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https://www.readbyqxmd.com/read/29156850/harness-the-synergy-between-targeted-therapy-and-immunotherapy-what-have-we-learned-and-where-are-we-headed
#1
REVIEW
Xiaoyan Liu, Qing Zhou, Yan Xu, Minjiang Chen, Jing Zhao, Mengzhao Wang
Since the introduction of imatinib for the treatment of chronic myelogenous leukemia, several oncogenic mutations have been identified in various malignancies that can serve as targets for therapy. More recently, a deeper insight into the mechanism of antitumor immunity and tumor immunoevasion have facilitated the development of novel immunotherapy agents. Certain targeted agents have the ability of inhibiting tumor growth without causing severe lymphocytopenia and amplifying antitumor immune response by increasing tumor antigenicity, enhancing intratumoral T cell infiltration, and altering the tumor immune microenvironment, which provides a rationale for combining targeted therapy with immunotherapy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156849/interest-of-integrins-targeting-in-glioblastoma-according-to-tumor-heterogeneity-and-cancer-stem-cell-paradigm-an-update
#2
REVIEW
Laure Malric, Sylvie Monferran, Julia Gilhodes, Sabrina Boyrie, Perrine Dahan, Nicolas Skuli, Julie Sesen, Thomas Filleron, Aline Kowalski-Chauvel, Elizabeth Cohen-Jonathan Moyal, Christine Toulas, Anthony Lemarié
Glioblastomas are malignant brain tumors with dismal prognosis despite standard treatment with surgery and radio/chemotherapy. These tumors are defined by an important cellular heterogeneity and notably contain a particular subpopulation of Glioblastoma-initiating cells, which recapitulate the heterogeneity of the original Glioblastoma. In order to classify these heterogeneous tumors, genomic profiling has also been undertaken to classify these heterogeneous tumors into several subtypes. Current research focuses on developing therapies, which could take into account this cellular and genomic heterogeneity...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156805/circulating-tumor-dna-shows-variable-clonal-response-of-breast-cancer-during-neoadjuvant-chemotherapy
#3
Ji-Yeon Kim, Donghyun Park, Dae-Soon Son, Seok Jin Nam, Seok Won Kim, Hae Hyun Jung, Yeon Jeong Kim, Gahee Park, Woong-Yang Park, Jeong Eon Lee, Yeon Hee Park
Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer (BC). In this study, we aimed to identify genetic alterations during the process of tumor clonal evolution and examine if ctDNA level well indicated clinical response to neoadjuvant chemotherapy (NAC) and BC recurrence. We performed targeted ultra-deep sequencing of plasma DNAs, matched germline DNAs and tumor DNAs from locally advanced BC patients. Serial plasma DNAs were collected at diagnosis, after the 1(st) cycle of NAC and after curative surgery...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156777/patients-with-nsclc-may-display-a-low-ratio-of-p-t790m-vs-activating-egfr-mutations-in-plasma-at-disease-progression-implications-for-personalised-treatment
#4
Marzia Del Re, Paola Bordi, Iacopo Petrini, Eleonora Rofi, Francesca Mazzoni, Lorenzo Belluomini, Enrico Vasile, Giuliana Restante, Francesco Di Costanzo, Alfredo Falcone, Antonio Frassoldati, Ron H N van Schaik, Christi M J Steendam, Antonio Chella, Marcello Tiseo, Riccardo Morganti, Romano Danesi
Introduction: NSCLC harboring activating mutations of EGFR is highly sensitive to first-line EGFR-tyrosine kinase inhibitors (TKIs), but drug resistance depending on the EGFR mutation p.T790M will occur in about 50-60% of patients. Detailed information on the amount of p.T790M plasmatic level associated with resistance to EGFR-TKIs and guidance to treatment with p.T790M-effective TKI depending on these levels, is lacking. Methods: This study enrolled p.T790M-positive patients (n=49) affected by EGFR-mutated NSCLC at progression to first-line EGFR-TKIs and, in selected cases (n=5), after second-line treatment with osimertinib...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156772/stat3-and-stat5a-are-potential-therapeutic-targets-in-castration-resistant-prostate-cancer
#5
Sambit K Mohanty, Kader Yagiz, Dinesh Pradhan, Daniel J Luthringer, Mahul B Amin, Serhan Alkan, Bekir Cinar
Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156754/functional-characterization-of-a-novel-transcript-of-ercc1-in-chemotherapy-resistance-of-ovarian-cancer
#6
Jia Liu, Lin Zhang, Ping Mao, Guoqiang Jiang, Likun Liu, Jing Wang, Wei Yang, Lawrence Owusu, Weiling Li
Approximately 15-20% of ovarian cancer patients receiving platinum-based chemotherapy are primary platinum-resistant. Identification of these patients and transfer to other more effective therapy could reduce the morbidity of ovarian cancer. ERCC1 is a DNA repair gene which can complex with XPF to repair cisplatin-induced DNA damage and cause chemotherapy resistance. In this study, we found a novel ERCC1 transcript initiated upstream of the normal transcription initiation site. The expression of this larger ERCC1 transcript dramatically increased following cisplatin treatment in ovarian cancer cells and was regulated by the MAPK pathway...
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
#7
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/29156697/exploring-brusatol-as-a-new-anti-pancreatic-cancer-adjuvant-biological-evaluation-and-mechanistic-studies
#8
Zheng Lu, Zheng-Quan Lai, Albert W N Leung, Po Sing Leung, Zhao-Shen Li, Zhi-Xiu Lin
Pancreatic cancer is highly resistant to chemotherapeutic agents and is known to have a poor prognosis. The development of new therapeutic entities is badly needed for this deadly malignancy. In this study, we demonstrated for the first time that brusatol, a natural quassinoid isolated from a Chinese herbal medicine named Bruceae Fructus, possessed potent cytotoxic effect against different pancreatic adenocarcinoma cell lines. Its anti-pancreatic cancer effect was comparable to that of the first-line chemotherapeutic agents such as gemcitabine and 5-fluorouracil, with a more favorable safety profile...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156686/crosstalk-between-mismatch-repair-and-base-excision-repair-in-human-gastric-cancer
#9
Valeria Simonelli, Giuseppe Leuzzi, Giorgia Basile, Mariarosaria D'Errico, Paola Fortini, Annapaola Franchitto, Valentina Viti, Ashley R Brown, Eleonora Parlanti, Barbara Pascucci, Domenico Palli, Alessandro Giuliani, Fabio Palombo, Robert W Sobol, Eugenia Dogliotti
DNA repair gene expression in a set of gastric cancers suggested an inverse association between the expression of the mismatch repair (MMR) gene MLH1 and that of the base excision repair (BER) gene DNA polymerase β (Polβ). To gain insight into possible crosstalk of these two repair pathways in cancer, we analysed human gastric adenocarcinoma AGS cells over-expressing Polβ or Polβ active site mutants, alone or in combination with MLH1 silencing. Next, we investigated the cellular response to the alkylating agent methyl methanesulfonate (MMS) and the purine analogue 6-thioguanine (6-TG), agents that induce lesions that are substrates for BER and/or MMR...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156680/vemurafenib-resistance-via-de-novo-rbm-genes-mutations-and-chromosome-5-aberrations-is-overcome-by-combined-therapy-with-palbociclib-in-thyroid-carcinoma-with-braf-v600e
#10
Zeus A Antonello, Nancy Hsu, Manoj Bhasin, Giovanni Roti, Mukta Joshi, Paul Van Hummelen, Emily Ye, Agnes S Lo, S Ananth Karumanchi, Christine R Bryke, Carmelo Nucera
Purpose: Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAF(V600E) represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAF(WT/V600E)-positive PTC patient-derived cells with P16(-/-) (CDKN2A(-/-))...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156528/actein-ameliorates-hepatic-steatosis-and-fibrosis-in-high-fat-diet-induced-nafld-by-regulation-of-insulin-and-leptin-resistant
#11
Hong-Jun Chen, Jin Liu
Insulin and leptin resistance are highly involved in metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Presently, no approved treatment is available. Actein is isolated from the rthizomes of Cimicifuga foetida, a triterpene glycoside, exhibiting important biological properties, such as anti-inflammatory, anti-cancer, and anti-oxidant activity. However, its effects on metabolic syndrome are poorly understood. The aims of the study were mainly to investigate the molecular mechanisms regulating insulin and leptin resistance, and lipogenic action of actein in high fat diet-fed mice...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156516/synergistic-anticancer-activity-of-20-s-ginsenoside-rg3-and-sorafenib-in-hepatocellular-carcinoma-by-modulating-pten-akt-signaling-pathway
#12
Mingxia Lu, Zhenghua Fei, Ganlu Zhang
Sorafenib, a multikinase inhibitor for hepatocellular carcinoma treatment, inhibits the Raf/MAPK/ERK signaling pathway. However, PI3K/Akt signaling pathway is activated by Sorafenib and cross-talks with the Raf/MAPK/ERK signaling pathway, leading to drug resistance. 20(S)-Ginsenoside Rg3 has been reported with significant anticancer effect to numerous carcinomas by inhibition of PI3K-Akt signaling pathway. Hence, we aim to examine the synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib via modulation of PTEN/Akt signaling pathway...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156509/the-role-of-exosomes-on-colorectal-cancer-a-review
#13
REVIEW
Lidia Ruiz-López, Isabel Blancas, José M Garrido, Nuria Mut-Salud, Marta Moya-Jódar, Antonio Osuna, Fernando Rodríguez-Serrano
Exosomes are extracellular microvesicles released from cells, which are involved in many biological and pathological processes, mainly due to their role in intercellular communication. Exosomes derived from colorectal cancer (CRC) cells are related to oncogenesis, tumor cell survival, chemo-resistance and metastasis. The role of the exosomes in these processes involves the transfer of proteins, RNAs or mutant versions of proto-oncogenes to the target cells. In recent years, great efforts have been made to identify useful biomarkers in CRC exosomes for diagnosis, prediction of prognosis and treatment response...
November 20, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29156452/an-international-consortium-update-pathophysiology-diagnosis-and-treatment-of-polycystic-ovarian-syndrome-in-adolescence
#14
Lourdes Ibáñez, Sharon E Oberfield, Selma F Witchel, Richard J Auchus, R Jeffrey Chang, Ethel Codner, Preeti Dabadghao, Feyza Darendeliler, Nancy Samir Elbarbary, Alessandra Gambineri, Cecilia Garcia Rudaz, Kathleen M Hoeger, Abel López-Bermejo, Ken Ong, Alexia S Peña, Thomas Reinehr, Nicola Santoro, Manuel Tena-Sempere, Rachel Tao, Bulent O Yildiz, Haya Alkhayyat, Asma Deeb, Dipesalema Joel, Reiko Horikawa, Francis de Zegher, Peter A Lee
This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels...
November 13, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/29156386/an-innovative-method-for-the-solidification-stabilization-of-pahs-contaminated-soil-using-sulfonated-oil
#15
Fujun Ma, Bin Wu, Qian Zhang, Deshan Cui, Qingbing Liu, Changsheng Peng, Fasheng Li, Qingbao Gu
Stabilization/solidification (S/S) has been successfully employed in many superfund sites contaminated with organic materials. However, this method's long-term effectiveness has not been fully evaluated and the increase in soil volume following treatment is unfavorable to follow-up disposal. The present study developed a novel method for the S/S of PAHs-contaminated soil with the facilitation of sulfonated oil (SO). Adding SO significantly improved the unconfined compressive strength (UCS) values of Portland cement and activated carbon (PC-AC) treated soil samples, and the UCS values of the soil sample treated with 0...
November 7, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29156381/structure-based-methods-to-predict-mutational-resistance-to-diarylpyrimidine-non-nucleoside-reverse-transcriptase-inhibitors
#16
Syeda Maryam Azeem, Alecia N Muwonge, Nehaben Thakkar, Kristina W Lam, Kathleen M Frey
Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a leading cause of HIV treatment failure. Often included in antiviral therapy, NNRTIs are chemically diverse compounds that bind an allosteric pocket of enzyme target reverse transcriptase (RT). Several new NNRTIs incorporate flexibility in order to compensate for lost interactions with amino acid conferring mutations in RT. Unfortunately, even successful inhibitors such as diarylpyrimidine (DAPY) inhibitor rilpivirine are affected by mutations in RT that confer resistance...
November 9, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29156353/in-situ-formation-of-textured-tin-coatings-on-biomedical-titanium-alloy-by-laser-irradiation
#17
Xueyang Zhao, Peng Zhang, Xiaojian Wang, Yun Chen, Hui Liu, Lianxi Chen, Yinying Sheng, Wei Li
The Ti-35Nb-7Zr-5Ta (TNZT) alloy has received much research attention among the biomedical titanium alloys for its low Young's modulus and outstanding biocompatibility. This paper provided an innovative technique for improving the wear and corrosion resistance of the TNZT alloy, by developing in-situ formed TiN coatings on the surface of the TNZT alloy through laser irradiation. The new technique combines the advantages of laser surface texturing and laser gas alloying. The experimental results showed that the phase compositions of the textured TNZT samples were β-Ti, martensitic α'' phase and TiN after laser texturing in N2...
November 14, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/29156346/abcg2-mediated-suppression-of-chlorin-e6-accumulation-and-photodynamic-therapy-efficiency-in-glioblastoma-cell-lines-can-be-reversed-by-ko143
#18
Sara A Abdel Gaber, Patricia Müller, Wolfgang Zimmermann, Dirk Hüttenberger, Rainer Wittig, Mahmoud H Abdel Kader, Herbert Stepp
BACKGROUND: Photodynamic therapy (PDT) of malignant brain tumors is a promising adjunct to standard treatment, especially if tumor stem cells thought to be responsible for tumor progression and therapy resistance were also susceptible to this kind of treatment. However, some photosensitizers have been reported to be substrates of ABCG2, one of the membrane transporters mediating resistance to chemotherapy. Here we investigate, whether inhibition of ABCG2 can restore sensitivity to photosensitizer chlorin e6-mediated PDT...
October 28, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29156291/engineering-the-next-generation-tin-containing-%C3%AE-titanium-alloys-with-high-strength-and-low-modulus-for-orthopedic-applications
#19
Sumit Bahl, Suvam Das, Satyam Suwas, Kaushik Chatterjee
Metastable β Ti alloys are the new emerging class of biomaterial for load bearing orthopedic applications. However, these alloys in the single β phase microstructure have insufficient strength for use in load bearing applications. It is imperative to strengthen these alloys by carefully designed thermo-mechanical processing routes that typically involve aging treatment. In this investigation two newly designed Sn based β Ti alloys of composition Ti-32Nb-(2, 4) Sn are evaluated. The effects of Sn content on the mechanical properties and biological performance of these alloys processed through designed thermo-mechanical processing route are investigated...
November 11, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/29156151/limited-evidence-of-fungicide-driven-triazole-resistant-i-aspergillus-fumigatus-i-in-hamilton-canada
#20
Eta Ashu, Ga Young Kim, Patrick Roy-Gayos, Kelly Dong, Adrian Forsythe, Victoria Giglio, Gregory Korfanty, Deborah Yamamura, Jianping Xu
Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen that can cause aspergillosis in humans. Over the last decade there have been increasing global reports of treatment failure due to triazole resistance. An emerging hypothesis states that agricultural triazole fungicide use causes clinical triazole-resistance. Here we test this hypothesis in Hamilton, Ontario, Canada by examining a total of 195 agricultural, urban and clinical isolates using 9 highly polymorphic microsatellite markers. For each isolate, the in vitro susceptibilities to itraconazole and voriconazole, two triazole drugs commonly used in the management of patients, were also determined...
November 20, 2017: Canadian Journal of Microbiology
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