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https://www.readbyqxmd.com/read/29141942/frailty-and-the-management-of-hematologic-malignancies
#1
Gregory A Abel, Heidi D Klepin
The majority of blood cancers occur in the elderly. This fact conspires with an aging population in many countries to make rigorous assessment for frailty increasingly important for hematologic oncologists. In this review, we first define frailty and its relevance for patients with hematologic malignancy. Next, we review current data regarding the impact of domains of frailty on outcomes for blood cancers including myelodysplastic syndromes (MDS), acute leukemia, non-Hodgkin lymphomas such as chronic lymphocytic leukemia (CLL), and multiple myeloma...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29134229/decursin-and-decursinol-angelate-molecular-mechanism-and-therapeutic-potential-in-inflammatory-diseases
#2
REVIEW
Adeeb Shehzad, Sajida Parveen, Munibah Qureshi, Fazli Subhan, Young Sup Lee
Epidemiological studies have shown that inflammation plays a critical role in the development and progression of various chronic diseases, including cancers, neurological diseases, hepatic fibrosis, diabetic retinopathy, and vascular diseases. Decursin and decursinol angelate (DA) are pyranocoumarin compounds obtained from the roots of Angelica gigas. Several studies have described the anti-inflammatory effects of decursin and DA. Decursin and DA have shown potential anti-inflammatory activity by modulating growth factors such as vascular endothelial growth factor, transcription factors such as signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells, cellular enzymes including matrix metalloproteinases cyclooxygenase, and protein kinases such as extracellular receptor kinase, phosphatidylinositol-3-kinase, and protein kinase C...
November 13, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29133623/immu-140-a-novel-sn-38-antibody-drug-conjugate-targeting-hla-dr-mediates-dual-cytotoxic-effects-in-hematological-cancers-and-malignant-melanoma
#3
Thomas M Cardillo, Serengulam V Govindan, Maria B Zalath, Diane L Rossi, Yang Wang, Chien-Hsing Chang, David M Goldenberg
HLA-DR is a member of the MHC class II antigen family expressed on hematological and solid tumors.  Antibodies directed against HLA-DR have demonstrated some clinical success, but toxicities limited development.  IMMU-140 is an anti-HLA-DR antibody-drug conjugate comprised of the active metabolite of irinotecan, SN-38, conjugated to a humanized anti-HLA-DR IgG4 antibody (IMMU-114); the IgG4 naked antibody is devoid of immune functions. Our aim was to determine if SN-38, the metabolite of a drug not commonly used in hematopoietic cancers, would be effective and safe when targeted to HLA-DR-expressing tumors...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29118010/cd38-antibodies-in-multiple-myeloma-back-to-the-future
#4
Niels W C J van de Donk, Paul G Richardson, Fabio Malavasi
CD38 is highly and uniformly expressed on MM cells, and at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of non-hematopoietic origin. CD38 is a transmembrane glycoprotein with ectoenzymatic activity, and also functions as receptor and adhesion molecule. Altogether, this has triggered the development of several CD38 antibodies including daratumumab (fully human), isatuximab (chimeric), and MOR202 (fully human). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38-positive immunesuppressor cells...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29118005/redirecting-t-cells-to-hematological-malignancies-with-bispecific-antibodies
#5
Mireya Paulina Velasquez, Challice L Bonifant, Stephen Gottschalk
There is a need to improve outcomes for patients with recurrent and/or refractory hematological malignancies. Immunotherapy holds the promise to meet this need since it does not rely on the cytotoxic mechanism of conventional therapies. Among different forms of immunotherapy, redirecting T cells to hematological malignancies with bispecific antibodies (BsAbs) is an attractive strategy. BsAbs are an 'off-the-shelf' product that is easily scalable in contrast to adoptive T-cell therapies. Among these, the bispecific T-cell engager (BiTE) blinatumomab has emerged as the most successful BsAb to date...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29108331/the-role-of-frontline-autologous-stem-cell-transplantation-for-primary-plasma-cell-leukemia-a-retrospective-multicenter-study-kmm160
#6
Sung-Hoon Jung, Je-Jung Lee, Kihyun Kim, Cheolwon Suh, Dok Hyun Yoon, Chang-Ki Min, Sang Kyun Sohn, Chul Won Choi, Ho Sup Lee, Hyo Jung Kim, Ho-Jin Shin, Soo-Mee Bang, Sung-Soo Yoon, Seong Kyu Park, Ho-Young Yhim, Min Kyoung Kim, Jae-Cheol Jo, Yeung-Chul Mun, Jae Hoon Lee, Jin Seok Kim
Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell neoplasm, with rapidly progressing clinical course. We evaluated the treatment status and survival outcomes of 69 Korean patients with pPCL. Of them, 59 patients were treated; 15 (25.4%) were treated initially with novel agent-based regimens with upfront autologous stem cell transplantation (ASCT), 7 (11.9%) with conventional chemotherapy with upfront ASCT, 21 (35.6%) with novel agent-based regimens only, and 16 (27.1%) were treated with conventional chemotherapy alone...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104288/combination-of-a-novel-hdac-6-inhibitor-acy-241-and-anti-pd-l1-antibody-enhances-anti-tumor-immunity-and-cytotoxicity-in-multiple-myeloma
#7
A Ray, D S Das, Y Song, T Hideshima, Y-T Tai, D Chauhan, K C Anderson
Leukemia accepted article preview online, 06 November 2017. doi:10.1038/leu.2017.322.
November 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29104260/antimicrobial-and-anti-proliferative-effects-of-skin-mucus-derived-from-dasyatis-pastinaca-linnaeus-1758
#8
Virginia Fuochi, Giovanni Li Volti, Giuseppina Camiolo, Francesco Tiralongo, Cesarina Giallongo, Alfio Distefano, Giulio Petronio Petronio, Ignazio Barbagallo, Maria Viola, Pio Maria Furneri, Michelino Di Rosa, Roberto Avola, Daniele Tibullo
Resistance to chemotherapy occurs in various diseases (i.e., cancer and infection), and for this reason, both are very difficult to treat. Therefore, novel antimicrobial and chemotherapic drugs are needed for effective antibiotic therapy. The aim of the present study was to assess the antimicrobial and anti-proliferative effects of skin mucus derived from Dasyatis pastinaca (Linnaeus, 1758). Our results showed that skin mucus exhibited a significant and specific antibacterial activity against Gram-negative bacteria but not against Gram-positive bacteria...
November 1, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29099494/prognostic-value-of-antigen-expression-in-multiple-myeloma-a-pethema-gem-study-on-1-265-patients-enrolled-in-four-consecutive-clinical-trials
#9
P Arana, B Paiva, M-T Cedena, N Puig, L Cordon, M-B Vidriales, N C Gutierrez, F Chiodi, L Burgos, L-L Anglada, J Martinez-Lopez, M-T Hernandez, A-I Teruel, M Gironella, M-A Echeveste, L Rosiñol, R Martinez, A Oriol, J De la Rubia, A Orfao, J Blade, J-J Lahuerta, M-V Mateos, J F S Miguel
Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Amongst different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly-diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols...
November 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29098502/cadmium-pyrithione-suppresses-tumor-growth-in-vitro-and-in-vivo-through-inhibition-of-proteasomal-deubiquitinase
#10
Xin Chen, Jinjie Wu, Qianqian Yang, Xiaolan Zhang, Peiquan Zhang, Siyan Liao, Zhimin He, Xuejun Wang, Chong Zhao, Jinbao Liu
The ubiquitin-proteasome system (UPS) is indispensable to the protein quality control in eukaryotic cells. Due to the remarkable clinical success of using proteasome inhibitors for clinical treatment of multiple myeloma, it is anticipated that targeting the UPS upstream of the proteasome step be an effective strategy for cancer therapy. Deubiquitinases (DUB) are proteases that remove ubiquitin from target proteins and therefore regulate multiple cellular processes including some signaling pathways altered in cancer cells...
November 3, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29089645/identification-and-characterization-of-hla-a24-specific-xbp1-cd138-syndecan-1-and-cs1-slamf7-peptides-inducing-antigens-specific-memory-cytotoxic-t-lymphocytes-targeting-multiple-myeloma
#11
J Bae, T Hideshima, G L Zhang, J Zhou, D B Keskin, N C Munshi, K C Anderson
XBP1 (X-box binding protein 1), CD138 (Syndecan-1), and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29076054/prevalence-of-use-and-cost-of-biological-drugs-for-cancer-treatment-a-5-year-picture-from-southern-italy
#12
Simona Lucchesi, Ilaria Marcianò, Paolo Panagia, Rosanna Intelisano, Maria Pia Randazzo, Carmela Sgroi, Giuseppe Altavilla, Mariacarmela Santarpia, Vincenzo Adamo, Tindara Franchina, Francesco Ferraù, Paolina Reitano, Gianluca Trifirò
BACKGROUND AND OBJECTIVES: Considering the clinical and economic burden of biological drugs in cancer treatment, it is necessary to explore how these drugs are used in routine care in Italy and how they affect the sustainability of the National Health Services. This study aimed to investigate the prevalence of use and costs of biological drugs for cancer treatment in a general population of Southern Italy in the years 2010-2014. METHODS: This was a retrospective, observational study using data from the healthcare administrative databases of Messina Province for the years 2010-2014...
October 26, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29071527/-immuno-proteasomes-as-therapeutic-target-in-acute-leukemia
#13
Jacqueline Cloos, Margot Sf Roeten, Niels E Franke, Johan van Meerloo, Sonja Zweegman, Gertjan Jl Kaspers, Gerrit Jansen
The clinical efficacy of proteasome inhibitors in the treatment of multiple myeloma has encouraged application of proteasome inhibitor containing therapeutic interventions in (pediatric) acute leukemia. Here, we summarize the positioning of bortezomib, as first-generation proteasome inhibitor, and second-generation proteasome inhibitors in leukemia treatment from a preclinical and clinical perspective. Potential markers for proteasome inhibitor sensitivity and/or resistance emerging from leukemia cell line models and clinical sample studies will be discussed focusing on the role of immunoproteasome and constitutive proteasome (subunit) expression, PSMB5 mutations, and alternative mechanisms of overcoming proteolytic stress...
October 25, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29066491/igm-myeloma-with-plasma-cell-leukemia-case-report-and-literature-review
#14
Saurabh Chhabra, Sandeep Jain, Amanda Fowler, Valeriy Sedov, Amarendra K Neppalli, Cynthia A Schandl, John Lazarchick
IgM multiple myeloma (MM) is a rare entity representing approximately 0.5% of all MM. It should be distinguished from malignant neoplasms of B cells with plasmacytic differentiation such as Waldenstrom macroglobulinemia (WM) and marginal zone lymphoma with plasmacytic differentiation. Plasma cell leukemia (PCL) is a rare and aggressive variant of MM characterized by the presence of circulating plasma cells. We present a case report of a patient who presented with IgM MM in primary PCL phase with high-risk cytogenetics...
September 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/29064593/combination-therapy-incorporating-bcl-2-inhibition-with-venetoclax-for-the-treatment-of-refractory-primary-plasma-cell-leukemia-with-t-11-14
#15
Wilson I Gonsalves, Francis K Buadi, Shaji K Kumar
Primary plasma cell leukemia (pPCL) is the most aggressive form of the plasma cell (PC) malignancy, multiple myeloma (MM). It has been commonly associated with the presence of a chromosome translocation involving the immunoglobulin heavy chain (IgH) locus on 14q32, i.e. t (11;14). Results from early phase clinical trials utilizing the selective bcl-2 inhibitor, venetoclax, as a single agent in patients with relapsed MM have had remarkable efficacy among patients with t (11;14) abnormality. The present case demonstrates the ability of a combination regimen incorporating bcl-2 inhibition with daratumumab, bortezomib, venetoclax and dexamethasone to induce a rapid and very deep hematologic response in a pPCL patient with t (11;14), even in a setting of very refractory disease...
October 24, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29064484/jam-a-as-a-prognostic-factor-and-new-therapeutic-target-in-multiple-myeloma
#16
A G Solimando, A Brandl, K Mattenheimer, C Graf, M Ritz, A Ruckdeschel, T Stühmer, Z Mokhtari, M Rudelius, J Dotterweich, M Bittrich, V Desantis, R Ebert, P Trerotoli, M A Frassanito, A Rosenwald, A Vacca, H Einsele, F Jakob, A Beilhack
Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis...
September 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29061667/novel-yap1-activator-identified-by-transcription-based-functional-screen-limits-multiple-myeloma-growth
#17
Junichi Maruyama, Kazutoshi Inami, Fumiyoshi Michishita, Xinliang Jiang, Hiroaki Iwasa, Kentaro Nakagawa, Mari Ishigami-Yuasa, Hiroyuki Kagechika, Norio Miyamura, Jun Hirayama, Hiroshi Nishina, Daichi Nogawa, Kouhei Yamamoto, Yutaka Hata
Yes-associated protein 1 (YAP1) interacts with numerous transcription factors including TEA-domain family proteins (TEAD) and p73. YAP1 is negatively regulated by the tumor suppressor Hippo pathway. In human cancers, the deregulation of the Hippo pathway and YAP1 gene amplification lead to the activation of YAP1, which induces epithelial-mesenchymal transition (EMT) and drug resistance. YAP1 inhibitors are expected to be useful in cancer therapy. On the other hand, in certain cancers, YAP1 up-regulates p73-dependent gene transcription and behaves as a tumor suppressor...
October 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29061005/-clinical-application-value-of-peripheral-blood-diagnostic-report
#18
Y Xing, J Z Wang, C W Pu, C X Qu, K Shang, N Dong, P Wu, H F Wang
Objective: To explore the clinical application value of peripheral blood diagnostic report. Methods: 557 peripheral blood diagnostic reports were collected from Peking University First Hospital, YANDA LU DAOPEI Hospital and Beijing United Family Hospital. The results were analyzed and summarized according to different blood cell morphology character for the first time and review cases, respectively. Results: Two hundred and one samples from first time patients were found abnormal complete blood count or leukocyte differential count, they were summarized as anemia, anemia accompanied with leukopenia or thrombopenia, abnormal white blood cell count or leukocyte differential count and abnormal platelet count...
October 17, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29051895/chronic-lymphocytic-leukemia-a-rare-cause-of-pathological-fracture-of-the-femur
#19
Parita Soni, Nidhi Aggarwal, Anand Rai, Vivek Kumar, Kamholz Stephan, Yoon Taek, Kupfer Yizhak
The incidence rate of chronic lymphocytic leukemia (CLL) in the United States is approximately 0.005%; men are at slightly higher risk than women. Bony involvement or pathological fracture rarely occurs in CLL, and it may be the initial presentation. An 85-year-old woman presented with acute respiratory failure secondary to pneumonia. Symptomatology included dyspnea. She was found to have pathological fracture of the femur caused by CLL. The diagnosis of CLL had been made 6 years previously, but the patient had refused therapy...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29046749/an-unusual-case-of-chronic-lymphocytic-leukemia-multiple-myeloma-and-cardiac-amyloidosis
#20
Dongyan Liu, Hakim T Uqdah, Alisha D Gordy
Light chain amyloidosis has very rarely been reported in association with chronic lymphocytic leukemia (CLL). We reported on a 76-years-old female who presented with simultaneous kappa-restricted chronic lymphocytic leukemia (CLL) and a lambda-restricted multiple myeloma with plasma cells causing AL amyloidosis involving the heart. While monoclonal immunoglobulins occasionallyproduced by CLL have previously been implicated in AL amyloidosis, there only a few cases reported of AL amyloidosis resulting from a distinct plasma cell dyscrasia that is not clonally related to the concurrent CLL...
October 2017: Journal of Community Hospital Internal Medicine Perspectives
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