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https://www.readbyqxmd.com/read/28646810/synergistic-anti-breast-cancer-effects-of-combined-treatment-with-oleuropein-and-doxorubicin-in-vivo
#1
Maha H Elamin, Abdelsalam B Elmahi, Maha H Daghestani, Ebtesam M Al-Olayan, Reem A Al-Ajmi, Afrah F Alkhuriji, Sherifa S Hamed, Manal F Elkhadragy
Context • Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies Objective • The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646744/systematic-biobanking-novel-imaging-techniques-and-advanced-molecular-analysis-for-precise-tumor-diagnosis-and-therapy-the-polish-mobit-project
#2
Jacek Niklinski, Adam Kretowski, Marcin Moniuszko, Joanna Reszec, Anna Michalska-Falkowska, Magdalena Niemira, Michal Ciborowski, Radoslaw Charkiewicz, Dorota Jurgilewicz, Miroslaw Kozlowski, Rodryg Ramlau, Cezary Piwkowski, Miroslaw Kwasniewski, Monika Kaczmarek, Andrzej Ciereszko, Tomasz Wasniewski, Robert Mroz, Wojciech Naumnik, Ewa Sierko, Magdalena Paczkowska, Joanna Kisluk, Anetta Sulewska, Adam Cybulski, Zenon Mariak, Boguslaw Kedra, Jacek Szamatowicz, Paweł Kurzawa, Lukasz Minarowski, Angelika Edyta Charkiewicz, Barbara Mroczko, Jolanta Malyszko, Christian Manegold, Lothar Pilz, Heike Allgayer, Mohammed L Abba, Hartmut Juhl, Frauke Koch
Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized...
June 21, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28646535/targeting-stat3-by-ho3867-induces-apoptosis-in-ovarian-clear-cell-carcinoma
#3
Kristin Bixel, Uksha Saini, Hemant Kumar Bid, John Fowler, Maria Riley, Ross Wanner, Kalpana Deepa Priya Dorayappan, Sneha Rajendran, Ikuo Konishi, Noriomi Matsumura, David E Cohn, Karuppaiyah Selvendiran
Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. STAT3 expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6)...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#4
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28646232/inhibition-of-erk1-2-restores-gsk3%C3%AE-activity-and-protein-synthesis-levels-in-a-model-of-tuberous-sclerosis
#5
Rituraj Pal, Vitaliy V Bondar, Carolyn J Adamski, George G Rodney, Marco Sardiello
Tuberous sclerosis (TS) is a multi-organ autosomal dominant disorder that is best characterized by neurodevelopmental deficits and the presence of benign tumors. TS pathology is caused by mutations in tuberous sclerosis complex (TSC) genes and is associated with insulin resistance, decreased glycogen synthase kinase 3β (GSK3β) activity, activation of the mammalian target of rapamycin complex 1 (mTORC1), and subsequent increase in protein synthesis. Here, we show that extracellular signal-regulated kinases (ERK1/2) respond to insulin stimulation and integrate insulin signaling to phosphorylate and thus inactivate GSK3β, resulting in increased protein synthesis that is independent of Akt/mTORC1 activity...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646148/mir-15b-5p-resensitizes-colon-cancer-cells-to-5-fluorouracil-by-promoting-apoptosis-via-the-nf-%C3%AE%C2%BAb-xiap-axis
#6
Ci Zhao, Qi Zhao, Chunhui Zhang, Guangyu Wang, Yuanfei Yao, Xiaoyi Huang, Fei Zhan, Yuanyuan Zhu, Jiaqi Shi, Jianan Chen, Feihu Yan, Yanqiao Zhang
Drug resistance, which is closely correlated with an imbalance in apoptosis, endows colorectal cancer (CRC) with enhanced progression capacity irrespective of the treatment with therapeutics. We report that miR-15b-5p is a tumor suppressor whose level is globally decreased in CRC cells and tissues. Over-expression of miR-15b-5p not only promoted 5-fluorouracil (5-FU)-induced cellular apoptosis but also reversed the chemoresistance of 5-FU in vitro and in vivo. As a key mediator of inflammation-induced cancer, miR-15b-5p enhances these therapeutic effects are mainly attributed to targeting of the NF-κB signaling pathway through negative regulation of NF-κB1 and one of its kinase complexes IKK-α...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646117/cyclin-dependent-kinase-9-is-a-novel-specific-molecular-target-in-adult-t-cell-leukemia-lymphoma
#7
Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Takaori-Kondo Akifumi, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida
Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII).  The deregulation of CDK9/P-TEFb has important implications for many cancer types.  BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase I studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#8
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28645940/t-cell-receptors-for-clinical-therapy-in-vitro-assessment-of-toxicity-risk
#9
Andre Kunert, Matthias Obenaus, Cor Hj Lamers, Thomas Blankenstein, Reno Debets
Adoptive therapy with T cell receptor (TCR)-engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs, and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against Cancer Germline Antigens...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645939/combined-btk-and-pi3k%C3%AE-inhibition-with-acalabrutinib-and-acp-319-improves-survival-and-tumor-control-in-cll-mouse-model
#10
Carsten U Niemann, Helena I Mora-Jensen, Eman L Dadashian, Fanny Krantz, Todd Covey, Shih-Shih Chen, Nicholas- Chiorazzi, Raquel Izumi, Roger Ulrich, Brian J Lannutti, Adrian Wiestner, Sarah E M Herman
Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of BTK and PI3K-delta is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3K-delta and BTK inhibitors. <p>Experimental design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3K-delta inhibitor ACP-319 in vivo We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645563/bruceine-d-inhibits-hepatocellular-carcinoma-growth-by-targeting-%C3%AE-catenin-jagged1-pathways
#11
Ziying Cheng, Xing Yuan, Yi Qu, Xia Li, Guozhen Wu, Chenwei Li, Xianpeng Zu, Niao Yang, Xisong Ke, Juan Zhou, Ning Xie, Xike Xu, Shanrong Liu, Yunheng Shen, Huiliang Li, Weidong Zhang
Hepatocellular carcinoma (HCC) is known for high mortality and limited available treatments. Aberrant activation of the Wnt and Notch signaling pathways is critical to liver carcinogenesis and progression. Here, we identified a small molecule, bruceine D (BD), as a Notch inhibitor, using an RBP-Jκ-dependent luciferase-reporter system. BD significantly inhibited liver tumor growth and enhanced the therapeutic effects of sorafenib in various murine HCC models. Mechanistically, BD promotes proteasomal degradation of β-catenin and the depletion of its nuclear accumulation, which in turn disrupts the Wnt/β-catenin-dependent transcription of the Notch ligand Jagged1 in HCC...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28645562/anti-myeloma-effects-of-ruxolitinib-combined-with-bortezomib-and-lenalidomide-a-rationale-for-jak-stat-pathway-inhibition-in-myeloma-patients
#12
Mariana B de Oliveira, Veruska L Fook-Alves, Angela I P Eugenio, Rodrigo C Fernando, Luiz Felipe G Sanson, Mariana F de Carvalho, Walter M T Braga, Faith E Davies, Gisele W B Colleoni
JAK proteins have been linked with survival and proliferation of multiple myeloma (MM) cells; therefore, JAK inhibition could be a therapeutic strategy for MM. We evaluated JAK1 and JAK2 expression in MM patients and the effects of JAK/STAT pathway inhibition on apoptosis, cell cycle, gene and protein expression in RPMI-8226 and U266 MM cell lines. 57% of patients presented overexpression of JAK2 and 27%, of JAK1. After treatment with ruxolitinib and bortezomib, RPMI-8226 and U266 presented 50% of cells in late apoptosis, reduction of anti-apoptotic genes expression and higher number of cells in SubG0 phase...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28645115/a-comprehensive-review-of-heregulins-her3-and-her4-as-potential-therapeutic-targets-in-cancer
#13
REVIEW
Jose Mauricio Mota, Katharine Ann Collier, Ricardo Lima Barros Costa, Timothy Taxter, Aparna Kalyan, Caio A Leite, Young Kwang Chae, Francis J Giles, Benedito A Carneiro
Heregulins (HRGs) bind to the receptors HER3 or HER4, induce receptor dimerization, and trigger downstream signaling that leads to tumor progression and resistance to targeted therapies. Increased expression of HRGs has been associated with worse clinical prognosis; therefore, attempts to block HRG-dependent tumor growth have been pursued. This manuscript summarizes the function and signaling of HRGs and review the preclinical evidence of its involvement in carcinogenesis, prognosis, and treatment resistance in several malignancies such as colorectal cancer, non-small cell lung cancer, ovarian cancer, and breast cancer...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28645102/expression-of-p63-and-cd44-in-oral-squamous-cell-carcinoma-and-correlation-with-clinicopathological-parameters
#14
Nasrollah Saghravanian, Kazem Anvari, Narges Ghazi, Bahram Memar, Maryam Shahsavari, Monavar Afzal Aghaee
Squamous cell carcinoma (SCC) is the sixth most frequent malignant tumor of the head and neck region. Despite advances in therapeutic options over the last decades, the rate of mortality and morbidity has not been improved markedly. A small subset of cells, cancer stem cells (CSCs), with self-renewal properties have become a major focus of current cancer research. CD44 and p63 are identified as candidate stem cell markers in normal squamous epithelium and SCC. The role of these markers in oral squamous cell carcinoma (OSCC) is still debatable...
June 15, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28644558/current-understanding-of-cancer-stem-cells-review-of-their-radiobiology-and-role-in-head-and-neck-cancers
#15
REVIEW
Paul Ambrose Reid, Puthenparampil Wilson, Yanrui Li, Loredana Gabriela Marcu, Eva Bezak
Evidence of cancer cells that bear attributes analogous to those of normal stem cells has developed a hierarchical model of cancer's architecture and progression. This subset of cancer stem cells (CSCs) drives the progression and therapy resistance of cancers. Research to identify the phenotypes of these CSCs presents evidence of a subpopulation that is more resistant to therapy and may proliferate in response. Literature shows that CSCs typically represent around 1%-10% of cell populations in head and neck cancer but this proportion may increase in response to a therapeutic radiation dose...
June 23, 2017: Head & Neck
https://www.readbyqxmd.com/read/28644138/comparative-analysis-of-primary-versus-relapse-refractory-dlbcl-identifies-shifts-in-mutation-spectrum
#16
Danielle M Greenawalt, Winnie S Liang, Sakina Saif, Justin Johnson, Petar Todorov, Austin Dulak, Daniel Enriquez, Rebecca Halperin, Ambar Ahmed, Vladislav Saveliev, John Carpten, David Craig, J Carl Barrett, Brian Dougherty, Michael Zinda, Stephen Fawell, Jonathan R Dry, Kate Byth
Current understanding of the mutation spectrum of relapsed/refractory (RR) tumors is limited. We performed whole exome sequencing (WES) on 47 diffuse large B cell lymphoma (DLBCL) tumors that persisted after R-CHOP treatment, 8 matched to primary biopsies. We compared genomic alterations from the RR cohort against two treatment-naïve DLBCL cohorts (n=112). While the overall number and types of mutations did not differ significantly, we identified frequency changes in DLBCL driver genes. The overall frequency of MYD88 mutant samples increased (12% to 19%), but we noted a decrease in p...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644090/transdermal-administration-of-melatonin-coupled-to-cryopass-laser-treatment-as-noninvasive-therapy-for-prostate-cancer
#17
Laura Terraneo, Paola Bianciardi, Eleonora Virgili, Elena Finati, Michele Samaja, Rita Paroni
Melatonin, a pineal gland hormone, exerts oncostatic activity in several types of human cancer, including prostate, the most common neoplasia and the third most frequent cause of male cancer death in the developed world. The growth of androgen-sensitive LNCaP prostate cancer cells in mice is inhibited by 3 mg/kg/week melatonin (0.09 mg/mouse/week) delivered by i.p. injections, which is equivalent to a dose of 210 mg/week in humans. The aim of this study is to test an alternative noninvasive delivery route based on transdermal administration of melatonin onto the tumor area followed by cryopass-laser treatment...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28644032/receptor-and-microenvironment-dual-recognizable-nanogel-for-targeted-chemotherapy-of-highly-metastatic-malignancy
#18
Jinjin Chen, Jianxun Ding, Weiguo Xu, Tianmeng Sun, Haihua Xiao, Xiuli Zhuang, Xuesi Chen
Targeted delivery of chemotherapeutic drugs to the desired lesion sites is the main objective in malignancy treatment, especially in highly metastatic malignancies. However, extensive studies around the world on traditional targeting strategies of recognizing either over-expressed receptors or microenvironments in tumors show great limitations, owing to the off-target effect and tumor homogeneity. Integration of both receptor-mediated targeting (RMT) and environment-mediated targeting (EMT) enhances the tumor accumulation and subsequent cell uptake at the same time, which may avoid these limitations...
June 23, 2017: Nano Letters
https://www.readbyqxmd.com/read/28643862/tumor-angiogenesis-revisited-regulators-and-clinical-implications
#19
REVIEW
Roberto Ronca, Mohammed Benkheil, Stefania Mitola, Sofie Struyf, Sandra Liekens
Since Judah Folkman hypothesized in 1971 that angiogenesis is required for solid tumor growth, numerous studies have been conducted to unravel the angiogenesis process, analyze its role in primary tumor growth, metastasis and angiogenic diseases, and to develop inhibitors of proangiogenic factors. These studies have led in 2004 to the approval of the first antiangiogenic agent (bevacizumab, a humanized antibody targeting vascular endothelial growth factor) for the treatment of patients with metastatic colorectal cancer...
June 23, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28643387/non-gaussian-diffusion-imaging-with-a-fractional-order-calculus-model-to-predict-response-of-gastrointestinal-stromal-tumor-to-second-line-sunitinib-therapy
#20
Lei Tang, Yi Sui, Zheng Zhong, Frederick C Damen, Jian Li, Lin Shen, Yingshi Sun, Xiaohong Joe Zhou
PURPOSE: To demonstrate the clinical value of a non-Gaussian diffusion model using fractional order calculus (FROC) for early prediction of the response of gastrointestinal stromal tumor to second-line sunitinib targeted therapy. METHODS: Fifteen patients underwent sunitinib treatment after imatinib resistance. Diffusion-weighted imaging with multiple b-values was performed before treatment (baseline) and 2 weeks (for early prediction of response) after initiating sunitinib treatment...
June 22, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
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