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Modelling somatic growth

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https://www.readbyqxmd.com/read/27910069/lkb1-as-a-tumor-suppressor-in-uterine-cancer-mouse-models-and-translational-studies
#1
Christopher G Peña, Diego H Castrillón
The LKB1 tumor suppressor was identified in 1998 as the gene mutated in the Peutz-Jeghers Syndrome (PJS), a hereditary cancer predisposition characterized by gastrointestinal polyposis and a high incidence of cancers, particularly carcinomas, at a variety of anatomic sites including the gastrointestinal tract, lung, and female reproductive tract. Women with PJS have a high incidence of carcinomas of the uterine corpus (endometrium) and cervix. The LKB1 gene is also somatically mutated in human cancers arising at these sites...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27873321/life-history-traits-of-the-long-nosed-skate-dipturus-oxyrinchus
#2
A Bellodi, C Porcu, R Cannas, Al Cau, M F Marongiu, A Mulas, S Vittori, M C Follesa
This work investigates life-history traits of the long-nosed skate Dipturus oxyrinchus, which is a common by-catch in Sardinian waters. The reproductive variables were analysed from 979 specimens sampled during scientific and commercial hauls. Females (10·4-117·5 cm total length, LT ) attained larger sizes than males (14·5-99·5 cm LT ). To evaluate age and growth, a sub-sample of 130 individuals (76 females and 54 males) were used. The age was estimated by annuli counts of sectioned vertebral centra...
November 21, 2016: Journal of Fish Biology
https://www.readbyqxmd.com/read/27843891/establishment-and-maintenance-of-the-human-na%C3%A3-ve-cd4-t-cell-compartment
#3
REVIEW
Susana L Silva, Ana E Sousa
The naïve CD4(+) T-cell compartment is considered essential to guarantee immune competence throughout life. Its replenishment with naïve cells with broad diverse receptor repertoire, albeit with reduced self-reactivity, is ensured by the thymus. Nevertheless, cumulative data support a major requirement of post-thymic proliferation both for the establishment of the human peripheral naïve compartment during the accelerated somatic growth of childhood, as well as for its lifelong maintenance. Additionally, a dynamic equilibrium is operating at the cell level to fine-tune the T-cell receptor threshold to activation and survival cues, in order to counteract the continuous naïve cell loss by death or conversion into memory/effector cells...
2016: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/27832915/can-stopping-nerves-stop-cancer
#4
REVIEW
Jami L Saloman, Kathryn M Albers, Andrew D Rhim, Brian M Davis
The nervous system is viewed as a tissue affected by cancer and as a conduit for the transmission of cancer pain and perineural invasion. Here, we review recent studies that indicate a more direct role. Several studies have shown that reducing stress or suppressing sympathetic drive correlates with improved outcomes and prolonged survival. Recent studies using animal models of visceral and somatic cancer further support a role for the nervous system in cancer progression. Specifically, nerve ablation had a profound impact on disease progression, including delayed development of precancerous lesions, and decreased tumor growth and metastasis...
November 7, 2016: Trends in Neurosciences
https://www.readbyqxmd.com/read/27810487/triclosan-exposure-results-in-alterations-of-thyroid-hormone-status-and-retarded-early-development-and-metamorphosis-in-cyprinodon-variegatus
#5
Joseph G Schnitzler, Bruno Frédérich, Mélanie Dussenne, Peter H M Klaren, Frédéric Silvestre, Krishna Das
Thyroid hormones are critically involved in somatic growth, development and metamorphosis of vertebrates. The structural similarity between thyroid hormones and triclosan, an antimicrobial compound widely employed in consumer personal care products, suggests triclosan can have adverse effects on the thyroid system. The sheepshead minnow, Cyprinodon variegatus, is now used in ecotoxicological studies that have recently begun to focus on potential disruption of the thyroid axis by endocrine disrupting compounds...
December 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27797914/oocyte-somatic-cell-interactions-in-the-human-ovary-novel-role-of-bone-morphogenetic-proteins-and-growth-differentiation-factors
#6
REVIEW
Hsun-Ming Chang, Jie Qiao, Peter C K Leung
BACKGROUND: Initially identified for their capability to induce heterotopic bone formation, bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor β superfamily. Using cellular and molecular genetic approaches, recent studies have implicated intra-ovarian BMPs as potent regulators of ovarian follicular function. The bi-directional communication of oocytes and the surrounding somatic cells is mandatory for normal follicle development and oocyte maturation...
October 26, 2016: Human Reproduction Update
https://www.readbyqxmd.com/read/27790870/critical-roles-of-cyclin-d1-in-mouse-embryonic-fibroblast-cell-reprogramming
#7
Hye-Rim Oh, Junghoon Kim, Jungho Kim
Although pluripotent stem cells hold great promise in the fields of human disease modeling and regenerative medicine, the molecular basis of Oct-4, Sox2, Klf4, and c-Myc (OSKM)-induced cellular reprogramming remains unclear. To investigate the molecular mechanisms involved in cellular reprogramming, we studied the immediate effects of expression of the OSKM reprogramming factors on mouse embryonic fibroblasts (MEFs) in this study. Induction of the OSKM reprogramming factors significantly altered primary MEF growth properties...
October 28, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27780883/human-umbilical-perivascular-cells-a-novel-source-of-mscs-to-support-testicular-niche-regeneration
#8
Leila Maghen, Ekaterina Shlush, Itai Gat, Melissa Filice, Tanya Barretto, Keith Jarvi, Kirk Lo, Andree S Gauthier-Fisher, Clifford L Librach
The expansion of functional testicular biopsy-derived human spermatogonial stem cells (hSSC) ex-vivo may enable the restoration of fertility in pre-pubertal males having undergone gonadotoxic therapies or men with severe male factor infertility. Various somatic cells are known to regulate SSC homeostasis and spermatogenesis in the developing and adult testis. Prior attempts to recapitulate this niche demonstrated the requirement of feeder cells, such as endogenous testicular somatic cells, for germ cell expansion ex-vivo...
October 25, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27774607/erythrocytosis-in-hepatocellular-carcinoma-portends-poor-prognosis-by-respiratory-dysfunction-secondary-to-mitochondrial-dna-mutations
#9
Shizhong Ke, Shuzhen Chen, Zihui Dong, Christopher S Hong, Qi Zhang, Liang Tang, Pinghua Yang, Jian Zhai, Hexin Yan, Feng Shen, Zhengping Zhuang, Wen Wen, Hongyang Wang
: Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma (HCC). Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear. Here we demonstrated an inverse relationship between EPO production and overall prognosis in our cohort of 664 patients as well as in data from The Cancer Genome Atlas (TCGA). In the subset of HCC patients with erythrocytosis, we identified somatic mutations of mitochondrial DNA, resulting impairment of respiratory metabolism, which sequentially led to depletion of α-ketoglutarate, stabilization of hypoxia inducible factor-α and expression of target genes such as EPO...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27751729/genomic-biomarkers-of-a-randomized-trial-comparing-first-line-everolimus-and-sunitinib-in-patients-with-metastatic-renal-cell-carcinoma
#10
James J Hsieh, David Chen, Patricia I Wang, Mahtab Marker, Almedina Redzematovic, Ying-Bei Chen, S Duygu Selcuklu, Nils Weinhold, Nancy Bouvier, Kety H Huberman, Umesh Bhanot, Michael S Chevinsky, Parul Patel, Patrizia Pinciroli, Helen H Won, Daoqi You, Agnes Viale, William Lee, A Ari Hakimi, Michael F Berger, Nicholas D Socci, Emily H Cheng, Jennifer Knox, Martin H Voss, Maurizio Voi, Robert J Motzer
BACKGROUND: Metastatic renal cell carcinoma (RCC) patients are commonly treated with vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin inhibitors. Correlations between somatic mutations and first-line targeted therapy outcomes have not been reported on a randomized trial. OBJECTIVE: To evaluate the relationship between tumor mutations and treatment outcomes in RECORD-3, a randomized trial comparing first-line everolimus (mTOR inhibitor) followed by sunitinib (VEGF inhibitor) at progression with the opposite sequence in 471 metastatic RCC patients...
October 14, 2016: European Urology
https://www.readbyqxmd.com/read/27750381/molecular-heterogeneity-of-non-small-cell-lung-carcinoma-patient-derived-xenografts-closely-reflect-their-primary-tumors
#11
Dennis Wang, Nhu-An Pham, Jiefei Tong, Shingo Sakashita, Ghassan Allo, Lucia Kim, Naoki Yanagawa, Vibha Raghavan, Yuhong Wei, Christine To, Quang M Trinh, Maud H W Starmans, Michelle A Chan-Seng-Yue, Dianne Chadwick, Lei Li, Chang-Qi Zhu, Ni Liu, Ming Li, Sharon Lee, Vladimir Ignatchenko, Dan Strumpf, Paul Taylor, Nadeem Moghal, Geoffrey Liu, Paul C Boutros, Thomas Kislinger, Melania Pintilie, Igor Jurisica, Frances A Shepherd, John D McPherson, Lakshmi Muthuswamy, Michael F Moran, Ming-Sound Tsao
Availability of lung cancer models that closely mimic human tumors remains a significant gap in cancer research, as tumor cell lines and mouse models may not recapitulate the spectrum of lung cancer heterogeneity seen in patients. We aimed to establish a patient-derived tumor xenograft (PDX) resource from surgically resected non-small cell lung cancer (NSCLC). Fresh tumor tissue from surgical resection was implanted and grown in the subcutaneous pocket of non-obese severe combined immune deficient (NOD SCID) gamma mice...
October 17, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27730431/genetic-mechanisms-of-adpkd
#12
Do Yeon Kim, Jong Hoon Park
Autosomal dominant polycystic kidney disease is caused by mutation of PKD1 (polycystic kidney disease-1) or PKD2 (polycystic kidney disease-2). PKD1 and PKD2 encode PC1 (polycystin-1) and PC2 (polycystin-2), respectively. In addition, the mutation of cilia-associated proteins is also a recognized major factor of pathogenesis, since PC1 and PC2 are located in primary cilium. Abnormalities of PC1 or PC2 lead to aberrant signaling through downstream pathways, such as the negative growth regulation, G protein activation, and canonical and non-canonical Wnt pathways...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27729523/germline-replications-and-somatic-mutation-accumulation-are-independent-of-vegetative-life-span-in-arabidopsis
#13
J Matthew Watson, Alexander Platzer, Anita Kazda, Svetlana Akimcheva, Sona Valuchova, Viktoria Nizhynska, Magnus Nordborg, Karel Riha
In plants, gametogenesis occurs late in development, and somatic mutations can therefore be transmitted to the next generation. Longer periods of growth are believed to result in an increase in the number of cell divisions before gametogenesis, with a concomitant increase in mutations arising due to replication errors. However, there is little experimental evidence addressing how many cell divisions occur before gametogenesis. Here, we measured loss of telomeric DNA and accumulation of replication errors in Arabidopsis with short and long life spans to determine the number of replications in lineages leading to gametes...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27723723/microenvironment-dependent-growth-of-preneoplastic-and-malignant-plasma-cells-in-humanized-mice
#14
Rituparna Das, Till Strowig, Rakesh Verma, Srinivas Koduru, Anja Hafemann, Stephanie Hopf, Mehmet H Kocoglu, Chiara Borsotti, Lin Zhang, Andrew Branagan, Elizabeth Eynon, Markus G Manz, Richard A Flavell, Madhav V Dhodapkar
Most human cancers, including myeloma, are preceded by a precursor state. There is an unmet need for in vivo models to study the interaction of human preneoplastic cells in the bone marrow microenvironment with non-malignant cells. Here, we genetically humanized mice to permit the growth of primary human preneoplastic and malignant plasma cells together with non-malignant cells in vivo. Growth was largely restricted to the bone marrow, mirroring the pattern in patients with myeloma. Xenografts captured the genomic complexity of parental tumors and revealed additional somatic changes...
November 2016: Nature Medicine
https://www.readbyqxmd.com/read/27715402/effects-of-cyclin-dependent-kinase-9-inhibition-on-zebrafish-larvae
#15
Gianfranco Matrone, John J Mullins, Carl S Tucker, Martin A Denvir
CDK9 is a known regulator of cellular transcription, growth and proliferation. Small molecule inhibitors are currently being developed and assessed in clinical trials as anti-cancer drugs. The zebrafish embryo provides an ideal model to explore the effects of CDK9 inhibition in-vivo. This has not been adequately explored previously at the level of a whole organism. We have compared and contrasted the effects of pharmacological and molecular inhibition of CDK9 on somatic growth, apoptosis and cellular proliferation in zebrafish larvae between 0 to 120 hours post fertilisation (hpf) using flavopiridol, a selective CDK9 antagonist, and CDK9-targeting morpholino...
October 7, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27702896/mutational-landscape-of-egfr-myc-and-kras-driven-genetically-engineered-mouse-models-of-lung-adenocarcinoma
#16
David G McFadden, Katerina Politi, Arjun Bhutkar, Frances K Chen, Xiaoling Song, Mono Pirun, Philip M Santiago, Caroline Kim-Kiselak, James T Platt, Emily Lee, Emily Hodges, Adam P Rosebrock, Roderick T Bronson, Nicholas D Socci, Gregory J Hannon, Tyler Jacks, Harold Varmus
Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene...
October 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27682877/tumour-suppressor-gene-cdkna2-status-on-chromosome-9p-in-resected-renal-tissue-improves-prognosis-of-localised-kidney-cancer
#17
Ismail El-Mokadem, Thomas Kidd, Norman Pratt, Stewart Fleming, Ghulam Nabi
BACKGROUND: Genetic alterations on chromosome 9p, including inactivation of the tumour suppressor gene, CDKN2A, result in cellular proliferation and growth of tumours. Our aim was to use microsatellite analysis and fluorescence in situ hybridization (FISH) to characterise the architecture of this region. RESULTS: Seventy-five out of 77 clear cell renal cell cancers (tumour/normal pairs) were interpretable for LOH analysis on chromosome 9p (two tumours were excluded, as all five primers were uninformative)...
September 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27681435/truncating-prolactin-receptor-mutations-promote-tumor-growth-in-murine-estrogen-receptor-alpha-mammary-carcinomas
#18
Obi L Griffith, Szeman Ruby Chan, Malachi Griffith, Kilannin Krysiak, Zachary L Skidmore, Jasreet Hundal, Julie A Allen, Cora D Arthur, Daniele Runci, Mattia Bugatti, Alexander P Miceli, Heather Schmidt, Lee Trani, Krishna-Latha Kanchi, Christopher A Miller, David E Larson, Robert S Fulton, William Vermi, Richard K Wilson, Robert D Schreiber, Elaine R Mardis
Estrogen receptor alpha-positive (ERα+) luminal tumors are the most frequent subtype of breast cancer. Stat1(-/-) mice develop mammary tumors that closely recapitulate the biological characteristics of this cancer subtype. To identify transforming events that contribute to tumorigenesis, we performed whole genome sequencing of Stat1(-/-) primary mammary tumors and matched normal tissues. This investigation identified somatic truncating mutations affecting the prolactin receptor (PRLR) in all tumor and no normal samples...
September 27, 2016: Cell Reports
https://www.readbyqxmd.com/read/27671533/how-old-are-you-genet-age-estimates-in-a-clonal-animal
#19
M K Devlin-Durante, M W Miller, W F Precht, I B Baums
Foundation species such as redwoods, seagrasses and corals are often long-lived and clonal. Genets may consist of hundreds of members (ramets) and originated hundreds to thousands of years ago. As climate change and other stressors exert selection pressure on species, the demography of populations changes. Yet, because size does not indicate age in clonal organisms, demographic models are missing data necessary to predict the resilience of many foundation species. Here, we correlate somatic mutations with genet age of corals and provide the first, preliminary estimates of genet age in a colonial animal...
November 2016: Molecular Ecology
https://www.readbyqxmd.com/read/27649385/embryonic-stem-like-cells-from-rabbit-blastocysts-cultured-with-melatonin-could-differentiate-into-three-germ-layers-in-vitro-and-in-vivo
#20
Ruxue Wei, Xueming Zhao, Haisheng Hao, Weihua Du, Huabin Zhu
The rabbit is considered an important model animal from which to obtain embryonic stem cells because of the utility of this animal in physiology and reproductive research. Here, we derived rabbit ES-like (rES-like) cells from blastocysts of superovulated Japanese white rabbits using culture medium containing 10(-7)  M melatonin, 10 ng/mL basic fibroblast growth factor, and 1,000 IU/mL human leukemia inhibitory factor. This concentration of melatonin had the most significant positive effects on the proliferation inner cell mass-derived cells (improving rates from 19...
November 2016: Molecular Reproduction and Development
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