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https://www.readbyqxmd.com/read/28822004/in-vitro-validation-of-the-hippo-pathway-as-a-pharmacological-target-for-canine-mammary-gland-tumors
#1
Samantha Guillemette, Charlène Rico, Philippe Godin, Derek Boerboom, Marilène Paquet
Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs. Some clinical and molecular similarities between certain CMT subtypes and breast cancer make them a potential model for the study of the human disease. As misregulated Hippo signaling is thought to play an important role in breast cancer development and also occurs in CMTs, we sought to determine if Hippo represents a valid pharmacological target for the treatment of CMTs. Six CMT cell lines were assessed for their expression of the Hippo pathway effectors YAP and TAZ and for their sensitivity to verteporfin, an inhibitor of YAP-mediated transcriptional coactivation...
August 18, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28821938/depth-of-response-predicts-the-clinical-outcome-of-advanced-her2-positive-gastric-cancer-to-trastuzumab-based-first-line-chemotherapy
#2
Shigenori Kadowaki, Toshiki Masuishi, Tetsuya Eto, Yukiya Narita, Hiroya Taniguchi, Takashi Ura, Masashi Ando, Masahiro Tajika, Yasumasa Niwa, Yasushi Yatabe, Kei Muro
PURPOSE: Accumulating evidence suggests that response-related parameters such as depth of response (DpR) might be associated with survival in colorectal cancer, which has not been shown in gastric cancer. This study aimed to evaluate whether DpR was associated with clinical outcomes in HER2-positive AGC patients treated with trastuzumab-based chemotherapy. METHODS: Fifty-seven HER2-positive AGC patients who were treated with trastuzumab in combination with fluoropyrimidines plus cisplatin therapy as first-line treatment were retrospectively enrolled...
August 18, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28821931/targeting-angiogenesis-for-radioimmunotherapy-with-a-177-lu-labeled-antibody
#3
Emily B Ehlerding, Saige Lacognata, Dawei Jiang, Carolina A Ferreira, Shreya Goel, Reinier Hernandez, Justin J Jeffery, Charles P Theuer, Weibo Cai
PURPOSE: Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. METHODS: The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with (177)Lu (t 1/2 6...
August 18, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28821813/metabolomic-and-lipidomic-profiling-identifies-the-role-of-the-rna-editing-pathway-in-endometrial-carcinogenesis
#4
Tatiana Altadill, Tyrone M Dowdy, Kirandeep Gill, Armando Reques, Smrithi S Menon, Cristian P Moiola, Carlos Lopez-Gil, Eva Coll, Xavier Matias-Guiu, Silvia Cabrera, Angel Garcia, Jaume Reventos, Stephen W Byers, Antonio Gil-Moreno, Amrita K Cheema, Eva Colas
Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821565/down-regulation-of-xiap-enhances-the-radiosensitivity-of-esophageal-cancer-cells-in-vivo-and-in-vitro
#5
Xin Wen, Xin-Rui Han, Shao-Hua Fan, Zi-Feng Zhang, Lu Chen, Gao Yi, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
The study investigated the effects of XIAP gene silencing on the radiosensitivity of esophageal cancer (EC) cells. Western blotting was used to select EC cell lines with XIAP overexpression. Selected EC9706 and KYSE30 cell lines were both divided into four groups: the blank control group, the negative control (NC) group (transfected with pBSHH1), the siRNA-enhanced group (transfected with pBSHH1-XIAP1-siRNA), and the siRNA-decreased group (transfected with pBSHH1-XIAP2-siRNA). Expressions of XIAP were measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting, cell survival and viability by MTT assay and colony formation assay, and cell apoptosis by flow cytometry, respectively...
August 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28821560/optoacoustic-detection-of-early-therapy-induced-tumor-cell-death-using-a-targeted-imaging-agent
#6
Bangwen Xie, Michal R Tomaszewski, Andre Neves, Susana Ros, De-En Hu, Sarah McGuire, Stefanie Roshy Mullins, David A Tice, Richard C A Sainson, Sarah E Bohndiek, Robert W Wilkinson, Kevin M Brindle
The development of new treatments and their deployment in the clinic may be assisted by imaging methods that allow an early assessment of treatment response in individual patients. The C2A domain of Synaptotagmin-I (C2Am), which binds to the phosphatidylserine (PS) exposed by apoptotic and necrotic cells, has been developed as an imaging probe for detecting cell death. Multispectral optoacoustic tomography (MSOT) is a real-time and clinically applicable imaging modality that was used here with a near infrared (NIR) fluorophore-labeled C2Am to image tumor cell death in mice treated with a TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) agonist and with 5-fluorouracil (5-FU)...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821559/synergy-of-wee1-and-mtor-inhibition-in-mutant-kras-driven-lung-cancers
#7
Josephine Hai, Shengwu Liu, Lauren Bufe, Khanh Do, Ting Chen, Xiaoen Wang, Christine Ng, Shuai Li, Ming-Sound Tsao, Geoffrey I Shapiro, Kwok-Kin Wong
Purpose:KRAS-activating mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC), but efforts to directly target mutant KRAS have proved a formidable challenge. Therefore, multi-targeted therapy may offer a plausible strategy to effectively treat KRAS-driven NSCLCs. Here, we evaluate the efficacy and mechanistic rationale for combining mTOR and WEE1 inhibition as a potential therapy for lung cancers harboring KRAS mutations. <p>Experimental Design: We investigated the synergistic effect of combining mTOR and WEE1 inhibitors on cell viability, apoptosis, and DNA damage repair response using a panel of human KRAS-mutant and wild type NSCLC cell lines and patient-derived xenograft cell lines...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821557/selected-alkylating-agents-can-overcome-drug-tolerance-of-g0-like-tumor-cells-and-eradicate-brca1-deficient-mammary-tumors-in-mice
#8
Marina Pajic, Sohvi Blatter, Charlotte Guyader, Maaike Gonggrijp, Ariena Kersbergen, Aslı Küçükosmanoğlu, Wendy Sol, Rinske Drost, Jos Jonkers, Piet Borst, Sven Rottenberg
We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse.<br /><br />Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53-mutant breast cancer. Due to the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore no BRCA1-dependent acquired resistance occurs. To characterize the cell cycle stage from which Brca1(-/-);p53(-/-) mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell cycle indicator (FUCCI) construct into the tumor cells...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821192/could-the-pd-1-pathway-be-a-potential-target-for-treating-small-intestinal-adenocarcinoma
#9
Ramya Thota, Raul S Gonzalez, Jordan Berlin, Dana B Cardin, Chanjuan Shi
Objectives: The programmed death 1 (PD-1) pathway is upregulated in the immune microenvironment of many cancers. In this study, we examined the PD-1 pathway and the immune microenvironment of small intestinal adenocarcinomas by immunohistochemistry. Methods: From our department pathology archives we identified 42 small intestinal adenocarcinomas from between 2000 and 2015, with blocks available for IHC studies. Tumors were immunohistochemically stained for CD3, CD4, CD8, CD20, PD-1, and programmed death ligand 1 (PD-L1) expression...
September 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28821159/inhibition-of-dna-pk-enhances-chemosensitivity-of-b-cell-precursor-acute-lymphoblastic-leukemia-cells-to-doxorubicin
#10
Fatemeh Alikarami, Majid Safa, Mohammad Faranoush, Parisa Hayat, Ahmad Kazemi
DNA damage repair pathways greatly affect the response to genotoxic drugs in cancer cells, so inhibition of such pathways could be a potentially useful strategy to enhance chemosensitivity. DNA-dependent protein kinase (DNA-PK) plays a crucial role in the repair of DNA double-strand breaks (DSBs) that are probably one of the most detrimental types of DNA damage. It has been shown that DNA-PK is highly expressed in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Less well appreciated was the effect of DNA-PK inhibition on sensitivity of BCP-ALL cells to DNA-damaging agents...
August 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28820328/lps-induced-inflammatory-response-triggers-cell-cycle-reactivation-in-murine-neuronal-cells-through-retinoblastoma-proteins-induction
#11
Barbara D'Angelo, Carlo Astarita, Silvia Boffo, Mina Massaro-Giordano, Carmelina Iannuzzi, Antonella Caporaso, Marcella Macaluso, Antonio Giordano
Cell cycle reactivation in adult neurons is an early hallmark of neurodegeneration. The lipopolysaccharide (LPS) is a well-known pro-inflammatory factor that provokes neuronal cell death via glial cells activation. The retinoblastoma (RB) family includes RB1/p105, retinoblastoma-like 1 (RBL1/p107), and retinoblastoma-like 2 (Rb2/p130). Several studies have indicated that RB proteins exhibit tumor suppressor activities, and play a central role in cell cycle regulation. In this study, we assessed LPS-mediated inflammatory effect on cell cycle reactivation and apoptosis of neuronally differentiated cells...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820254/blockade-of-asparagine-endopeptidase-inhibits-cancer-metastasis
#12
Qi Qi, Obiamaka Obianyo, Yuhong Du, Haian Fu, Shiyong Li, Keqiang Ye
Asparagine endopeptidase (AEP), also called legumain, is highly expressed in various solid tumors, promoting cancer cell invasion, migration, and metastasis. It has been proposed to be a prognostic marker and therapeutic target for cancer treatment. However, an effective nonpeptide, small-molecule inhibitor against this protease has not yet been identified. Here we show that a family of xanthine derivatives selectively inhibit AEP and suppress matrix metalloproteinase (MMP) cleavage, leading to the inhibition of cancer metastasis...
August 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28820062/urokinase-type-plasminogen-activator-and-the-molecular-mechanisms-of-its-regulation-in-cancer
#13
Juan Francisco Santibanez
Urokinase type plasminogen activator (uPA) is a 53-kDa serine protease initially synthesized as a catalytically inactive single chain polypeptide. Inactive-uPA is subject to proteolytic cleavage which results in the two-chain active protein. uPA plays key roles in the enhancement of cell malignancy during tumor progression. uPA is finely regulated in normal cells, but dysregulated in tumor cells, which results in increased cellular invasion capacities reflecting changes in uPA activity and expression during tumor progression...
August 18, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28820000/novel-combination-strategies-for-enhancing-efficacy-of-immune-checkpoint-inhibitors-in-the-treatment-of-metastatic-solid-malignancies
#14
Michael J Flynn, James M G Larkin
Immune-checkpoint inhibitor (ICPI) drugs, which include antibodies against CTLA-4, PD-1 and PD-L1, have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced NSCLC and melanoma. However, these drugs remain effective only in a minority of unselected patients. Areas covered: This review will focus on mechanisms of resistance to ICPI and underline the importance of identification of novel predictive markers of responsiveness...
August 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28819841/microscale-laminar-vortices-for-high-purity-extraction-and-release-of-circulating-tumor-cells
#15
Soojung Claire Hur, James Che, Dino Di Carlo
Circulating tumor cells (CTCs) are disseminated tumor cells that reflect the tumors of origin and can provide a liquid biopsy that would potentially enable noninvasive tumor profiling, treatment monitoring, and identification of targeted treatments. Accurate and rapid purification of CTCs holds great potential to improve cancer care but the task remains technically challenging. Microfluidic isolation of CTCs within microscale vortices enables high-throughput and size-based purification of rare CTCs from bodily fluids...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28819703/novel-prostate-cancer-immunotherapy-with-a-dna-encoded-anti-prostate-specific-membrane-antigen-monoclonal-antibody
#16
Kar Muthumani, Liron Marnin, Sagar B Kudchodkar, Alfredo Perales-Puchalt, Hyeree Choi, Sangya Agarwal, Veronica L Scott, Emma L Reuschel, Faraz I Zaidi, Elizabeth K Duperret, Megan C Wise, Kimberly A Kraynyak, Kenneth E Ugen, Niranjan Y Sardesai, J Joseph Kim, David B Weiner
Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma. Current immunotherapy approaches to target PSMA include peptide, cell, vector or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb). Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life...
August 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28819584/the-recent-advances-on-liver-cancer-stem-cells-biomarkers-separation-and-therapy
#17
REVIEW
Yanhong Xiao, Mei Lin, Xingmao Jiang, Jun Ye, Ting Guo, Yujuan Shi, Xuefeng Bian
As the third major reason of mortality related to cancer in the world, liver cancer is also the fifth most frequent cancer. Unluckily, a majority of patients succumb and relapse though many progresses have been made in detection and therapy of liver cancer. It has been put forward that in liver cancer, cancer stem cells (CSCs) hold main responsibility for the formation, invasion, metastasis, and recurrence of tumor. Strategies that are intended to target liver CSCs are playing a more and more significant role in supervising the development of liver cancer treatment and assessing new therapeutic methods...
2017: Analytical Cellular Pathology (Amsterdam)
https://www.readbyqxmd.com/read/28819582/relationship-of-metabolic-alterations-and-pd-l1-expression-in-cisplatin-resistant-lung-cancer
#18
M Wangpaichitr, H Kandemir, Y Y Li, C Wu, Djm Nguyen, L G Feun, M T Kuo, N Savaraj
Despite numerous reports on immune checkpoint inhibitor for the treatment of non-small cell lung cancer (NSCLC), the response rate remains low but durable. Thus cisplatin still plays a major role in the treatment of NSCLC. While there are many mechanisms involved in cisplatin resistance, alteration in metabolic phenotypes with elevated levels of reactive oxygen species (ROS) are found in several cisplatin resistant tumors. These resistant cells become more reliant on mitochondria oxidative metabolism instead of glucose...
April 28, 2017: Cell & Developmental Biology
https://www.readbyqxmd.com/read/28819559/growth-inhibitory-efficacy-of-natural-products-in-a-model-for-triple-negative-molecular-subtype-of-clinical-breast-cancer
#19
Nitin Telang
Global gene expression profiling identifies predictive and prognostic biomarkers and rationalizes breast cancer subtype-targeted treatment. The Anthracyclin/Taxol and survival pathway specific small molecular inhibitors, constitute current treatment options. These options are associated with acquired tumor resistance and emergence of drug-resistant cancer stem cells. Dietary supplements and constitutive bioactive phytochemicals with relatively low systemic toxicity may provide testable alternatives for current therapy...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28819458/focused-ultrasound-hyperthermia-mediated-drug-delivery-using-thermosensitive-liposomes-and-visualized-with-in-vivo-two-photon-microscopy
#20
Marc A Santos, David E Goertz, Kullervo Hynynen
The future of nanomedicines in oncology requires leveraging more than just the passive drug accumulation in tumors through the enhanced permeability and retention effect. Promising results combining mild hyperthermia (HT) with lyso-thermosensitive liposomal doxorubicin (LTSL-DOX) has led to improved drug delivery and potent antitumor effects in pre-clinical studies. The ultimate patient benefit from these treatments can only be realized when robust methods of HT can be achieved clinically. One of the most promising methods of non-invasive HT is the use of focused ultrasound (FUS) with MRI thermometry for anatomical targeting and feedback...
2017: Theranostics
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