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https://www.readbyqxmd.com/read/29156800/comparative-molecular-analyses-of-left-sided-colon-right-sided-colon-and-rectal-cancers
#1
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/29156708/a-preclinical-evaluation-of-the-mek-inhibitor-refametinib-in-her2-positive-breast-cancer-cell-lines-including-those-with-acquired-resistance-to-trastuzumab-or-lapatinib
#2
John O'Shea, Mattia Cremona, Clare Morgan, Malgorzata Milewska, Frankie Holmes, Virginia Espina, Lance Liotta, Joyce O'Shaughnessy, Sinead Toomey, Stephen F Madden, Aoife Carr, Naomi Elster, Bryan T Hennessy, Alex J Eustace
Purpose: The MEK/MAPK pathway is commonly activated in HER2-positive breast cancer, but little investigation of targeting this pathway has been undertaken. Here we present the results of an in vitro preclinical evaluation of refametinib, an allosteric MEK1/2 inhibitor, in HER2-positive breast cancer cell lines including models of acquired resistance to trastuzumab or lapatinib. Methods: A panel of HER2-positive breast cancer cells were profiled for mutational status and also for anti-proliferative response to refametinib alone and in combination with the PI3K inhibitor (PI3Ki) copanlisib and the HER2-targeted therapies trastuzumab and lapatinib...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156699/cell-specific-regulation-of-proliferation-by-ano1-tmem16a-in-breast-cancer-with-different-er-pr-and-her2-status
#3
Huizhe Wu, Hui Wang, Shu Guan, Jing Zhang, Qiuchen Chen, Xiaodong Wang, Ke Ma, Pengfei Zhao, Haishan Zhao, Weifan Yao, Feng Jin, Qinghuan Xiao, Minjie Wei
The calcium-activated chloride channel Ano1 (TMEM16A) is overexpressed in many tumors. However, conflicting data exist regarding the role of Ano1 in cell proliferation. Here, we performed immunohistochemistry to investigate the expression of Ano1 and Ki67 in 403 patients with breast cancer, and analyzed the association between the expression of Ano1 and Ki67 in breast cancer subtypes categorized according to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156674/novel-combinations-of-pi3k-mtor-inhibitors-with-dacomitinib-or-chemotherapy-in-pten-deficient-patient-derived-tumor-xenografts
#4
Irene Brana, Nhu-An Pham, Lucia Kim, Shingo Sakashita, Ming Li, Christine Ng, Yuhui Wang, Peter Loparco, Rafael Sierra, Lisa Wang, Blaise A Clarke, Benjamin G Neel, Lillian L Siu, Ming-Sound Tsao
PTEN inactivation occurs commonly in human cancers and putatively activates the PI3K/AKT/ mTOR pathway. Activation of this pathway has been involved in resistance to chemotherapy or anti-EGFR/HER2 therapies. We evaluated the combination of PI3K-mTOR inhibitors with chemotherapy or the pan-HER inhibitor dacomitinib in PTEN-deficient patient-derived tumor xenografts (PDX). Three PDXs were selected for their lack of PTEN expression by immunohistochemistry: a triple-negative breast cancer (TNBC), a KRAS G12R low-grade serous ovarian cancer (LGSOC), and KRAS G12C and TP53 R181P lung adenocarcinoma (LADC)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155879/subtypes-of-breast-cancer-show-different-spatial-distributions-of-brain-metastases
#5
Sunghyon Kyeong, Yoon Jin Cha, Sung Gwe Ahn, Sang Hyun Suh, Eun Ju Son, Sung Jun Ahn
The aim of our study was to test the hypothesis that the spatial distribution of breast cancer brain metastases (BM) differ according to their biological subtypes. MR images of 100 patients with BM from primary breast cancer were retrospectively reviewed. Patients were divided according to the biological subtype of the primary tumor, (triple-negative: 24, HER2 positive: 48, luminal: 28). All images marked with BMs were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database...
2017: PloS One
https://www.readbyqxmd.com/read/29154981/egfr-family-inhibition-identifies-p38-mapk-as-a-potential-therapeutic-target-in-bladder-cancer
#6
Regina Mora Vidal, Sergio Regufe da Mota, Annette Hayden, Hannah Markham, James Douglas, Graham Packham, Simon J Crabb
Objective To investigate perturbations in downstream signalling pathway activation and potential resistance mechanisms to EGFR and/or HER2 inhibition in cell line models of bladder cancer. Methods We undertook a structured screening approach by phosphokinase array, followed by validation steps, to detect activated downstream signalling pathway nodes after therapeutic inhibition of EGFR and/or HER2 in bladder cancer cell lines. Results Erlotinib treatment of RT112 cells induced phosphorylation of 9 activated phospho-protein targets (p38 MAPK (Thr180/Tyr182), GSK-3α/β (Ser21/9), MEK1/2 (Ser218/222, Ser222/226), Akt (Ser473), TOR (Ser2448), Src (Tyr419), p27 (Thr198), p27 (Thr157) and PLCγ-1 (Tyr783)) whereas STAT4 (Tyr693) phosphorylation was reduced...
November 15, 2017: Urology
https://www.readbyqxmd.com/read/29154173/prognostic-value-of-tumour-infiltrating-lymphocytes-in-small-her2-positive-breast-cancer
#7
Carmen Criscitiello, Vincenzo Bagnardi, Giancarlo Pruneri, Andrea Vingiani, Angela Esposito, Nicole Rotmensz, Giuseppe Curigliano
BACKGROUND: The standard treatment for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is still controversial. Our aim was to assess the prognostic role of tumour-infiltrating lymphocytes (TILs) in patients with stage pT1a-b HER2-positive BC. PATIENTS AND METHODS: Haematoxylin and eosin slides from node-negative, pT1a-b HER2-positive BC surgical specimens were retrieved from pathology archives to assess TILs and their association with outcome...
November 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29153588/azole-hydrazone-derivatives-design-synthesis-in-vitro-biological-evaluation-dual-egfr-her2-inhibitory-activity-cell-cycle-analysis-and-molecular-docking-study-as-anticancer-agents
#8
Madlen B Labib, John N Philoppes, Phoebe F Lamie, Esam R Ahmed
In this research, three series of azole-hydrazone derivatives namely, benzimidazole, benzoxazole and benzothiazole were designed and synthesized. Their structures were confirmed by elemental analysis and spectroscopic techniques. Stereochemical configuration of the synthesized compounds (Z/E) was determined. The new derivatives were tested in vitro against both human breast adenocarcinoma (MCF-7) and human hepatic adenocarcinoma (HepG2) cell lines. The most active compounds 3h (IC50 = 0.067 μM against MCF-7) and 3l (IC50 = 0...
November 15, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29151971/the-predictive-and-prognostic-role-of-stromal-tumor-infiltrating-lymphocytes-in-her2-positive-breast-cancer-with-trastuzumab-based-treatment-a-meta-analysis-and-systematic-review
#9
Tao Xu, Bang-Shun He, Xiang-Xiang Liu, Xiu-Xiu Hu, Kang Lin, Yu-Qin Pan, Hui-Ling Sun, Hong-Xin Peng, Xiao-Xiang Chen, Shu-Kui Wang
Background Tumor-infiltrating lymphocytes (TILs) are white blood cells that have left the bloodstream and migrated into a tumor, involving in the prognosis of breast cancer (BC) patients. Published studies reported the value of TILs in patients with HER2-positive receiving trastuzumab-based treatment. However, the results obtained remain controversial. Here, we conducted this study to explore the predictive and prognostic role of TILs for HER2-positive BC patients receiving trastuzumab therapies. Method To identify the related published studies, a comprehensive literature search dating up to July 2017 was performed in the databases of PubMed, PMC, Web of Science and China National Knowledge Infrastructure (CNKI) according to predefined selection criteria...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151938/comparison-of-her2-and-lauren-classification-between-biopsy-and-surgical-resection-samples-primary-and-metastatic-samples-of-gastric-cancer
#10
Miao-Zhen Qiu, Si-Mei Shi, Min Chen, Jing Wang, Qi-Nian Wu, Hui Sheng, Hui-Zhong Zhang, Jing-Ping Yun, Zhi-Wei Zhou, Feng-Hua Wang, Da-Jun Yang, Rui-Hua Xu
Purpose: Patients with advanced or metastatic adenocarcinoma of the stomach or esophagogastric junction for whom trastuzumab therapy is being considered, assessment for tumor human epidermal growth factor receptor-2 (HER2) status is necessary. Can the HER2 status and Lauren classification of the biopsy sample truly represent the HER2 status in the gastric cancer? Methods: Formalin-fixed, paraffin-embedded sections of 116 pair surgically resected and biopsy specimens as well as 80 pair primary and metastatic lesions of gastric cancer patients were analyzed...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151694/survival-analysis-based-on-human-epidermal-growth-factor-2-status-in-stage-ii-iii-gastric-cancer
#11
Jang Ho Cho, Jae Yun Lim, Jae Yong Cho
AIM: To investigate human epidermal growth factor 2 (HER2) overexpression and validate its prognostic effect in stage II-III gastric cancer. METHODS: We reviewed the data of patients who were diagnosed with gastric cancer between March 2008 and October 2013 at the Yonsei University Medical Center. Among these patients, 384 patients who met the inclusion criteria were analyzed retrospectively. RESULTS: Thirty-two (8.3%) of the 384 stage II-III gastric cancer patients exhibited HER2 overexpression...
November 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29150351/combined-hormonal-contraceptive-use-and-risk-of-breast-cancer-in-a-population-of-women-with-a-family-history
#12
Giovanni Grandi, Angela Toss, Angelo Cagnacci, Luigi Marcheselli, Silvia Pavesi, Fabio Facchinetti, Stefano Cascinu, Laura Cortesi
BACKGROUND: We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic. MATERIALS AND METHODS: We performed a retrospective cohort study by reviewing the data from 2527 women (4.5% BRCA mutation carriers, 72.2% high risk, and 23.3% intermediate risk using the Modena criteria and the Tyrer-Cuzick model). RESULTS: We did not find any specific feature of breast cancer (infiltration, hormone receptor and HER2 status, onset before age 35 years, multiple diagnoses) in the CHC users (P > ...
November 14, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29148540/single-cell-heterogeneity-in-ductal-carcinoma-in-situ-of-breast
#13
Michael J Gerdes, Yesim Gökmen-Polar, Yunxia Sui, Alberto Santamaria Pang, Nicole LaPlante, Adrian L Harris, Puay-Hoon Tan, Fiona Ginty, Sunil S Badve
Heterogeneous patterns of mutations and RNA expression have been well documented in invasive cancers. However, technological challenges have limited the ability to study heterogeneity of protein expression. This is particularly true for pre-invasive lesions such as ductal carcinoma in situ of the breast. Cell-level heterogeneity in ductal carcinoma in situ was analyzed in a single 5 μm tissue section using a multiplexed immunofluorescence analysis of 11 disease-related markers (EGFR, HER2, HER4, S6, pmTOR, CD44v6, SLC7A5 and CD10, CD4, CD8 and CD20, plus pan-cytokeratin, pan-cadherin, DAPI, and Na+K+ATPase for cell segmentation)...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148091/intrinsic-subtypes-of-breast-cancers-initially-assessed-as-probably-benign-or-of-low-suspicion-on-ultrasonography-differ-according-to-tumor-size
#14
Jieun Koh, Min Jung Kim, Hee Jung Moon, Jung Hyun Yoon, Vivian Youngjean Park, Eun-Kyung Kim
OBJECTIVES: To investigate whether the intrinsic subtypes of breast cancers initially assessed as American College of Radiology Breast Imaging and Reporting System (BI-RADS) category 3 or 4a differ according to tumor size. METHODS: A total of 444 breast cancers in 439 patients initially assessed as BI-RADS 3 or 4a through ultrasound-guided core needle biopsy were included. Tumors were classified by the size criterion of 10 mm or smaller or larger than 10 mm and categorized as the luminal type (estrogen receptor [ER] positive and/or progesterone receptor [PR] positive and human epidermal growth factor receptor 2 [HER2] negative), HER2 type (HER2 positive regardless of ER or PR status), or triple-negative type (ER negative, PR negative, and HER2 negative)...
November 17, 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/29147626/functional-t-cells-targeting-tumor-associated-antigens-are-predictive-for-recurrence-free-survival-of-patients-with-radically-operated-non-small-cell-lung-cancer
#15
Seyer Safi, Yoshikane Yamauchi, Anchana Rathinasamy, Slava Stamova, Martin Eichhorn, Arne Warth, Geraldine Rauch, Hendrik Dienemann, Hans Hoffmann, Philipp Beckhove
In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immunospot assay. The phenotype and function of T cells specific for tumor-associated antigens (TAAs) in the blood or tumor tissue of 9 NSCLC patients were characterized in detail using TNF-α, IL-2, and IFN-γ cytokine capture assays...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147611/chloroquine-supplementation-increases-the-cytotoxic-effect-of-curcumin-against-her2-neu-overexpressing-breast-cancer-cells-in-vitro-and-in-vivo-in-nude-mice-while-counteracts-it-in-immune-competent-mice
#16
L Masuelli, M Granato, M Benvenuto, R Mattera, R Bernardini, M Mattei, G d'Amati, G D'Orazi, A Faggioni, R Bei, M Cirone
Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated the in vitro and in vivo anti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147072/paradoxical-association-of-postoperative-plasma-sphingosine-1-phosphate-with-breast-cancer-aggressiveness-and-chemotherapy
#17
Rajesh Ramanathan, Ali Raza, Jamie Sturgill, Debra Lyon, Jessica Young, Nitai C Hait, Kazuaki Takabe
Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that has been shown to serve an important regulatory function in breast cancer progression. This study analyzes plasma S1P levels in breast cancer patients undergoing adjuvant therapy as compared to healthy control volunteers. 452 plasma S1P samples among 158 breast cancer patients, along with 20 healthy control volunteers, were analyzed. Mean S1P levels did not significantly differ between cancer patients and controls. Smoking was associated with higher S1P levels in cancer patients...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29146695/first-in-human-her2-targeted-imaging-using-89-zr-pertuzumab-pet-ct-dosimetry-and-clinical-application-in-patients-with-breast-cancer
#18
Gary A Ulaner, Serge K Lyashchenko, Christopher Riedl, Shutian Ruan, Pat B Zanzonico, Diana Lake, Komal Jhaveri, Brian Zeglis, Jason S Lewis, Joseph A O'Donoghue
In this first-in-human study, we evaluate the safety and dosimetry of (89)Zr-pertuzumab PET/CT for HER2-targeted imaging in patients with HER2-postive breast cancer. Materials and Methods: Patients with HER2-positive breast cancer and evidence of distant metastases were enrolled in an Institutional Review Board (IRB)-approved prospective clinical trial. Pertuzumab was conjugated with deferoxamine and radiolabeled with (89)Zr. Patients underwent (89)Zr-pertuzumab PET/CT with 74 MBq of (89)Zr-pertuzumab in a total antibody mass of 20-50 mg of pertuzumab...
November 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29146616/therapeutic-potential-of-afatinib-for-cancers-with-erbb2-her2-transmembrane-domain-mutations-g660d-and-v659e
#19
Hiromasa Yamamoto, Shinichi Toyooka, Takashi Ninomiya, Shigemi Matsumoto, Masashi Kanai, Shuta Tomida, Katsuyuki Kiura, Manabu Muto, Ken Suzawa, Patrice Desmeules, Mark G Kris, Bob T Li, Marc Ladanyi
We previously reported on a family with hereditary lung cancer, in which a germline mutation in the transmembrane domain (G660D) of avian erythroblastic leukemia viral oncogene homolog 2 (erb-b2 receptor tyrosine kinase 2) (ERBB2; human epidermal growth factor receptor 2 [HER2]) seemed to be responsible for the cancer predisposition. Although few data are available on treatment, anti-ERBB2 therapeutic agents may be effective for ERBB2-mutant cancers. The familial lung cancer patient in one of the authors' institutes developed bone metastasis with enlarging lung tumors and was treated with the ERBB2 inhibitor afatinib...
November 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29146401/neratinib-after-trastuzumab-based-adjuvant-therapy-in-her2-positive-breast-cancer-extenet-5-year-analysis-of-a-randomised-double-blind-placebo-controlled-phase-3-trial
#20
Miguel Martin, Frankie A Holmes, Bent Ejlertsen, Suzette Delaloge, Beverly Moy, Hiroji Iwata, Gunter von Minckwitz, Stephen K L Chia, Janine Mansi, Carlos H Barrios, Michael Gnant, Zorica Tomašević, Neelima Denduluri, Robert Šeparović, Erhan Gokmen, Anna Bashford, Manuel Ruiz Borrego, Sung-Bae Kim, Erik Hugger Jakobsen, Audrone Ciceniene, Kenichi Inoue, Friedrich Overkamp, Joan B Heijns, Anne C Armstrong, John S Link, Anil Abraham Joy, Richard Bryce, Alvin Wong, Susan Moran, Bin Yao, Feng Xu, Alan Auerbach, Marc Buyse, Arlene Chan
BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry...
November 13, 2017: Lancet Oncology
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