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https://www.readbyqxmd.com/read/28214899/therapeutic-targeting-of-epithelial-plasticity-programs-focus-on-the-epithelial-mesenchymal-transition
#1
Reem Malek, Hailun Wang, Kekoa Taparra, Phuoc T Tran
Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28159516/tumor-targeted-ph-redox-dual-sensitive-unimolecular-nanoparticles-for-efficient-sirna-delivery
#2
Guojun Chen, Yuyuan Wang, Ruosen Xie, Shaoqin Gong
A unique pH/redox dual-sensitive cationic unimolecular nanoparticle (NP) enabling excellent endosomal/lysosomal escape and efficient siRNA decomplexation inside the target cells was developed for tumor-targeted delivery of siRNA. siRNA was complexed into the cationic core of the unimolecular NP through electrostatic interactions. The cationic core used for complexing siRNA contained reducible disulfide bonds that underwent intracellular reduction owing to the presence of high concentrations of reduced glutathione (GSH) inside the cells, thereby facilitating the decomplexation of siRNA from the unimolecular NPs...
January 31, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28120720/the-role-of-epidermal-growth-factor-receptor-in-the-management-of-gastrointestinal-carcinomas-present-status-and-future-perspectives
#3
Malik Quasir Mahmood, Shakti Dhar Shukla, Kamal Dua, Madhur D Shastri
BACKGROUND: The global burden of gastrointestinal cancers, including colorectal, stomach, and esophageal cancers is rising steadily. Several therapeutic approaches have been considered for the treatment of GI carcinomas. However, none showed to halt or cure the disease. There is a need to develop effective targeted molecular therapies; mainly to overcome the adverse effects of currently used treatment regimens, as well as, to benefit a large proportion of cancer patients who do not respond well to chemotherapeutics...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27993518/design-synthesis-and-biological-evaluation-of-novel-1-oxo-1-2-3-4-tetrahydropyrazino-1-2-a-indole-3-carboxamide-analogs-in-mcf-7-and-mda-mb-468-breast-cancer-cell-lines
#4
Ye Jin Kim, Jae Sung Pyo, Young-Suk Jung, Jae-Hwan Kwak
A series of novel 1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide analogs were designed and synthesized for developing pyrazinoindolone scaffolds as anti-breast cancer agents. Compounds 1h and 1i, having a furan-2-yl-methylamide and benzylamide group, respectively, exhibited more potent cytotoxicity in MDA-MB-468 triple-negative breast cancer (TNBC) cells than compounds possessing aliphatic groups. Compounds 2a and 2b, as (R)-enantiomers of 1h and 1i, also had inhibitory activity against MDA-MB-468 cells...
December 5, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27754054/os-15-02-matrix-metalloproteinase-2-knockout-protects-from-angiotensin-ii-induced-vascular-injury-in-part-via-inhibition-of-egfr-and-erk1-2-activation
#5
Pierre Paradis, Tlili Barhoumi, Muhammad Oneeb Rehman Mian, Julio C Fraulob-Aquino, Asia Rehman, Nourredine Idris-Khodja, Ernesto L Schiffrin
OBJECTIVE: Matrix metalloproteinase 2 (MMP2) is involved in cardiovascular disease. Whether MMP2 plays a role in hypertension and vascular damage is unknown. We hypothesized that Mmp2 knockout will prevent angiotensin (Ang) II-induced hypertension and vascular injury. DESIGN AND METHOD: Mmp2 knockout (Mmp2) and wild-type (WT) mice were infused with Ang II (1000 ng/kg/min, SC) for 14 days. Systolic blood pressure (SBP) was measured by telemetry, and mesenteric artery (MA) endothelial function and vascular remodeling by pressurized myography...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753039/a-rapid-and-sensitive-method-for-detection-of-the-t790m-mutation-of-egfr-in-plasma-dna
#6
Hideharu Kimura, Shingo Nishikawa, Hayato Koba, Taro Yoneda, Takashi Sone, Kazuo Kasahara
Epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors' (EGFR-TKIs) in non-small cell lung cancer (NSCLC). The aims of this study are to develop a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients, using PointMan™ EGFR DNA Enrichment Kit which is a novel method for selective amplification of genotype specific sequences.Pairs of blood samples and tumor tissues were collected from NSCLC patients with an EGFR activating mutation and who were resistant to EGFR-TKI treatment...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27726288/erlotinib-induces-the-human-non-small-cell-lung-cancer-cells-apoptosis-via-activating-ros-dependent-jnk-pathways
#7
Fenglian Shan, Zewei Shao, Shenghua Jiang, Zhaozhong Cheng
Although erlotinib (ERL) has drawn more and more attention toward its anticancer properties effect, the underlying mechanisms of ERL's anticancer properties effect remain unclear yet. So, the aim of this research was to explore the underlying anticancer mechanisms of ERL and to explore whether the reactive oxygen species (ROS)-dependent c-Jun N-terminal kinase (JNK) pathway contributed to the anticancer properties provided by ERL. In our study, we used MTT assay to detect the anticell growth ability of ERL on human non-small-cell lung cancer cell lines (A549)...
November 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27642974/os-15-02-matrix-metalloproteinase-2-knockout-protects-from-angiotensin-ii-induced-vascular-injury-in-part-via-inhibition-of-egfr-and-erk1-2-activation
#8
Pierre Paradis, Tlili Barhoumi, Muhammad Oneeb Rehman Mian, Julio C Fraulob-Aquino, Asia Rehman, Nourredine Idris-Khodja, Ernesto L Schiffrin
OBJECTIVE: Matrix metalloproteinase 2 (MMP2) is involved in cardiovascular disease. Whether MMP2 plays a role in hypertension and vascular damage is unknown. We hypothesized that Mmp2 knockout will prevent angiotensin (Ang) II-induced hypertension and vascular injury. DESIGN AND METHOD: Mmp2 knockout (Mmp2) and wild-type (WT) mice were infused with Ang II (1000 ng/kg/min, SC) for 14 days. Systolic blood pressure (SBP) was measured by telemetry, and mesenteric artery (MA) endothelial function and vascular remodeling by pressurized myography...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27633965/interaction-of-treatment-and-biomarker-in-advanced-nsclc
#9
Pingfu Fu, Afshin Dowlati, Nathan Pennell, Neelesh Sharma, Qizhi Yi, Balazs Halmos
PURPOSE: There has been a long-standing interest in the investigation of interactions in science. The objective of the study is to evaluate interaction between EGFR mutation and treatment from randomized, phase II study of chemotherapy versus chemotherapy plus erlotinib in patients with progressive NSCLC following clinical benefit from erlotinib. MATERIALS AND METHODS: Forty-six patients with advanced stage NSCLC and progression from erlotinib were randomized to receive chemotherapy (pemetrexed or docetaxel) or chemotherapy plus erlotinib between 2008 and 2012...
September 16, 2016: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/27519631/tamoxifen-has-a-proliferative-effect-in-endometrial-carcinoma-mediated-via-the-gper-egfr-erk-cyclin-d1-pathway-a-retrospective-study-and-an-in%C3%A2-vitro-study
#10
Lizhi Zhang, Yanmin Li, Lan Lan, Rong Liu, Yanhong Wu, Quanxin Qu, Ke Wen
Tamoxifen has been widely used to treat breast cancer as an endocrine therapy. However, tamoxifen is known to enhance the risk of developing endometrial cancer. We want to examine the effect of tamoxifen on endometrial cancer. In our retrospective study, we found that high grade, high stage, and lymph node metastasis were more common in tamoxifen users. In vitro 4-hydroxytamoxifen (OHT) induced cell proliferation and cell cycle promotion in type I and type II endometrial cancer cell lines, and this proliferation was blocked by GPER silencing...
December 5, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27358767/population-based-mri-atlases-of-spatial-distribution-are-specific-to-patient-and-tumor-characteristics-in-glioblastoma
#11
Michel Bilello, Hamed Akbari, Xiao Da, Jared M Pisapia, Suyash Mohan, Ronald L Wolf, Donald M O'Rourke, Maria Martinez-Lage, Christos Davatzikos
BACKGROUND AND PURPOSE: In treating glioblastoma (GB), surgical and chemotherapeutic treatment guidelines are, for the most part, independent of tumor location. In this work, we compiled imaging data from a large cohort of GB patients to create statistical atlases illustrating the disease spatial frequency as a function of patient demographics as well as tumor characteristics. MATERIALS AND METHODS: Two-hundred-six patients with pathology-proven glioblastoma were included...
2016: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27246726/icecream-randomised-phase-ii-study-of-cetuximab-alone-or-in-combination-with-irinotecan-in-patients-with-metastatic-colorectal-cancer-with-either-kras-nras-braf-and-pi3kca-wild-type-or-g13d-mutated-tumours
#12
Eva Segelov, Paul Waring, Jayesh Desai, Kate Wilson, Val Gebski, Subotheni Thavaneswaran, Elena Elez, Craig Underhill, Nick Pavlakis, Lorraine Chantrill, Louise Nott, Michael Jefford, Mustafa Khasraw, Fiona Day, Harpreet Wasan, Fortunato Ciardiello, Chris Karapetis, Warren Joubert, Guy van Hazel, Andrew Haydon, Tim Price, Sabine Tejpar, Niall Tebbutt, Jeremy Shapiro
BACKGROUND: Patients with metastatic colorectal cancer whose disease has progressed on oxaliplatin- and irinotecan-containing regimens may benefit from EGFR-inhibiting monoclonal antibodies if they do not contain mutations in the KRAS gene (are "wild type"). It is unknown whether these antibodies, such as cetuximab, are more efficacious in refractory metastatic colorectal cancer as monotherapy, or in combination with irinotecan. Lack of mutation in KRAS, BRAF and PIK3CA predicts response to EFGR-inhibitors...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27077749/enrichment-of-cells-with-cancer-stem-cell-like-markers-in-relapses-of-chemoresistant-patients-with-locally-advanced-head-and-neck-squamous-cell-carcinoma
#13
Juan J Grau, Ricard Mesía, Maria de la Iglesia-Vicente, Estrelania S Williams, Miren Taberna, Miguel Caballero, Ana-Belen Larque, Jorge de la Oliva, Carlos Cordón-Cardo, Josep Domingo-Domenech
BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) present different responses to chemotherapy and radiotherapy. One explanation may be the differences in the individual rates of stem cell-like cells. METHODS: We included patients with HNSCC and tumor progression or relapse. Tumor samples were obtained before and after primary chemotherapy, and immunohistochemical analyses were performed for CD44, HLA class I (HLA-I), pancytokeratin, and phosphorylated epidermal growth factor receptor (p-EGFR)...
2016: Oncology
https://www.readbyqxmd.com/read/27046001/choroidal-metastasis-as-a-presenting-manifestation-of-a-lung-adenocarcinoma-with-response-to-afatinib
#14
M Contreras-Díaz, A Medina-Tapia, G Martínez-Bernal, T Rueda-Rueda, F López-Herrero, F E Molina-Socola, J L Sánchez-Vicente
CASE REPORT: We present the case of a 55-year-old man with a non-small cell lung adenocarcinoma, who presented with choroidal metastasis. The patient showed a decrease in visual acuity. His evaluation revealed unilateral choroidal metastasis secondary to carcinoma of the lung. The patient received afatinib with complete regression of choroidal metastasis after one year follow-up. DISCUSSION: Choroidal metastasis may be the initial sign of lung cancer. This case highlights the importance of a thorough systemic evaluation in patients with choroidal tumours...
November 2016: Archivos de la Sociedad Española de Oftalmología
https://www.readbyqxmd.com/read/26985396/gene-mutation-discovery-research-of-non-smoking-lung-cancer-patients-due-to-indoor-radon-exposure
#15
REVIEW
Jung Ran Choi, Seong Yong Park, O Kyu Noh, Young Wha Koh, Dae Ryong Kang
Although the incidence and mortality for most cancers such as lung and colon are decreasing in several countries, they are increasing in several developed countries because of an unhealthy western lifestyles including smoking, physical inactivity and consumption of calorie-dense food. The incidences for lung and colon cancers in a few of these countries have already exceeded those in the United States and other western countries. Among them, lung cancer is the main cause of cancer death in worldwide. The cumulative survival rate at five years differs between 13 and 21 % in several countries...
2016: Annals of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/26967052/pi3k-akt-mtor-signaling-pathway-and-targeted-therapy-for-glioblastoma
#16
REVIEW
Xiaoman Li, Changjing Wu, Nianci Chen, Huadi Gu, Allen Yen, Liu Cao, Enhua Wang, Liang Wang
Glioblastoma multiform (GBM) is the most common malignant glioma of all the brain tumors and currently effective treatment options are still lacking. GBM is frequently accompanied with overexpression and/or mutation of epidermal growth factor receptor (EGFR), which subsequently leads to activation of many downstream signal pathways such as phosphatidylinositol 3-kinase (PI3K)/Akt/rapamycin-sensitive mTOR-complex (mTOR) pathway. Here we explored the reason why inhibition of the pathway may serve as a compelling therapeutic target for the disease, and provided an update data of EFGR and PI3K/Akt/mTOR inhibitors in clinical trials...
May 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/26797372/human-papillomavirus-and-epidermal-growth-factor-receptor-in-oral-cavity-and-oropharyngeal-squamous-cell-carcinoma-correlation-with-dynamic-contrast-enhanced-mri-parameters
#17
Yoon Seong Choi, Mina Park, Hyeong Ju Kwon, Yoon Woo Koh, Seung-Koo Lee, Jinna Kim
OBJECTIVE: The objective of this study was to investigate differences in dynamic contrast-enhanced MRI (DCE-MRI) parameters on the basis of the status of human papillomavirus (HPV) and epidermal growth factor receptor (EGFR) biomarkers in patients with squamous cell carcinoma (SCC) of the oral cavity and oropharynx by use of histogram analysis. MATERIALS AND METHODS: A total of 22 consecutive patients with oral cavity and oropharyngeal SCC underwent DCE-MRI before receiving treatment...
February 2016: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/26780078/-efficacy-and-safety-of-antivascular-drugs-after-anti-efgr-aflibercept-after-cetuximab-a-clinical-case
#18
Francesca Aroldi, Alberto Zaniboni
We describe a case of a man affected by colon adenocarcinoma with metachronous nodes and liver metastases (resected), exposed to first line therapy with FOLFOX-cetuximab. After disease progression, a second line based on FOLFIRI-aflibercept was started achieving an initial partial response followed by a long-lasting disease stability with a good tolerability.
December 2015: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/26727637/clinical-pathologic-and-genetic-features-of-wilms-tumors-with-wtx-gene-mutation
#19
Sanda Alexandrescu, Sara Akhavanfard, Marian H Harris, Sara O Vargas
Clinical and pathologic features of patients with WTX-mutated Wilms tumor (WT) have not been studied in detail. We characterize the clinical and pathologic findings in WT with WTX abnormalities and provide comparison with WT without WTX mutation. Clinical, gross, and microscopic features in 35 patients with WT were examined. Karyotype was examined in a subset of cases. All cases had been previously analyzed for WTX, WT1, and CTNNB1 aberrations via array comparative genomic hybridization; OncoMap 4 high throughput genotyping was performed on 18 cases...
January 4, 2016: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/26691822/nonadiabatic-dynamics-may-be-probed-through-electronic-coherence-in-time-resolved-photoelectron-spectroscopy
#20
Kochise Bennett, Markus Kowalewski, Shaul Mukamel
We present a hierarchy of Fermi golden rules (FGRs) that incorporate strongly coupled electronic/nuclear dynamics in time-resolved photoelectron spectroscopy (TRPES) signals at different levels of theory. Expansion in the joint electronic and nuclear eigenbasis yields the numerically most challenging exact FGR (eFGR). The quasistatic Fermi Golden Rule (qsFGR) neglects nuclear motion during the photoionization process but takes into account electronic coherences as well as populations initially present in the pumped matter as well as those generated internally by coupling between electronic surfaces...
February 9, 2016: Journal of Chemical Theory and Computation
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