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Tumor resistence

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https://www.readbyqxmd.com/read/29045828/prolonged-ikk%C3%AE-inhibition-improves-ongoing-ctl-antitumor-responses-by-incapacitating-regulatory-t-cells
#1
Christoph Heuser, Janine Gotot, Eveline Christina Piotrowski, Marie-Sophie Philipp, Christina Johanna Felicia Courrèges, Martin Sylvester Otte, Linlin Guo, Jonathan Leo Schmid-Burgk, Veit Hornung, Annkristin Heine, Percy Alexander Knolle, Natalio Garbi, Edgar Serfling, César Evaristo, Friedrich Thaiss, Christian Kurts
Regulatory T cells (Tregs) prevent autoimmunity but limit antitumor immunity. The canonical NF-κB signaling pathway both activates immunity and promotes thymic Treg development. Here, we report that mature Tregs continue to require NF-κB signaling through IκB-kinase β (IKKβ) after thymic egress. Mice lacking IKKβ in mature Tregs developed scurfy-like immunopathology due to death of peripheral FoxP3(+) Tregs. Also, pharmacological IKKβ inhibition reduced Treg numbers in the circulation by ∼50% and downregulated FoxP3 and CD25 expression and STAT5 phosphorylation...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045825/cerenkov-luminescence-imaging-on-evaluation-of-early-response-to-chemotherapy-of-drug-resistant-gastric-cancer
#2
Muhan Liu, Sheng Zheng, Xiaojun Zhang, Hongbo Guo, Xiaojing Shi, Xiaoyu Kang, Yawei Qu, Zhenhua Hu, Jie Tian
Apoptosis imaging enables a timely and specific assessment of treatment response in cancer patients. In this study, we applied a probe for positron emission tomography (PET), served as an optical biomaterial emitting Cerenkov photons, to in vivo optical imaging of tumor apoptosis, in order to evaluate early response to chemotherapy of drug-resistant gastric cancer. (68)Ga-DOTA-Annexin V was prepared as the apoptosis targeting probe. Wild type human gastric adenocarcinoma cell line SGC7901/WT and drug vincristine-resistant variant SGC7901/VCR were used to establish normal and vincristine-resistant xenograft to simulate treatment decision situation...
October 15, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29045527/braf-mutant-colorectal-cancer-prognosis-treatment-and-new-perspectives
#3
E Sanz-Garcia, G Argiles, E Elez, J Tabernero
The MAPK cascade plays a crucial role in tumor cell proliferation and survival. Accumulating evidence suggests that mutations in the BRAF oncogene are not only associated with poor prognosis but also linked with less benefit when treated with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Targeting this molecular aberration has thus become a matter of particular interest in mCRC drug development. In contrast to other malignances such as BRAF mutant (mt) melanoma, efficacy observed with BRAF inhibitors in mono-therapy in mCRC is poor...
July 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045505/surfaceome-profiling-enables-isolation-of-cancer-specific-exosomal-cargo-in-liquid-biopsies-from-pancreatic-cancer-patients
#4
J Castillo, V Bernard, F A San Lucas, K Allenson, M Capello, D U Kim, P Gascoyne, F C Mulu, B M Stephens, J Huang, H Wang, A A Momin, R O Jacamo, M Katz, R Wolff, M Javle, G Varadhachary, I I Wistuba, S Hanash, A Maitra, H Alvarez
Background: Detection of circulating tumor DNA (ctDNA) can be limited due to their relative scarcity in circulation, particularly while patients are actively undergoing therapy. Exosomes provide a vehicle through which cancer-specific material can be enriched from the compendium of circulating non-neoplastic tissue-derived nucleic acids. We performed a comprehensive profiling of the pancreatic ductal adenocarcinoma (PDAC) exosomal "surfaceome" in order to identify surface proteins that will render liquid biopsies amenable to cancer-derived exosome enrichment for downstream molecular profiling...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045072/cell-signaling-model-connects-vorinostat-pharmacokinetics-and-tumor-growth-response-in-multiple-myeloma-xenografts
#5
Charvi Nanavati, Donna Ruszaj, Donald E Mager
Multiple myeloma is a fatal hematological malignancy with high rates of drug resistance and relapse. Vorinostat, a histone deacetylase inhibitor, has shown promise in enhancing efficacy when combined with current myeloma therapies. In this study, temporal changes of critical proteins and cell proliferation were measured in myeloma cells exposed to vorinostat. A model linking biomarker dynamics to cell proliferation was developed that captured vorinostat effects on signal transduction and cell viability. The model structure and parameters were fixed to describe tumor dynamics in vivo, and tumor-specific growth and death rate parameters were estimated...
October 17, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29045061/suppression-of-mapk-signaling-in-braf-activated-pten-deficient-melanoma-by-blocking-%C3%AE-catenin-signaling-in-cancer-associated-fibroblasts
#6
Linli Zhou, Kun Yang, Spencer Dunaway, Zalfa Abdel-Malek, Thomas Andl, Ana Luisa Kadekaro, Yuhang Zhang
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with formation of a dynamic and optimized niche for tumor cells to grow and evade cell death induced by therapeutic agents. We recently reported that ablation of β-catenin expression in stromal fibroblasts and CAFs disrupted their biological activities in in vitro studies and in an in vivo B16F10 mouse melanoma model. Here, we show that the development of a BRAF-activated PTEN-deficient mouse melanoma was significantly suppressed in vivo after blocking β-catenin signaling in CAFs...
October 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29045039/design-of-potent-b-raf-v600e-inhibitors-by-mcss-strategy
#7
Ze-Feng Wang, Peng-Fei Wang, Jun-Ting Ma, Ying-Zi Chai, Hui-Min Hu, Wen-Long Gao, Zhong-Chang Wang, Bao-Zhong Wang, Hai-Liang Zhu
B-Raf kinase is a vital intermedium in the mitogen-activated protein kinase (MAPK) signaling pathway, which transforms extracellular signals into cellular mechanisms. Mutations in this kinase, for instance, the most common V600E mutation, can lead to the ERK signaling pathologically activated and hence cause severe diseases like somatic tumors. So far, the development of B-Raf inhibitors has made remarkable progress. However, the resistance and relapse of approved Raf drugs have been widely reported, and the optimization for old drugs and the discovery for new inhibitors still remain a significant task...
October 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29044514/ccdc6-the-identity-of-a-protein-known-to-be-partner-in-fusion
#8
REVIEW
Aniello Cerrato, Francesco Merolla, Francesco Morra, Angela Celetti
Coiled Coil Domain Containing 6 gene, CCDC6, was initially isolated as part of a tumorigenic DNA originated by the fusion of CCDC6 with the tyrosine kinase of RET receptor, following a paracentric inversion of chromosome 10. For a long time CCDC6 has been considered as an accidental partner of the RET protooncogene, providing the promoter and the first 101 aa necessary for the constitutive activation of the oncogenic Tyrosine Kinase (TK) RET in thyroid cells. With the advent of more refined diagnostic tools and bioinformatic algorithms, an exponential growth in fusion genes discoveries has allowed the identification of CCDC6 as partner of genes other than RET in different tumor types...
October 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29044222/rapid-generation-and-detection-of-biomimetic-oxygen-concentration-gradients-in-vitro
#9
Daud H Khan, Steven A Roberts, John Robert Cressman, Nitin Agrawal
Hypoxic regions exist within most solid tumors and often lead to altered cellular metabolism, metastasis, and drug resistance. Reliable generation and detection of biomimetic gaseous gradients in vitro is challenging due to low spatiotemporal resolution and poor longevity of gradients utilizing microfluidic techniques. Here, we present a novel and simplistic approach for producing gradients of dissolved oxygen (DO) within a lab-on-a-chip platform. Linear and stable DO gradients with high spatial resolution are established by introducing pre-gassed media into the gradient generating network...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29044153/tripalmitin-nanoparticle-formulations-significantly-enhance-paclitaxel-antitumor-activity-against-breast-and-lung-cancer-cells-in-vitro
#10
María Carmen Leiva, Raúl Ortiz, Rafael Contreras-Cáceres, Gloria Perazzoli, Iryna Mayevych, Juan Manuel López-Romero, Francisco Sarabia, Jose Manuel Baeyens, Consolación Melguizo, Jose Prados
Paclitaxel (PTX) is one of the drugs of choice in the treatment of breast and lung cancer. However, its severe side effects, including mielosuppression, cardiotoxicity and neurotoxicity, frequently cause treatment to be discontinued. Solid lipid nanoparticles (NPs) of glyceril tripalmitate (tripalmitin) loaded with PTX (Tripalm-NPs-PTX) including modifications by the addition of hexa(ethylene glycol), β-cyclodextrin and macelignan were developed. All NPs-PTX formulations displayed excellent hemocompatibility and significantly enhanced PTX antitumor activity in human breast (MCF7, MDAMB231, SKBR3 and T47D) and lung (A549, NCI-H520 and NCI-H460) cancer cells...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29043812/amphiphilic-modulation-of-glycosylated-antitumor-ether-lipids-results-in-a-potent-triamino-scaffold-against-epithelial-cancer-cell-lines-and-bt474-cancer-stem-cells
#11
Temilolu Idowu, Pranati Samadder, Gilbert Arthur, Frank M Schweizer
The problems of resistance to apoptosis-inducing drugs, recurrence, and metastases that have bedeviled cancer treatment have been attributed to the presence of cancer stem cells (CSCs) in tumors, and there is currently no clinically indicated drug for their eradication. We previously reported that glycosylated antitumor ether lipids (GAELs) display potent activity against CSCs. Here, we show that by carefully modulating the amphiphilic nature of a monoamine-based GAEL, we can generate a potent triamino scaffold that is active against a panel of hard-to-kill epithelial cancer cell lines (including triple-negative) and BT474 CSCs...
October 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29043413/cholecystokinin-receptor-antagonist-alters-pancreatic-cancer-microenvironment-and-increases-efficacy-of-immune-checkpoint-antibody-therapy-in-mice
#12
Jill P Smith, Shangzi Wang, Sandeep Nadella, Sandra A Jablonski, Louis M Weiner
Advanced pancreatic ductal adenocarcinoma (PDAC) has typically been resistant to chemotherapy and immunotherapy; therefore, novel strategies are needed to enhance therapeutic response. Cholecystokinin (CCK) has been shown to stimulate growth of pancreatic cancer. CCK receptors (CCKRs) are present on pancreatic cancer cells, fibroblasts, and lymphocytes. We hypothesized that CCKR blockade would improve response to immune checkpoint antibodies by promoting influx of tumor-infiltrating lymphocytes (TILs) and reducing fibrosis...
October 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29042994/immunological-mechanism-of-low-dose-priming-radiation-resistance-in-walker-256-tumor-model-mice
#13
Li Feng, Ling Qin, Dan Guo, Daping Deng, Feng Lu, Hailiang Li, Narisu Bao, Xiting Yang, Hongyu Ding, Jianguo Li
The aim of the present study was to investigate whether low-dose priming radiation induces antitumor immunity that can be augmented by the modulation of natural killer (NK) cell and cytokine activity using a mouse tumor model. Walker-256 cells were injected into the right flank of male BALB/c mice. At 7 days after inoculation, mice were divided into three groups, including group 1,2,3. In group 1 the mice were without radiation, in group 2 the mice were received 2 Gy radiation only, and in group 3 the mice were radiated with a priming dose of 75 mGy followed by 2 Gy radiation after 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042665/gdc-0449-improves-the-antitumor-activity-of-nano-doxorubicin-in-pancreatic-cancer-in-a-fibroblast-enriched-microenvironment
#14
Quan Zhou, Yongcun Zhou, Xiangrui Liu, Youqing Shen
Pancreatic cancer is one of the most lethal human cancers that currently does not have effective therapies. Novel treatments including nanomedicines and combination therapies are thus urgently needed for these types of deadly diseases. A key feature of pancreatic cancer is its tumor protective dense stroma, which is generated by cancer-associated fibroblasts (CAFs). The interaction between CAFs and pancreatic cancer cells abnormally activates sonic hedgehog (SHH) signaling and facilitates tumor growth, metastasis, and drug resistance...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042620/an-integrin-targeted-highly-diffusive-construct-for-photodynamic-therapy
#15
Oliver J Klein, Hushan Yuan, Nicholas H Nowell, Charalambos Kaittanis, Lee Josephson, Conor L Evans
Targeted antineoplastic agents show great promise in the treatment of cancer, having the ability to impart cytotoxicity only to specific tumor types. However, these therapies do not experience uniform uptake throughout tumors, leading to sub-lethal cell killing that can impart treatment resistance, and cause problematic off-target effects. Here we demonstrate a photodynamic therapy construct that integrates both a cyclic RGD moiety for integrin-targeting, as well as a 5 kDa PEG chain that passivates the construct and enables its rapid diffusion throughout tumors...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042522/-surgical-pathology-of-adulthood-epilepsy
#16
Hajime Miyata
Epilepsy may be the consequence of a wide range of disorders affecting the brain, including tumors and non-neoplastic lesions. A broad spectrum of structural brain lesions can be observed in epileptogenic brain tissue specimens surgically resected from patients with drug-resistant focal epilepsies. These include hippocampal sclerosis (HS), low-grade epilepsy-associated neuroepithelial tumors (LEAT), malformations of cortical development (MCD), vascular malformations, dual pathology, glial scar, and encephalitis, as well as no lesion...
October 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29042487/differential-response-of-glioma-stem-cells-to-arsenic-trioxide-therapy-is-regulated-by-mnk1-and-mrna-translation
#17
Jonathan B Bell, Frank Eckerdt, Harshil Dhruv, Darren Finlay, Sen Peng, Seungchan Kim, Barbara Kroczynska, Elspeth Beauchamp, Kristen Alley, Jessica Clymer, Stewart Goldman, Shi-Yuan Cheng, C David James, Ichiro Nakano, Craig Horbinski, Andrew P Mazar, Kristiina Vuori, Priya Kumthekar, Jeffery Raizer, Michael E Berens, Leonidas C Platanias
Mesenchymal (MES) and proneural (PN) are two distinct glioma stem cells (GSCs) populations that drive therapeutic resistance in glioblastoma (GBM). We screened a panel of 650 small molecules against patient-derived GBM cells to discover compounds targeting specific GBM subtypes. Arsenic trioxide (ATO), a FDA-approved drug that crosses the blood-brain barrier, was identified as a potent PN-specific compound in the initial screen and follow-up validation studies. Furthermore, MES and PN GSCs exhibited differential sensitivity to ATO...
October 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29042395/nuclear-receptor-profiling-in-prostatospheroids-and-castration-resistant-prostate-cancer
#18
Zhu Wang, Dinglan Wu, Chi-Fai Ng, Jeremy Yuen-Chun Teoh, Shan Yu, Yuliang Wang, Franky Leung Chan
Nuclear receptors (NRs), which belong to a superfamily of transcription factors and consist of a total of 48 members in humans, govern the expression of genes involved in a board range of developmental, reproductive, metabolic and immunological programs. Given the significant importance of androgen receptor and a few known NRs in the progression of prostate cancer, we surveyed the expression profiles of the entire NR superfamily in three-dimensional (3D) cultured prostatospheroids derived from different prostate cancer cell lines and a tumor xenograft model of castration-resistant prostate cancer VCaP-CRPC by quantitative real-time RT-PCR...
October 17, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29042278/a-ribonuclease-inhibitor-resistant-dimer-of-human-pancreatic-ribonuclease-displays-specific-antitumor-activity
#19
Ayush Attery, Punyatirtha Dey, Prajna Tripathi, Janendra K Batra
Human pancreatic ribonuclease (HPR) and bovine seminal ribonuclease (BS-RNase) are members of the RNase A superfamily. HPR is monomeric, whereas BS-RNase is dimeric. BS-RNase has strong antitumor and cytotoxic activities. However, HPR lacks cytotoxic activity as it is inactivated by intracellular cytosolic ribonuclease inhibitor (RI). Earlier, an RI-resistant cytotoxic variant of HPR, termed HPR-KNE was generated which contained three residues Lys7, Asn71 and Glu111 of HPR, known to interact with RI, mutated to alanine...
October 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29041002/astragaloside-iv-induced-mir-134-expression-reduces-emt-and-increases-chemotherapeutic-sensitivity-by-suppressing-creb1-signaling-in-colorectal-cancer-cell-line-sw-480
#20
Qi Ye, Li Su, Dagui Chen, Wenyi Zheng, Ye Liu
BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although chemotherapy is the primary means in colorectal cancer treatment, it is burdenerd by adverse drug effects. Drug-resistance is one of the most important challenges for chemotherapy and epithelial-mesenchymal transition (EMT) plays critical role in the development of drug resistance. AIMS: The aim of this study was to investigate the mechanisms underlying the effect of astragaloside IV (AS-IV) on miR-134 expression, EMT and chemotherapeutic sensitivity in CRC...
October 17, 2017: Cellular Physiology and Biochemistry
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