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https://www.readbyqxmd.com/read/29951568/osteoblast-sorting-and-intracellular-staining-of-cxcl12
#1
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
#2
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
#3
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...
June 18, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/29351753/mesenchymal-stem-cells-show-functional-defect-and-decreased-anti-cancer-effect-after-exposure-to-chemotherapeutic-drugs
#16
Chinnapaka Somaiah, Atul Kumar, Renu Sharma, Amit Sharma, Trishna Anand, Jina Bhattacharyya, Damodar Das, Sewali Deka Talukdar, Bithiah Grace Jaganathan
BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles. METHODS: We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine...
January 19, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29342200/inhibiting-tgf-beta-signaling-preserves-the-function-of-highly-activated-in-vitro-expanded-natural-killer-cells-in-aml-and-colon-cancer-models
#17
Folashade Otegbeye, Evelyn Ojo, Stephen Moreton, Nathan Mackowski, Dean A Lee, Marcos de Lima, David N Wald
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK cells are increasingly activated and more efficient at killing cancer cells. Adoptive transfer however introduces these activated cells into a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) from both cancer cells and their surrounding stroma...
2018: PloS One
https://www.readbyqxmd.com/read/29299123/inhibition-of-sdf-1-induced-migration-of-oncogene-driven-myeloid-leukemia-by-the-l-rna-aptamer-spiegelmer-nox-a12-and-potentiation-of-tyrosine-kinase-inhibition
#18
Ellen L Weisberg, Martin Sattler, Abdel Kareem Azab, Dirk Eulberg, Anna Kruschinski, Paul W Manley, Richard Stone, James D Griffin
Resistance to targeted tyrosine kinase inhibitors (TKI) remains a challenge for the treatment of myeloid leukemias. Following treatment with TKIs, the bone marrow microenvironment has been found to harbor a small pool of surviving leukemic CD34+ progenitor cells. The long-term survival of these leukemic cells has been attributed, at least in part, to the protective effects of bone marrow stroma. We found that the NOX-A12 'Spiegelmer', an L-enantiomeric RNA oligonucleotide that inhibits SDF-1α, showed in vitro and in vivo activity against BCR-ABL- and FLT3-ITD-dependent leukemia cells...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29235199/concise-review-adaptation-of-the-bone-marrow-stroma-in-hematopoietic-malignancies-current-concepts-and-models
#19
REVIEW
Ben Doron, Mithila Handu, Peter Kurre
The bone marrow stroma maintains hematopoiesis and coordinately regulates regenerative responses through dynamic interactions with hematopoietic stem and progenitor cells. Recent studies indicate that stromal components in the bone marrow of leukemia patients undergo a process of successive adaptation that in turn exerts dramatic effects on the hematopoietic stem cell compartment and promotes leukemic drug resistance. Therefore, functional changes in discrete marrow stromal populations can be considered an aspect of leukemia biogenesis in that they create an aberrant, self-reinforcing microenvironment...
March 2018: Stem Cells
https://www.readbyqxmd.com/read/29210715/blistering-and-skin-fragility-due-to-imatinib-therapy-loss-of-laminin-and-collagen-iv-as-a-possible-cause-of-cutaneous-basement-membrane-instability
#20
Sebastian Mühl, Jan Ehrchen, Dieter Metze
Imatinib mesylate (Glivec; Novartis AG, Basel, Switzerland) is a tyrosine kinase inhibitor which is used in the treatment of oncologic diseases like chronic myeloid leukemia and gastrointestinal stroma tumor (GIST). Among cutaneous side effects, bullous reactions are rare. The authors describe the case of a 66-year-old woman developing blistering and skin fragility on her hands, foot, lower legs, and back after intake of imatinib for treatment of GIST. Biopsy showed vacuolar alteration at the dermoepidermal junction (DEJ) associated with a few lymphocytes and a subepidermal blister...
May 2018: American Journal of Dermatopathology
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