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Annikka Weissferdt
Pulmonary sarcomatoid carcinomas belong to a group of neoplasms that remain incompletely understood. They are rare tumors of the bronchopulmonary system that incorporate a wide range of neoplasms that by definition contain a sarcomatoid component characterized by spindle or giant cells. Such classification has led to a heterogenous tumor category that includes neoplasms with different clinical, morphologic, and prognostic features. To date, the histopathologic diagnosis of pulmonary sarcomatoid carcinomas does not require the use of ancillary testing and is based on light microscopic criteria alone...
June 15, 2018: Advances in Anatomic Pathology
Natasja Leth Bergholt, Morten Foss, Anwer Saeed, Nikolaj Gadegaard, Helle Lysdahl, Martin Lind, Casper Bindzus Foldager
Understanding the behavior of chondrocytes in contact with artificial culture surfaces is becoming increasingly important in attaining appropriate ex vivo culture conditions of chondrocytes in cartilage regeneration. Chondrocyte transplantation-based cartilage repair requires efficiently expanded chondrocytes and the culture surface plays an important role in guiding the behavior of the cell. Micro- and nanoengineered surfaces make it possible to modulate cell behavior. We hypothesized that the combined influence of topography, substrate, and surface chemistry may affect the chondrocyte culturing in terms of proliferation and phenotypic means...
June 16, 2018: Journal of Biomedical Materials Research. Part A
Partha Hota, Chandra Dass, Maruti Kumaran, Xiaofeng Zhao, Nirag Jhala, Scott Simpson
Although the lung is a common site for metastatic disease from extrathoracic malignancies, a pattern of lepidic growth of these metastases is considered rare. A 67-year-old man with a history of partial hepatectomy for hepatocellular carcinoma (HCC) presented to our hospital with dyspnea and a nonproductive cough. Chest radiographs and computed tomography imaging demonstrated consolidation in the right upper lobe and an ipsilateral pleural effusion. Findings were initially suspected to be secondary to infection, given the radiographic appearance and the rapid development from a normal computed tomography 3 months previously...
April 2018: Radiology Case Reports
Baljinder S Dhinsa, Mariagrazia DeLisa, Rob Pollock, Adrienne M Flanagan, Jeremy Whelan, Jonathan Gregory
No abstract text is available yet for this article.
June 15, 2018: Oncology Research and Treatment
Arnav Mehta, Yeon Joo Kim, Lidia Robert, Jennifer Tsoi, Begoña Comin-Anduix, Beata Berent-Maoz, Alistair J Cochran, James Economou, Paul C Tumeh, Cristina Puig-Saus, Antoni Ribas
A promising arsenal of targeted and immunotherapy treatments for metastatic melanoma has emerged over the last decade. With these therapies, we now face new mechanisms of tumor acquired resistance. We report here a patient whose metastatic melanoma underwent dedifferentiation as a resistance mechanism to adoptive T cell transfer therapy (ACT) to the MART-1 antigen, a phenomenon that had only been observed in mouse studies to date. After an initial period of tumor regression, the patient presented in relapse with tumors lacking melanocytic antigens (MART-1, gp100) and expressing an inflammation-induced neural crest marker (NGFR)...
June 13, 2018: Cancer Discovery
Rebecca Lawson, Wolfgang Maret, Christer Hogstrand
Zinc is integral for the normal function of pancreatic β-cells in glycaemic control. Large amounts of zinc are secreted from β-cells following insulin exocytosis and regulated replenishment is required, which is thought to be mediated by the ZIP family of zinc importer proteins. Within Type 2 Diabetic patients, β-cells are stressed through prolonged stimulation by hyperglycaemia and this is thought to be a major factor contributing to loss of β-cell identity and mass. However, the consequences for the β-cell zinc status remain largely unexplored...
September 2018: Journal of Trace Elements in Medicine and Biology
Shuang Wang, Lichuan Yang, Raoxian Bai, Shuaiwei Ren, Yuyu Niu, Weizhi Ji, Yuanye Ma, Yongchang Chen
The tumor suppressor p53 is a key regulator of cell apoptosis and cell cycle arrest. Recent studies show that the delicate balance of p53 expression is important for neural tube defects, neuronal degeneration, embryonic lethality, as well as differentiation and dedifferentiation. Moreover, p53 showed different regulatory patterns between rodent and primate embryonic stem cells (ESCs). However, the role of p53 and apoptosis stimulating protein of p53 (ASPP) during neural differentiation (ND) from primate ESCs is still unknown...
June 12, 2018: Cell Cycle
Yen-An Tang, Yu-Feng Chen, Yi Bao, Sylvia Mahara, Siti Maryam J M Yatim, Gokce Oguz, Puay Leng Lee, Min Feng, Yu Cai, Ern Yu Tan, Sau Shung Fong, Zi-Huan Yang, Ping Lan, Xiao-Jian Wu, Qiang Yu
Colorectal cancer patients often relapse after chemotherapy, owing to the survival of stem or progenitor cells referred to as cancer stem cells (CSCs). Although tumor stromal factors are known to contribute to chemoresistance, it remains not fully understood how CSCs in the hypoxic tumor microenvironment escape the chemotherapy. Here, we report that hypoxia-inducible factor (HIF-1α) and cancer-associated fibroblasts (CAFs)-secreted TGF-β2 converge to activate the expression of hedgehog transcription factor GLI2 in CSCs, resulting in increased stemness/dedifferentiation and intrinsic resistance to chemotherapy...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yosuke Yamada, Yasuhiro Yamada
There is increasing evidence that cancer cells acquire epigenetic abnormalities as well as genetic mutations during cancer initiation, maintenance, and progression. However, the role of epigenetic regulation in cancer development, especially at the organismal level, remains to be elucidated. Here, we describe the causative role of epigenetic abnormalities in cancer, referring to our in vivo studies using induced pluripotent stem cell technology. We first summarize epigenetic reorganization during cellular reprogramming and introduce our in vivo reprogramming system for investigating the impact of dedifferentiation-driven epigenetic disruption in cancer development...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Hong Zhi, Fu-Han Gong, Wen-Lin Cheng, Kongbo Zhu, Long Chen, Yuyu Yao, Xingzhou Ye, Xue-Yong Zhu, Hongliang Li
BACKGROUND: Tollip, a well-established endogenous modulator of Toll-like receptor signaling, is involved in cardiovascular diseases. The aim of this study was to investigate the role of Tollip in neointima formation and its associated mechanisms. METHODS AND RESULTS: In this study, transient increases in Tollip expression were observed in platelet-derived growth factor-BB-treated vascular smooth muscle cells and following vascular injury in mice. We then applied loss-of-function and gain-of-function approaches to elucidate the effects of Tollip on neointima formation...
June 10, 2018: Journal of the American Heart Association
Shiyan Yu, Kevin Tong, Yanlin Zhao, Iyshwarya Balasubramanian, George S Yap, Ronaldo P Ferraris, Edward M Bonder, Michael P Verzi, Nan Gao
Paneth cells are post-mitotic intestinal epithelial cells supporting the stem cell niche and mucosal immunity. Paneth cell pathologies are observed in various gastrointestinal diseases, but their plasticity and response to genomic and environmental challenges remain unclear. Using a knockin allele engineered at the mouse Lyz1 locus, we performed detailed Paneth cell-lineage tracing. Irradiation induced a subset of Paneth cells to proliferate and differentiate into villus epithelial cells. RNA sequencing (RNA-seq) revealed that Paneth cells sorted from irradiated mice acquired a stem cell-like transcriptome; when cultured in vitro, these individual Paneth cells formed organoids...
May 23, 2018: Cell Stem Cell
Samada Muraleedharan, Carolina Freitas, Petra Mann, Timo Glatter, Simon Ringgaard
Vibrio parahaemolyticus exists as swimmer and swarmer cells, specialized for growth in liquid and on solid environments, respectively. Swarmer cells are characteristically highly elongated due to an inhibition of cell division, but still need to divide in order to proliferate and expand the colony. It is unknown how long swarmer cells divide without diminishing the population of long cells required for swarming behavior. Here we show that swarmer cells divide but the placement of the division site is cell length-dependent; short swarmers divide at mid-cell, while long swarmers switch to a specific non-mid-cell placement of the division site...
June 8, 2018: Molecular Microbiology
Joshua S MacCready, Anthony G Vecchiarelli
In many rod-shaped bacteria, the Min system is well known for generating a cell-pole to cell-pole standing wave oscillation with a single node at mid-cell to align cell division. In filamentous E. coli cells, the single-node standing wave transitions into a multi-nodal oscillation. These multi-nodal dynamics have largely been treated simply as an interesting byproduct of artificially elongated cells. However, a recent in vivo study by Muraleedharan et al. shows how multi-nodal Min dynamics are used to align non-mid-cell divisions in the elongated swarmer cells of Vibrio parahaemolyticus (in press)...
June 8, 2018: Molecular Microbiology
Lorenzo Alibardi
The formation of the regenerating tail blastema of lizards occurs by the multiplication of stem cells but also some dedifferentiation from adult cells may take place after tail loss by autotomy, as it is suggested in the present study. Using 5BrdU-immunocytochemistry and transmission electron microscopy it is shown that part of the damaged tissues undergo progressive cytological de-differentiation (cell reprogramming). This occurs for muscle, fibrocytes, chondrocytes, adipocytes, and cells derived from the spinal cord during the initial 3-8 days post-autotomy of the tail in the wall lizard Podarcis muralis...
June 8, 2018: Journal of Morphology
Matthew C Costello, Aaron T Buss
Visual working memory (VWM) is essential for executive function and is known to be compromised in older adults. Yet, the cognitive and neural processes associated with these age-related changes remain inconclusive. The purpose of this study is to explore such factors with a dynamic neural field (DNF) model that was manipulated to replicate the behavioral performances of younger and older adults in a change detection task. Although previous work has successfully modeled children and younger adult VWM performance, this study represents the first attempt to model older adult VWM performance within the DNF architecture...
June 7, 2018: Journal of Cognitive Neuroscience
Helge L Waldum, Kjell Öberg, Øystein F Sørdal, Arne K Sandvik, Bjørn I Gustafsson, Patricia Mjønes, Reidar Fossmark
Stem cells are considered the origin of neoplasms in general, and malignant tumours in particular, and the stage at which the stem cells stop their differentiation determines the degree of malignancy. However, there is increasing evidence supporting an alternative paradigm. Tumours may develop by dedifferentiation from mature cells able to proliferate. Studies of gastric carcinogenesis demonstrate that mature neuroendocrine (NE) cells upon long-term overstimulation may develop through stages of hyperplasia, dysplasia, and rather benign tumours, into highly malignant carcinomas...
2018: Therapeutic Advances in Gastroenterology
Fang Yao, Peng Yu, Yue Li, Xinli Yuan, Zheng Li, Tao Zhang, Fei Liu, Yingbao Wang, Yin Wang, Dandan Li, Baihui Ma, Chang Shu, Wei Kong, Bingying Zhou, Li Wang
Background -Histone variants endow chromatin with specific structures, and play essential roles in development and diseases. However, little is known about their roles in controlling cell identity in vascular diseases. Methods -Given the cell heterogeneity in atherosclerotic lesions, we applied single-cell RNA-Seq to analyze diseased human arteries, and identified histone variant H2A.Z as a key histone signature to maintain vascular smooth muscle cell (VSMC) identity. Results -We show that H2A.Z occupies genomic regions near VSMC marker genes and its occupancy is decreased in VSMCs undergoing dedifferentiation...
June 5, 2018: Circulation
Yiting Jia, Meili Wang, Chenfeng Mao, Fang Yu, Yingbao Wang, Rui Xiao, Changtao Jiang, Lemin Zheng, Qingbo Xu, Ming Zheng, Yi Fu, Qinghua Hu, Wei Kong
Vascular smooth muscle cells (VSMCs) are highly phenotypically plastic, and loss of the contractile phenotype in VSMCs has been recognized at the early onset of the pathology of a variety of vascular diseases. However, the endogenous regulatory mechanism to maintain contractile phenotype in VSMCs remains elusive. Moreover, little has been known about the role of the mitochondrial bioenergetics in terms of VSMC homeostasis. Herein, we asked if glycoprotein COMP (Cartilage oligomeric matrix protein) is involved in mitochondrial bioenergetics and therefore regulates VSMCs homeostasis...
June 4, 2018: Cell Death & Disease
Cedric Lebacle, Aydin Pooli, Thomas Bessede, Jacques Irani, Allan J Pantuck, Alexandra Drakaki
Long recognized to confer an extremely poor prognosis, sarcomatoid dedifferentiation of renal cell carcinoma (sRCC) is a tumor phenotype that is finally beginning to be better understood on the molecular and genetic levels. With an overall incidence that ranges from 1 to 32% depending on associated RCC subtype, the survival of sarcomatoid RCC patients rarely exceeds 2 years. The main reasons for its poor outcome include its aggressive biology, its tendency to present at an advanced or metastatic stage at the time of diagnosis, its high rate of tumor recurrence after nephrectomy, and its limited response to systemic therapies...
June 1, 2018: World Journal of Urology
Hadi Fattah, Volker Vallon
BACKGROUND: A significant portion of patients who are affected by acute kidney injury (AKI) do not fully recover due to largely unclear reasons. Restoration of tubular function has been proposed to be a prerequisite for glomerular filtration rate (GFR) recovery. SUMMARY: Proximal tubular cells dedifferentiate during the tubular injury phase, which is required for subsequent cell proliferation and replacement of lost epithelial cells. Experimental studies indicate that some cells fail to redifferentiate and continue to produce growth factors (e...
May 31, 2018: Nephron
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