journal
MENU ▼
Read by QxMD icon Read
search

Molecular Oncology

journal
https://www.readbyqxmd.com/read/28548388/epithelial-mesenchymal-plasticity-how-have-quantitative-mathematical-models-helped-improve-our-understanding
#1
REVIEW
Mohit Kumar Jolly, Satyendra C Tripathi, Jason A Somarelli, Samir M Hanash, Herbert Levine
Phenotypic plasticity, the ability of cells to reversibly alter their phenotypes in response to signals, presents a significant clinical challenge to treating solid tumors. Tumor cells utilize phenotypic plasticity to evade therapies, metastasize, and colonize distant organs. As a result, phenotypic plasticity can accelerate tumor progression. A well-studied example of phenotypic plasticity is the bidirectional conversions among epithelial, mesenchymal, and hybrid epithelial/mesenchymal phenotype(s). These conversions can alter a repertoire of cellular traits associated with multiple hallmarks of cancer, such as metabolism, immune-evasion, invasion and metastasis...
May 26, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28548345/emt-and-met-necessary-or-permissive-for-metastasis
#2
REVIEW
Mohit Kumar Jolly, Kathryn E Ware, Shivee Gilja, Jason A Somarelli, Herbert Levine
Epithelial-to-mesenchymal transition (EMT) and its reverse mesenchymal-to-epithelial transition (MET) have been suggested to play crucial roles in metastatic dissemination of carcinomas. These phenotypic transitions between states are not binary. Instead, carcinoma cells often exhibit a spectrum of epithelial/mesenchymal phenotype(s). While epithelial-mesenchymal plasticity has been observed pre-clinically and clinically, whether any of these phenotypic transitions are indispensable for metastatic outgrowth remains an unanswered question...
May 26, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544747/k-ras-mutation-and-amplification-status-is-predictive-of-resistance-and-high-basal-pakt-is-predictive-of-sensitivity-to-everolimus-in-biliary-tract-cancer-cell-lines
#3
Yvonne Yeung, David K Lau, Fiona Chionh, Hoanh Tran, Janson W T Tse, Andrew J Weickhardt, Mehrdad Nikfarjam, Andrew M Scott, Niall C Tebbutt, John M Mariadason
Advanced biliary tract cancer (BTC) has a poor prognosis and limited treatment options. The PI3K/Akt/mTOR signaling pathway is hyperactivated in a subset of BTCs and clinical activity to the mTOR inhibitor everolimus has been observed in some BTC patients. The goal of this study was to identify biomarkers predictive of everolimus response. Twenty BTC cell lines were assessed for everolimus sensitivity with a spectrum of growth inhibitory responses observed. Molecular biomarkers of sensitivity and resistance were identified by interrogation of the activation status of the Ras/MAPK and PI3K/Akt/mTOR pathways...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544627/epithelial-to-mesenchymal-transition-transcription-factors-in-cancer-associated-fibroblasts
#4
REVIEW
Josep Baulida
Beyond inducing epithelial-to-mesenchymal transcription (EMT), transcriptional factors of the Snail, ZEB and Twist families (EMT-TFs) control global plasticity programs affecting cell stemness and fate. Literature addressing the reactivation of these factors in adult tumour cells is very extensive, as they enable cancer cell plasticity and fuel both tumour initiation and metastatic spread. Incipient data reveal that EMT-TFs are also expressed in fibroblasts, providing these with additional properties. Here, I will review recent reports on the expression of EMT-TFs in cancer-associated fibroblasts (CAFs)...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544498/cancer-metastasis-through-the-prism-of-epithelial-to-mesenchymal-transition-in-circulating-tumor-cells
#5
REVIEW
Douglas S Micalizzi, Daniel A Haber, Shyamala Maheswaran
Metastasis of epithelial cancer cells to distal sites is a particularly critical stage of cancer progression that typically marks the incurability of the disease. It is governed by a complex series of events including invasion and intravasation of tumor cells into the stroma and blood, respectively. Epithelial to mesenchymal transition (EMT), a phenotypic change marked by the loss of epithelial characteristics and the acquisition of invasive mesenchymal properties, is implicated in the dissemination of tumor cells...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544264/ampk-%C3%AE-1-reduces-tumor-progression-and-improves-survival-in-p53-null-mice
#6
Vanessa P Houde, Sara Donzelli, Andrea Sacconi, Sandra Galic, Joanne A Hammill, Jonathan L Bramson, Robert A Foster, Theodoros Tsakiridis, Bruce E Kemp, Giuseppe Grasso, Giovanni Blandino, Paola Muti, Gregory R Steinberg
The AMP-activated protein kinase (AMPK) is a heterotrimeric protein complex that is an important sensor of cellular energy status. Reduced expression of the AMPK β1 isoform has been linked to reduced survival in different cancers but whether this accelerates tumor progression and the potential mechanism mediating these effects is not known. Further, it is unknown whether AMPK β1 is implicated in tumorigenesis and if so what tissues may be most sensitive. In the current study we find that in the absence of the tumor suppressor p53, germline genetic deletion of AMPK β1 accelerates the appearance of a T cell lymphoma that reduces lifespan compared to p53 deficiency alone...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544151/the-emt-spectrum-and-therapeutic-opportunities
#7
REVIEW
Dominic Chih-Cheng Voon, Ruby Yun-Ju Huang, Rebecca A Jackson, Jean Paul Thiery
Carcinomas are phenotypically arrayed along an EMT spectrum, a developmental program currently exploited to understand the acquisition of drug resistance through a re-routing of growth factor signalling. This review collates the current approaches employed in developing therapeutics against cancer-associated EMT, and provides an assessment of their respective strengths and drawbacks. We reflect on the close relationship between EMT and chemoresistance against current targeted therapeutics, with a special focus on the epigenetic mechanisms that links these processes...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28510269/kallikrein-related-peptidase-4-induces-cancer-associated-fibroblast-features-in-prostate-derived-stromal-cells
#8
T Kryza, L M Silva, N Bock, R A Fuhrman-Luck, C R Stephens, J Gao, H Samaratunga, M G Lawrence, J D Hooper, Y Dong, G P Risbridger, J A Clements
The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intra-epithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peri-stromal interface...
May 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28504856/cell-free-dna-copy-number-variations-in-plasma-from-colorectal-cancer-patients
#9
Jian Li, Rachel L Dittmar, Shu Xia, Huijuan Zhang, Meijun Du, Chiang-Ching Huang, Brooke R Druliner, Lisa Boardman, Liang Wang
To evaluate clinical utility of cell free DNA (cfDNA), we performed whole genome sequencing to systematically examine plasma cfDNA copy number variations (CNVs) in a cohort of patients with colorectal cancer (CRC, n=80), polyps (n=20) and healthy controls (n=35). We initiallycompared cfDNA yield in 20 paired serum-plasma samples and observed significantly higher cfDNA concentration in serum (median=81.20ng, range 7.18-500ng/ml) than in plasma (median=5.09ng, range 3.76-62.8ng/ml) (p<0.0001). However, tumor-derived cfDNA content was significantly lower in serum than in matched plasma samples tested...
May 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28500786/dovitinib-enhances-temozolomide-efficacy-in-glioblastoma-cells
#10
Thatchawan Thanasupawat, Suchitra Natarajan, Amy Rommel, Aleksandra Glogowska, Hugo Bergen, Jerry Krcek, Marshall Pitz, Jason Beiko, Sherry Krawitz, Inder M Verma, Saeid Ghavami, Thomas Klonisch, Sabine Hombach-Klonisch
The multikinase inhibitor and FDA-approved drug Dovitinib (Dov) crosses the blood-brain-barrier and was recently used as single drug application in clinical trials for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in GB cells are unknown. We used GB patient cells and cell lines to show that Dov downregulated the stem cell protein Lin28 and its target High Mobility Group protein A2 (HMGA2). The Dov-induced reduction in pSTAT3(Tyr705) phosphorylation demonstrated that Dov negatively affects the STAT3-LIN28-Let-7-HMGA2 regulatory axis in GB cells...
May 13, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28486761/panitumumab-interaction-with-tas-102-leads-to-combinational-anticancer-effects-via-blocking-of-egfr-mediated-tumor-response-to-trifluridine
#11
Yuji Baba, Toshiya Tamura, Yoshihiko Satoh, Masamitsu Gotou, Hiroshi Sawada, Shunsuke Ebara, Kazunori Shibuya, Jumpei Soeda, Kazuhide Nakamura
Panitumumab is a monoclonal antibody developed against the human epidermal growth factor receptor (EGFR). TAS-102 is a novel chemotherapeutic agent containing trifluridine (FTD) as the active cytotoxic component. Both panitumumab and TAS-102 have been approved for the treatment of metastatic colorectal cancer. In this study, we revealed the mechanism underlying the anticancer effects of panitumumab/TAS-102 combination using preclinical models. Panitumumab/FTD co-treatment showed additive antiproliferative effects in LIM1215 and synergistic antiproliferative effects in SW48 colon cancer cells...
May 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28486750/stromal-spock1-supports-invasive-pancreatic-cancer-growth
#12
Veronique L Veenstra, Helene Damhofer, Cynthia Waasdorp, Anne Steins, Hemant M Kocher, Jan Paul Medema, Hanneke W van Laarhoven, Maarten F Bijlsma
Pancreatic ductal adenocarcinoma (PDAC) is marked by an abundant stromal deposition. This stroma is suspected to harbor both tumor-promoting as well as -suppressing properties. This is underscored by the disappointing results of stroma targeting in clinical studies. Given the complexity of tumor-stroma interaction in PDAC, there is a need to identify the stromal proteins that are predominantly tumor-promoting. One possible candidate is SPOCK1 that we previously identified in a screening effort in PDAC. We extensively mined PDAC gene expression datasets, and used species-specific transcript analysis in mixed-species models for PDAC to study the patterns and driver mechanisms of SPOCK1 expression in PDAC...
May 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28453235/endothelial-cells-activate-the-cancer-stem-cell-associated-nanogp8-pathway-in-colorectal-cancer-cells-in-a-paracrine-fashion
#13
Rui Wang, Rajat Bhattacharya, Xiangcang Ye, Fan Fan, Delphine R Boulbes, Ling Xia, Lee M Ellis
In colorectal cancer (CRC), cancer stem cells (CSCs) have been hypothesized to mediate cell survival and chemoresistance. Previous studies from our laboratory described a role for liver parenchymal endothelial cells (LPECs) in mediating the CSC phenotype in CRC cells in a paracrine/angiocrine fashion. The objectives of this study were to determine whether endothelial cells (ECs) from different organs can induce the CSC phenotype in CRC cells and to elucidate the signaling pathways involved. We treated a newly developed CRC cell line (HCP-1) and established CRC cell lines (HT29 and SW480) with conditioned medium (CM) from primary ECs isolated from non-malignant liver, lung, colon mucosa, and kidney...
April 28, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28453226/palbociclib-induces-activation-of-ampk-and-inhibits-hepatocellular-carcinoma-in-a-cdk4-6-independent-manner
#14
Feng-Shu Hsieh, Yao-Li Chen, Man-Hsin Hung, Pei-Yi Chu, Ming-Hsien Tsai, Li-Ju Chen, Yung-Jen Hsiao, Chih-Ting Shih, Mao-Ju Chang, Tzu-I Chao, Chung-Wai Shiau, Kuen-Feng Chen
Palbociclib, a CDK4/6 inhibitor, has recently been approved for hormone receptor-positive breast cancer patients. The effects of palbociclib as a treatment for other malignancies, including hepatocellular carcinoma (HCC), are of great clinical interest and are under active investigation. Here, we report the effects and a novel mechanism of action of palbociclib in HCC. We found that palbociclib induced both autophagy and apoptosis in HCC cells through a mechanism involving 5' AMP-activated protein kinase (AMPK) activation and protein phosphatase 5 (PP5) inhibition...
April 28, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28453190/synergistic-activity-of-everolimus-and-5-aza-2-deoxycytidine-in-medullary-thyroid-carcinoma-cell-lines
#15
Giovanni Vitale, Alessandra Dicitore, Daniele Pepe, Davide Gentilini, Elisa Stellaria Grassi, Maria Orietta Borghi, Giulia Gelmini, Maria Celeste Cantone, Germano Gaudenzi, Gabriella Misso, Anna Maria Di Blasio, Leo J Hofland, Michele Caraglia, Luca Persani
Medullary thyroid cancer (MTC) is a tumor highly resistant to chemo- and radiotherapy. Drug resistance can be induced by epigenetic changes such as aberrant DNA methylation. To overcome drug resistance, we explored a promising approach based on the use of 5-aza-2'-deoxycytidine (AZA), a demethylating agent, in combination with the mTOR inhibitor everolimus in MTC cells (MZ-CRC-1 and TT). This combined treatment showed a strong synergistic antiproliferative activity through the induction of apoptosis. The effect of everolimus and/or AZA on genome-wide expression profiling was evaluated by Illumina BeadChip in MZ-CRC-1 cells...
April 28, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28432815/immunoassays-for-the-quantification-of-alk-and-phosphorylated-alk-support-the-evaluation-of-on-target-alk-inhibitors-in-neuroblastoma
#16
Elizabeth R Tucker, Jennifer R Tall, Laura S Danielson, Sharon Gowan, Yann Jamin, Simon P Robinson, Udai Banerji, Louis Chesler
Targeted inhibition of Anaplastic Lymphoma Kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies, however the presence of resistant mutations necessitates both the development of more potent compounds and pharmacodynamic methods with which to determine their efficacy. We describe immunoassays designed to quantitate phosphorylation of ALK, and their use in preclinical models of neuroblastoma, a pediatric malignancy in which gain-of-function ALK mutations predict a poor overall outcome to conventional treatment...
April 22, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28423230/gain-of-function-p53-activates-multiple-signaling-pathways-to-induce-oncogenicity-in-lung-cancer-cells
#17
Catherine A Vaughan, Shilpa Singh, Steven R Grossman, Brad Windle, Swati Palit Deb, Sumitra Deb
Gain-of-function (GOF) mutants of p53 upregulate genes implicated in cell proliferation and oncogenesis. Here, we report that GOF p53 induces tumorigenicity through simultaneous activation of key oncogenic pathways including those controlling putative tumor-initiating cell functions. We determined that in cells expressing p53-R273H, GOF p53 simultaneously upregulates genes from multiple signaling pathways by recognizing promoters containing distinct transcription factor (TF) binding sites. Our analytical data support a model in which GOF p53 complexes with two TFs on the promoter-a mediator protein, Med17, and a histone acetyl transferase, activating histone acetylation-and enhances gene expression to signal cell proliferation and oncogenesis...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28417568/cisplatin-resistant-cancer-cells-are-sensitive-to-aurora-kinase-a-inhibition-by-alisertib
#18
Lihong Wang, Janet Arras, Ahmed Katsha, Saif Hamdan, Abbes Belkhiri, Jeffrey Ecsedy, Wael El-Rifai
De novo and acquired resistance to platinum therapy such as cisplatin (CDDP) is a clinical challenge in gastric cancer treatment. Aberrant expression and activation of Aurora kinase A (AURKA) and eukaryotic translation initiation factor 4E (eIF4E) are detected in several cancer types. Herein, we investigated the role of AURKA in CDDP resistance in gastric cancer. Western blot analysis demonstrated overexpression of AURKA and phosphorylation of eIF4E in acquired and de novo CDDP-resistant gastric cancer models...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28417539/usp22-mediates-the-multidrug-resistance-of-hepatocellular-carcinoma-via-the-sirt1-akt-mrp1-signaling-pathway
#19
Sunbin Ling, Jie Li, Qiaonan Shan, Haojiang Dai, Di Lu, Xue Wen, Penghong Song, Haiyang Xie, Lin Zhou, Jimin Liu, Xiao Xu, Shusen Zheng
Drug treatments for hepatocellular carcinoma (HCC) often fail because of multidrug resistance (MDR). The mechanisms of MDR are complex but cancer stem cells (CSCs), which are able to self-renew and differentiate, have recently been shown to be involved. The deubiquitinating enzyme ubiquitin-specific protease 22 (USP22) is a marker for CSCs. This study aimed to elucidate the role of USP22 in MDR of HCC and the underlying mechanisms. Using in vitro and in vivo assays, we found that modified USP22 levels were responsible for the altered drug-resistant phenotype of BEL7402 and BEL/FU cells...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28397399/belinostat-exerts-anti-tumor-cytotoxicity-through-the-ubiquitin-proteasome-pathway-in-lung-squamous-cell-carcinoma
#20
Li Ren Kong, Tuan Zea Tan, Weijie Richard Ong, Chonglei Bi, Hung Huynh, Soo Chin Lee, Wee Joo Chng, Pieter Johan Adam Eichhorn, Boon Cher Goh
There have been advances in personalized therapy directed by molecular profiles in lung adenocarcinoma but not in lung squamous cell carcinoma (SCC). The lack of actionable driver oncogenes in SCC has restricted the use of small molecule inhibitors. Here, we show that SCC cell lines displayed differential sensitivities to belinostat, a pan-histone deacetylase (HDAC) inhibitor. Phosphoproteomic analysis of belinostat-treated SCC cells revealed significant downregulation of the MAPK pathway, along with induction of apoptosis...
April 11, 2017: Molecular Oncology
journal
journal
41656
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"