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https://www.readbyqxmd.com/read/28549032/expression-of-phosphoinositide-3-kinase-p110%C3%AE-and-p110%C3%AE-subunits-and-pik3ca-mutation-in-patients-with-advanced-gastric-carcinoma
#1
Kyungeun Kim, Hyoun Wook Lee
Activation of phosphoinositide 3-kinase (PI3K) is pivotal for the activity of the oncogenic PI3K/AKT signaling pathway. This study assessed the expression of 2 PI3K isoform proteins, p110α and p110β, and PIK3CA mutational status in advanced gastric carcinoma (AGC) and their correlation with clinicopathologic factors. Tissue microarray blocks were generated from 99 AGCs and immunohistochemically stained for p110α and p110β. Analysis of mutations in the PIK3CA gene, which encodes p110α, was performed using the PNAClamp PIK3CA Mutation Detection kit...
May 25, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28548125/next-generation-sequencing-based-molecular-characterization-of-primary-urinary-bladder-adenocarcinoma
#2
Somak Roy, Dinesh Pradhan, Wayne L Ernst, Stephanie Mercurio, Yana Najjar, Rahul Parikh, Anil V Parwani, Reetesh K Pai, Rajiv Dhir, Marina N Nikiforova
Primary bladder adenocarcinoma is a rare and aggressive tumor with poor clinical outcomes and no standard of care therapy. Molecular biology of this tumor is unknown due to the lack of comprehensive molecular profiling studies. The study aimed to identify genomic alterations of clinical and therapeutic significance using next-generation sequencing and compare genomic profile of primary bladder adenocarcinoma with that of high-grade urothelial carcinoma and colorectal adenocarcinoma. A cohort of 15 well-characterized primary bladder adenocarcinoma was subjected to targeted next-generation sequencing for the identification of mutations and copy-number changes in 51 cancer-related genes...
May 26, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28545226/emergence-of-cd26-cancer-stem-cells-with-metastatic-properties-in-colorectal-carcinogenesis
#3
Alvin Ho-Kwan Cheung, Deepak Narayanan Iyer, Colin Siu-Chi Lam, Lui Ng, Sunny K M Wong, Hung-Sing Lee, Timothy Wan, Johnny Man, Ariel K M Chow, Ronnie T Poon, Roberta Pang, Wai-Lun Law
Colorectal cancer results from genetic aberrations which accumulate over a long period of time, with malignant and metastatic properties acquired at a relatively late stage. A subpopulation of CD26+ colorectal cancer stem cells are known to be implicated in metastasis. We quantified CD26+ cancer cells in 11 primary tumor samples by flow cytometry, and showed that tumors having confirmed or suspected metastases harbored a relatively high CD26+ level in these samples. We hypothesized that this subpopulation of cancer stem cells arises in the late stage of carcinogenesis from the bulk of tumor daughter cells which are CD26-...
May 23, 2017: International Journal of Molecular Sciences
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
#4
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/28542142/deletion-of-pdcd5-in-mice-led-to-the-deficiency-of-placenta-development-and-embryonic-lethality
#5
Ge Li, Chentong Xu, Xin Lin, Liujing Qu, Dan Xia, Beiqi Hongdu, Yan Xia, Xiaokun Wang, Yaxin Lou, Qihua He, Dalong Ma, Yingyu Chen
Programmed cell death 5 (PDCD5) is an apoptosis promoter molecule that displays multiple biological activities. However, the function of PDCD5 in vivo has not yet been investigated. Here, we generated a Pdcd5 knockout mouse model to study the physiological role of PDCD5 in vivo. Knockout of the Pdcd5 gene resulted in embryonic lethality at mid-gestation. Histopathological analysis revealed dysplasia in both the LZs and JZs in Pdcd5(-/-) placentas with defects in spongiotrophoblasts and trophoblast giant cells...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28540249/liquid-biopsies-for-bladder-cancer
#6
EDITORIAL
Douglas G Ward, Richard T Bryan
The development of accurate urinary biomarkers for the non-invasive detection of urothelial bladder cancer (UBC) could transform patient pathways by reducing reliance on cystoscopy, and the identification of highly prognostic (or even predictive) biomarkers could better guide patient management. A number of approaches are being utilised to address these challenges in both urinary- and plasma-borne tumour DNA (tDNA), so-called "liquid biopsies". Next generation sequencing (NGS) and droplet digital PCR (ddPCR) allow detection of very low levels of such tDNA amongst a large excess of non-tumour DNA, the former permitting large mutation panels to be assessed and the latter potentially identifying ultrarare mutant alleles yet restricted for multiplexing...
April 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28539475/the-brain-microenvironment-mediates-resistance-in-luminal-breast-cancer-to-pi3k-inhibition-through-her3-activation
#7
David P Kodack, Vasileios Askoxylakis, Gino B Ferraro, Qing Sheng, Mark Badeaux, Shom Goel, Xiaolong Qi, Ram Shankaraiah, Z Alexander Cao, Rakesh R Ramjiawan, Divya Bezwada, Bhushankumar Patel, Yongchul Song, Carlotta Costa, Kamila Naxerova, Christina S F Wong, Jonas Kloepper, Rita Das, Angela Tam, Jantima Tanboon, Dan G Duda, C Ryan Miller, Marni B Siegel, Carey K Anders, Melinda Sanders, Monica V Estrada, Robert Schlegel, Carlos L Arteaga, Elena Brachtel, Alan Huang, Dai Fukumura, Jeffrey A Engelman, Rakesh K Jain
Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28538219/molecular-alterations-in-patients-with-pulmonary-adenocarcinoma-presenting-with-malignant-pleural-effusion-at-the-first-diagnosis
#8
Erika F Rodriguez, Maryam Shabihkhani, Jamal Carter, Zahra Maleki
OBJECTIVES: The aim of this study was to report cytologic and molecular features of pulmonary adenocarcinoma patients presenting with a malignant pleural effusion at the first diagnosis. STUDY DESIGN: Patients who had a cytopathologic diagnosis conclusive for lung adenocarcinoma for the first time on their pleural fluid specimen, and molecular testing done, were studied. The control group consisted of patients with a malignant pleural effusion that developed during disease progression...
May 25, 2017: Acta Cytologica
https://www.readbyqxmd.com/read/28537764/gefitinib-and-egfr-gene-copy-number-aberrations-in-esophageal-cancer
#9
Russell D Petty, Asa Dahle-Smith, David A J Stevenson, Aileen Osborne, Doreen Massie, Caroline Clark, Graeme I Murray, Susan J Dutton, Corran Roberts, Irene Y Chong, Wasat Mansoor, Joyce Thompson, Mark Harrison, Anirban Chatterjee, Stephen J Falk, Sean Elyan, Angel Garcia-Alonso, David Walter Fyfe, Jonathan Wadsley, Ian Chau, David R Ferry, Zosia Miedzybrodzka
Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Methods A prespecified, blinded molecular analysis of Cancer Esophagus Gefitinib trial tumors was conducted to compare efficacy of gefitinib with that of placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF, and PIK3CA mutation status...
May 24, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28536037/identification-of-molecular-targets-in-vulvar-cancers
#10
Marguerite L Palisoul, Mary M Mullen, Rebecca Feldman, Premal H Thaker
OBJECTIVES: To identify molecular alterations that contribute to vulvar cancer pathogenesis with the intent of identifying molecular targets for treatment. METHODS: After retrospective analysis of a database of molecularly-profiled gynecologic cancer patients, 149 vulvar cancer patients were included and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and gene amplification (C/FISH)...
May 20, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28533663/low-grade-slightly-elevated-and-polypoid-colorectal-adenomas-display-differential-%C3%AE-catenin-tcf-lef-activity-c-myc-and-cyclin-d1-expression
#11
Tian-Wen Yang, Yun-Han Gao, Sha-Ying Ma, Qiang Wu, Zhong-Fu Li
AIM: To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas. METHODS: Colorectal tumors were collected from 24 patients with slightly elevated adenomas and 23 patients with polypoid adenomas. Five commonly mutated genes (APC, BRAF, KRAS, NRAS, and PIK3CA) were selected for mutational analysis. Paraffin-embedded tumor sections were used to calculate the apoptotic index (AI) and Ki-67 labeling index (KLI)...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28532501/pik3ca-hotspot-mutations-differentially-impact-responses-to-met-targeting-in-met-driven-and-non-driven-preclinical-cancer-models
#12
Lluís Nisa, Pascal Häfliger, Michaela Poliaková, Roland Giger, Paola Francica, Daniel Matthias Aebersold, Roch-Philippe Charles, Yitzhak Zimmer, Michaela Medová
BACKGROUND: The MET receptor tyrosine kinase represents a promising target in cancer. PIK3CA activating mutations are common in several tumor types and can potentially confer resistance to anti-receptor tyrosine kinase therapy. METHODS: MET and/or PI3K pathway inhibition was assessed in NIH3T3 cells harboring MET-activating point mutation with or without ectopic expression of PIK3CA(E545K) and PIK3CA(H1047R), as well as in MET-expressing head and neck cancer cells with endogenous PIK3CA mutations...
May 22, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28525374/the-effect-of-rapamycin-nvp-bez235-aspirin-and-metformin-on-pi3k-akt-mtor-signaling-pathway-of-pik3ca-related-overgrowth-spectrum-pros
#13
Yasuyo Suzuki, Yasushi Enokido, Kenichiro Yamada, Mie Inaba, Kumiko Kuwata, Naoki Hanada, Tsuyoshi Morishita, Seiji Mizuno, Nobuaki Wakamatsu
The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway is critical for cellular growth and metabolism. Recently, mosaic or segmental overgrowth, a clinical condition caused by heterozygous somatic activating mutations in PIK3CA, was established as PIK3CA-related overgrowth spectrum (PROS). In this study, we report a Japanese female diagnosed with PROS, who presented with hyperplasia of the lower extremities, macrodactyly, multiple lipomatosis, and sparse hair. Sequencing and mutant allele frequency analysis of PIK3CA from affected tissues revealed that the patient had a heterozygous mosaic mutation (c...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525363/targeted-sequencing-of-tonsillar-and-base-of-tongue-cancer-and-human-papillomavirus-positive-unknown-primary-of-the-head-and-neck-reveals-prognostic-effects-of-mutated-fgfr3
#14
Cinzia Bersani, Lars Sivars, Linnea Haeggblom, Sebastian DiLorenzo, Michael Mints, Andreas Ährlund-Richter, Nikolaos Tertipis, Eva Munck-Wikland, Anders Näsman, Torbjörn Ramqvist, Tina Dalianis
BACKGROUND: Human papillomavirus positive (HPV+) tonsillar cancer (TSCC), base of tongue cancer (BOTSCC) and unknown primary cancer of the head and neck (HNCUP) have better outcome than corresponding HPV- cancers. To find predictive markers for response to treatment, and correlations and differences in mutated oncogenes and suppressor genes between HPV+ TSCC/BOTSSCC and HPV+ HNCUP and HPV- TSCC/BOTSCC targeted next-generation sequencing was performed of frequently mutated regions in 50 cancer related genes...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524162/targeted-sequencing-based-analyses-of-candidate-gene-variants-in-ulcerative-colitis-associated-colorectal-neoplasia
#15
Sanjiban Chakrabarty, Vinay Koshy Varghese, Pranoy Sahu, Pradyumna Jayaram, Bhadravathi M Shivakumar, Cannanore Ganesh Pai, Kapaettu Satyamoorthy
BACKGROUND: Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. METHODS: Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28523248/the-keap1-nrf2-system-in-cancer
#16
REVIEW
Keiko Taguchi, Masayuki Yamamoto
Cancer cells first adapt to the microenvironment and then propagate. Mutations in tumor suppressor genes or oncogenes are frequently found in cancer cells. Comprehensive genomic analyses have identified somatic mutations and other alterations in the KEAP1 or NRF2 genes and in well-known tumor suppressor genes or oncogenes, such as TP53, CDKN2A, PTEN, and PIK3CA, in various types of cancer. Aberrant NRF2 activation in cancer cells occurs through somatic mutations in the KEAP1 or NRF2 gene as well as through other mechanisms that disrupt the binding of KEAP1 to NRF2...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28522256/sporadic-early-onset-diffuse-gastric-cancers-have-high-frequency-of-somatic-cdh1-alterations-but-low-frequency-of-somatic-rhoa-mutations-compared-with-late-onset-cancers
#17
Soo Young Cho, Jun Won Park, Yang Liu, Young Soo Park, Ju Hee Kim, Hanna Yang, Hyejin Um, Woo Ri Ko, Byung Il Lee, Sun Young Kwon, Seung Wan Ryu, Chae Hwa Kwon, Do Youn Park, Jae-Hyuk Lee, Sang Il Lee, Kyu Sang Song, Hoon Hur, Sang-Uk Han, Heekyung Chang, Su-Jin Kim, Byung-Sik Kim, Jeong-Hwan Yook, Moon-Won Yoo, Beom-Su Kim, In-Seob Lee, Myeong-Cherl Kook, Nina Thiessen, An He, Chip Stewart, Andrew Dunford, Jaegil Kim, Juliann Shih, Gordon Saksena, Andrew D Cherniack, Steven Schumacher, Amaro-Taylor Weiner, Mara Rosenberg, Gad Getz, Eun Gyeong Yang, Min Hee Ryu, Adam J Bass, Hark Kyun Kim
BACKGROUND & AIMS: Early-onset gastric cancer, which develops in younger patients than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea...
May 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28521409/evaluation-of-a-novel-approach-to-circulating-tumor-cell-isolation-for-cancer-gene-panel-analysis-in-patients-with-breast-cancer
#18
Soo Jeong Lee, Cham Han Lee, Sung Ho Choi, Sei Hyun Ahn, Byung Ho Son, Jong Won Lee, Jong Han Yu, Nak-Jung Kwon, Woo Chung Lee, Kap-Seok Yang, Dong Hyoung Lee, Du Yeol Han, Mi So Choi, Pyeong-Soo Park, Hyun Kyung Lee, Myoung Shin Kim, Jinseon Lee, Byung Hee Jeon
Liquid biopsy isolation of circulating tumor cells (CTCs) allows the genomic analysis of CTCs, which is useful in the determination of personalized cancer therapy. In the present study, CTCs from patients with breast cancer were enriched and successfully analyzed using cancer gene panel analysis. Blood samples from 11 patients with breast cancer were collected and CTCs enriched for using size-based filtration. The enriched CTCs were analyzed using immunofluorescence staining with antibodies directed against epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 45...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28513830/association-between-mutations-of-critical-pathway-genes-and-survival-outcomes-according-to-the-tumor-location-in-colorectal-cancer
#19
Dae-Won Lee, Sae-Won Han, Yongjun Cha, Jeong Mo Bae, Hwang-Phill Kim, Jaemyun Lyu, Hyojun Han, Hyoki Kim, Hoon Jang, Duhee Bang, Iksoo Huh, Taesung Park, Jae-Kyung Won, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Tae-You Kim
BACKGROUND: Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC. METHODS: Targeted next-generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and transforming growth factor β [TGF-β]) was performed for 516 patients with stage III or high-risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy...
May 17, 2017: Cancer
https://www.readbyqxmd.com/read/28507801/the-novel-negative-checkpoint-regulator-vista-is-expressed-in-gastric-carcinoma-and-associated-with-pd-l1-pd-1-a-future-perspective-for-a-combined-gastric-cancer-therapy
#20
Christine Böger, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken
A combined blockade of V-domain Ig suppressor of T-cell activation (VISTA) and PD-1 is a promising new cancer treatment option, which was efficient in murine tumor models and is currently tested in first phase I studies. Here, we analyzed the VISTA expression in a large and well-characterized gastric cancer (GC) cohort on 464 therapy-naive GC samples and 14 corresponding liver metastases using immunohistochemistry. Staining results were correlated with clinico-pathological characteristics, genetic alterations and survival...
2017: Oncoimmunology
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