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https://www.readbyqxmd.com/read/29168312/curcumin-mediated-down-regulation-of-%C3%AE-v-%C3%AE-3-integrin-and-up-regulation-of-pyruvate-dehydrogenase-kinase-4-pdk4-in-erlotinib-resistant-sw480-colon-cancer-cells
#1
Samira Javadi, Kobra Rostamizadeh, Jalal Hejazi, Maliheh Parsa, Mojtaba Fathi
Erlotinib is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor, but the development of erlotinib resistance during chemotherapy can lead to treatment failure. To shed light on the erlotinib-resistant pathway, this study investigated the effect of combination therapy using curcumin- and erlotinib-loaded nanoparticles on the expression of αv β3 integrin and pyruvate dehydrogenase kinase 4 (PDK4) in an erlotinib-resistant SW480 colon cancer cell line. An erlotinib-resistant SW480 colon cancer cell line was produced by long-term exposure to erlotinib...
November 23, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29163822/structural-basis-of-the-therapeutic-anti-pd-l1-antibody-atezolizumab
#2
Fei Zhang, Xiaoqiang Qi, Xiaoxiao Wang, Diyang Wei, Jiawei Wu, Lingling Feng, Haiyan Cai, Yugang Wang, Naiyan Zeng, Ting Xu, Aiwu Zhou, Ying Zheng
Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155449/baicalein-inhibits-acinar-to-ductal-metaplasia-of-pancreatic-acinal-cell-ar42j-via-improving-the-inflammatory-microenvironment
#3
Wei-Ling Pu, Ying-Ying Luo, Ru-Yu Bai, Ao-Wei Guo, Kun Zhou, Yun-Sha Zhang, Lin Miao, Curzio Rüegg, Micheal O Hottiger, Xiu-Mei Gao, Li-Kang Sun
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29152681/trichothecenes-immunomodulatory-effects-mechanisms-and-anti-cancer-potential
#4
REVIEW
Qinghua Wu, Xu Wang, Eugenie Nepovimova, Anca Miron, Qianying Liu, Yun Wang, Dongxiao Su, Hualin Yang, Li Li, Kamil Kuca
Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated...
November 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29142786/extraordinary-clinical-benefit-to-sequential-treatment-with-targeted-therapy-and-immunotherapy-of-a-braf-v600e-and-pd-l1-positive-metastatic-lung-adenocarcinoma
#5
Shuyu D Li, Annia Martial, Alexa B Schrock, Jane J Liu
Background: The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29127303/comprehensive-genomic-analysis-of-oesophageal-squamous-cell-carcinoma-reveals-clinical-relevance
#6
Peina Du, Peide Huang, Xuanlin Huang, Xiangchun Li, Zhimin Feng, Fengyu Li, Shaoguang Liang, Yongmei Song, Jan Stenvang, Nils Brünner, Huanming Yang, Yunwei Ou, Qiang Gao, Lin Li
Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs)...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109782/berunda-polypeptides-multi-headed-fusion-proteins-promote-subcutaneous-administration-of-rapamycin-to-breast-cancer-in-vivo
#7
Jugal P Dhandhukia, Zhe Li, Santosh Peddi, Shruti Kakan, Arjun Mehta, David Tyrpak, Jordan Despanie, J Andrew MacKay
Recombinant Elastin-Like Polypeptides (ELPs) serve as attractive scaffolds for nanoformulations because they can be charge-neutral, water soluble, high molecular weight, monodisperse, biodegradable, and decorated with functional proteins. We recently reported that fusion of the FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) reduces rapamycin (Rapa) toxicity and enables intravenous (IV) therapy in both a xenograft breast cancer model and a murine autoimmune disease model. Rapa has poor solubility, which leads to variable oral bioavailability or drug precipitation following parenteral administration...
2017: Theranostics
https://www.readbyqxmd.com/read/29105711/a-novel-bacteriochlorin-styrylnaphthalimide-conjugate-for-simultaneous-photodynamic-therapy-and-fluorescence-imaging
#8
Pavel A Panchenko, Mikhail A Grin, Olga A Fedorova, Marina A Zakharko, Dmitriy A Pritmov, Andrey F Mironov, Antonina N Arkhipova, Yuri V Fedorov, Gediminas Jonusauskas, Raisa I Yakubovskaya, Natalia B Morozova, Anastasia A Ignatova, Alexey V Feofanov
Propargyl-15(2),17(3)-dimethoxy-13(1)-amide of bacteriochlorin e (BChl) and a 4-(4-N,N-dimethylaminostyryl)-N-alkyl-1,8-naphthalimide bearing azide group in the N-alkyl fragment were conjugated by the copper(i)-catalyzed 1,3-dipolar cycloaddition to produce a novel dyad compound BChl-NI for anticancer photodynamic therapy (PDT) combining the modalities of a photosensitizer (PS) and a fluorescence imaging agent. A precise photophysical investigation of the conjugate in solution using steady-state and time-resolved optical spectroscopy revealed that the presence of the naphthalimide (NI) fragment does not decrease the photosensitizing ability of the bacteriochlorin (BChl) core as compared with BChl; however, the fluorescence of naphthalimide is completely quenched due to resonance energy transfer (RET) to BChl...
November 6, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29104951/folate-peg-conjugates-of-a-far-red-light-activatable-paclitaxel-prodrug-to-improve-selectivity-toward-folate-receptor-positive-cancer-cells
#9
Pritam Thapa, Mengjie Li, Radha Karki, Moses Bio, Pallavi Rajaputra, Gregory Nkepang, Sukyung Woo, Youngjae You
We recently demonstrated the far-red light-activatable prodrug of paclitaxel (PTX), Pc-(L-PTX)2. Upon illumination with a 690 nm laser, Pc-(L-PTX)2 showed combinational cell killing from rapid photodynamic therapy damage by singlet oxygen, followed by sustained chemotherapy effects from locally released PTX. However, its high lipophilicity (log D7.4 > 3.1) caused aggregation in aqueous solutions and has nonselectivity toward cancer cells. To solve these important problems, we prepared folic acid (FA)-conjugated and photoactivatable prodrugs of PTX with a polyethylene glycol (PEG) spacer of various chain lengths: FA-PEG n -Pc-L-PTX [n = 0 (0k, 5), ∼23 (1k, 7a), ∼45 (2k, 7b), ∼80 (3...
October 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/29103158/sirt3-deacetylates-and-promotes-degradation-of-p53-in-pten-defective-non-small-cell-lung-cancer
#10
Yanlu Xiong, Lei Wang, Shan Wang, Mingxing Wang, Jinbo Zhao, Zhipei Zhang, Xiaofei Li, Lintao Jia, Yong Han
PURPOSE: In non-small cell lung cancer (NSCLC), success of targeted therapy has promoted researches explicitly orientated based on genetic background. Although PTEN deficiency is common in NSCLC, carcinogenesis about such genetic type has not been fully explored. Here, we have found that classical tumor suppressor P53 could be modulated by deacetylase sirtuin-3 (SIRT3) depending on the PTEN condition in NSCLC, which may be a novel breakpoint for handling PTEN deficiency NSCLC. METHODS: First, we examined SIRT3 and P53 expression files in PTEN-deficient NSCLC clinical samples and investigated their correlation...
November 4, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29072601/molecular-dynamics-simulations-and-dynamic-network-analysis-reveal-the-allosteric-unbinding-of-monobody-to-h-ras-triggered-by-r135k-mutation
#11
Duan Ni, Kun Song, Jian Zhang, Shaoyong Lu
Ras proteins, as small GTPases, mediate cell proliferation, survival and differentiation. Ras mutations have been associated with a broad spectrum of human cancers and thus targeting Ras represents a potential way forward for cancer therapy. A recently reported monobody NS1 allosterically disrupts the Ras-mediated signaling pathway, but its efficacy is reduced by R135K mutation in H-Ras. However, the detailed mechanism is unresolved. Here, using molecular dynamics (MD) simulations and dynamic network analysis, we explored the molecular mechanism for the unbinding of NS1 to H-Ras and shed light on the underlying allosteric network in H-Ras...
October 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29072302/merkel-cell-carcinoma
#12
REVIEW
Jürgen C Becker, Andreas Stang, James A DeCaprio, Lorenzo Cerroni, Celeste Lebbé, Michael Veness, Paul Nghiem
Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer with neuroendocrine features. MCC pathogenesis is associated with either the presence of Merkel cell polyomavirus or chronic exposure to ultraviolet light (UV), which can cause a characteristic pattern of multiple DNA mutations. Notably, in the Northern hemisphere, the majority of MCC cases are of viral aetiology; by contrast, in areas with high UV exposure, UV-mediated carcinogenesis is predominant. The two aetiologies share similar clinical, histopathological and prognostic characteristics...
October 26, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29058879/critical-overview-of-the-use-of-ru-ii-polypyridyl-complexes-as-photosensitizers-in-one-photon-and-two-photon-photodynamic-therapy
#13
Franz Heinemann, Johannes Karges, Gilles Gasser
Photodynamic Therapy (PDT) is an emerging technique to treat certain types of cancer, bacterial, fungal, and viral infections, and skin diseases. In past years, different research groups developed new ruthenium-containing photosensitizers (PSs) with tuned photophysical and biological properties to better fit the requirements of PDT. In this Account, we report and discuss the latest results in this research area, emphasizing particularly our own research. For example, inspired by the DNA intercalating complex [Ru(bpy)2(dppz)](2+) (bpy = 2,2'-bipyridine; dppz = (dipyrido[3,2-a:2',3'-c]phenazine), a series of ruthenium complexes bearing differently functionalized dppz ligands were synthesized to target DNA...
October 23, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29057232/expanded-molecular-interrogation-for-potential-actionable-targets-in-non-squamous-non-small-cell-lung-cancer
#14
REVIEW
Kah Weng Lau, Claudia Seng, Tony K H Lim, Daniel S W Tan
The advent of targeted therapies has established new standards of care for defined molecular subsets of non-small cell lung cancer (NSCLC). Not only has this led to significant changes in the routine clinical management of lung cancer e.g., multiplexed genomic testing, but it has provided important principles and benchmarks for determining "actionability". At present, the clinical paradigms are most evolved for EGFR mutations and ALK rearrangements, where multiple randomized phase III trials have determined optimal treatment strategies in both treatment naïve and resistant settings...
September 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29046623/biocompatible-d-a-semiconducting-polymer-nanoparticle-with-light-harvesting-unit-for-highly-effective-photoacoustic-imaging-guided-photothermal-therapy
#15
Jinfeng Zhang, Caixia Yang, Rui Zhang, Rui Chen, Zhenyu Zhang, Wenjun Zhang, Shih-Hao Peng, Xiaoyuan Chen, Gang Liu, Chain-Shu Hsu, Chun-Sing Lee
The development of nanotheranostic agents that integrate diagnosis and therapy for effective personalized precision medicine has obtained tremendous attention in the past few decades. In this report, biocompatible electron donor-acceptor conjugated semiconducting polymer nanoparticles (PPor-PEG NPs) with light-harvesting unit is prepared and developed for highly effective photoacoustic imaging guided photothermal therapy. To the best of our knowledge, it is the first time that the concept of light-harvesting unit is exploited for enhancing the photoacoustic signal and photothermal energy conversion in polymer-based theranostic agent...
April 5, 2017: Advanced Functional Materials
https://www.readbyqxmd.com/read/29045438/gold-nanorod-reshaping-in-vitro-and-in-vivo-using-a-continuous-wave-laser
#16
David Harris-Birtill, Mohan Singh, Yu Zhou, Anant Shah, Pakatip Ruenraroengsak, Maria Elena Gallina, George B Hanna, Anthony E G Cass, Alexandra E Porter, Jeffrey Bamber, Daniel S Elson
Gold nanorods (GNRs) are increasingly being investigated for cancer theranostics as they possess features which lend themselves in equal measures as contrast agents and catalysts for photothermal therapy. Their optical absorption spectral peak wavelength is determined by their size and shape. Photothermal therapy using GNRs is typically established using near infrared light as this allows sufficient penetration into the tumour matrix. Continuous wave (CW) lasers are the most commonly applied source of near infrared irradiation on GNRs for tumour photothermal therapy...
2017: PloS One
https://www.readbyqxmd.com/read/29044466/massage-therapy-decreases-cancer-related-fatigue-results-from-a-randomized-early-phase-trial
#17
Becky Kinkead, Pamela J Schettler, Erika R Larson, Dedric Carroll, Margaret Sharenko, James Nettles, Sherry A Edwards, Andrew H Miller, Mylin A Torres, Boadie W Dunlop, Jeffrey J Rakofsky, Mark Hyman Rapaport
BACKGROUND: Cancer-related fatigue (CRF) is a prevalent and debilitating symptom experienced by cancer survivors, yet treatment options for CRF are limited. In this study, we evaluated the efficacy of weekly Swedish massage therapy (SMT) versus an active control condition (light touch [LT]) and waitlist control (WLC) on persistent CRF in breast cancer survivors. METHODS: This early phase, randomized, single-masked, 6-week investigation of SMT, LT, and WLC enrolled 66 female stage 0-III breast cancer survivors (age range, 32-72 years) who had received surgery plus radiation and/or chemotherapy/chemoprevention with CRF (Brief Fatigue Inventory > 25)...
October 17, 2017: Cancer
https://www.readbyqxmd.com/read/29033001/the-role-of-micrornas-in-photodynamic-therapy-of-cancer
#18
Sherien M El-Daly, Mohammed L Abba, Amira M Gamal-Eldeen
Photodynamic therapy (PDT) is a non-invasive treatment modality used in the management of both benign and malignant conditions. It involves the administration of a photosensitizing agent followed by local light irradiation, which activates the photosensitizer, resulting in tissue damage. An in-depth understanding of the molecular mechanisms and mediators of PDT is important, not only for appreciating how this treatment modality is effective, but also as an avenue for understanding potential shortfalls and untoward effects that can be managed or improved...
October 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29020442/two-photon-photosensitizer-polymer-conjugates-for-combined-cancer-cell-death-induction-and-two-photon-fluorescence-imaging-structure-photodynamic-therapy-efficiency-relationship
#19
Cristina Cepraga, Sophie Marotte, Edna Ben Daoud, Arnaud Favier, Pierre-Henri Lanoë, Cyrille Monnereau, Patrice Baldeck, Chantal Andraud, Jacqueline Marvel, Marie-Thérèse Charreyre, Yann Leverrier
One of the challenges of photodynamic therapy is to increase the penetration depth of light irradiation in the tumor tissues. Although two-photon excitation strategies have been developed, the two-photon absorption cross sections of clinically used photosensitizers are generally low (below 300 GM). Besides, photosensitizers with high cross section values are often non-water-soluble. In this research work, a whole family of photosensitizer-polymer conjugates was synthesized via the covalent binding of a photosensitizer with a relatively high cross section along a biocompatible copolymer chain...
November 10, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29018777/rationale-feasibility-and-acceptability-of-ketogenic-diet-for-cancer-treatment
#20
REVIEW
Hae-Yun Chung, Yoo Kyoung Park
Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possibility of the use of ketogenic diet for oncology patients...
September 2017: Journal of Cancer Prevention
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