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Tumor dormancy

Hussein F Aqbi, Liliya Tyutyunyk-Massey, Rebecca C Keim, Savannah E Butler, Theresa Thekkudan, Supriya Joshi, Timothy M Smith, Dipankar Bandyopadhyay, Michael O Idowu, Harry D Bear, Kyle K Payne, David A Gewirtz, Masoud H Manjili
Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy...
April 24, 2018: Oncotarget
Yuying Liu, Jiadi Lv, Xiaoyu Liang, Xiaonan Yin, Le Zhang, Degao Chen, Xun Jin, Roland Fiskesund, Ke Tang, Jingwei Ma, Huafeng Zhang, Wenqian Dong, Siqi Mo, Tianzhen Zhang, Feiran Cheng, Yabo Zhou, Jing Xie, Ning Wang, Bo Huang
Dormancy is recognized as a critical biological event for tumorigenic cells surviving in an extremely harsh environment. Understanding the molecular process of dormancy can unlock novel approaches to tackle cancers. We recently reported that stem-like tumor-repopulating cells (TRC) sense mechanical signals and rapidly proliferate in a 90 Pa soft fibrin matrix. Here we show that a stiff mechanical environment induces TRC dormancy via an epigenetic program initiated by translocation of Cdc42, a cytosolic regulator of mechanotransduction, into the nucleus, where it promotes transcription of hydroxymethylating enzyme Tet2...
May 15, 2018: Cancer Research
Mitsuhiro Kamiyoshihara, Hitoshi Igai, Takashi Ibe, Fumi Ohsawa, Ryohei Yoshikawa, Kimihiro Shimizu, Akira Mogi, Ken Shirabe, Hiroyuki Kuwano
BACKGROUND: The standard approach for treating recurrence after complete resection of primary non-small cell lung cancer has been controversial. We present here a multidisciplinary strategy for postoperative recurrence in patients with primary lung cancer. PATIENTS AND METHODS: Over the last 7 years, we examined the disease-free survival and overall survival of 70 patients who underwent multidisciplinary treatment for recurrence after surgical resection of primary lung cancer...
April 2018: Kyobu Geka. the Japanese Journal of Thoracic Surgery
Tian Du, Li Zhu, Kevin M Levine, Nilgun Tasdemir, Adrian V Lee, Dario A A Vignali, Bennett Van Houten, George C Tseng, Steffi Oesterreich
Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). ILC differs from IDC in a number of histological and clinical features, such as single strand growth, difficulty in detection, and frequent late recurrences. To understand the molecular pathways involved in the clinical characteristics of ILC, we compared the gene expression profiles of luminal A ILC and luminal A IDC using data from TCGA and utilized samples from METABRIC as a validation data set...
May 8, 2018: Scientific Reports
Xiao-Lin Luo, Chengcheng Deng, Xiao-Dong Su, Fang Wang, Zhen Chen, Xing-Ping Wu, Shao-Bo Liang, Jihong Liu, Liwu Fu
A high rate of disease relapse makes epithelial ovarian cancer (EOC) the leading cause of death among all gynecological malignancies. These relapses are often due to tumor dormancy. Here we identify the RNA polymerase II transcriptional Mediator subunit 12 (MED12) as an important molecular regulator of tumor dormancy. MED12 knockout (KO) induced dormancy of EOC cells in vitro and in vivo, and microarray analysis showed that MED12 KO decreased expression of EGFR. Restoration of EGFR expression in MED12 KO cells restored proliferation...
May 7, 2018: Cancer Research
Katrina L Watson, Robert A Jones, Bruce Anthony, Roger A Moorehead
The miR-200 family of microRNAs consisting of miR-141, miR-200a, miR-200b, miR-200c and miR-429 are emerging as important regulators of breast cancer progression. This family of microRNAs maintain mammary epithelial identity and downregulation of miR-200 expression has been associated with epithelial-to-mesenchymal transition in mammary tumors. Therefore, re-expression of one or more miR-200 family members in mammary tumor cells with mesenchymal characteristics may restore an epithelial phenotype including growth and metastasis suppression...
April 24, 2018: Experimental Cell Research
Walid Djema, Catherine Bonnet, Frédéric Mazenc, Jean Clairambault, Emilia Fridman, Pierre Hirsch, François Delhommeau
OBJECTIVE: Modeling and analysis of cell population dynamics enhance our understanding of cancer. Here we introduce and explore a new model that may apply to many tissues. ANALYSES: An age-structured model describing coexistence between mutated and ordinary stem cells is developed and explored. The model is transformed into a nonlinear time-delay system governing the dynamics of healthy cells, coupled to a nonlinear differential-difference system describing dynamics of unhealthy cells...
April 17, 2018: Journal of Theoretical Biology
Jordan A Krall, Ferenc Reinhardt, Oblaise A Mercury, Diwakar R Pattabiraman, Mary W Brooks, Michael Dougan, Arthur W Lambert, Brian Bierie, Hidde L Ploegh, Stephanie K Dougan, Robert A Weinberg
Patients undergoing surgical resection of primary breast tumors confront a risk for metastatic recurrence that peaks sharply 12 to 18 months after surgery. The cause of early metastatic relapse in breast cancer has long been debated, with many ascribing these relapses to the natural progression of the disease. Others have proposed that some aspect of surgical tumor resection triggers the outgrowth of otherwise-dormant metastases, leading to the synchronous pattern of relapse. Clinical data cannot distinguish between these hypotheses, and previous experimental approaches have not provided clear answers...
April 11, 2018: Science Translational Medicine
Nicola Graham, Bin-Zhi Qian
Bone metastasis is the most advanced stage of many cancers and indicates a poor prognosis for patients due to resistance to anti-tumor therapies. The establishment of metastasis within the bone is a multistep process. To ensure survival within the bone marrow, tumor cells must initially colonize a niche in which they can enter dormancy. Subsequently, reactivation permits the proliferation and growth of the tumor cells, giving rise to a macro-metastasis displayed clinically as a bone metastatic lesion. Here, we review the evidences that suggest mesenchymal stromal cells play an important role in each of these steps throughout the development of bone metastasis...
April 9, 2018: International Journal of Molecular Sciences
Amit S Yadav, Poonam R Pandey, Ramesh Butti, N N V Radharani, Shamayita Roy, Shaileshkumar R Bhalara, Mahadeo Gorain, Gopal C Kundu, Dhiraj Kumar
Advancements in the early detection of cancer coupled with improved surgery, radiotherapy, and adjuvant therapy led to substantial increase in patient survival. Nevertheless, cancer metastasis is the leading cause of death in several cancer patients. The majority of these deaths are associated with metastatic relapse kinetics after a variable period of clinical remission. Most of the cancer recurrences are thought to be associated with the reactivation of dormant disseminated tumor cells (DTCs). In this review, we have summarized the cellular and molecular mechanisms related to DTCs and the role of microenvironmental niche...
2018: Frontiers in Oncology
Jessica Yang, Omid Hamid, Richard D Carvajal
The ability of uveal melanoma cells to enter and exit dormancy plays a fundamental role in the development of metastatic disease.  Neddylation blockade is a promising strategy to prolong tumor dormancy via impaired angiogenesis and prevent the establishment of metastases via elimination of cancer stem-like cells.
April 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Thomas Wieder, Thomas Eigentler, Ellen Brenner, Dipl Biol, Martin Röcken
Immune checkpoints are accessory molecules that either promote or inhibit T cell activation. Two inhibitory molecules, cytotoxic T cell antigen 4 (CTLA-4) and programmed death 1 (PD-1), got high attention, as inhibition of CTLA-4 or PD-1 signaling provides the first immune therapy that significantly improves the survival of patients with metastatic solid cancers. Inhibition of CTLA-4 or PD-1 was first studied in and approved for patients with metastatic melanoma. Blocking immune checkpoints is also efficient in non-small-cell lung cancer, renal cell cancers, hypermutated gastro-intestinal cancers and others...
March 26, 2018: Journal of Allergy and Clinical Immunology
Gao Xiaolei, Liang Xinhua, Tang Yaling
Disease metastasis and relapse in many cancer patients several years (even decades) after surgical remission have been recently acknowledged as cases of cancer dormancy. Although cases of minimal residual disease are well documented, knowledge on its biological mechanisms and clinical implications remains limited. To date, numerous reviews have summarized the three potential models that may explain this phenomenon, including the angiogenic, immunologic, and cellular dormancy. In this study, we discuss newly uncovered mechanisms governing tumor cell dormancy in head and neck cancer, emphasizing on the crosstalk between dormant tumor cells and their microenvironments...
February 1, 2018: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
Kristen D Brantley, Anders Kjærsgaard, Deirdre Cronin-Fenton, Rami Yacoub, Anja S Nielsen, Kristina L Lauridsen, Stephen Hamilton-Dutoit, Timothy L Lash
BACKGROUND: Expression of human paracrine hormones stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) may potentiate late breast cancer recurrence. We tested the hypothesis that expression of STC1 and STC2 in primary breast tumors is more strongly associated with late versus early recurrences. METHODS: 541 estrogen receptor positive, tamoxifen treated (ER+/TAM+) and 300 estrogen receptor negative, tamoxifen untreated (ER-/TAM-) breast cancer patients who experienced recurrence within ten years of primary diagnosis and matched recurrence-free controls were selected from a cohort of 11,251 Danish breast cancer patients diagnosed with stage I, II, or III breast cancer during 1985-2001...
March 28, 2018: Cancer Epidemiology, Biomarkers & Prevention
Hong Jiang, Tai-Lai Luo, Jian Kang, Zhi-Kai Xu, Li-Mei Wang
Dormancy-associated antigens encoded by the dormancy survival regulon (DosR) genes are required for survival of Mycobacterium tuberculosis (Mtb) in macrophages. However, mechanisms underlying survival of Mtb in macrophages remains to be elucidated. A recombinant Mycobacterium smegmatis strain (rMs) expressing a fusion protein of two dormancy‑associated antigens Rv2031c and Rv2626c from Mtb was constructed in the present study. In an in vitro culture, growth rate of rMs was lower compared with Ms. A total of 24 h following infection of murine macrophages with rMs or Ms, percentage of viable cells decreased and the number of bacteria in viable cells increased compared with Ms, demonstrating that virulence and intracellular survival of rMs were enhanced...
March 16, 2018: Molecular Medicine Reports
Jing Huang, Peng Guo, Marsha A Moses
The acquisition of the angiogenic phenotype is an essential component of the escape from tumor dormancy. Although several classic in vitro assays (e.g., proliferation, migration, and others) and in vivo models have been developed to investigate and characterize angiogenic and non-angiogenic cell phenotypes, these methods are time and labor intensive, and often require expensive reagents and instruments, as well as significant expertise. In a recent study, we used a novel quantitative phase imaging (QPI) technique to conduct time-lapse and labeling-free characterizations of angiogenic and non-angiogenic human osteosarcoma KHOS cells...
February 16, 2018: Journal of Visualized Experiments: JoVE
Li-Yuan Yu-Lee, Guoyu Yu, Yu-Chen Lee, Song-Chang Lin, Jing Pan, Tianhong Pan, Kai-Jie Yu, Bin Liu, Chad J Creighton, Jaime Rodriguez-Canales, Pamela Andrea Villalobos, Ignacio Ivan Wistuba, Eulàlia de Nadal, Francesc Posas, Gary E Gallick, Sue-Hwa Lin
Bone metastasis from prostate cancer (PCa) can occur years after prostatectomy, due to reactivation of dormant disseminated tumor cells (DTC) in the bone, yet the mechanism by which DTC are initially induced into a dormant state in the bone remains to be elucidated. We show here that the bone microenvironment confers dormancy to C4-2B4 PCa cells, as they become dormant when injected into mouse femurs but not under the skin. Live-cell imaging of dormant cells at the single cell level revealed that conditioned medium from differentiated, but not undifferentiated osteoblasts induced C4-2B4 cellular quiescence, suggesting that differentiated osteoblasts present locally around the tumor cells in the bone conferred dormancy to PCa cells...
March 7, 2018: Cancer Research
Hussein F Aqbi, Matthew Wallace, Samay Sappal, Kyle K Payne, Masoud H Manjili
Tumor immunoediting consisting of three phases of elimination, equilibrium or dormancy, and escape has been supported by preclinical and clinical data. A comprehensive understanding of the molecular mechanisms by which antitumor immune responses regulate these three phases are important for developing highly tailored immunotherapeutics that can control cancer. To this end, IFN-γ produced by Th1 cells, cytotoxic T cells, NK cells, and NKT cells is a pleiotropic cytokine that is involved in all three phases of tumor immunoediting, as well as during inflammation-mediated tumorigenesis processes...
February 22, 2018: Journal of Leukocyte Biology
Gianluca Colella, Flavio Fazioli, Michele Gallo, Annarosaria De Chiara, Gaetano Apice, Carlo Ruosi, Amelia Cimmino, Filomena de Nigris
Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and help determine the most promising individual treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may have a multitude of genomic aberrations that give rise to more than 70 different histopathological subtypes...
February 21, 2018: International Journal of Molecular Sciences
Ilaria Roato, Riccardo Ferracini
Tumor mass is constituted by a heterogeneous group of cells, among which a key role is played by the cancer stem cells (CSCs), possessing high regenerative properties. CSCs directly metastasize to bone, since bone microenvironment represents a fertile environment that protects CSCs against the immune system, and maintains their properties and plasticity. CSCs can migrate from the primary tumor to the bone marrow (BM), due to their capacity to perform the epithelial-to-mesenchymal transition. Once in BM, they can also perform the mesenchymal-to-epithelial transition, allowing them to proliferate and initiate bone lesions...
February 20, 2018: Cancers
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