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Experimental Hematology & Oncology

Stefan S Schönsteiner, Heidi Bauder Mißbach, Axel Benner, Silja Mack, Thomas Hamel, Michael Orth, Bernhard Landwehrmeyer, Sigurd D Süßmuth, Carolin Geitner, Regine Mayer-Steinacker, Anneliese Riester, Andrea Prokein, Elfriede Erhardt, Jelena Kunecki, Anna M Eisenschink, Rainer Rawer, Hartmut Döhner, Elisabeth Kirchner, Richard F Schlenk
BACKGROUND: Chemotherapy-induced polyneuropathy (CIPN) is a common toxicity after chemotherapy, immunomodulatory drugs or proteasome inhibitors, which is difficult to treat and may also have impact on quality of life. The objective of the study was to evaluate whole-body vibration (WBV) on the background of an integrated program (IP) including massage, passive mobilization and physical exercises on CIPN. PATIENTS AND METHODS: In an exploratory phase-2 study patients with CIPN (NCI CTC grade 2/3) were randomized for WBV plus IP (experimental) to IP alone (standard)...
2017: Experimental Hematology & Oncology
Gabriela Andries, Michael Karass, Srikanth Yandrapalli, Katherine Linder, Delong Liu, John Nelson, Rahul Pawar, Savneek Chugh
BACKGROUND: Atypical hemolytic uremic syndrome is a rare disorder which is known to cause acute thrombotic microangiopathy during pregnancy with poor maternal and fetal outcomes. Atypical hemolytic uremic syndrome is caused mostly by dysregulation of alternative complement pathway secondary to genetic mutations. Most of the cases reported have been in the post-partum period. We report a rare case of a patient who presents with thrombotic microangiopathy in the first trimester of her eleventh pregnancy and was successfully treated with eculizumab...
2017: Experimental Hematology & Oncology
Julie Støve Bødker, Marianne Tang Severinsen, Tarec Christoffer El-Galaly, Rasmus Froberg Brøndum, Maria Bach Laursen, Steffen Falgreen, Mette Nyegaard, Alexander Schmitz, Lasse Hjort Jakobsen, Anna Amanda Schönherz, Hanne Due, Linn Reinholdt, Martin Bøgsted, Karen Dybkær, Hans Erik Johnsen
BACKGROUND: The concept of precision medicine in cancer includes individual molecular studies to predict clinical outcomes. In the present N = 1 case we retrospectively have analysed lymphoma tissue by exome sequencing and global gene expression in a patient with unexpected long-term remission following relaps. The goals were to phenotype the diagnostic and relapsed lymphoma tissue and evaluate its pattern. Furthermore, to identify mutations available for targeted therapy and expression of genes to predict specific drug effects by resistance gene signatures (REGS) for R-CHOP as described at http://www...
2017: Experimental Hematology & Oncology
Natalia-Del Pilar Vanegas, Jean-Paul Vernot
BACKGROUND: Leukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells. METHODS: A leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line...
2017: Experimental Hematology & Oncology
Michele Moschetta, Gabriel Mak, Joana Hauser, Catriona Davies, Mario Uccello, Hendrik-Tobias Arkenau
BACKGROUND: Targeting BRAF V600E mutation has been proven effective in the treatment of several types of cancer. In endometrial adenocarcinoma, the BRAF V600E mutation has been rarely reported. Whether targeting BRAF oncogene may represent a plausible therapeutic strategy for the rare patients with BRAF-mutated endometrial cancer remains to be ascertained in prospective studies. CASE PRESENTATION: We report herein the case of a heavily pre-treated patient with recurrent microsatellite instability high (MSI-H) BRAF V600E mutated endometrial adenocarcinoma, which was successfully treated with the V600E targeting agent dabrafenib...
2017: Experimental Hematology & Oncology
Ningfei An, Bo Cen, Houjian Cai, Jin H Song, Andrew Kraft, Yubin Kang
BACKGROUND: Receptor tyrosine kinase, c-Kit (CD117) plays a pivotal role in the maintenance and expansion of hematopoietic stem/progenitor cells (HSPCs). Additionally, over-expression and/or mutational activation of c-Kit have been implicated in numerous malignant diseases including acute myeloid leukemia. However, the translational regulation of c-Kit expression remains largely unknown. METHODS AND RESULTS: We demonstrated that loss of Pim1 led to specific down-regulation of c-Kit expression in HSPCs of Pim1(-/-) mice and Pim1(-/-)2(-/-)3(-/-) triple knockout (TKO) mice, and resulted in attenuated ERK and STAT3 signaling in response to stimulation with stem cell factor...
2016: Experimental Hematology & Oncology
Shuyong Wei, Kankan Wang
Long noncoding RNAs (lncRNAs) have emerged as a class of pivotal regulators of gene expression. Recent studies have shown that lncRNAs contribute to the initiation, maintenance, and development of acute myeloid leukemia (AML). In this review, we summarize the current knowledge of the lncRNAs that play critical roles in AML. We first briefly describe the characteristics of lncRNAs, and then focus on their regulatory roles in AML, including the modulation of differentiation, proliferation, cell cycle, and apoptosis...
2015: Experimental Hematology & Oncology
Ibrahim Fanous, Patrick Dillon
Breast cancer is the most frequent cause of cancer of women in much of the world. In countries with screening programs, breast cancer is often detected before clinical symptoms are apparent, but occasionally the occurrence of a paraneoplastic syndrome precedes the identification of cancer. In breast cancer, there are known to be paraneoplastic endocrine syndromes and neurologic syndromes. The neurologic syndromes are often hard to identify and treat. The neurologic syndromes associated with breast cancer include cerebellar degeneration, sensorimotor neuropathy, retinopathy, stiff-persons syndrome, encephalitis, and opsoclonus-myoclonus...
2015: Experimental Hematology & Oncology
Magdalena Kovacsovics-Bankowski, Todd W Kelley, Olga Efimova, Soo Jin Kim, Andrew Wilson, Sabina Swierczek, Josef Prchal
BACKGROUND: Pegylated-interferon alpha (PegINFα) treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) has resulted in long-term clinical response, decreased JAK2(V617F) allelic burden and restoration of polyclonal hematopoiesis. The mechanisms of the beneficial effects of PegINFα are not clear, but available evidence suggests direct suppression of JAK2-mutated clone, induction of dormant stem cells to proliferation, and augmentation of an immune effect against PV and ET clones...
2015: Experimental Hematology & Oncology
Joseph M Wu, Ardalan Oraee, Barbara B Doonan, John T Pinto, Tze-Chen Hsieh
BACKGROUND: The NAD(P)H: quinone oxidoreductase (NQO1) confers protection against semiquinones and also elicits oxidative stress. The C609T polymorphism of the NQO1 gene, designated NQO1*2, significantly reduces its enzymatic activity due to rapid degradation of protein. Since down regulation of NQO1 mRNA expression correlates with increased susceptibility for developing different types of cancers, we investigated the link between leukemia and the NQO1*2 genotype by mining a web-based microarray dataset, ONCOMINE...
2015: Experimental Hematology & Oncology
Zihai Li, Delong Liu
No abstract text is available yet for this article.
2015: Experimental Hematology & Oncology
Hanna Grauers Wiktorin, Tina Nilsson, Ann Jansson, Lars Palmqvist, Anna Martner
BACKGROUND: Acute myeloid leukemia (AML) carrying nucleophosmin 1 (NPM1) mutations (NPMc(+)) is regarded as a separate entity of myeloid neoplasms due to its distinct biological and clinical features. However, NPMc(+) alone displays low leukemogenic activity and cooperating events appear crucial for AML to develop. Dysregulation of homeobox genes, such as HOXA9 and MEIS1, is a common transcriptional signature of NPMc(+) AML. Furthermore, the pathogenic role for NPMc(+) in AML remains incompletely understood...
2015: Experimental Hematology & Oncology
David Berz, Victoria M Raymond, Jordan H Garst, Mark G Erlander
BACKGROUND: The increasing understanding of non-small cell lung cancer (NSCLC) biology over the last two decades has led to the identification of multiple molecular targets. This led to the development of multiple targeted therapies in the primary and secondary resistance setting and the epidermal growth factor receptor (EGFR) gene remains the most frequently observed molecular target in NSCLC. Tissue biopsies remain the standard for the identification of such EGFR mutations. Obtaining serial tissue biopsies, especially in the secondary resistance setting is associated with multiple medical and logistical challenges...
2015: Experimental Hematology & Oncology
Eddy C Hsueh, Kalyan C Gorantla
With the rapid succession of new effective agents for melanoma in the recent years, the paradigm for treatment of metastatic melanoma is changing. The success of combining multiple effective agents compared with outcomes of monotherapy also brings increasing complexity in the treatment algorithm for various subsets of metastatic melanoma patients. We reviewed the recent reports on novel melanoma therapy to shed light on rational decision-making in treating these patients.
2015: Experimental Hematology & Oncology
Suleiman Al-Hammadi, Saeeda Almarzooqi, Alia Albawardi, Abdul-Kader Souid
BACKGROUND: Blocking mTOR (molecular target of rapamycin) by sirolimus has been shown to suppress cellular respiration. The bearing of this impaired cellular bioenergetics on the mode-of-action of mTOR inhibitors has yet to be illustrated. METHODS: This study investigated in vitro effects of several molecularly-targeted therapies on O2 consumption in thymic fragments from C57BL/6 mice. RESULTS: Thymocyte respiration (µM O2 min(-1) mg(-1)) was reduced by sirolimus and everolimus (p ≤ 0...
2015: Experimental Hematology & Oncology
Bernardo López-Andrade, Francesca Sartori, Antonio Gutiérrez, Lucia García, Vanesa Cunill, María Antonia Durán, Antonia Sampol, Marta Bernués, Julio Iglesias, Rafael Ramos, Josep Lladó, María Sánchez, Juan Carlos Amat, Jordi Martínez-Serra
B Acute Lymphoblastic leukemia (B-ALL) with Philadelphia chromosome (Ph') is a neoplasm of lymphoblast committed to the B cell lineage. The clinical presentation of B-ALL Ph'+ is similar to B-ALL, but is more common in adults than in children. The e1a3 rare variant is produced by the fusion of BCR exon 1 to ABL exon 3. The presence of this translocation has been associated with good disease outcome for chronic myeloid leukemia in a very small series of only 5 cases; there is no such evidence for B-ALL. We report two new cases of B-ALL Ph+ with the rare e1a3 fusion transcript...
2015: Experimental Hematology & Oncology
Katherine Linder, Deepthi Gandhiraj, Madhura Hanmantgad, Karen Seiter, Delong Liu
BACKGROUND: The current standard of care for relapsed and refractory acute lymphoblastic leukemia (ALL) is combination chemotherapy. CASE PRESENTATION: We report a case of highly refractory ALL who was treated with blinatumomab. The ALL in this patient relapsed within a month after completion of hyperCVAD regimen and was refractory to high dose mitoxantrone/cytarabine and CLAG regimens. CONCLUSION: This highly refractory pre-B Ph(-) ALL was induced to complete remission after one course of single agent blinatumomab...
2015: Experimental Hematology & Oncology
Tao Liu, Xiaobo Li, Shuo You, Soumitra S Bhuyan, Lei Dong
AMD3100, also known as plerixafor, was originally developed as an anti-human immunodeficiency virus (HIV) drug, and later characterized as a C-X-C chemokine receptor type 4 (CXCR4) antagonist. Previous reviews have focused on the application of AMD3100 in the treatment of HIV, but a comprehensive evaluation of AMD3100 in the treatment of leukemia, solid tumor, and diagnosis is lacking. In this review, we broadly describe AMD3100, including the background, functional mechanism and clinical applications. Until the late 1990s, CXCR4 was known as a crucial factor for hematopoietic stem and progenitor cell (HSPC) retention in bone marrow...
2015: Experimental Hematology & Oncology
Lisa Repsold, Etheresia Pretorius, Annie Margaretha Joubert
BACKGROUND: Platelets are known contributors to the vascularization, metastasis and growth of tumors. Upon their interaction with cancer cells they are activated resulting in degranulation and release of constituents. Since the apoptotic- and autophagic effects of 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) has been shown to occur in vitro and this compound was designed to bind to carbonic anhydrase II (CAII), the possible occurrence of these cell death mechanisms in platelets as circulatory components, is of importance...
2015: Experimental Hematology & Oncology
Jingchen Shao, Susann Li, Lars Palmqvist, Linda Fogelstrand, Stella Y Wei, Kiran Busayavalasa, Kui Liu, Viktor M Liu
PTEN acts as a phosphatase for PIP3 and negatively regulates the PI3K/AKT pathway, and p27(KIP1) is a cyclin-dependent kinase inhibitor that regulates the G1 to S-phase transition by binding to and regulating the activity of cyclin-dependent kinases. Genetic alterations of PTEN or CDKN1B (p27(KIP1)) are common in hematological malignancies. To better understand how mutations in these two genes might cooperate in leukemogenesis, we inactivated both genes in the hematological compartment in mice. Here, we show that the combined inactivation of Pten and Cdkn1b results in a more severe myeloproliferative neoplasm phenotype associated with lower hemoglobin, enlarged spleen and liver, and shorter lifespan compared to inactivation of Pten alone...
2015: Experimental Hematology & Oncology
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