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intratumoral chemotherapy

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https://www.readbyqxmd.com/read/28094402/mesoporous-carbon-nanoshells-for-high-hydrophobic-drug-loading-multimodal-optical-imaging-controlled-drug-release-and-synergistic-therapy
#1
Hui Wang, Kui Wang, Qingxin Mu, Zachary R Stephen, Yanyan Yu, Shuiqin Zhou, Miqin Zhang
Loading and controlled release of sufficient hydrophobic drugs to tumor cells has been the bottleneck in chemotherapy for decades. Herein we report the development of a fluorescent and mesoporous carbon nanoshell (FMP-CNS) that exhibits a loading capacity for the hydrophobic drug paclitaxel (PTX) as high as ∼80 wt% and releases the drug in a controllable fashion under NIR irradiation (825 nm) at an intensity of 1.5 W cm(-2). The high drug loading is primarily attributed to its mesoporous structure and to the supramolecular π-stacking between FMP-CNSs and PTX molecules...
January 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/28087981/humanized-chondroitinase-abc-sensitizes-glioblastoma-cells-to-temozolomide
#2
Alena Cristina Jaime-Ramirez, Nina Dmitrieva, Ji Young Yoo, Yeshavanth Banasavadi-Siddegowda, Jianying Zhang, Theresa Relation, Chelsea Bolyard-Blessing, Jeffrey Wojton, Balveen Kaur
INTRODUCTION: Malignant gliomas (GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extra cellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM...
January 14, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28075526/cetuximab-strongly-enhances-immune-cell-infiltration-into-liver-metastatic-sites-in-colorectal-cancer
#3
Yuka Inoue, Shoichi Hazama, Nobuaki Suzuki, Yukio Tokumitsu, Shinsuke Kanekiyo, Shinobu Tomochika, Ryouichi Tsunedomi, Yoshihiro Tokuhisa, Michihisa Iida, Kazuhiko Sakamoto, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Hiroaki Nagano
Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28065619/tumor-associated-macrophage-expression-of-pd-l1-in-implants-of-high-grade-serous-ovarian-carcinoma-a-comparison-of-matched-primary-and-metastatic-tumors
#4
Chelsea E Gottlieb, Anne M Mills, Janet V Cross, Kari L Ring
OBJECTIVE: Data on PD-L1 expression in high grade serous ovarian carcinoma (HGSOC) is mixed. Some studies report robust tumor staining and others identify expression limited to tumor-associated macrophages (TAM). TAM PD-L1 expression is induced in HGSOC metastatic implants from patients who have undergone chemotherapy. However, it is unclear whether TAM acquisition of PD-L1 plays a role in treatment naïve tumors. We investigated PD-L1 expression in primary ovarian tumors and matched metastatic implants from predominantly treatment-naïve HGSOC...
January 5, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28062556/the-cellular-origin-and-evolution-of-breast-cancer
#5
Mei Zhang, Adrian V Lee, Jeffrey M Rosen
In this review, we will discuss how the cell of origin may modulate breast cancer intratumoral heterogeneity (ITH) as well as the role of ITH in the evolution of cancer. The clonal evolution and the cancer stem cell (CSC) models, as well as a model that integrates clonal evolution with a CSC hierarchy, have all been proposed to explain the development of ITH. The extent of ITH correlates with clinical outcome and reflects the cellular complexity and dynamics within a tumor. A unique subtype of breast cancer, the claudin-low subtype that is highly resistant to chemotherapy and most closely resembles mammary epithelial stem cells, will be discussed...
January 6, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28059585/initiation-of-aberrant-dna-methylation-patterns-and-heterogeneity-in-precancerous-lesions-of-human-hepatocellular-cancer
#6
Ryan A Hlady, Dan Zhou, William Puszyk, Lewis R Roberts, Chen Liu, Keith D Robertson
While intratumor heterogeneity contributes to disease progression, metastasis, and resistance to chemotherapy, it also provides a route to understanding the evolution and drivers of disease. Defects in epigenetic landscapes are intimately linked to pathogenesis of a variety of human diseases, with epigenetic deregulation promoting tumorigenesis. Understanding epigenetic heterogeneity is crucial in hepatocellular carcinoma (HCC), where epigenetic alterations are frequent, early, and pathogenic events. We determined genome-wide DNA methylation and copy number variation leveraging the Infinium 450 K in a series of regenerative nodules from within single patient livers...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28053020/blocking-tumor-educated-msc-paracrine-activity-halts-osteosarcoma-progression
#7
Serena Rubina Baglio, Tonny Lagerweij, Maria Pérez Lanzón, Dung Xuan Ho, Nicolas Léveillé, Sonia A Melo, Anne-Marie Cleton-Jansen, Ekaterina S Jordanova, Laura Roncuzzi, Michelina Greco, Monique A J van Eijndhoven, Giulia Grisendi, Massimo Dominici, Roberta Bonafede, Sinead Lougheed, Tanja D de Gruijl, Nicoletta Zini, Silvia Cervo, Agostino Steffan, Vincenzo Canzonieri, Aare Martson, Katre Maasalu, Sulev Koks, Thomas Wurdinger, Nicola Baldini, Dirk M Pegtel
PURPOSE: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets. EXPERIMENTAL DESIGN: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma we evaluated the effect of tumor extracellular vesicle (EV)-educated mesenchymal stem cells (TEMSCs) on osteosarcoma progression...
January 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28046887/we-fg-bra-02-docetaxel-eluting-brachytherapy-spacers-for-local-chemo-radiation-therapy-in-prostate-cancer
#8
J Belz, R Kumar, G Makrigiorgos, A D'Amico, P Nguyen, R Cormack, S Sridhar
PURPOSE: We propose an innovative combinatorial treatment strategy of Local ChemoRadiation Therapy (LCRT) using a sustained drug delivery platform in the form of a spacer to locally radio-sensitize the prostate with Docetaxel (DTX) enabling a synergistic cure with the use of lower radiation doses. These biodegradable spacers are physically similar to the inert spacers routinely used in prostate brachytherapy but are now loaded with formulations of DTX. METHODS: Spacers were loaded with ∼500µg Docetaxel (DTX) for prostate cancer studies...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28045618/tumor-markers-for-early-diagnosis-for-brain-metastasis-of-hepatocellular-carcinoma-a-case-series-and-literature-review-for-effective-loco-regional-treatment
#9
Kenya Kamimura, Yuji Kobayashi, Yoshifumi Takahashi, Hiroyuki Abe, Daisuke Kumaki, Takeshi Yokoo, Hiroteru Kamimura, Norihiro Sakai, Akira Sakamaki, Satoshi Abe, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai
Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately <1 year of survival from the time of diagnosis. A molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time...
January 3, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28035323/the-role-of-pd-l1-expression-and%C3%A2-intratumoral-lymphocytes-in%C3%A2-response%C3%A2-to-perioperative-chemotherapy%C3%A2-for-urothelial-carcinoma
#10
F Erlmeier, A K Seitz, G Hatzichristodoulou, L Stecher, M Retz, J E Gschwend, W Weichert, H R Kübler, T Horn
Introduction: Immunological pathways are relevant for the effectiveness of conventional cytotoxic chemotherapy. Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma. Objective: To monitor PD-L1 expression on tumor cells and intratumoral infiltration with CD8 positive lymphocytes during perioperative chemotherapy for urothelial cancer and to evaluate their use as potential predictive markers for chemotherapy. Patients and Methods: Sixty-four patients with muscle-invasive urothelial cancer were included in the analysis...
October 27, 2016: Bladder Cancer
https://www.readbyqxmd.com/read/28029650/tumor-infiltrating-lymphocytes-predict-prognosis-of-breast-cancer-patients-treated-with-anti-her-2-therapy
#11
Tan-Huan Chen, Ying-Chun Zhang, Yu-Ting Tan, Xin An, Cong Xue, Ying-Fei Deng, Wei Yang, Xia Yuan, Yan-Xia Shi
PURPOSE: Infiltration of tumor associated lymphocytes and count of its different phenotypes are potentially new independent predictor of prognosis in breast cancer. However, research related to it is less reported in breast cancer patients treated with anti-Her-2 therapy. Thus, we evaluated the relationship between survival and tumor infiltrating lymphocytes including its different phenotypes in tumors of such patients. METHODS: Between 1999 and 2010, 98 patients diagnosed with primary breast cancer and treated with anti-Her-2 therapy at Sun-Yat-Sen University Cancer Center were included in the study...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28012777/sequential-administration-of-a-mva-based-muc1-cancer-vaccine-and-the-tlr9-ligand-litenimod-li28-improves-local-immune-defense-against-tumors
#12
Emmanuelle Schaedler, Christelle Remy-Ziller, Julie Hortelano, Nadine Kehrer, Marie-Christine Claudepierre, Tanja Gatard, Christopher Jakobs, Xavier Préville, Antoine F Carpentier, Karola Rittner
TG4010 is an immunotherapeutic vaccine based on Modified Vaccinia virus Ankara (MVA) encoding the human tumor-associated antigen MUC1 and human IL-2. In combination with first-line standard of care chemotherapy in advanced metastatic non-small-cell lung cancer (NSCLC), repeated subcutaneous injection of TG4010 improved progression-free survival in phase 2b clinical trials. In preclinical tumor models, MVATG9931, the research version of TG4010, conferred antigen-specific responses against the weak antigen human MUC1...
December 21, 2016: Vaccine
https://www.readbyqxmd.com/read/28003545/anti-pd-1-antitumor-immunity-is-enhanced-by-local-and-abrogated-by-systemic-chemotherapy-in-gbm
#13
Dimitrios Mathios, Jennifer E Kim, Antonella Mangraviti, Jillian Phallen, Chul-Kee Park, Christopher M Jackson, Tomas Garzon-Muvdi, Eileen Kim, Debebe Theodros, Magdalena Polanczyk, Allison M Martin, Ian Suk, Xiaobu Ye, Betty Tyler, Chetan Bettegowda, Henry Brem, Drew M Pardoll, Michael Lim
The immunosuppressive effects of chemotherapy present a challenge for designing effective cancer immunotherapy strategies. We hypothesized that although systemic chemotherapy (SC) exhibits negative immunologic effects, local chemotherapy (LC) can potentiate an antitumor immune response. We show that LC combined with anti-programmed cell death protein 1 (PD-1) facilitates an antitumor immune response and improves survival (P < 0.001) in glioblastoma. LC-treated mice had increased infiltration of tumor-associated dendritic cells and clonal expansion of antigen-specific T effector cells...
December 21, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27965041/trichodermin-induces-c-jun-n-terminal-kinase-dependent-apoptosis-caused-by-mitotic-arrest-and-dna-damage-in-human-p53-mutated-pancreatic-cancer-cells-and-xenografts
#14
Ming-Hsien Chien, Tzong-Huei Lee, Wei-Jiunn Lee, Yen-Hsiu Yeh, Tsai-Kun Li, Po-Chuan Wang, Jih-Jung Chen, Jyh-Ming Chow, Yung-Wei Lin, Michael Hsiao, Shih-Wei Wang, Kuo-Tai Hua
Pancreatic cancer is an aggressive malignancy, which generally responds poorly to chemotherapy. In this study, trichodermin, an endophytic fungal metabolite from Nalanthamala psidii, was identified as a potent and selective antitumor agent in human pancreatic cancer. Trichodermin exhibited antiproliferative effects against pancreatic cancer cells, especially p53-mutated cells (MIA PaCa-2 and BxPC-3) rather than normal pancreatic epithelial cells. We found that trichodermin induced caspase-dependent and mitochondrial intrinsic apoptosis...
December 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27936723/tumor-microenvironment-responsive-nanoparticle-delivery-of-chemotherapy-for-enhanced-selective-cellular-uptake-and-transportation-within-tumor
#15
Wen-Chia Huang, Shih-Hong Chen, Wen-Hsuan Chiang, Chu-Wei Huang, Chun-Liang Lo, Chorng-Shyan Chern, Hsin-Cheng Chiu
A novel drug delivery strategy featured with enhanced uptake of nanoparticles (NPs) by targeted tumor cells and subsequent intratumoral cellular hitchhiking of chemotherapy to deep tumor regions was described. The NP delivery system was obtained from assembly of poly(lactic acid-co-glycolic acid)-grafted hyaluronic acid (HA-g-PLGA) together with an anticancer drug, SN38, in aqueous phase, followed by implementing the NP surface with a layer of methoxypoly(ethylene glycol)-b-poly(histamine methacrylamide) (mPEG-b-PHMA) via hydrophobic association to improve the colloidal stability both in vitro and in vivo...
December 12, 2016: Biomacromolecules
https://www.readbyqxmd.com/read/27924163/highly-effective-auger-electron-therapy-in-an-orthotopic-glioblastoma-xenograft-model-using-convection-enhanced-delivery
#16
Helge Thisgaard, Bo Halle, Charlotte Aaberg-Jessen, Birgitte Brinkmann Olsen, Anne Sofie Nautrup Therkelsen, Johan Hygum Dam, Niels Langkjær, Sune Munthe, Kjell Någren, Poul Flemming Høilund-Carlsen, Bjarne Winther Kristensen
Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [(125)I]5-Iodo-2'-deoxyuridine ((125)I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED)...
2016: Theranostics
https://www.readbyqxmd.com/read/27923226/intraoperative-tumoral-bleeding-of-hypervascular-medulloblastoma-after-ventricular-drainage-a-case-report
#17
Han-Seung Ryu, Tae-Young Jung, Moon-Soo Han, Seul-Ki Kim, Kyung-Hwa Lee
We report a rare case of intraoperative tumoral bleeding of a hypervascular medulloblastoma. A 12-year-old girl presented with dizziness and nausea. Brain magnetic resonance (MR) images revealed an approximately 4.2-cm enhanced mass on the cerebellar vermis associated with mild perilesional edema and increased cerebral blood volume. Angiography showed tumoral staining and developed occipital and circular dural sinuses in the venous phase. A suboccipital craniotomy was performed. To relieve the intracranial pressure, cerebrospinal fluid (CSF) was drained via a lateral ventricular catheter in the occipital horn...
December 7, 2016: Pediatric Neurosurgery
https://www.readbyqxmd.com/read/27917904/glycoprotein-130-is-associated-with-adverse-postoperative-clinical-outcomes-of-patients-with-late-stage-non-metastatic-gastric-cancer
#18
Yifan Cao, Heng Zhang, Hao Liu, Chao Lin, Ruochen Li, Songyang Wu, Hongyong He, He Li, Jiejie Xu
The interaction of glycoprotein 130 (gp130) with the cytokines of Interleukin-6 (IL-6) family has proved to play a crucial part in several cancers. Our current study is designed to discover the clinical prognostic significance of gp130 in non-metastatic gastric cancer. We examined intratumoral gp130 expression in retrospectively enrolled 370 gastric cancer patients who underwent radical gastrectomy with standard D2 lymphadenectomy at Zhongshan Hospital of Fudan University during 2007 and 2008 by immunohistochemical staining...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916291/intratumoral-immunization-by-p19arf-and-interferon-%C3%AE-gene-transfer-in-a-heterotopic-mouse-model-of-lung-carcinoma
#19
João Paulo Portela Catani, Ruan F V Medrano, Aline Hunger, Paulo Del Valle, Sandy Adjemian, Daniela Bertolini Zanatta, Guido Kroemer, Eugenia Costanzi-Strauss, Bryan E Strauss
Therapeutic strategies that act by eliciting and enhancing antitumor immunity have been clinically validated as an effective treatment modality but may benefit from the induction of both cell death and immune activation as primary stimuli. Using our AdRGD-PG adenovector platform, we show here for the first time that in situ gene transfer of p19Arf and interferon-β (IFNβ) in the LLC1 mouse model of lung carcinoma acts as an immunotherapy. Although p19Arf is sufficient to induce cell death, only its pairing with IFNβ significantly induced markers of immunogenic cell death...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27914909/benefits-pitfalls-and-risks-of-phytotherapy-in-clinical-practice-in-otorhinolaryngology
#20
O Laccourreye, A Werner, L Laccourreye, P Bonfils
OBJECTIVES: To elucidate the benefits, pitfalls and risks of phytotherapy in the clinical practice of otorhinolaryngology. MATERIAL AND METHODS: The PubMed and Cochrane databases were searched using the following keywords: phytotherapy, phytomedicine, herbs, otology, rhinology, laryngology, otitis, rhinitis, laryngitis and otorhinolaryngology. Seventy-two articles (18 prospective randomized studies, 4 Cochrane analyses, 4 meta-analysis and 15 reviews of the literature) devoted to clinical studies were analyzed...
November 30, 2016: European Annals of Otorhinolaryngology, Head and Neck Diseases
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