Geeta Pachori, Supriya Singh Toor, Rashmi Sharma, Tushar Bayla
Background and Aims: Fine Needle aspiration cytology has emerged as an essential pre-biopsy investigation to rule out or confirm malignancy in superficial as well as deep seated lesions. Radiological assistance has proved to be a blessing for obtaining adequate samples. With unwavering leading position of lung cancer in terms of incidence and mortality, it has become necessary to study the trends of our population and assess the usefulness of techniques aiding in early diagnosis. The objective is to obtain prevalence of lung cancer and utility of various methods in obtaining cytological material for assessment in intrathoracic lesions...
July 2020: Journal of Cytology
Parinaz Mehdipour, Sajid A Marhon, Ilias Ettayebi, Ankur Chakravarthy, Amir Hosseini, Yadong Wang, Fabíola Attié de Castro, Helen Loo Yau, Charles Ishak, Sagi Abelson, Catherine A O'Brien, Daniel D De Carvalho
Cancer therapies that target epigenetic repressors can mediate their effects by activating retroelements within the human genome. Retroelement transcripts can form double-stranded RNA (dsRNA) that activates the MDA5 pattern recognition receptor1-6 . This state of viral mimicry leads to loss of cancer cell fitness and stimulates innate and adaptive immune responses7,8 . However, the clinical efficacy of epigenetic therapies has been limited. To find targets that would synergize with the viral mimicry response, we sought to identify the immunogenic retroelements that are activated by epigenetic therapies...
October 21, 2020: Nature
Kiyomi Morita, Feng Wang, Katharina Jahn, Tianyuan Hu, Tomoyuki Tanaka, Yuya Sasaki, Jack Kuipers, Sanam Loghavi, Sa A Wang, Yuanqing Yan, Ken Furudate, Jairo Matthews, Latasha Little, Curtis Gumbs, Jianhua Zhang, Xingzhi Song, Erika Thompson, Keyur P Patel, Carlos E Bueso-Ramos, Courtney D DiNardo, Farhad Ravandi, Elias Jabbour, Michael Andreeff, Jorge Cortes, Kapil Bhalla, Guillermo Garcia-Manero, Hagop Kantarjian, Marina Konopleva, Daisuke Nakada, Nicholas Navin, Niko Beerenwinkel, P Andrew Futreal, Koichi Takahashi
Clonal diversity is a consequence of cancer cell evolution driven by Darwinian selection. Precise characterization of clonal architecture is essential to understand the evolutionary history of tumor development and its association with treatment resistance. Here, using a single-cell DNA sequencing, we report the clonal architecture and mutational histories of 123 acute myeloid leukemia (AML) patients. The single-cell data reveals cell-level mutation co-occurrence and enables reconstruction of mutational histories characterized by linear and branching patterns of clonal evolution, with the latter including convergent evolution...
October 21, 2020: Nature Communications
Yong-Hee Cho, Eun Ji Ro, Jeong-Su Yoon, Tomohiro Mizutani, Dong-Woo Kang, Jong-Chan Park, Tae Il Kim, Hans Clevers, Kang-Yell Choi
5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes WNT3 transcription, leading to activation of the WNT/β-catenin pathway in ApcMin/+ /Lgr5EGFP mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment...
October 21, 2020: Nature Communications
Virve Alanen, Sanna Iivanainen, Martti Arffman, Jussi Pekka Koivunen
BACKGROUND: With the first and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), clinical benefit and rash correlate together. EGFR TKI-induced rash can be alleviated with tetracyclines, but it is unknown whether the use of tetracyclines can increase the survival of non-small-cell lung cancer (NSCLC) patients treated with EGFR TKIs. METHODS: We collected all the patients (n=1271) who had reimbursement for EGFR TKIs (gefitinib, erlotinib and afatinib) in Finland 2011-2016, had purchased TKIs, and had data available at nationwide cancer registry...
October 2020: ESMO Open
Deepak Parashar, Bindu Nair, Anjali Geethadevi, Jasmine George, Ajay Nair, Shirng-Wern Tsaih, Ishaque P Kadamberi, Gopa Kumar Gopinadhan Nair, Yiling Lu, Ramani Ramchandran, Denise S Uyar, Janet S Rader, Prahlad T Ram, Gordon B Mills, Sunila Pradeep, Pradeep Chaluvally-Raghavan
Peritoneal spread is the primary mechanism of metastasis of ovarian cancer, and survival of ovarian cancer cells in the peritoneal cavity as non-adherent spheroids and their adherence to the mesothelium of distant organs lead to cancer progression, metastasis and mortality. However, the mechanisms that govern this metastatic process in ovarian cancer cells remain poorly understood. In this study, we cultured ovarian cancer cell lines in adherent (AD) and in non-adherent (NAD) conditions in vitro and analyzed changes in mRNA and protein levels to identify mechanisms of tumor cell survival and proliferation in AD and NAD cells...
October 21, 2020: Cancer Research
Stefan Thomann, Sofia M E Weiler, Simone Marquard, Fabian Rose, Claudia R Ball, Marcell Tóth, Teng Wei, Carsten Sticht, Sarah Fritzsche, Stephanie Roessler, Carolina De La Torre, Eduard Ryschich, Olga Ermakova, Carolin Mogler, Daniel Kazdal, Norbert Gretz, Hanno Glimm, Eugen Rempel, Peter Schirmacher, Kai Breuhahn
The oncogene yes-associated protein (YAP) controls liver tumor initiation and progression via cell extrinsic functions by creating a tumor-supporting environment in conjunction with cell autonomous mechanisms. However, how YAP controls organization of the microenvironment and in particular the vascular niche, which contributes to liver disease and hepatocarcinogenesis, is poorly understood. To understand heterotypic cell communication, we dissected murine and human liver endothelial cell (EC) populations into liver sinusoidal endothelial cells (LSECs) and continuous endothelial cells (CECs) through histo-morphological and molecular characterization...
October 21, 2020: Cancer Research
Yanhao Lai, Jill M Beaver, Eduardo Laverde, Yuan Liu
Trinucleotide repeat (TNR) instability is the cause of over 40 human neurodegenerative diseases and certain types of cancer. TNR instability can result from DNA replication, repair, recombination, and gene transcription. Emerging evidence indicates that DNA base damage and base excision repair (BER) play an active role in regulating somatic TNR instability. These processes may potentially modulate the onset and progression of TNR-related diseases, given that TNRs are hotspots of DNA base damage that are present in mammalian cells with a high frequency...
September 2020: DNA Repair
Kaikai Zhao, Youjiao Si, Liangchao Sun, Xiangjiao Meng, Jinming Yu
INTRODUCTION: There is no standard treatment for locoregional recurrent (LR) esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy (RT) previously. This retrospective study aimed to examine the efficacy and toxicity of re-irradiation (re-RT) for ESCC patients with LR. PATIENTS AND METHODS: A total of 252 patients were enrolled. Gross tumor volumes for re-RT were defined using contrast enhanced computed tomography and/or positron emission tomography/computed tomography...
October 21, 2020: Radiation Oncology
Belgin Sever, Mehlika Dilek Altıntop, Gülşen Akalın Çiftçi, Ahmet Özdemir
BACKGROUND: Targeted therapies acting on specific molecular targets in cancer cells with better curative efficacy and lower toxicity have come into prominence for the management of non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). COX-2 stands out as a plausible target for anticancer agents due to its pivotal role in tumor initiation, progression and invasion. OBJECTIVES: Due to the importance of triazolothiadiazine scaffold in targeted anticancer drug discovery, the aim of this work is the design of new triazolothiadiazines as potential anticancer agents for the targeted therapy of NSCLC and CRC...
October 21, 2020: Medicinal Chemistry
Carlos Cordon-Cardo, Elisabet Pujadas, Ania Wajnberg, Robert Sebra, Gopi Patel, Adolfo Firpo-Betancourt, Mary Fowkes, Emilia Sordillo, Alberto Paniz-Mondolfi, Jill Gregory, Florian Krammer, Viviana Simon, Luis Isola, Patrick Soon-Shiong, Judith A Aberg, Valentin Fuster, David L Reich
Coronavirus disease 2019 (COVID-19), like cancer, is a complex disease with clinical phases of progression. Initially conceptualized as a respiratory disease, COVID-19 is increasingly recognized as a multi-organ and heterogeneous illness. Disease staging is a method for measuring the progression and severity of an illness using objective clinical and molecular criteria. Integral to cancer staging is "metastasis," defined as the spread of a disease-producing agent, including neoplastic cells and pathogens such as certain viruses, from the primary site to distinct anatomic locations...
October 10, 2020: Cancer Cell
Haichao Zhao, Changzhou Chen, Xidong Chen, Donglin Zhang, Jian Li, Chuanli Yang, Chongren Ren, Xiaojing Ren, Xifeng Fu, Yanjun Li, Jiefeng He, Haoliang Zhao
The carbon catabolite repressor 4-negative on TATA (CCR4-NOT) complex, abbreviated CNOT, has deadenylation and 3'-5' exonuclease activity, mediates deadenylation in the degradation of RNA, initiates the exonuclease degradation pathway, and participates in tumor gene regulation. CNOT proteins comprise a family of global transcriptional regulators that are evolutionarily conserved in eukaryotic cells. Several subunit types of the CNOT complex have been discovered; however, little is known about the role of different subunits in tumorigenesis and development...
October 20, 2020: DNA and Cell Biology
Petro Halkowycz, Charles E Grimshaw, Walter Keung, Paul Tanis, Chris Proffitt, Kim Peacock, Ron de Jong, Mark Sabat, Urmi Banerjee, Jacques Ermolieff
Two different signaling pathways lead to the activation of the transcription factor NF-κB, initiating distinct biological responses: The canonical NF-κB pathway activation has been implicated in host immunity and inflammatory responses, whereas the noncanonical pathway activation has been involved in lymphoid organ development and B-cell maturation, as well as in the development of chronic inflammatory diseases and some hematologic cancers. The NF-κB-inducing kinase (NIK) is a cytoplasmic Ser/Thr kinase and is a key regulator of the noncanonical pathway...
October 21, 2020: SLAS Discovery
Yuichi Ozawa, Yuhei Harutani, Jun Oyanagi, Hiroaki Akamatsu, Eriko Murakami, Ryota Shibaki, Atsushi Hayata, Takeya Sugimoto, Masanori Tanaka, Toshiaki Takakura, Katsuyuki Furuta, Yuka Okuda, Kouichi Sato, Shunsuke Teraoka, Hiroki Ueda, Nahomi Tokudome, Yuka Kitamura, Junya Fukuoka, Masanori Nakanishi, Yasuhiro Koh, Nobuyuki Yamamoto
CD24, a heavily glycosylated glycosylphosphatidylinositol-anchored surface protein, inhibits phagocytosis as potently as CD47. The relationship between such anti-phagocytic factors and immune-response with immune-checkpoint inhibitors (ICI) remains unexplored. We evaluated CD24 and CD47 tumor proportion scores (TPS) in 68 of the 106 patients with advanced non-small cell lung cancer who participated in a prospective observational study of ICI treatment. We also explored the impact of CD24 TPS and CD47 TPS on ICI efficacy and serum cytokine changes...
October 21, 2020: Cancer Science
Jean-Pascal Capp, Frédéric Thomas
Similarities between microbial and cancer cells were noticed in recent years and serve as a basis for an atavism theory of cancer. Cancer cells would rely on the reactivation of an ancestral "genetic program" that would have been repressed in metazoan cells. Here we argue that cancer cells resemble unicellular organisms mainly in their similar way to exploit cellular stochasticity to produce cell specialization and maximize proliferation. Indeed, the relationship between low stochasticity, specialization, and quiescence found in normal differentiated metazoan cells is lost in cancer...
September 25, 2020: IScience
Annelies Demeyer, Yasmine Driege, Ioannis Skordos, Julie Coudenys, Kelly Lemeire, Dirk Elewaut, Jens Staal, Rudi Beyaert
The protease MALT1 is a key regulator of NF-κB signaling and a novel therapeutic target in autoimmunity and cancer. Initial enthusiasm supported by preclinical results with MALT1 inhibitors was tempered by studies showing that germline MALT1 protease inactivation in mice results in reduced regulatory T cells and lethal multi-organ inflammation due to expansion of IFN-γ-producing T cells. However, we show that long-term MALT1 inactivation, starting in adulthood, is not associated with severe systemic inflammation, despite reduced regulatory T cells...
October 23, 2020: IScience
Natascia Marino, Rana German, Xi Rao, Ed Simpson, Sheng Liu, Jun Wan, Yunlong Liu, George Sandusky, Max Jacobsen, Miranda Stoval, Sha Cao, Anna Maria V Storniolo
Histologically normal tissue adjacent to the tumor can provide insight of the microenvironmental alterations surrounding the cancerous lesion and affecting the progression of the disease. However, little is known about the molecular changes governing cancer initiation in cancer-free breast tissue. Here, we employed laser microdissection and whole-transcriptome profiling of the breast epithelium prior to and post tumor diagnosis to identify the earliest alterations in breast carcinogenesis. Furthermore, a comprehensive analysis of the three tissue compartments (microdissected epithelium, stroma, and adipose tissue) was performed on the breast donated by either healthy subjects or women prior to the clinical manifestation of cancer (labeled "susceptible normal tissue")...
2020: NPJ Breast Cancer
Xing Zhang, Xin Gu, Jia-Gen Li, Xian-Jie Hu
BACKGROUND: Esophageal cancer is one of the most common causes of cancer-related death. Some patients with esophageal cancer have distant metastases at the time of diagnosis, but metastasis to the thyroid gland (MTG) and multifocal thyroid lesions alone are extremely rare. CASE SUMMARY: In this case report, we present a case of a 69-year-old male with esophageal MTG. The patient visited our hospital for a routine body check-up, which revealed multifocal nodules in his thyroid lobes and enlarged cervical lymph nodes...
October 6, 2020: World Journal of Clinical Cases
Dayong Xiao, Siyuan Dong, Shize Yang, Zhenghua Liu
Background: Lung adenocarcinoma (ACA) is the most common subtype of non-small-cell lung cancer. About 70%-80% patients are diagnosed at an advanced stage; therefore, the survival rate is poor. It is urgent to discover accurate markers that can differentiate the late stages of lung ACA from the early stages. With the development of biochips, researchers are able to efficiently screen large amounts of biological analytes for multiple purposes. Methods: Our team downloaded GSE75037 and GSE32863 from the Gene Expression Omnibus (GEO) database...
2020: PeerJ
Dan Wang, Mingyue Li, Jing Li, Xuechao Wan, Yan Huang, Chenji Wang, Pu Zhang, Yangguang Xu, Zhe Kong, Yali Lu, Xinmei Wang, Chuan Liu, Chaoneng Ji, Liang Li
The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs...
2020: Disease Markers
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