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https://www.readbyqxmd.com/read/30317726/-clinicopathologic-features-of-breast-lymphoma-in-core-needle-biopsy
#1
J Rao, M Ruan, B H Yu, X Q Li, W T Yang, R H Shui
Objective: To investigate the clinicopathologic features and differential diagnosis of breast lymphoma in core needle biopsy. Methods: Seventy-two cases of breast lymphoma in core needle biopsy between 2011 and 2016 were extracted from the pathology database of Fudan University Shanghai Cancer Center. The clinicopathologic features were analyzed. The histological diagnosis of the tumors was based on the WHO classifications of tumors of hematopoietic and lymphoid tissues. Immunohistochemistry and molecular methods were performed to detect related antigens and genes...
October 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/30262563/activina-a-new-leukemia-promoting-factor-conferring-migratory-advantage-to-b-cell-precursor-acute-lymphoblastic-leukemic-cells
#2
Federica Portale, Giulia Cricrì, Silvia Bresolin, Monica Lupi, Stefania Gaspari, Daniela Silvestri, Barbara Russo, Noemi Marino, Paolo Ubezio, Fabio Pagni, Patrizia Vergani, Geertruy Te Kronnie, Maria Grazia Valsecchi, Franco Locatelli, Carmelo Rizzari, Andrea Biondi, Erica Dander, Giovanna D'Amico
B-cell precursor-Acute Lymphoblastic Leukemia modulates the bone marrow niche to become leukemia-supporting and chemoprotective by reprogramming the stromal microenvironment. New therapies targeting the leukemia/stroma interplay can be instrumental to improve disease outcome. We identified ActivinA, a TGF-β family member, with a well-described promoting role in several solid malignancies, as a new potentially targetable leukemia-favoring factor. ActivinA resulted overexpressed in the leukemic bone marrow and its production was strongly induced in mesenchymal stromal cells after culture with leukemic cells...
September 27, 2018: Haematologica
https://www.readbyqxmd.com/read/30247803/characteristics-of-live-parameters-of-the-hs-5-human-bone-marrow-stromal-cell-line-cocultured-with-the-leukemia-cells-in-hypoxia-for-the-studies-of-leukemia-stroma-cross-talk
#3
Paulina Podszywalow-Bartnicka, Agata Kominek, Magdalena Wolczyk, Marta D Kolba, Julian Swatler, Katarzyna Piwocka
The unique bone marrow microenvironment is created by stromal cells and such physical conditions as hypoxia. Both hypoxia and interactions with stromal cells have a significant impact on the biology of leukemia cells, changing their sensitivity to antileukemic therapies. Thus, it is crucial to introduce biological systems, which enable the investigation of leukemia-stroma cross-talk and verification of novel therapies effectiveness under such bone marrow niche-mimicking conditions. Here, we have established an experimental setup based on the hypoxic co-culture of stromal cells with different cell lines derived from various leukemia patients...
July 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/30228947/imids-mobilize-acute-myeloid-leukemia-blasts-to-peripheral-blood-through-downregulation-of-cxcr4-but-fail-to-potentiate-arac-idarubicin-activity-in-preclinical-models-of-non-del5q-5q-aml
#4
Belen Lopez-Millan, Rafael Diaz de la Guardia, Heleia Roca-Ho, Eduardo Anguita, Abul B M M K Islam, Damia Romero-Moya, Cristina Prieto, Francisco Gutierrez-Agüera, Jose Antonio Bejarano-Garcia, Jose Antonio Perez-Simon, Paula Costales, Montse Rovira, Pedro Marín, Silvia Menendez, Mar Iglesias, Jose Luis Fuster, Alvaro Urbano-Ispizua, Fernando Anjos-Afonso, Clara Bueno, Pablo Menendez
Treatment for acute myeloid leukemia (AML) remains suboptimal and many patients remain refractory or relapse upon standard chemotherapy based on nucleoside analogs plus anthracyclines. The crosstalk between AML cells and the BM stroma is a major mechanism underlying therapy resistance in AML. Lenalidomide and pomalidomide, a new generation immunomodulatory drugs (IMiDs), possess pleiotropic anti-leukemic properties including potent immune-modulating effects and are commonly used in hematological malignances associated with intrinsic dysfunctional BM such as myelodysplastic syndromes and multiple myeloma...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/30210236/targeting-the-autophagy-in-bone-marrow-stromal-cells-overcomes-resistance-to-vorinostat-in-chronic-lymphocytic-leukemia
#5
Lu Ding, Wan Zhang, Lili Yang, Helene Pelicano, Kaiwen Zhou, Ran Yin, Ruibin Huang, Junyi Zeng
Background: The bone marrow microenvironment constitutes a sanctuary for leukemia cells. Recent evidence indicates that environment-mediated drug resistance arises from a reciprocal influence between tumor cells and the surrounding stroma. The present study aimed to investigate the effect of chronic lymphocytic leukemia (CLL) cells on the metabolism of bone marrow stroma, to determine the role of this metabolic change in the stroma in vorinostat resistance of CLL cells, and thus to assess a novel strategy to target stroma and achieve the maximum therapeutic effect of vorinostat...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29951568/osteoblast-sorting-and-intracellular-staining-of-cxcl12
#6
Weihuan Wang, Gurnoor Majihail, Cui Lui, Lan Zhou
Osteoblasts are bone marrow endosteum-lining niche cells playing important roles in the regulation of hematopoietic stem cells by secreting factors and cell adhesion molecules. Characterization of primary osteoblasts has been achieved through culture of outgrowth of collagenase treated bone. Immunophenotyping and flow-based analysis of long bone osteoblasts offer a simplified and rapid approach to characterize osteoblasts. We describe a modified procedure of isolating mouse bone marrow osteoblastic cells based on cell surface immunophenotyping...
May 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29927435/-the-morphological-and-molecular-biological-signs-of-impaired-endometrial-receptivity-in-infertility-in-women-suffering-from-external-genital-endometriosis
#7
N B Paramonova, E A Kogan, A V Kolotovkina, O V Burmenskaya
OBJECTIVE: To study endometrial receptivity in infertile women with external genital endometriosis (EGE). SUBJECTS AND METHODS: Clinical, morphological, immunohistochemical, and molecular genetic examinations of endometrial aspiration pipelle biopsy specimens obtained on days 22-24 of the menstrual cycle from 94 infertile women with endometriosis: 50 women with Stage I-II EGE and 44 women with ovarian endometrioid cysts (OEC). A control group consisted of 54 women with tubal peritoneal factor of infertility (TPFI) and a successful attempt at IVF...
2018: Arkhiv Patologii
https://www.readbyqxmd.com/read/29911998/hif2%C3%AE-in-the-uterine-stroma-permits-embryo-invasion-and-luminal-epithelium-detachment
#8
Leona Matsumoto, Yasushi Hirota, Tomoko Saito-Fujita, Norihiko Takeda, Tomoki Tanaka, Takehiro Hiraoka, Shun Akaeda, Hidetoshi Fujita, Ryoko Shimizu-Hirota, Shota Igaue, Mitsunori Matsuo, Hirofumi Haraguchi, Mayuko Saito-Kanatani, Tomoyuki Fujii, Yutaka Osuga
Although it has been reported that hypoxia inducible factor 2 α (Hif2a), a major transcriptional factor inducible by low oxygen tension, is expressed in the mouse uterus during embryo implantation, its role in pregnancy outcomes remains unclear. This study aimed to clarify functions of uterine HIF using transgenic mouse models. Mice with deletion of Hif2a in the whole uterus (Hif2a-uKO mice) showed infertility due to implantation failure. Supplementation with progesterone (P4) and leukemia inhibitory factor (LIF) restored decidual growth arrest and aberrant position of implantation sites in Hif2a-uKO mice, respectively, but did not rescue pregnancy failure...
July 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29911936/inhibition-of-the-raf-1-kinase-inhibitory-protein-rkip-by-locostatin-induces-cell-death-and-reduces-the-cxcr4-mediated-migration-of-chronic-lymphocytic-leukemia-cells
#9
Kyle Crassini, Tahni Pyke, Yandong Shen, William S Stevenson, Richard I Christopherson, Stephen P Mulligan, Oliver Giles Best
The Raf-1 kinase inhibitory protein (RKIP) is an important regulatory element in multiple signaling pathways, including MAPK-ERK1/2. We investigated whether targeted disruption of RKIP is a therapeutic option for chronic lymphocytic leukemia (CLL). The RKIP inhibitor locostatin-induced apoptosis of CLL cells, irrespective of poor prognostic indications or treatment history. Locostatin down-regulated MAPK-ERK1/2 and AKT phosphorylation, decreased expression of the chemokine receptor CXCR4 (p = .04) and reduced the migratory capacity of CLL cells toward stroma-derived factor 1α (SDF-1α, p = ...
June 18, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29861847/biological-and-metabolic-effects-of-iacs-010759-an-oxphos-inhibitor-on-chronic-lymphocytic-leukemia-cells
#10
Hima V Vangapandu, Brandon Alston, Joshua Morse, Mary L Ayres, William G Wierda, Michael J Keating, Joseph R Marszalek, Varsha Gandhi
Blood cells from patients with chronic lymphocytic leukemia (CLL) are replicationally quiescent but transcriptionally, translationally, and metabolically active. Recently, we demonstrated that oxidative phosphorylation (OxPhos) is a predominant pathway in CLL for energy production and is further augmented in the presence of the stromal microenvironment. Importantly, CLL cells from patients with poor prognostic markers showed increased OxPhos. From these data, we theorized that OxPhos can be targeted to treat CLL...
May 18, 2018: Oncotarget
https://www.readbyqxmd.com/read/29725010/a-retinoic-acid-dependent-stroma-leukemia-crosstalk-promotes-chronic-lymphocytic-leukemia-progression
#11
Diego Farinello, Monika Wozińska, Elisa Lenti, Luca Genovese, Silvia Bianchessi, Edoardo Migliori, Nicolò Sacchetti, Alessia di Lillo, Maria Teresa Sabrina Bertilaccio, Claudia de Lalla, Roberta Valsecchi, Sabrina Bascones Gleave, David Lligé, Cristina Scielzo, Laura Mauri, Maria Grazia Ciampa, Lydia Scarfò, Rosa Bernardi, Dejan Lazarevic, Blanca Gonzalez-Farre, Lucia Bongiovanni, Elias Campo, Andrea Cerutti, Maurilio Ponzoni, Linda Pattini, Federico Caligaris-Cappio, Paolo Ghia, Andrea Brendolan
In chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival, and expansion. However, the nature of the stromal cells and molecular pathways involved remain largely unknown. Here, we demonstrate that leukemic B lymphocytes induce the activation of retinoid acid synthesis and signaling in the microenvironment. Inhibition of RA-signaling in stromal cells causes deregulation of genes associated with adhesion, tissue organization and chemokine secretion including the B-cell chemokine CXCL13...
May 3, 2018: Nature Communications
https://www.readbyqxmd.com/read/29681510/germline-genetic-ikzf1-variation-and-predisposition-to-childhood-acute-lymphoblastic-leukemia
#12
Michelle L Churchman, Maoxiang Qian, Geertruy Te Kronnie, Ranran Zhang, Wenjian Yang, Hui Zhang, Tobia Lana, Paige Tedrick, Rebekah Baskin, Katherine Verbist, Jennifer L Peters, Meenakshi Devidas, Eric Larsen, Ian M Moore, Zhaohui Gu, Chunxu Qu, Hiroki Yoshihara, Shaina N Porter, Shondra M Pruett-Miller, Gang Wu, Elizabeth Raetz, Paul L Martin, W Paul Bowman, Naomi Winick, Elaine Mardis, Robert Fulton, Martin Stanulla, William E Evans, Mary V Relling, Ching-Hon Pui, Stephen P Hunger, Mignon L Loh, Rupert Handgretinger, Kim E Nichols, Jun J Yang, Charles G Mullighan
Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Here we report coding germline IKZF1 variation in familial childhood ALL and 0.9% of presumed sporadic B-ALL, identifying 28 unique variants in 45 children...
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29592525/meis1-is-specifically-upregulated-in-kidney-myofibroblasts-during-aging-and-injury-but-is-not-required-for-kidney-homeostasis-or-fibrotic-response
#13
Monica Chang-Panesso, Farid F Kadyrov, Flavia G Machado, Ashish Kumar, Benjamin D Humphreys
The homeobox transcription factor Meis1 is required for mammalian development, and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1 is known to be expressed in kidney stroma, but its function in kidney is undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in kidney development and disease and tested the hypothesis using cell lineage tracing and cell-specific Meis1 deletion in development, aging, and fibrotic disease. We observed strong expression of Meis1 in platelet-derived growth factor receptor-β-positive pericytes and perivascular fibroblasts, both in adult mouse kidney and to a lesser degree in human kidney...
August 1, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29580262/treatment-of-b-cell-precursor-acute-lymphoblastic-leukemia-with-the-galectin-1-inhibitor-ptx008
#14
Helicia Paz, Eun Ji Joo, Chih-Hsing Chou, Fei Fei, Kevin H Mayo, Hisham Abdel-Azim, Haike Ghazarian, John Groffen, Nora Heisterkamp
BACKGROUND: Drug resistance of B-cell precursor acute lymphoblastic leukemia (BP-ALL) cells is conferred by both intrinsic and extrinsic factors, which could be targeted to promote chemo-sensitization. Our previous studies showed that Galectin-3, a lectin that clusters galactose-modified glycoproteins and that has both an intracellular and extracellular location, protects different subtypes of BP-ALL cells against chemotherapy. Galectin-1 is related to Galectin-3 and its expression was previously reported to be restricted to the MLL subtype of BP-ALL...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29508386/bepridil-exhibits-anti-leukemic-activity-associated-with-notch1-pathway-inhibition-in-chronic-lymphocytic-leukemia
#15
Stefano Baldoni, Beatrice Del Papa, Erica Dorillo, Patrizia Aureli, Filomena De Falco, Chiara Rompietti, Daniele Sorcini, Emanuela Varasano, Debora Cecchini, Tiziana Zei, Ambra Di Tommaso, Emanuela Rosati, Gabriela Alexe, Giovanni Roti, Kimberly Stegmaier, Mauro Di Ianni, Franca Falzetti, Paolo Sportoletti
Dysregulated NOTCH1 signaling, by either gene mutations or microenvironment interactions, has been increasingly linked to chronic lymphocytic leukemia (CLL). Thus, inhibiting NOTCH1 activity represents a potential therapeutic opportunity for this disease. Using gene expression-based screening, we identified the calcium channel modulator bepridil as a new NOTCH1 pathway inhibitor. In primary CLL cells, bepridil induced selective apoptosis even in the presence of the protective stroma. Cytotoxic effects of bepridil were independent of NOTCH1 mutation and other prognostic markers...
August 15, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29500416/sipa1-deficiency-unleashes-a-host-immune-mechanism-eradicating-chronic-myelogenous-leukemia-initiating-cells
#16
Yan Xu, Satoshi Ikeda, Kentaro Sumida, Ryusuke Yamamoto, Hiroki Tanaka, Nagahiro Minato
Chronic myelogenous leukemia (CML) caused by hematopoietic stem cells expressing the Bcr-Abl fusion gene may be controlled by Bcr-Abl tyrosine kinase inhibitors (TKIs). However, CML-initiating cells are resistant to TKIs and may persist as minimal residual disease. We demonstrate that mice deficient in Sipa1, which encodes Rap1 GTPase-activating protein, rarely develop CML upon transfer of primary hematopoietic progenitor cells (HPCs) expressing Bcr-Abl, which cause lethal CML disease in wild-type mice. Resistance requires both T cells and nonhematopoietic cells...
March 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29487418/hif1%C3%AE-drives-chemokine-factor-pro-tumoral-signaling-pathways-in-acute-myeloid-leukemia
#17
Amina M Abdul-Aziz, Manar S Shafat, Yu Sun, Christopher R Marlein, Rachel E Piddock, Stephen D Robinson, Dylan R Edwards, Zhigang Zhou, Angela Collins, Kristian M Bowles, Stuart A Rushworth
Approximately 80% of patients diagnosed with acute myeloid leukemia (AML) die as a consequence of failure to eradicate the tumor from the bone marrow microenvironment. We have recently shown that stroma-derived interleukin-8 (IL-8) promotes AML growth and survival in the bone marrow in response to AML-derived macrophage migration inhibitory factor (MIF). In the present study we show that high constitutive expression of MIF in AML blasts in the bone marrow is hypoxia-driven and, through knockdown of MIF, HIF1α and HIF2α, establish that hypoxia supports AML tumor proliferation through HIF1α signaling...
May 2018: Oncogene
https://www.readbyqxmd.com/read/29487069/the-interplay-of-leukemia-cells-and-the-bone-marrow-microenvironment
#18
REVIEW
Delfim Duarte, Edwin D Hawkins, Cristina Lo Celso
The interplay of cancer cells and surrounding stroma is critical in disease progression. This is particularly evident in hematological malignancies that infiltrate the bone marrow and peripheral lymphoid organs. Despite clear evidence for the existence of these interactions, the precise repercussions on the growth of leukemic cells are poorly understood. Recent development of novel imaging technology and preclinical disease models has advanced our comprehension of leukemia-microenvironment crosstalk and has potential implications for development of novel treatment options...
April 5, 2018: Blood
https://www.readbyqxmd.com/read/29444110/leukemia-inhibitory-factor-produced-by-fibroblasts-within-tumor-stroma-participates-in-invasion-of-oral-squamous-cell-carcinoma
#19
Yae Ohata, Maiko Tsuchiya, Hideaki Hirai, Satoshi Yamaguchi, Takumi Akashi, Kei Sakamoto, Akira Yamaguchi, Tohru Ikeda, Kou Kayamori
The interaction between cancer cells and the cancer stroma plays a crucial role in tumor progression and metastasis in diverse malignancies, including oral cancer. However, the mechanism underlying this interaction remains incompletely elucidated. Here, to investigate the interaction between oral cancer cells and fibroblasts, which are major cellular components of the tumor stroma, we conducted an in vitro study by using human oral squamous cell carcinoma (OSCC) cell lines and normal human dermal fibroblasts (NHDFs)...
2018: PloS One
https://www.readbyqxmd.com/read/29377497/reduced-cell-division-control-protein-42-activity-compromises-hematopoiesis-supportive-function-of-fanconi-anemia-mesenchymal-stromal-cells
#20
Jian Xu, Xue Li, Allison Cole, Zachary Sherman, Wei Du
Hematopoietic stem cells preserve their ability to self-renew and differentiate to different lineages in the bone marrow (BM) niche, which is composed in large part by BM stromal cells. Studies have shown that altered signaling in the BM niche results in leukemia initiation or progression. Fanconi anemia (FA) is an inherited BM failure syndrome associated with extremely high risk of leukemic transformation. By using two FA mouse models, here we have investigated the hematopoiesis-supportive function of FA BM mesenchymal stroma cells (MSCs)...
May 2018: Stem Cells
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