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https://www.readbyqxmd.com/read/28214331/pomc-maintains-tumor-initiating-properties-of-tumor-tissue-derived-long-term-cultured-breast-cancer-stem-cells
#1
Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P Zhou, Mien-Chie Hung, Xiaoming Xie
The identification and understanding of the molecular network of cancer stem cells (CSCs) have had a profound impact on our view of carcinogenesis and treatment strategy. Unfortunately, a major problem is that serial passages of CSCs from clinical solid tumor specimens currently are not available in any lab, and thus, reported data are difficult to confirm and intensively interrogated. Here, we have generated two tumor tissue-derived breast CSC (BCSC) lines that showed prolonged maintenance over 20 serial passages in vitro, while retaining their tumor-initiating biological properties...
February 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28214198/tumor-derived-cd4-cd25-regulatory-t-cells-inhibit-dendritic-cells-function-by-ctla-4
#2
Xin Chen, Yong Du, Qingqing Hu, ZhiMing Huang
PURPOSE: CD4+CD25+regulatoryT cells (Tregs) play an important role in anti-tumor immune responses. Poor prognosis and declining survival rates have intimate connection with high Treg expression in cancer patients. Cytotoxic T Lymphocyte-associated protein (CTLA-4) is one of the most prominent molecules on Treg. In our previous research, we have demonstrated that HCC-derived Tregs can interfere with Dendritic cells (DCs) function and down-modulate CD80/CD86 on DCs in vitro in a cell-contact dependent way...
December 21, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#3
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212885/epinephrine-promotes-cox-2-dependent-immune-suppression-in-myeloid-cells-and-cancer-tissues
#4
Ravikumar Muthuswamy, Nana J Okada, Frank J Jenkins, Kandace McGuire, Priscilla F McAuliffe, Herbert J Zeh, David L Bartlett, Callen Wallace, Simon Watkins, Jill D Henning, Dana H Bovbjerg, Pawel Kalinski
Activation of the sympathetic nervous system (e.g., due to stress) has been implicated in cancer progression and recurrence, but its cancer-promoting effects have been variable between different studies. Here, we report that although catecholamines, mediators of systemic sympathetic activity, display only weak immunosuppressive impact on their own, their combination with inflammatory signals leads to the induction of COX-2 and multiple COX-2-dependent suppressive factors in human myeloid cells and cancer tissues...
February 14, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#5
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211886/a-novel-approach-for-the-identification-of-efficient-combination-therapies-in-primary-human-acute-myeloid-leukemia-specimens
#6
I Baccelli, J Krosl, G Boucher, I Boivin, V-P Lavallée, J Hébert, S Lemieux, A Marinier, G Sauvageau
Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211476/novel-roles-for-staufen1-in-embryonal-and-alveolar-rhabdomyosarcoma-via-c-myc-dependent-and-independent-events
#7
Tara E Crawford Parks, Kristen A Marcellus, Jonathan Langill, Aymeric Ravel-Chapuis, Jean Michaud, Kyle N Cowan, Jocelyn Côté, Bernard J Jasmin
Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle beds, and express key myogenic regulatory factors. However, their developmental program remains blocked in the proliferative phase with cells unable to exit the cell cycle to fuse into myotubes. Recently, we uncovered a key role for the RNA-binding protein Staufen1 during myogenic differentiation through the regulation of c-myc translation. Given the known implication of c-myc in rhabdomyosarcoma, we hypothesized in the current work that Staufen1 controls rhabdomyosarcoma tumorigenesis...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211314/procedure-for-horizontal-transfer-of-patient-derived-xenograft-tumors-to-eliminate-corynebacterium-bovis
#8
Christopher A Manuel Stacey M Bagby Julie A Reisinger Umarani Pugazhenthi Todd M Pitts Stephen B Keysar John J Arcaroli And Jori K Leszczynski
Human patient-derived xenograft (PDX) tumors, propagated in immunodeficient mice, are rapidly growing in use as amodelfor cancer research. Horizontal transfer between mice, without in vitro cell culture, allows these tumors to retainmany of their unique characteristics from their individual patient of origin. However, the immunodeficient mouse strainsused to grow these tumors are susceptible to numerous opportunistic pathogens, including Corynebacterium bovis. At ourinstitution, 2 in vivo tumor banks of PDX tumors had been maintained within nude mouse colonies enzootically infectedwith C...
February 16, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28210910/astrocyte-induced-reelin-expression-drives-proliferation-of-her2-breast-cancer-metastases
#9
Rahul Jandial, Cecilia Choy, Danielle M Levy, Mike Y Chen, Khairul I Ansari
Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain elusive. Reelin is an archetypal extracellular glycoprotein that regulates migration, proliferation, and lamination of neurons. It is epigenetically silenced in various cancers, and its expression in multiple myelomas is linked to poor patient survival...
February 17, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#10
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28209986/nf-%C3%AE%C2%BAb-signaling-regulates-cell-autonomous-regulation-of-cxcl10-in-breast-cancer-4t1-cells
#11
Won Jong Jin, Bongjun Kim, Darong Kim, Hea-Young Park Choo, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee
The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells...
February 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28209916/diabetic-concentrations-of-metformin-inhibit-platelet-mediated-ovarian-cancer-cell-progression
#12
Rafaela Erices, Sofía Cubillos, Raúl Aravena, Felice Santoro, Monica Marquez, Renan Orellana, Carolina Ramírez, Pamela González, Patricia Fuenzalida, María Loreto Bravo, Bárbara Oliva, Sumie Kato, Carolina Ibañez, Jorge Brañes, Erasmo Bravo, Catalina Alonso, Karen García, Clemente Arab, Vicente A Torres, Alejandro S Godoy, Jaime Pereira, Galdo Bustos, Julio Cesar Cardenas, Mauricio A Cuello, Gareth I Owen
Clinical studies have suggested a survival benefit in ovarian cancer patients with type 2 diabetes mellitus taking metformin, however the mechanism by which diabetic concentrations of metformin could deliver this effect is still poorly understood. Platelets not only represent an important reservoir of growth factors and angiogenic regulators, they are also known to participate in the tumor microenvironment implicated in tumor growth and dissemination. Herein, we investigated if diabetic concentrations of metformin could impinge upon the previously reported observation that platelet induces an increase in the tube forming capacity of endothelial cells (angiogenesis) and upon ovarian cancer cell aggressiveness...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209178/tumor-initiating-cells-a-critical-review-of-isolation-approaches-and-new-challenges-in-targeting-strategies
#13
REVIEW
Komal Qureshi-Baig, Pit Ullmann, Serge Haan, Elisabeth Letellier
Most cancers contain a subpopulation of highly tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Targeting TICs may be essential to achieve cure, because of their self-renewal and tumorigenic properties as well as their resistance to conventional therapies. Despite significant advances in TIC biology, their isolation and identification remain largely disputed and incompletely established. In this review, we discuss the latest developments in isolation and culturing approaches of TICs, with focus on colorectal cancer (CRC)...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28208747/multinucleated-giant-cancer-cells-produced-in-response-to-ionizing-radiation-retain-viability-and-replicate-their-genome
#14
Razmik Mirzayans, Bonnie Andrais, April Scott, Ying W Wang, Piyush Kumar, David Murray
Loss of wild-type p53 function is widely accepted to be permissive for the development of multinucleated giant cells. However, whether therapy-induced multinucleation is associated with cancer cell death or survival remains controversial. Herein, we demonstrate that exposure of p53-deficient or p21(WAF1) (p21)-deficient solid tumor-derived cell lines to ionizing radiation (between 2 and 8 Gy) results in the development of multinucleated giant cells that remain adherent to the culture dish for long times post-irradiation...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208677/targeting-protein-kinase-ck2-evaluating-cx-4945-potential-for-gl261-glioblastoma-therapy-in-immunocompetent-mice
#15
Laura Ferrer-Font, Lucia Villamañan, Nuria Arias-Ramos, Jordi Vilardell, Maria Plana, Maria Ruzzene, Lorenzo A Pinna, Emilio Itarte, Carles Arús, Ana Paula Candiota
Glioblastoma (GBM) causes poor survival in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment but resistance always ensues. Protein kinase CK2 (CK2) contributes to tumour development and proliferation in cancer, and it is overexpressed in human GBM. Accordingly, targeting CK2 in GBM may benefit patients. Our goal has been to evaluate whether CK2 inhibitors (iCK2s) could increase survival in an immunocompetent preclinical GBM model. Cultured GL261 cells were treated with different iCK2s including CX-4945, and target effects evaluated in vitro...
February 12, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28206986/in-situ-generated-d-peptidic-nanofibrils-as-multifaceted-apoptotic-inducers-to-target-cancer-cells
#16
Xuewen Du, Jie Zhou, Huainin Wang, Junfeng Shi, Yi Kuang, Wu Zeng, Zhimou Yang, Bing Xu
Nanofibrils of small molecules, as a new class of biofunctional entities, exhibit emergent properties for controlling cell fates, but the relevant mechanism remains to be elucidated and the in vivo effect has yet to be examined. Here, we show that D-peptide nanofibrils, generated by enzyme-instructed self-assembly (EISA), pleiotropically activate extrinsic death signaling for selectively killing cancer cells. Catalyzed by alkaline phosphatases and formed in situ on cancer cells, D-peptide nanofibrils present autocrine proapoptotic ligands to their cognate receptors in a juxtacrine manner, as well as directly cluster the death receptors...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28205649/comparative-studies-of-oxaliplatin-based-platinum-iv-complexes-in-different-in-vitro-and-in-vivo-tumor-models
#17
Simone Göschl, Ekaterina Schreiber-Brynzak, Verena Pichler, Klaudia Cseh, Petra Heffeter, Ute Jungwirth, Michael A Jakupec, Walter Berger, Bernhard K Keppler
Using platinum(iv) prodrugs of clinically established platinum(ii) compounds is a strategy to overcome side effects and acquired resistances. We studied four oxaliplatin-derived platinum(iv) complexes with varying axial ligands in various in vitro and in vivo settings. The ability to interfere with DNA (pUC19) in the presence and absence of a reducing agent (ascorbic acid) was investigated in cell-free experiments. Cytotoxicity was compared under normoxic and hypoxic conditions in monolayer cultures and multicellular spheroids of colon carcinoma cell lines...
February 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28205624/the-small-molecule-auten-99-autophagy-enhancer-99-prevents-the-progression-of-neurodegenerative-symptoms
#18
Tibor Kovács, Viktor Billes, Marcell Komlós, Bernadette Hotzi, Anna Manzéger, Anna Tarnóci, Diána Papp, Fanni Szikszai, Janka Szinyákovics, Ákos Rácz, Béla Noszál, Szilvia Veszelka, Fruzsina R Walter, Mária A Deli, Laszlo Hackler, Robert Alfoldi, Orsolya Huzian, Laszlo G Puskas, Hanna Liliom, Krisztián Tárnok, Katalin Schlett, Adrienn Borsy, Ervin Welker, Attila L Kovács, Zsolt Pádár, Attila Erdős, Adam Legradi, Annamaria Bjelik, Károly Gulya, Balázs Gulyás, Tibor Vellai
Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205583/flavichalasines-a-m-cytochalasan-alkaloids-from-aspergillus-flavipes
#19
Guangzheng Wei, Dongdong Tan, Chunmei Chen, Qingyi Tong, Xiao-Nian Li, Jinfeng Huang, Junjun Liu, Yongbo Xue, Jianping Wang, Zengwei Luo, Hucheng Zhu, Yonghui Zhang
Two new tetracyclic cytochalasans, flavichalasines A and B (1 and 2), three new pentacyclic cytochalasans, flavichalasines C-E (3-5), and eight new tricyclic cytochalasans, flavichalasines F-M (6-13), together with eight known analogues (14-21), were isolated from the solid culture of Aspergillus flavipes. Structures of these new compounds were elucidated on the basis of extensive spectroscopic analyses including 1D, 2D NMR and HRESIMS data. Their absolute configurations were determined by comparison of their experimental ECD with either computed ECD or experimental ECD spectrum of known compound...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205448/association-between-red-meat-consumption-and-colon-cancer-a-systematic-review-of-experimental-results
#20
Nancy D Turner, Shannon K Lloyd
A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in those populations consuming a westernized diet. Determination of causation specifically by red or processed meat is contingent upon identification of plausible mechanisms that lead to colorectal cancer. We conducted a systematic review of the available evidence to determine the availability of plausible mechanistic data linking red and processed meat consumption to colorectal cancer risk...
January 1, 2017: Experimental Biology and Medicine
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