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intratumoral chemotherapy

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https://www.readbyqxmd.com/read/29353083/combining-ultrasound-and-intratumoral-administration-of-doxorubicin-loaded-microspheres-to-enhance-tumor-cell-killing
#1
Anh-Vu Do, Sean M Geary, Dongrim Seol, Phillip Tobias, Daniel Carlsen, Nattawut Leelakanok, James A Martin, Aliasger K Salem
Melanoma is an incurable disease for which alternative treatments to chemotherapy alone are sought. Here, using a melanoma model, we investigated the antitumor potential of combining ultrasound (US) with poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with doxorubicin (DOX). The aim was to achieve synergistic tumoricidal activity through direct and indirect US-mediated damage of tumor cells combined with sustained and potentially controllable release (when combined with US) of DOX from microspheres...
January 15, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29352488/understanding-intratumor-heterogeneity-by-combining-genome-analysis-and-mathematical-modeling
#2
REVIEW
Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy...
January 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29338444/adp53-gendicine-12-years-in-clinic-the-first-approved-gene-therapy-product-for-cancer
#3
Wei-Wei Zhang, Jianglong Li, Dinggang Li, Jiliang Liu, Xiuqin Li, Wei Li, Xiaolong Xu, Michael J Zhang, Lois Chandler, Hong Lin, Aiguo Hu, Wei Xu, Dominic Man-Kit Lam
Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech Company, was approved by CFDA in 2003. It has been used in clinical oncology for 12 years since it entered the market in 2004. As the first-in-class product for cancer gene therapy, Gendicine met its expectation and demonstrated with ample clinical data that it is safe and effective for treating cancer. SiBiono manufactured 41 batches in compliant with CFDA QC/QA requirements. Total 169,571 vials (1.0x1012 vector particles per vial) were used in more than 50,000 patients, among them about 5,000 were international form over 50 nations outside China...
January 16, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29331808/simultaneous-inhibition-of-hedgehog-signaling-and-tumor-proliferation-remodels-stroma-and-enhances-pancreatic-cancer-therapy
#4
Jun Zhao, Huamin Wang, Cheng-Hui Hsiao, Diana S-L Chow, Eugene J Koay, Yaan Kang, Xiaoxia Wen, Qian Huang, Ying Ma, James A Bankson, Stephen E Ullrich, Willem Overwijk, Anirban Maitra, David Piwnica-Worms, Jason B Fleming, Chun Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has an excessive desmoplastic stroma that can limit the intratumoral delivery of chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both stromal and tumor compartments need to be addressed in order to effectively treat PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation (M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts (CAFs), while PTX can inhibit tumor proliferation...
January 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29330466/target-engagement-imaging-of-parp-inhibitors-in-small-cell-lung-cancer
#5
Brandon Carney, Susanne Kossatz, Benjamin H Lok, Valentina Schneeberger, Kishore K Gangangari, Naga Vara Kishore Pillarsetty, Wolfgang A Weber, Charles M Rudin, John T Poirier, Thomas Reiner
Insufficient chemotherapy response and rapid disease progression remain concerns for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316433/tim-3-regulates-cd103-dendritic-cell-function-and-response-to-chemotherapy-in-breast-cancer
#6
Álvaro de Mingo Pulido, Alycia Gardner, Shandi Hiebler, Hatem Soliman, Hope S Rugo, Matthew F Krummel, Lisa M Coussens, Brian Ruffell
Intratumoral CD103+ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103+ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8+ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29315855/near-infrared-upconversion-mesoporous-cerium-oxide-hollow-biophotocatalyst-for-concurrent-ph-h2-o2-responsive-o2-evolving-synergetic-cancer-therapy
#7
Chi Yao, Wenxing Wang, Peiyuan Wang, Mengyao Zhao, Xiaomin Li, Fan Zhang
Tumor hypoxia is typically presented in the central region of solid tumors, which is mainly caused by an inadequate blood flow and oxygen supply. In the conventional treatment of hypoxic human tumors, not only the oxygen-dependent photodynamic therapy (PDT), but also antitumor drug-based chemotherapy, is considerably limited. The use of direct oxygen delivering approach with oxygen-dependent PDT or chemotherapy may potentiate the reactive oxygen species (ROS)-mediated cytotoxicity of the drug toward normal tissues...
January 8, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29312541/energy-metabolism-in-glioblastoma-stem-cells-ppar%C3%AE-a-metabolic-adaptor-to-intratumoral-microenvironment
#8
Alessia Fidoamore, Loredana Cristiano, Chiara Laezza, Renato Galzio, Elisabetta Benedetti, Benedetta Cinque, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Maria Grazia Cifone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini
Glioblastoma (GB), the most-common cancer in the adult brain, despite surgery and radio/ chemotherapy, is to date almost incurable. Many hypoxic tumors, including GB, show metabolic reprogramming to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. Peroxisome Proliferator-activated Receptors (PPAR), particularly the α isotype, have been involved in the control of energetic metabolism. Herein, we characterized patient-derived GB neurospheres focusing on their energetic metabolism and PPARα expression...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305923/junction-opener-protein-increases-nanoparticle-accumulation-in-solid-tumors
#9
Christine E Wang, Roma C Yumul, Jonathan Lin, Yilong Cheng, André Lieber, Suzie H Pun
Carcinomas contain tight junctions that can limit the penetration and therefore therapeutic efficacy of anticancer agents, especially those delivered by nano-carrier systems. The junction opener (JO) protein is a virus-derived protein that can transiently open intercellular junctions in epithelial tumors by cleaving the junction protein desmoglein-2 (DSG2). Co-administration of JO was previously shown to significantly increase the efficacy of various monoclonal antibodies and chemotherapy drugs in murine tumor models by allowing for increased intratumoral penetration of the drugs...
January 3, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29301832/pharmacological-inhibition-of-nos-activates-ask1-jnk-pathway-augmenting-docetaxel-mediated-apoptosis-in-triple-negative-breast-cancer
#10
Daniel Dávila-González, Dong Soon Choi, Roberto R Rosato, Sergio Granados-Principal, John G Kuhn, Wen-Feng Li, Wei Qian, Wen Chen, Anthony J Kozielski, Helen H Wong, Bhuvanesh Dave, Jenny C Chang
PURPOSE: Chemoresistance in triple negative breast cancer (TNBC) is associated with the activation of a survival mechanism orchestrated by the endoplasmic reticulum (EnR) stress response and by inducible nitric oxide synthase (iNOS). Our aim was to determine the effects of pharmacological NOS-inhibition on TNBC. EXPERIMENTAL DESIGN: TNBC cell lines, SUM-159PT, MDA-MB-436, and MDA-MB-468, were treated with docetaxel and NOS-inibitor (L-NMMA) for 24, 48 and 72 hours...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29289495/mechanism-of-action-pharmacokinetics-efficacy-and-safety-of-transarterial-therapies-using-ethiodized-oil-preclinical-review-in-liver-cancer-models
#11
Ron C Gaba, Regina M Schwind, Sebastien Ballet
PURPOSE: To systematically review mechanism of action, pharmacokinetics (PKs), efficacy, and safety of ethiodized oil-based locoregional therapy (LRT) for liver cancer in preclinical models. MATERIALS AND METHODS: A MEDLINE search was performed from 1988 to 2016. Search terms included hepatocellular carcinoma (HCC), HCC, liver-cell carcinoma, liver, hepatic, hepatocarcinoma, transarterial or chemoembolization, TACE, animal, Lipiodol, Ethiodol, iodized oil, and/or poppy-seed oil...
December 28, 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/29276148/testosterone-diminishes-cabazitaxel-efficacy-and-intratumoral-accumulation-in-a-prostate-cancer-xenograft-model
#12
Lisanne Mout, Ronald de Wit, Debra Stuurman, Esther Verhoef, Ron Mathijssen, Corrina de Ridder, Martijn Lolkema, Wytske van Weerden
Inactivation of the androgen receptor (AR) pathway by androgen deprivation therapy (ADT) is the mainstay of (metastatic) prostate cancer therapy. Ultimately, the AR pathway will be re-activated despite castrate levels of circulating androgens. Thereby, maintaining its role even in castration resistant prostate cancer (CRPC). The recent STAMPEDE and CHAARTED trials showed that docetaxel in combination with ADT increased survival in hormone sensitive prostate cancer patients, suggesting cross-talk between AR signaling and chemotherapy efficacy...
December 20, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29251630/cancer-associated-fibroblasts-regulate-endothelial-adhesion-protein-lpp-to-promote-ovarian-cancer-chemoresistance
#13
Cecilia S Leung, Tsz-Lun Yeung, Kay-Pong Yip, Kwong-Kwok Wong, Samuel Y Ho, Lingegowda S Mangala, Anil K Sood, Gabriel Lopez-Berestein, Jianting Sheng, Stephen Tc Wong, Michael J Birrer, Samuel C Mok
The molecular mechanism by which cancer-associated fibroblasts (CAFs) confer chemoresistance in ovarian cancer is poorly understood. The purpose of the present study was to evaluate the roles of CAFs in modulating tumor vasculature, chemoresistance, and disease progression. Here, we found that CAFs upregulated the lipoma-preferred partner (LPP) gene in microvascular endothelial cells (MECs) and that LPP expression levels in intratumoral MECs correlated with survival and chemoresistance in patients with ovarian cancer...
December 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29250164/radiofrequency-heat-enhanced-direct-intratumoral-chemotherapy-for-prostate-cancer
#14
Xia Wu, Feng Zhang, Peng Hu, Lumin Chen, Guocan Han, Weixian Bai, Jingfeng Luo, Ran Chen, Yurong Zhou, Jihong Sun, Xiaoming Yang
A novel, minimally invasive interventional technique, radiofrequency heat (RFH), has been suggested to improve the efficacy of chemotherapy for solid organ tumors. However, the treatment for prostate cancer has not been completely characterized. The aim of the present study was to investigate the in vitro and in vivo efficiency of chemotherapy in combination with RFH for the treatment of prostate cancer. The following four treatment groups were included: i) No treatment (control); ii) RFH-only; iii) chemotherapy (docetaxel)-only; and iv) combination therapy of docetaxel and RFH in human prostate cancer (HPC) cell lines and mice with HPC xenografts...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29245896/metabolomic-mapping-of-cancer-stem-cells-for-reducing-and-exploiting-tumor-heterogeneity
#15
Elisabet Cuyàs, Sara Verdura, Salvador Fernández-Arroyo, Joaquim Bosch-Barrera, Begoña Martin-Castillo, Jorge Joven, Javier A Menendez
Personalized cancer medicine based on the analysis of tumors en masse is limited by tumor heterogeneity, which has become a major obstacle to effective cancer treatment. Cancer stem cells (CSC) are emerging as key drivers of inter- and intratumoral heterogeneity. CSC have unique metabolic dependencies that are required not only for specific bioenergetic/biosynthetic demands but also for sustaining their operational epigenetic traits, i.e. self-renewal, tumor-initiation, and plasticity. Given that the metabolome is the final downstream product of all the -omic layers and, therefore, most representative of the biological phenotype, we here propose that a novel approach to better understand the complexity of tumor heterogeneity is by mapping and cataloging small numbers of CSC metabolomic phenotypes...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29233603/individual-susceptibility-analysis-using-patient-derived-slice-cultures-of-colorectal-carcinoma
#16
Rasmus Sönnichsen, Laura Hennig, Vera Blaschke, Karsten Winter, Justus Körfer, Susann Hähnel, Astrid Monecke, Christian Wittekind, Boris Jansen-Winkeln, René Thieme, Ines Gockel, Kerstin Grosser, Arved Weimann, Christoph Kubick, Volker Wiechmann, Achim Aigner, Ingo Bechmann, Florian Lordick, Sonja Kallendrusch
BACKGROUND: Nonresponse to chemotherapy in colorectal carcinoma (CRC) is still a clinical problem. For most established treatment regimens, no predictive biomarkers are available. Patient-derived tumor slice culture may be a promising ex vivo technology to assess the drug susceptibility in individual tumors. METHODS: Patient-derived slice cultures of CRC specimens were prepared according to a standardized protocol and treated with different concentrations of 5-fluorouracil (5-FU) and an adapted FOLFOX regimen (5-FU and oxaliplatin) to investigate histologic response...
November 21, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29228656/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#17
Stefanie Avril, Yasemin Dincer, Katharina Malinowsky, Claudia Wolff, Sibylle Gündisch, Alexander Hapfelmeier, Melanie Boxberg, Holger Bronger, Karl-Friedrich Becker, Barbara Schmalfeldt
Despite frequent initial response rates of epithelial ovarian cancer to platinum-based chemotherapy the majority of patients develop drug resistance. Our aim was to evaluate differential expression of signaling-pathway proteins in platinum-sensitive versus platinum-resistant primary epithelial ovarian cancer specimens to identify predictive biomarkers for treatment response. 192 patients were studied comprising of independent training (n = 89) and validation (n = 103) cohorts. Full-length proteins were extracted from paraffin-embedded samples including multiple regions per tumor to account for intratumoral heterogeneity...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228608/expression-of-mir-195-is-associated-with-chemotherapy-sensitivity-of-cisplatin-and-clinical-prognosis-in-gastric-cancer
#18
Rui Ye, Bo Wei, Sheng Li, Wei Liu, Juntao Liu, Luan Qiu, Xuan Wu, Zhifei Zhao, Jianxiong Li
Gastric cancer has higher morbidity and mortality than other cancers for the low diagnosis rate and few therapies. MiR-195 has been reported to be involved in the occurrence, development and prognosis of various cancers. However, the function of miR-195 in gastric cancer remains largely unknown. Herein, the aims of this study were to probe the functional mechanism of miR-195 and its chemotherapy sensitivity as well as clinical prognosis in gastric cancer. We screened out low-expressed miR-195 through microarray analysis and further confirmed miR-195 was widely down-regulated in gastric cancer cells...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209626/neovascular-prostate-specific-membrane-antigen-expression-is-associated-with-improved-overall-survival-under-palliative-chemotherapy-in-patients-with-pancreatic-ductal-adenocarcinoma
#19
Katharina Stock, Konrad Steinestel, Rebekka Wiesch, Jan-Henrik Mikesch, Anna Hansmeier, Marcel Trautmann, Nora Beller, Jan Rehkämper, Eva Wardelmann, Birthe Heitkötter, Wolfgang Hartmann, Jan Sperveslage, Sebastian Huss
Aims: Expression of PSMA (prostate-specific membrane antigen) has been demonstrated in various cancers, including pancreatic ductal adenocarcinoma (PDAC). However, PSMA expression in PDAC-associated neovasculature has so far not been systematically analyzed. Methods and Results: We analyzed PSMA expression in 81 PDAC tissue samples from 61 patients. Microvessel density (MVD) was assessed by software-based image analysis and showed a mean MVD of 63.7 microvessels/0...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29187403/photodynamic-priming-mitigates-chemotherapeutic-selection-pressures-and-improves-drug-delivery
#20
Huang-Chiao Huang, Imran Rizvi, Joyce Liu, Sriram Anbil, Ashish Kalra, Helen Lee, Yan Baglo, Nancy Paz, Douglas Hayden, Stephen P Pereira, Brian W Pogue, Jonathan B Fitzgerald, Tayyaba Hasan
Physiological barriers to drug delivery and selection for drug resistance limit survival outcomes in cancer patients. In this study, we present preclinical evidence that a subtumoricidal photodynamic priming (PDP) strategy can relieve drug delivery barriers in the tumor microenvironment to safely widen the therapeutic window of a nanoformulated cytotoxic drug. In orthotopic xenograft models of pancreatic cancer, combining PDP with nanoliposomal irinotecan (nal-IRI) prevented tumor relapse, reduce metastasis and increase both progression-free survival and 1-year disease-free survival...
November 29, 2017: Cancer Research
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