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https://www.readbyqxmd.com/read/29161613/molecular-characterization-of-urothelial-carcinoma-of-the-bladder-and-upper-urinary-tract
#1
Ji Yun Lee, Kyung Kim, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han-Yong Choi, Ghee-Young Kwon, Kyoung-Mee Kim, Jeeyun Lee, Ho Yeong Lim, Se Hoon Park
PURPOSE: A better understanding of the molecular basis of urothelial carcinoma (UC) is needed to refine the clinical decision-making process. METHODS AND MATERIALS: We performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes in UC using Ampliseq v2. Copy number variations (CNVs) were detected with nCounter assay. Genetic alterations between upper tract UC (UTUC) and urinary bladder UC (UBUC) were compared...
November 18, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29156800/comparative-molecular-analyses-of-left-sided-colon-right-sided-colon-and-rectal-cancers
#2
Mohamed E Salem, Benjamin A Weinberg, Joanne Xiu, Wafik S El-Deiry, Jimmy J Hwang, Zoran Gatalica, Philip A Philip, Anthony F Shields, Heinz-Josef Lenz, John L Marshall
Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29153866/a-phase-i-trial-of-the-pi3k-inhibitor-buparlisib-combined-with-capecitabine-in-patients-with-metastatic-breast-cancer
#3
Autumn J McRee, Paul K Marcom, Dominic T Moore, William C Zamboni, Zachary A Kornblum, Zhiyuan Hu, Rachel Phipps, Carey K Anders, Katherine Reeder-Hayes, Lisa A Carey, Karen E Weck, Charles M Perou, E Claire Dees
BACKGROUND: Buparlisib is an oral pan-class I phosphotidyinositol-3-kinase (PI3K) inhibitor. The present phase I study evaluated the safety, pharmacokinetics, and efficacy of buparlisib with capecitabine in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients received buparlisib once daily (range, 50 to 100 mg) for 3 weeks with capecitabine twice daily (range, 1000 to 1250 mg/m(2)) for 2 weeks with a 1-week break. Dose escalation used a traditional "3 + 3" design with standard definitions of dose-limiting toxicity (DLT) and maximum tolerated dose...
October 28, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29153543/-aspirin-and-colorectal-cancer
#4
REVIEW
Adrien Grancher, Pierre Michel, Frédéric Di Fiore, David Sefrioui
Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity...
November 15, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29152088/aspirin-exerts-high-anti-cancer-activity-in-pik3ca-mutant-colon-cancer-cells
#5
Mancang Gu, Reiko Nishihara, Yang Chen, Wanwan Li, Yan Shi, Yohei Masugi, Tsuyoshi Hamada, Keisuke Kosumi, Li Liu, Annacarolina da Silva, Jonathan A Nowak, Tyler Twombly, Chunxia Du, Hideo Koh, Wenbin Li, Jeffrey A Meyerhardt, Brian M Wolpin, Marios Giannakis, Andrew J Aguirre, Adam J Bass, David A Drew, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Evidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA-mutant colorectal carcinoma, but not in PIK3CA-wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA-mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA-mutant colon cancer cells than for PIK3CA-wild-type colon cancer cells...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29140069/dual-functions-of-cyclometalated-iridium-iii-complexes-anti-metastasis-and-lysosome-damaged-photodynamic-therapy
#6
Fang-Xin Wang, Mu-He Chen, Yan-Nan Lin, Hang Zhang, Cai-Ping Tan, Liang-Nian Ji, Zongwan Mao
Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can inhibit several cancerous processes including cell migration, invasion, colony formation and angiogenesis effectively. Interestingly, they show much higher singlet oxygen quantum yield in acidic solution than in neutral solution. Upon irradiation at 425 nm with low energy (1.2 J·cm(-2)), they can induce apoptosis through lysosomal damage, evaluation of ROS level and activation of caspase-3/7...
November 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29137436/tumor-biopsy-stratification-based-on-mtor-pathway-activity-and-functional-mutations-in-the-upstream-genes-pik3ca-and-pten
#7
Jean-François Laes, Sebastien Sauvage, Gregori Ghitti
The mechanistic target of the rapamycin (mTOR) pathway is frequently activated in human cancers. Our objective was to evaluate relationships between mTOR-pathway activity and functional mutations in the upstream genes PIK3CA and PTEN in solid-tumor biopsies from a broad selection of cancer types. Formalin-fixed paraffin-embedded (FFPE) tumor samples were analyzed by immunohistochemistry (IHC) and next-generation sequencing (NGS). TOR-pathway activation was identified by expression (by IHC) of the downstream effector p-4E-BP1...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133142/dedifferentiated-endometrial-carcinomas-with-neuroendocrine-features-a-clinicopathologic-immunohistochemical-and-molecular-genetic-study
#8
Iñigo Espinosa, Antonio De Leo, Emanuela D'Angelo, Juan M Rosa-Rosa, Marina Corominas, Alan Gonzalez, José Palacios, Jaime Prat
Undifferentiated endometrial carcinoma is an aggressive type of uterine cancer which is occasionally associated with a low-grade endometrioid carcinoma component. This combination is referred to as "dedifferentiated endometrioid endometrial carcinoma." Neuroendocrine expression may occur in undifferentiated endometrial carcinoma but its significance in dedifferentiated endometrial carcinomas is unknown. To gain insight into the pathogenesis of these tumors we have analyzed the immunophenotype (ARID1A, MLH1, PMS2, MSH2, MSH6, p53, b-catenin, SMARCB1, synaptophysin, chromogranin A, and CD56) and mutational status (PTEN, KRAS, PIK3CA, TP53 and POLE) of 4 dedifferentiated endometrial carcinomas with strong and diffuse neuroendocrine expression...
November 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/29131028/mir-142-5p-suppresses-tumorigenesis-by-targeting-pik3ca-in-non-small-cell-lung-cancer
#9
Zhao Wang, Zhimin Liu, Xiaojie Fang, Han Yang
BACKGROUND/AIMS: Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating lung cancer growth and progression are not fully identified yet. METHODS: In this study, the expression of miR-142-5p was measured in non-small cell lung cancer tissue and cell lines by qRT-PCR. The functional assays including the cell viability, colony formation, cell migration and invasion were performed in miR-142-5p mimic or inhibitor transfected cell lines (in vitro) and the cell tumorigenesis in nude mice (in vivo)...
October 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29128266/molecular-profiling-of-patients-with-advanced-colorectal-cancer-princess-margaret-cancer-centre-experience
#10
Joanne W Chiu, Monika K Krzyzanowska, Stefano Serra, Jennifer J Knox, Neesha C Dhani, Helen Mackay, David Hedley, Malcolm Moore, Geoffrey Liu, Ronald L Burkes, Christine Brezden-Masley, Michael H Roehrl, Kenneth J Craddock, Ming-Sound Tsao, Tong Zhang, Celeste Yu, Suzanne Kamel-Reid, Lillian L Siu, Philippe L Bedard, Eric X Chen
BACKGROUND: Molecular aberrations in KRAS, NRAS, BRAF, and PIK3CA have been well-described in advanced colorectal cancer. The incidences of other mutations are less known. We report results of molecular profiling of advanced colorectal cancer in an academic cancer center. PATIENTS AND METHODS: Patients with advanced colorectal were enrolled in an institution-wide molecular profiling program. Profiling was performed on formalin-fixed paraffin embedded archival tissues using a customized MassArray panel (23 genes, 279 mutations) or the Illumina MiSeq TruSeq Cancer Panel (48 genes, 212 amplicons, ≥ 500× coverage) in a Clinical Laboratory Improvement Amendments-certified laboratory...
October 23, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29127303/comprehensive-genomic-analysis-of-oesophageal-squamous-cell-carcinoma-reveals-clinical-relevance
#11
Peina Du, Peide Huang, Xuanlin Huang, Xiangchun Li, Zhimin Feng, Fengyu Li, Shaoguang Liang, Yongmei Song, Jan Stenvang, Nils Brünner, Huanming Yang, Yunwei Ou, Qiang Gao, Lin Li
Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs)...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29127140/cancer-genes-mutation-profiling-in-calcifying-epithelial-odontogenic-tumour
#12
Sílvia Ferreira de Sousa, Marina Gonçalves Diniz, Josiane Alves França, Thaís Dos Santos Fontes Pereira, Rennan Garcias Moreira, Jean Nunes Dos Santos, Ricardo Santiago Gomez, Carolina Cavalieri Gomes
AIMS: To identify calcifying epithelial odontogenic tumour (CEOT) mutations in oncogenes and tumour suppressor genes. METHODS: A panel of 50 genes commonly mutated in cancer was sequenced in CEOT by next-generation sequencing. Sanger sequencing was used to cover the region of the frameshift deletion identified in one sample. RESULTS: Missense single nucleotide variants (SNVs) with minor allele frequency (MAF) <1% were detected in PTEN, MET and JAK3...
November 10, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29124000/human-papillomavirus-associated-head-and-neck-squamous-cell-carcinoma-controversies-and-new-concepts
#13
REVIEW
Nuzhat Husain, Azfar Neyaz
High-risk human papillomavirus (HR-HPV) is a causative agent for an increasing subset of oropharyngeal squamous cell carcinoma. HPV 16 accounts for 90% of cases. The chance for malignant transformation due to infection with high-risk HPV is proportional to the expression of the viral oncogene products E6 and E7, which inactivate p53 and retinoblastoma (Rb) tumor suppressor functions. P16 is a surrogate marker of HPV associated HNSCC and 2+/3+ expression in more than 75% cells is diagnostic. Molecular demonstration of integrated virus by in situ hybridization is specific but has low sensitivity...
September 2017: Journal of Oral Biology and Craniofacial Research
https://www.readbyqxmd.com/read/29123093/prevalence-and-detection-of-low-allele-fraction-variants-in-clinical-cancer-samples
#14
Hyun-Tae Shin, Yoon-La Choi, Jae Won Yun, Nayoung K D Kim, Sook-Young Kim, Hyo Jeong Jeon, Jae-Yong Nam, Chung Lee, Daeun Ryu, Sang Cheol Kim, Kyunghee Park, Eunjin Lee, Joon Seol Bae, Dae Soon Son, Je-Gun Joung, Jeeyun Lee, Seung Tae Kim, Myung-Ju Ahn, Se-Hoon Lee, Jin Seok Ahn, Woo Yong Lee, Bo Young Oh, Yeon Hee Park, Jeong Eon Lee, Kwang Hyuk Lee, Hee Cheol Kim, Kyoung-Mee Kim, Young-Hyuck Im, Keunchil Park, Peter J Park, Woong-Yang Park
Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29120753/mitochondrial-oxphos-induced-by-rb1-deficiency-in-breast-cancer-implications-for-anabolic-metabolism-stemness-and-metastasis
#15
REVIEW
Eldad Zacksenhaus, Mariusz Shrestha, Jeff C Liu, Ioulia Vorobieva, Philip E D Chung, YoungJun Ju, Uri Nir, Zhe Jiang
A switch from catabolic to anabolic metabolism, a major hallmark of cancer, enables rapid cell duplication, and is driven by multiple oncogenic alterations, including PIK3CA mutation, MYC amplification, and TP53 loss. However, tumor growth requires active mitochondrial function and oxidative phosphorylation (OXPHOS). Recently, loss of the retinoblastoma (RB1) tumor suppressor in breast cancer was shown to induce mitochondrial protein translation (MPT) and OXPHOS. Here, we discuss how increased OXPHOS can enhance anabolic metabolism and cell proliferation, as well as cancer stemness and metastasis...
November 2017: Trends in Cancer
https://www.readbyqxmd.com/read/29115399/loss-of-the-clock-gene-per2-is-associated-with-cancer-development-and-altered-expression-of-important-tumor-related-genes-in-oral-cancer
#16
Honggang Xiong, Yixin Yang, Kai Yang, Dan Zhao, Hong Tang, Xiongwen Ran
Recent studies have demonstrated that abnormal expression of the clock gene PER2 is closely associated with the development of a variety of cancer types. However, the expression of PER2 in oral squamous cell carcinoma (OSCC), a common malignant tumor in humans, and its correlations with the clinicopathological parameters and survival time of OSCC patients and the altered expression of important tumor-related genes remain unclear. In the present study, we detected the mRNA and protein expression levels of PER2, PIK3CA, PTEN, P53, P14ARF and caspase‑8 in OSCC tissues and cancer-adjacent oral mucosa by reverse transcription-quantitative PCR (RT-qPCR), western blotting and immunohistochemistry...
October 31, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29113722/the-landscape-of-somatic-mutations-in-indonesian-cervical-cancer-is-predominated-by-the-pi3k-pathway
#17
Vivian M Spaans, I Nyoman Bayu Mahendra, Gatot Purwoto, Marjolijn D Trietsch, Michelle Osse, Natalja Ter Haar, Alexander A W Peters, Gert J Fleuren, Ekaterina S Jordanova
OBJECTIVE: To investigate the prevalence of somatic mutations in Indonesian cervical carcinoma patients in the context of histology and human papillomavirus (HPV) type. METHODS: In total 174 somatic hot-spot mutations in 13 genes were analyzed by mass spectrometry in 137 Indonesian cervical carcinomas. RESULTS: In 66/137 tumors (48%) 95 mutations were identified. PIK3CA was most frequently mutated (24%), followed by FBXW7 (7%), CTNNB1 (6%), and PTEN (6%)...
November 4, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29113583/aberrant-akt-activation-during-implantation-window-in-infertile-women-with-intramural-uterine-fibroids
#18
Annu Makker, Madhu Mati Goel, Dipti Nigam, Abbas Ali Mahdi, Vinita Das, Anjoo Agarwal, Amita Pandey, Abnish Gautam
The objective of the study was to examine the expression and cellular distribution of key signaling components of the phosphatidylinositol-3-kinase (PI3K)/Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Protein Kinase B (PKB/Akt) pathway during the window of implantation in infertile women with noncavity-distorting intramural uterine fibroids (n = 21) as compared to fertile controls (n = 15). Relative gene expression analysis of PIK3CA, PTEN, Akt1, and Akt2 genes in midluteal endometrial biopsies was performed by real-time polymerase chain reaction...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29113237/microrna-10a-suppresses-breast-cancer-progression-via-pi3k-akt-mtor-pathway
#19
Kongliang Ke, Tingting Lou
Previous studies have demonstrated that microRNA-10a (miR-10a) regulates various opposing biological functions in breast cancer. The aim of the present study was to investigate the exact functions of miR-10a in the pathogenesis of breast cancer. miR-10a expression was initially detected in two human breast cancer cell lines, MCF-7 and MDA-MB-231 and a normal human mammary epithelial cell line MCF-10A. The proliferation, migration and apoptosis of breast cancer cells were analyzed using MTT assays, Transwell assays and flow cytometry, respectively, following transfection of MCF-7 and MDA-MB-231 cells with an miR-10a mimic or anti-miR-10a...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29110857/inter-relationship-between-pd-l1-expression-and-clinic-pathological-features-and-driver-gene-mutations-in-pulmonary-sarcomatoid-carcinomas
#20
Filippo Lococo, Federica Torricelli, Giulio Rossi, Marco Alifano, Diane Damotte, Cristian Rapicetta, Ione Tamagnini, Alberto Cavazza, Simonetta Piana, Carla Galeone, Massimiliano Paci, Alessia Ciarrocchi
INTRODUCTION: Pulmonary Sarcomatoid Carcinoma (PSC) is a rare subset of NSCLC, associated with worse prognosis and resistant to platinum-based regimens. Recent investigations have shown high levels of PD-L1 expression in PSC, providing a rationale for the potential use of immunotherapy. In this study, we investigated whether the PD-L1 expression was related to clinico-pathologic and molecular characteristics. MATERIALS AND METHODS: Fortythree surgically-resected PSCs were selected from 2006 to 2014 and clinical information retrieved...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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