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https://www.readbyqxmd.com/read/29239031/molecular-alterations-of-neuroendocrine-tumours-of-the-lung
#1
REVIEW
Giulio Rossi, Luca Bertero, Caterina Marchiò, Mauro Papotti
Neuroendocrine tumours of the lung comprise low [typical carcinoid (TC)], intermediate [atypical carcinoid (AC)] and high-grade [small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC)] malignancies, while a pre-invasive lesion [diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)] may generate a subset of peripheral carcinoid tumours. These neoplasms are differentiated conventionally based on mitotic rate, presence of necrosis and cytological details, according to the 2015 World Health Organisation (WHO) classification...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29232546/breaking-down-barriers-to-chemoresistance-role-of-chemotherapy-induced-osteoblastic-jagged1
#2
Khalid S Mohammad, Theresa A Guise
Bone metastases are incurable. The bone microenvironment has always been a suspect for this clinical enigma, but the exact mechanisms have been unclear. In this issue of Cancer Cell, Zheng and colleagues provide evidence that chemotherapy itself induces chemoresistance of bone metastases, mediated by osteoblast Jagged1-induced tumor Notch signaling.
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29228002/comparative-cell-cycle-transcriptomics-reveals-synchronization-of-developmental-transcription-factor-networks-in-cancer-cells
#3
Johan Boström, Zuzana Sramkova, Alena Salašová, Helena Johard, Diana Mahdessian, Radek Fedr, Carolyn Marks, Jiřina Medalová, Karel Souček, Emma Lundberg, Sten Linnarsson, Vítězslav Bryja, Petra Sekyrova, Mikael Altun, Michael Andäng
The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors (TFs) and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchronized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression. We developed a novel algorithm for data analysis that enables efficient visualization and data comparisons and identified cell cycle synchronization of Notch signalling and TFs associated with development...
2017: PloS One
https://www.readbyqxmd.com/read/29220293/pathologic-angiogenesis-of-malignant-vascular-sarcomas-implications-for-treatment
#4
Jalal A Khan, Robert G Maki, Vinod Ravi
Angiosarcoma, epithelioid hemangioendothelioma, and Kaposi sarcoma are classified according to the line of differentiation that these neoplastic cells most closely resemble: the endothelial cell. Although these malignant vascular sarcomas demonstrate immunohistochemical and ultrastructural features typical of this lineage, they vary dramatically in presentation and behavior, reflecting oncologic mechanisms unique to each. Antineoplastic therapies offer significant benefit, but because of the rarity of these cancers, novel therapies are slow to develop, and treatment options for these cancers remain limited...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29218101/delta-notch-like-epidermal-growth-factor-related-receptor-dner-orchestrates-stemness-and-cancer-progression-in-prostate-cancer
#5
Lijun Wang, Qi Wu, Shan Zhu, Zhiyu Li, Jingping Yuan, Dehua Yu, Zhiliang Xu, Juanjuan Li, Shengrong Sun, Changhua Wang
DNER, Delta/Notch-like epidermal growth factor (EGF)-related receptor, is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats. The function of DNER in prostate cancer has not been evaluated. Here, we showed that the upregulation of DNER is observed in various cancers, including prostate cancer. Knockdown of DNER in PC-3 cells inhibited cell proliferation, migration and invasion as well as tumorigenesis in PC-3 xenografts. DNER knockdown specifically inhibited cell growth in spheroids...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29208636/homeodomain-interacting-protein-kinase-promotes-tumorigenesis-and-metastatic-cell-behavior
#6
Jessica A Blaquiere, Kenneth Kin Lam Wong, Stephen D Kinsey, Jin Wu, Esther M Verheyen
Aberrations in signaling pathways that regulate tissue growth often lead to tumorigenesis. Homeodomain interacting protein kinase (Hipk) family members are reported to have distinct and contradictory effects on cell proliferation and tissue growth. From these studies it is clear that much remains to be learned about the roles of Hipk family protein kinases in proliferation and cell behaviour. Previous work has shown that Drosophila Hipk is a potent growth regulator, thus we predicted that it could have a role in tumorigenesis...
November 20, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29207146/interference-of-notch-1-inhibits-the-proliferation-and-invasion-of-breast-cancer-cells-involvement-of-the-%C3%AE-%C3%A2-catenin-signaling-pathway
#7
Xi Xi Lai, Gang Li, Baochai Lin, Han Yang
Breast cancer is one of the most common types of carcinoma in humans. The aim of the present study was to identify the role of Notch 1 in the proliferation and invasion of human breast cancer cells. Firstly, the levels of Notch 1 were determined by western blot analysis in breast cancer cell lines, and the results revealed that the expression levels of Notch 1 were markedly higher in MDA‑MB‑231 and MCF‑7 cells, and lower in MCF‑10A cells, compared with human mammary epithelial cells. An MTT assay was used to determine the viability of breast cancer cells...
November 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29206870/loss-of-polarity-alters-proliferation-and-differentiation-in-low-grade-endometrial-cancers-by-disrupting-notch-signaling
#8
Erin Williams, Alejandro Villar-Prados, Jessica Bowser, Russell Broaddus, Andrew B Gladden
Cell adhesion and apicobasal polarity together maintain epithelial tissue organization and homeostasis. Loss of adhesion has been described as a prerequisite for the epithelial to mesenchymal transition. However, what role misregulation of apicobasal polarity promotes tumor initiation and/or early progression remains unclear. We find that human low-grade endometrial cancers are associated with disrupted localization of the apical polarity protein Par3 and Ezrin while, the adhesion molecule E-cadherin remains unchanged, accompanied by decreased Notch signaling, and altered Notch receptor localization...
2017: PloS One
https://www.readbyqxmd.com/read/29202800/genistein-induces-apoptosis-of-colon-cancer-cells-by-reversal-of-epithelial-to-mesenchymal-via-a-notch1-nf-%C3%AE%C2%BAb-slug-e-cadherin-pathway
#9
Panpan Zhou, Chunling Wang, Zebin Hu, Wenruo Chen, Wentao Qi, Aike Li
BACKGROUND: Genistein has been known to inhibit proliferation and induce apoptosis in several kinds of cancer cells. While knowledge of genistein in regulating epithelial mesenchymal transition (EMT) of colon cancer cells is unknown. METHODS: To investigate the effects and mechanisms of genistein on EMT of colon cancer cells, HT-29 cells were used and treated by genistein and TNF-α in this paper. EMT was determined by cell invasion assays using a transwell chamber and the expression changes of EMT-related markers were confirmed by RT-PCR, Western blotting, and immunofluorescence staining...
December 4, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29198824/inhibition-of-farnesyltransferase-potentiates-notch-targeted-therapy-against-glioblastoma-stem-cells
#10
Yufang Ma, Zhixiang Cheng, Jing Liu, Luke Torre-Healy, Justin D Lathia, Ichiro Nakano, Yan Guo, Reid C Thompson, Michael L Freeman, Jialiang Wang
Accumulating evidence suggests that cancer cells with stem cell-like phenotypes drive disease progression and therapeutic resistance in glioblastoma (GBM). NOTCH regulates self-renewal and resistance to chemoradiotherapy in GBM stem cells. However, NOTCH-targeted γ-secretase inhibitors (GSIs) exhibited limited efficacy in GBM patients. We found that farnesyltransferase inhibitors (FTIs) significantly improved sensitivity to GSIs. This combination showed significant antineoplastic and radiosensitizing activities in GBM stem cells, whereas non-stem GBM cells were resistant...
November 23, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29197587/analysis-of-mirna-expression-profiles-in-melatonin-exposed-gc-1-spg-cell-line
#11
Xiaoling Zhu, Shuxiong Chen, Yanwen Jiang, Ying Xu, Yun Zhao, Lu Chen, Chunjin Li, Xu Zhou
Melatonin is an endocrine neurohormone secreted by pinealocytes in the pineal gland. It exerts diverse physiological effects, such as circadian rhythm regulator and antioxidant. However, the functional importance of melatonin in spermatogenesis regulation remains unclear. The objectives of this study are to: (1) detect melatonin affection on miRNA expression profiles in GC-1 spg cells by miRNA deep sequencing (DeepSeq) and (2) define melatonin affected miRNA-mRNA interactions and associated biological processes using bioinformatics analysis...
November 29, 2017: Gene
https://www.readbyqxmd.com/read/29196129/stanniocalcin-1-augments-stem-like-traits-of-glioblastoma-cells-through-binding-and-activating-notch1
#12
Yong Li, Zhi-Cheng He, Xiao-Ning Zhang, Qing Liu, Cong Chen, Zheng Zhu, Qian Chen, Yu Shi, Xiao-Hong Yao, You-Hong Cui, Xia Zhang, Yan Wang, Hsiang-Fu Kung, Yi-Fang Ping, Xiu-Wu Bian
Glioblastoma (GBM) is a fatal tumor and comprises heterogeneous cells in which a subpopulation with stem cell-like properties is included. Cancer cells with stem cell-like properties account for tumor initiation, drug resistance and recurrence. To identify and characterize specific factors in regulating stem-like traits is critical for GBM therapeutic. Here, we showed that Stanniocalcin-1 (STC1), a secretory glycoprotein, functions as a novel stimulator for stem-like traits of GBM cells. We found STC1 was prominently expressed in glioma spheres which are mainly comprised of glioma stem-like cells...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29193083/integrating-expression-related-snps-into-genome-wide-gene-pathway-based-analysis-identified-novel-lung-cancer-susceptibility-genes
#13
Yuzhuo Wang, Weibing Wu, Meng Zhu, Cheng Wang, Wei Shen, Yang Cheng, Liguo Geng, Zhihua Li, Jiahui Zhang, Juncheng Dai, Hongxia Ma, Liang Chen, Zhibin Hu, Guangfu Jin, Hongbing Shen
Traditional pathway analysis map single nucleotide polymorphisms (SNPs) to genes according to physical position, which lacks sufficient biological bases. Here we incorporated genetics of gene expression into gene and pathway based analysis to identify genes and pathways associated with lung cancer risk. We identified expression related SNPs (eSNPs) in lung tissues and integrated these eSNPs into three lung cancer genome wide association studies (GWASs), including 12,843 lung cancer cases and 12,639 controls...
November 30, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29188408/phase-ib-trial-of-the-anti-cancer-stem-cell-dll4-binding-agent-demcizumab-with-pemetrexed-and-carboplatin-as-first-line-treatment-of-metastatic-non-squamous-nsclc
#14
Mark J McKeage, Dusan Kotasek, Ben Markman, Manuel Hidalgo, Michael J Millward, Michael B Jameson, Dean L Harris, Robert J Stagg, Ann M Kapoun, Lu Xu, Brett G M Hughes
BACKGROUND: Delta-like ligand 4-Notch (DLL4-Notch) signaling contributes to the maintenance of chemotherapy-resistant cancer stem cells and tumor vasculature. OBJECTIVE: This phase IB trial of demcizumab, an IgG2 humanized monoclonal antibody directed against DLL4, was undertaken to determine its maximum tolerated dose, safety, immunogenicity, preliminary efficacy, pharmacokinetics, and pharmacodynamics, combined with standard chemotherapy. PATIENTS AND METHODS: Forty-six treatment-naive patients with metastatic non-squamous non-small cell lung cancer (NSCLC) were enrolled in this open-label, dose-escalation study using a standard 6 + 6 design...
November 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29187638/numb-prevents-a-complete-epithelial-mesenchymal-transition-by-modulating-notch-signalling
#15
Federico Bocci, Mohit K Jolly, Satyendra C Tripathi, Mitzi Aguilar, Samir M Hanash, Herbert Levine, José N Onuchic
Epithelial-mesenchymal transition (EMT) plays key roles during embryonic development, wound healing and cancer metastasis. Cells in a partial EMT or hybrid epithelial/mesenchymal (E/M) phenotype exhibit collective cell migration, forming clusters of circulating tumour cells-the primary drivers of metastasis. Activation of cell-cell signalling pathways such as Notch fosters a partial or complete EMT, yet the mechanisms enabling cluster formation remain poorly understood. Using an integrated computational-experimental approach, we examine the role of Numb-an inhibitor of Notch intercellular signalling-in mediating EMT and clusters formation...
November 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29187584/a-novel-bispecific-c-met-ctla-4-antibody-targeting-lung-cancer-stem-cell-like-cells-with-therapeutic-potential-in-human-non-small-cell-lung-cancer
#16
Jian-Feng Li, Yuan-Yuan Niu, Yan-Li Xing, Feng Liu
A novel paradigm in tumor biology suggests that non-small cell lung cancer (NSCLC) growth is driven by lung cancer stem cell-like cells (LCSCs), but here are still not any effective strategies to remove LCSCs. The bispecific antibody is a novel antibody, which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. Here, we designed and synthesized a new bispecific antibody (BsAb), BsAb-5, that can target cellular-mesenchymal to epithelial transition factor (c-MET) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in CD166+ LCSCs with high affinity and specificity, for the first time...
November 29, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29184875/assessing-cosmetic-results-after-conventional-thyroidectomy-using-the-easy-eye_c-a-double-blind-randomized-controlled-trial
#17
Kwan Ho Lee, Eun Young Kim, Chan Heun Park, Yong Lai Park, Ji Sup Yun, Ga Young Lee
Purpose: The incidence of thyroid cancer is relatively high, especially in young women, and postoperative scarring after thyroidectomy is an important problem for both patients and clinicians. Currently, there is no available product that can be used for wound protection during thyroid surgery. We used the EASY-EYE_C, a new silicone-based wound protector. Methods: We conducted a double-blind randomized controlled trial to assess the efficacy of the EASY-EYE_C with surgical scars...
November 2017: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/29181054/predictive-values-of-notch-signalling-in-renal-carcinoma
#18
Dorota Jędroszka, Magdalena Orzechowska, Andrzej K Bednarek
Introduction: Notch signalling, an evolutionarily conserved mechanism of cellular differentiation and tissue remodelling, is frequently deregulated in several human malignancies, including renal cell carcinoma (RCC). However, the prognostic value of individual Notch pathway members in RC subtypes remains indefinable. The present study investigates whether the differential expression of Notch members has a contrary effect on disease-free survival (DFS) in clear cell renal cell carcinoma (KIRC), papillary cell renal cell carcinoma (KIRP) and chromophobe renal cell carcinoma (KICH) patients...
October 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29176671/inhibition-of-delta-induced-notch-signaling-using-fucose-analogs
#19
Michael Schneider, Vivek Kumar, Lars Ulrik Nordstrøm, Lei Feng, Hideyuki Takeuchi, Huilin Hao, Vincent C Luca, K Christopher Garcia, Pamela Stanley, Peng Wu, Robert S Haltiwanger
Notch is a cell-surface receptor that controls cell-fate decisions and is regulated by O-glycans attached to epidermal growth factor-like (EGF) repeats in its extracellular domain. Protein O-fucosyltransferase 1 (Pofut1) modifies EGF repeats with O-fucose and is essential for Notch signaling. Constitutive activation of Notch signaling has been associated with a variety of human malignancies. Therefore, tools that inhibit Notch activity are being developed as cancer therapeutics. To this end, we screened L-fucose analogs for their effects on Notch signaling...
November 27, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29175872/notch-pathway-inhibition-targets-chemoresistant-insulinoma-cancer-stem-cells
#20
Ylenia Capodanno, Floryne O Buishand, Lisa Y Pang, Jolle Kirpensteijn, Jan A Mol, David J Argyle
Insulinomas (INS) are the most common neuroendocrine pancreatic tumours in humans and dogs. The long-term prognosis for malignant INS is still poor due to a low success rate of the current treatment modalities, particularly chemotherapy. A better understanding of the molecular processes underlying the development and progression of INS is required to develop novel targeted therapies. Cancer stem cells (CSCs) are thought to be critical for the engraftment and chemoresistance of many tumours, including INS. This study was aimed to characterise and target INS CSCs in order to develop novel targeted therapies...
November 24, 2017: Endocrine-related Cancer
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