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Tumor dormancy

A M Decker, Y Jung, F Cackowski, R S Taichman
Approximately 80% of prostate cancers exhibit some degree of bone metastasis. The role of the bone marrow and the hematopoietic stem cell (HSC) niche in attracting metastatic cells and maintaining dormancy of disseminated tumor cells (DTCs) is an increasingly important topic towards the development of novel prostate cancer therapies. This paper reviews aspects of the HSC niche that lead to prostate cancer cell homing and dormancy in the bone marrow. This review also discusses the role of DTCs in the niche environment and discusses the role of erythropoietin in targeting DTCs within the HSC niche...
September 2016: Journal of Bone Oncology
Frank Cackowski, Matthew R Eber, James Rhee, Ann Decker, Kenji Yumoto, Janice E Berry, Eunsohl Lee, Yusuke Shiozawa, Younghun Jung, Julio A Aguirre-Ghiso, Russell S Taichman
Many prostate cancer (PCa) recurrences are thought to be due to reactivation of disseminated tumor cells (DTCs). We previously found a role of the TAM family of receptor tyrosine kinases TYRO3, AXL and MERTK in PCa dormancy regulation. However, the mechanism and contributions of the individual TAM receptors is largely unknown. Knockdown of MERTK, but not AXL or TYRO3 by shRNA in PCa cells induced a decreased ratio of P-Erk1/2 to P-p38, increased expression of p27, NR2F1, SOX2, and NANOG, induced higher levels of histone H3K9me3 and H3K27me3, and induced a G1/G0 arrest, all of which are associated with dormancy...
October 18, 2016: Journal of Cellular Biochemistry
Madhav V Dhodapkar
All cases of multiple myeloma (MM) are preceded by precursor states termed as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). Genetic analyses of MGUS cells have provided evidence that it is a genetically advanced lesion wherein tumor cells carry many of the genetic changes found in MM cells. Intraclonal heterogeneity is also established early during the MGUS phase. While the genetic features of MGUS or SMM cells at baseline may predict disease risk, transition to MM involves altered growth of pre-existing clones...
October 13, 2016: Blood
Thomas J Bartosh, Mujib Ullah, Suzanne Zeitouni, Joshua Beaver, Darwin J Prockop
Patients with breast cancer often develop malignant regrowth of residual drug-resistant dormant tumor cells years after primary treatment, a process defined as cancer relapse. Deciphering the causal basis of tumor dormancy therefore has obvious therapeutic significance. Because cancer cell behavior is strongly influenced by stromal cells, particularly the mesenchymal stem/stromal cells (MSCs) that are actively recruited into tumor-associated stroma, we assessed the impact of MSCs on breast cancer cell (BCC) dormancy...
October 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
Alina I Doban, Mircea Lazar
We propose a new approach for tumor immunotherapy which is based on a switching control strategy defined on domains of attraction of equilibria of interest. For this, we consider a recently derived model which captures the effects of the tumor cells on the immune system and viceversa, through predator-prey competition terms. Additionally, it incorporates the immune system's mechanism for producing hunting immune cells, which makes the model suitable for immunotherapy strategies analysis and design. For computing domains of attraction for the tumor nonlinear dynamics, and thus, for deriving immunotherapeutic strategies we employ rational Lyapunov functions...
September 22, 2016: Mathematical Biosciences
Sandra Casimiro, Arlindo R Ferreira, André Mansinho, Irina Alho, Luis Costa
Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteotropic factors...
2016: International Journal of Molecular Sciences
N Linde, G Fluegen, J A Aguirre-Ghiso
The majority of cancer deaths are due to metastases that can occur years or decades after primary tumor diagnosis and treatment. Disseminated tumor cells (DTCs) surviving in a dormant state in target organs appear to explain the timing of this phenomenon. Knowledge on this process is important as it might provide a window of opportunity to prevent recurrences by eradicating dormant DTCs and/or by maintaining DTCs in a dormant state. Importantly, this research might offer markers of dormancy for early monitoring of metastatic relapse...
2016: Advances in Cancer Research
Loreto Boix, Juan Manuel López-Oliva, Ana Carolina Rhodes, Jordi Bruix
miR122 is the prevalent miRNA in adult healthy liver and it is responsible for liver stem cell differentiation towards hepatocyte lineage. Its expression is frequently lost in hepatocellular carcinoma (HCC). We studied the effects of restoring miR122 expression in a distinctive cell line derived from human HCC-BCLC9 cells-with a solid stem-like cell profile, high tumor initiating ability and undetectable miR122 expression. We generated a stable BCLC9 cell line that expresses miR122 (BCLC9-miR122). Restitution of miR122 in BCLC9 cells, decreases cell proliferation rate and reduces significantly tumor size in vivo...
September 7, 2016: Oncotarget
Masoud H Manjili, Savannah E Butler
The immunogenic tumor dormancy has been demonstrated in animal models of cancer, which can explain clinical observations such as an increased incidence of cancer following organ transplantation. The role of immune cell populations in the maintenance of, or escape from, tumor dormancy and subsequent recurrence is poorly understood. Here, we provide a review of literature related to the contribution of Tregs in tumor dormancy or recurrence. Based on clinical results, we suggest that anecdotal reports on the association of human Tregs with poor prognosis are circumstantial rather than implying a cause-effect direction...
September 7, 2016: Immunological Investigations
Daniel Rusiecki, Boleslaw Lach, Branavan Manoranjan, Adam Fleming, Olufemi Ajani, Sheila K Singh
We report a childhood case of thalamic atypical extraventricular neurocytoma that progressed to highly anaplastic ganglioglioma (GG) after eight years of dormancy following subtotal resection and chemotherapy. The neurocytoma displayed immunoreactivity only for synaptophysin, beta-catenin, S-100 and CD56. The GG acquired strong immunoreactivity for chromogranin, glial fibrillary acidic protein, neuron specific enolase and p53 and showed a very high proliferation rate approaching 50% in some areas. Tumor transformation was associated with overexpression of components of the sonic hedgehog (Shh) and Wnt developmental signaling pathways, which are known to regulate tumor-initiating cells in malignant brain neoplasms...
September 2, 2016: Human Pathology
E E Mowers, M N Sharifi, K F Macleod
Autophagy is a highly conserved self-degradative process that has a key role in cellular stress responses and survival. Recent work has begun to explore the function of autophagy in cancer metastasis, which is of particular interest given the dearth of effective therapeutic options for metastatic disease. Autophagy is induced upon progression of various human cancers to metastasis and together with data from genetically engineered mice and experimental metastasis models, a role for autophagy at nearly every phase of the metastatic cascade has been identified...
September 5, 2016: Oncogene
Györgyi Műzes, Ferenc Sipos
Cancer patients, though frequently entering complete remission after successful surgery, and/or irradiation, and chemotherapy years or even decades later may exhibit overt metastases and aggressive, mostly fatal recurrence on the basis of clinically silent persistence of disseminated tumor cells. Cellular dormancy is a mode of hibernation/inactivity caused by a temporary mitotic arrest. It represents the critical phenomenon of latency making metastatic cancer cells highly refractory to conventional therapies...
September 1, 2016: Anti-cancer Agents in Medicinal Chemistry
Sarah A Bliss, Garima Sinha, Oleta A Sandiford, Lisa M Williams, Daniel J Engelberth, Khadidiatou Guiro, Leidy L Isenalumhe, Steven J Greco, Seda Ayer, Margarette Bryan, Rakesh Kumar, Nicholas M Ponzio, Pranela Rameshwar
Dormant breast cancers resurge as metastatic disease after a long dormancy period in the bone marrow, where cancer cells interact with mesenchymal stem cells (MSC). However, the nature of early interactions between breast cancer cells and MSCs in the bone marrow microenvironment that facilitate adaptation to a quiescent state remains poorly understood. Here, we report that breast cancer cells prime MSC to release exosomes containing distinct miRNA contents, such as miR-222/223, which in turn promotes quiescence in a subset of cancer cells and confers drug resistance...
October 1, 2016: Cancer Research
Irina Kareva
UNLABELLED: Existence of tumor dormancy, or cancer without disease, is supported both by autopsy studies that indicate presence of microscopic tumors in men and women who die of trauma (primary dormancy), and by long periods of latency between excision of primary tumors and disease recurrence (metastatic dormancy). Within dormant tumors, two general mechanisms underlying the dynamics are recognized, namely, the population existing at limited carrying capacity (tumor mass dormancy), and solitary cell dormancy, characterized by long periods of quiescence marked by cell cycle arrest...
2016: Biology Direct
Jasmine M De Cock, Tsukasa Shibue, Anushka Dongre, Zuzana Keckesova, Ferenc Reinhardt, Robert A Weinberg
The emergence of metastatic disease in cancer patients many years or decades after initial successful treatment of primary tumors is well documented but poorly understood at the molecular level. Recent studies have begun exploring the cell-intrinsic programs causing disseminated tumor cells to enter latency and the cellular signals in the surrounding non-permissive tissue microenvironment that maintain the latent state. However, relatively little is known about the mechanisms that enable disseminated tumor cells to escape cancer dormancy or tumor latency...
August 16, 2016: Cancer Research
Jean-Marc Pascussi, Julie Giraud, Emmanuelle Samalin, Fanny Grillet, Julie Pannequin
Metastatic process is described as a "dissemination of neoplastic cells in a distant secondary site, in which cells proliferate to develop a mass of cells partially differentiated". The vast majority of death in solid cancers is the consequence of metastasis development which lead to vital organ dysfunction. In the present review, either recent discoveries or controversial subjects associated with metastasis process will be discussed. Indeed epithelia-mesenchymal transition (EMT), circulating tumor cells, tumor dormancy, colonization in distant organ and cancer stem cells are tackled...
June 2016: Bulletin du Cancer
Stephen P Cavnar, Annie Xiao, Anne E Gibbons, Andrew D Rickelmann, Taylor Neely, Kathryn E Luker, Shuichi Takayama, Gary D Luker
Malignant cells from breast cancer and other common cancers such as prostate and melanoma may persist in bone marrow as quiescent, non-dividing cells that remain viable for years or even decades before resuming proliferation to cause recurrent disease. This phenomenon, referred to clinically as tumor dormancy, poses tremendous challenges to curing patients with breast cancer. Quiescent tumor cells resist chemotherapy drugs that predominantly target proliferating cells, limiting success of neo-adjuvant and adjuvant therapies...
June 2016: Tomography: a Journal for Imaging Research
Jeffrey W Pollard
No abstract text is available yet for this article.
July 21, 2016: New England Journal of Medicine
S Talukdar, L Emdad, S K Das, D Sarkar, P B Fisher
Cancer is a multifactor and multistep process that is affected intrinsically by the genetic and epigenetic makeup of tumor cells and extrinsically by the host microenvironment and immune system. A key component of cancer involves a unique subpopulation of highly malignant cancerous cells referred to as cancer stem cells (CSCs). CSCs are positioned at the apex of the tumor hierarchy with an ability to both self-renew and also generate non-CSC/differentiated progeny, which contribute to the majority of the tumor mass...
2016: Advances in Cancer Research
Lingcheng Zeng, Yiqing Zhao, Taohui Ouyang, Tianyuan Zhao, Suojun Zhang, Jian Chen, Jiasheng Yu, Ting Lei
Label-retaining cells, which are characterized by dormancy or slow cycling, may be identified in a number of human normal and cancer tissues, and these cells demonstrate stem cell potential. In glioblastoma, label-retaining assays to enrich glioma stem cells remain to be fully investigated. In the present study, glioblastoma sphere cells cultured in serum-free medium were initially stained with the cell membrane fluorescent marker DiI. The fluorescence intensity during cell proliferation and sphere reformation was observed...
August 2016: Oncology Letters
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