective-on-milestones-in-multiple-myeloma-research
#7
REVIEW
Domenico Ribatti
The first well-documented case of multiple myeloma was reported in 1844 by Samuel Solly. In this article, the author presents a historical review of the disease. In particular, the review is focused on the main steps, including the definition of Bence Jones proteinuria, the characterization of tumoral plasma cells and serum globulins, and the fundamental contribution of Jan Waldenstrom. Finally, treatment of multiple myeloma, as well as the development of new agents, is discussed.
March 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29159010/multiple-myeloma-presenting-as-acute-renal-failure-in-the-absence-of-other-characteristic-features
#8
Zachary N Gastelum, Diana M Biggs, Aaron Scott
This case report describes a 54-year-old, asymptomatic man who presented with hyperkalemia on routine lab testing who was later found to have acute renal failure, unresponsive to fluid resuscitation, with minimal improvement after hemodialysis. After a comprehensive evaluation ruled out common causes of acute renal failure, the patient underwent testing with a bone survey, urine protein electrophoresis (UPEP), serum protein electrophoresis (SPEP), and immunoelectrophoresis for suspected plasma cell dyscrasia and received plasmapheresis for hyperviscosity syndrome and nephrotoxicity, which resulted in improved renal function...
September 20, 2017: Curēus
https://www.readbyqxmd.com/read/29114293/solitary-giant-extradural-plasmacytoma
#9
H Raghavendra, M Dilip Kumar, Manas Panigraghi, Shailaja M Reddy
Solitary plasmacytoma of the skull is very rare, and only a few cases have been reported in the literature. It remains controversial whether solitary plasmacytoma of the skull is essentially identical with solitary plasmacytoma of bone or not. Solitary plasmacytoma of bone including solitary plasmacytoma of the skull is characterized by a radiologically solitary bone lesion, neoplastic plasma cells in the biopsy specimen, fewer than 5% plasma cells in bone marrow, <2.0 g/dl monoclonal protein in the serum when present and negative urine test for Bence Jones protein (monoclonal light chain)...
October 2017: Asian Journal of Neurosurgery
https://www.readbyqxmd.com/read/29093408/the-long-term-outcomes-after-vad-plus-sct-therapy-in-a-patient-with-al-amyloidosis-and-severe-factor-x-deficiency
#10
Dosuke Iwadate, Eiko Hasegawa, Junichi Hoshino, Noriko Hayami, Keiichi Sumida, Masayuki Yamanouchi, Akinari Sekine, Masahiro Kawada, Rikako Hiramatsu, Tatsuya Suwabe, Naoki Sawa, Mitsuhiro Yuasa, Atsushi Wake, Takeshi Fujii, Kenichi Ohashi, Kenmei Takaichi, Yoshifumi Ubara
A 55-year-old man was admitted to our institute to undergo evaluation for proteinuria (5.4 g/day) with lambda-type Bence-Jones protein (BJP). Primary amyloid light chain (AL) amyloidosis and acquired factor X deficiency were diagnosed. High-dose melphalan combined with autologous stem cell transplantation was performed. After three years, the patient's proteinuria normalized, he was negative for urinary BJP, and his factor X activity improved to 105%. Serial renal biopsy showed no progression of amyloid deposition at a biopsy after 5 years, but showed a slight increase in the amyloid deposition after 11 years...
March 1, 2018: Internal Medicine
https://www.readbyqxmd.com/read/28916410/kinetic-stability-and-sequence-structure-studies-of-urine-derived-bence-jones-proteins-from-multiple-myeloma-and-light-chain-amyloidosis-patients
#11
Luis M Blancas-Mejía, Emily B Martin, Angela Williams, Jonathan S Wall, Marina Ramirez-Alvarado
It is now accepted that the ability of a protein to form amyloid fibrils could be associated both kinetic and thermodynamic protein folding parameters. A recent study from our laboratory using recombinant full-length (encompassing the variable and constant domain) immunoglobulin light chains found a strong kinetic control of the protein unfolding for these proteins. In this study, we are extending our analysis by using urine-derived Bence Jones proteins (BJPs) from five patients with light chain (AL) amyloidosis and four patients with multiple myeloma (MM)...
November 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28856420/iodine-based-contrast-media-multiple-myeloma-and-monoclonal-gammopathies-literature-review-and-esur-contrast-media-safety-committee-guidelines
#12
Fulvio Stacul, Michele Bertolotto, Henrik S Thomsen, Gabriele Pozzato, Donatella Ugolini, Marie-France Bellin, Georg Bongartz, Olivier Clement, Gertraud Heinz-Peer, Aart van der Molen, Peter Reimer, Judith A W Webb
OBJECTIVES: Many radiologists and clinicians still consider multiple myeloma (MM) and monoclonal gammopathies (MG) a contraindication for using iodine-based contrast media. The ESUR Contrast Media Safety Committee performed a systematic review of the incidence of post-contrast acute kidney injury (PC-AKI) in these patients. METHODS: A systematic search in Medline and Scopus databases was performed for renal function deterioration studies in patients with MM or MG following administration of iodine-based contrast media...
February 2018: European Radiology
https://www.readbyqxmd.com/read/28845377/an-extremely-rare-manifestation-of-multiple-myeloma-an-immunoglobulin-d-secreting-testicular-plasmacytoma
#13
Ashish Sharma, Tina Binazir, Alexandre Sintow, Chi Chan Lee, Sameer Shaharyar, Jason Tache
Multiple myelomas (MM) of the immunoglobulin D (IgD) subtype is rare amongst plasma cell malignancies. It can present a diagnostic challenge because of the low amount of immunoglobulin in the serum. The amount of monoclonal (M)-protein is often undetectable on electrophoresis. Historically, survival in these patients was typically shorter compared to the immunoglobulin A (IgA) and immunoglobulin G (IgG) subtypes due to advanced disease upon presentation. With the advent of better diagnostic techniques, the prognosis of this disease is changing...
June 27, 2017: Curēus
https://www.readbyqxmd.com/read/28799534/cutaneous-plasmacytosis-a-rare-entity-with-unique-presentation
#14
Subhra Dhar, Lalthleng Liani, Kamlakar Patole, Sandipan Dhar
Primary cutaneous plasmacytosis is a rare cutaneous disorder with extensive cutaneous plaques/papules mainly on the trunk and face. Cases have mostly been documented from Japan. We present here a rare case of cutaneous plasmacytosis from India of Mongolian descent. This 50-year-old female from Mizoram had extensive maculo-papular violaceous plaques distributed on the face, axillae, trunk and lower extremities. Initial and repeat skin biopsy revealed dense perivascular and periadnexal mature plasma cells. She also had lymphadenopathy...
August 9, 2017: Indian Journal of Dermatology, Venereology and Leprology
https://www.readbyqxmd.com/read/28798722/autonomic-neuropathy-and-albuminocytologic-dissociation-in-cerebrospinal-fluid-as-the-presenting-features-of-primary-amyloidosis-a-case-report
#15
Jingjing Li, Yi Li, Hongbing Chen, Shihui Xing, Huiyu Feng, Dawei Liu, Dilong Wang, Jinsheng Zeng, Yuhua Fan
OBJECTIVE: Primary amyloidosis is a disease with a poor prognosis and multi-organ involvement. Here, we report the clinical and pathological features of a patient with primary amyloidosis featuring autonomic neuropathy as the initial symptom and albuminocytologic dissociation in the cerebrospinal fluid (CSF). METHODS: The patient was a 60-year-old Chinese male with numbness, orthostatic hypotension, and gastrointestinal symptoms. For diagnosis, we performed an electromyogram (EMG), lumbar puncture, Bence Jones protein urine test, serum electrophoresis blood test, sural nerve and rectal membrane biopsies, transthyretin (TTR) gene sequencing, and bone marrow puncture...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28770116/cisplatin-induced-nephrotoxicity-and-hiv-associated-nephropathy-mimickers-of-myeloma-like-cast-nephropathy
#16
Muhammad Siddique Khurram, Ahmed Alrajjal, Warda Ibrar, Jacob Edens, Umer Sheikh, Ameer Hamza, Hong Qu
Myeloma cast nephropathy is an obstructing disorder of renal tubules, caused by precipitation of Bence Jones proteins. Myeloma-like cast nephropathy (MLCN) has been reported in the literature to occur in various primary renal and nonrenal diseases. We present a series of three rare cases of cast nephropathy, two of which are HIV patients, and the third patient is receiving cisplatin-based chemotherapy. However, in all three patients plasma cell dyscrasia has been ruled out. A 30-year-old male was admitted to the hospital with facial cellulitis...
2017: Case Reports in Nephrology
https://www.readbyqxmd.com/read/28694632/late-onset-familial-amyloidotic-polyneuropathy-with-bence-jones-proteinuria-and-cardiomyopathy
#17
Sira Carrasco García de León, Amalia Hernández González, Carmen Orellana Alonso, Laura Burriel Lobo
Familial amyloidotic polyneuropathy is a genetically determined disease characterized by deposition of an anomalous transthyretin. A high index of suspicion is needed for this multisymptomatic and lethal disease to be diagnosed. The patient was a 70-year-old male examined due to hypesthesia in the hands and feet, plus difficulty walking. A neurophysiological study delivered the diagnosis of axonal sensorimotor polyneuropathy. He later developed cardiac symptoms and diarrhea. Urine laboratory analyses revealed a monoclonal spike of light chains (kappa)...
July 2017: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/28544666/identifying-target-reference-points-for-harvesting-assessment-limited-wildlife-populations-a-case-study
#18
Bryan S Stevens, James R Bence, William F Porter, Michael L Jones
Identifying appropriate strategies for sustainable harvest is a challenge for many terrestrial vertebrate species because of uncertain system dynamics, limited data to inform population models, and potentially conflicting objectives that seek to harvest and maintain populations at desirable levels. The absence of monitoring and assessment infrastructure needed to regularly estimate abundance accentuates this challenge for many species, and limits application of rigorous state-dependent frameworks for decision making that are commonly advocated in natural resource management...
September 2017: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/28278719/restoration-of-renal-function-in-patients-with-newly-diagnosed-multiple-myeloma-is-not-associated-with-improved-survival-a-population-based-study
#19
Joost C de Vries, Berdien Oortgiesen, Marc H Hemmelder, Eric van Roon, Robby E Kibbelaar, Nic Veeger, Mels Hoogendoorn
Renal impairment (RI) in patients with multiple myeloma (MM) is associated with poor prognosis. In this population-based cohort study, we assessed the effects of renal response, evaluated according to the IMWG-criteria, on overall survival (OS) in patients with newly diagnosed MM with RI at presentation. All included patients were diagnosed between January 2005 and January 2014 with MM and RI in Friesland, a province of the Netherlands. Of the 131 included patients, 61% achieved renal response. Using a time-varying exposure Cox model, no difference in OS between renal response and non-response was observed (HR = 1...
September 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28202864/clinical-presentation-of-tubulointerstitial-nephritis-caused-by-amyloid-light-chain-amyloidosis-in-a-patient-with-sj%C3%A3-gren-s-syndrome
#20
Reiko Inoue, Yoshihide Fujigaki, Kana Kobayashi, Yoshifuru Tamura, Tatsuru Ota, Shigeru Shibata, Tsuyoshi Ishida, Fukuo Kondo, Yutaka Yamaguchi, Shunya Uchida
We report a 70-year-old woman with Sjögren's syndrome who had severe renal dysfunction with mild proteinuria and elevated urinary low-molecular-weight proteins. Based on these clinical presentations, interstitial nephritis due to Sjögren's syndrome was strongly suspected. Unexpectedly, renal pathology revealed amyloid light-chain (AL) lambda-type depositions predominantly in the vasculatures with severe tubulointerstitial damage. Concentrated urine immunofixation was positive for Bence Jones lambda-type monoclonal proteins...
2017: Internal Medicine
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