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intratumoral chemotherapy

Mylène Sebagh, Nelly Bosselut, Alexandre Dos Santos, Marc-Antoine Allard, Aldrick Ruiz, Raphaël Saffroy, Daniel Cherqui, Eric Vibert, Denis Castaing, René Adam, Antonio Sa Cunha, Antoinette Lemoine
Effective individualized treatment of patients with colorectal liver metastases (CLM) requires tumor genotyping, usually based on the analysis of one single sample per patient. Therapy failure may partially be explained by sampling errors and/or intratumoral genetic heterogeneity. We aimed to demonstrate intratumoral genetic heterogeneity in CLM and enable pathologists to select tumor tissue for genotyping. All the tumors of 86 patients who underwent liver resection for a single CLM were reviewed. Of the 86 patients, 66 patients received chemotherapy and 20 patients did not receive chemotherapy before liver resection...
April 24, 2018: Oncotarget
Shuai Liu, Zheng Feng, Zhaoxia Jiang, Hao Wen, Junyan Xu, Herong Pan, Yu Deng, Lei Zhang, Xingzhu Ju, Xiaojun Chen, Xiaohua Wu
OBJECTIVE: This study aimed to explore the clinical and prognostic significance of pretreatment positron-emission tomography/computed tomography (PET/CT) parameters, especially 2-deoxy-2-(F)fluoro-D-glucose-based heterogeneity, in high-grade serous ovarian cancer (HGSC). MATERIALS AND METHODS: We retrospectively investigated 56 patients with HGSC who underwent PET/CT before primary surgery at our hospital between January 2010 and June 2015. None of these patients received neoadjuvant chemotherapy...
May 16, 2018: Nuclear Medicine Communications
Vanesa Gregorc, Rabab M Gaafar, Adolfo Favaretto, Francesco Grossi, Jacek Jassem, Andreas Polychronis, Paolo Bidoli, Marcello Tiseo, Riyaz Shah, Paul Taylor, Silvia Novello, Alberto Muzio, Alessandra Bearz, Laurent Greillier, Floriana Fontana, Giulia Salini, Antonio Lambiase, Mary O'Brien
BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer with highly vascularised tumours. It has poor prognosis and few treatment options after failure of first-line chemotherapy. NGR-hTNF is a vascular-targeting drug that increases penetration of intratumoral chemotherapy and T-cell infiltration by modifying the tumour microenvironment. In this trial, we aimed to investigate the efficacy and safety of NGR-hTNF in patients with malignant pleural mesothelioma who had progressed during or after a first-line treatment...
May 9, 2018: Lancet Oncology
Andrea R Di Sebastiano, Andrew Deweyert, Simon Benoit, Erin Iredale, Hu Xu, Cleusa De Oliveira, Eugene Wong, Susanne Schmid, Matthew O Hebb
Glioblastoma (GBM) is the leading cause of high fatality cancer arising within the adult brain. Electrotherapeutic approaches offer new promise for GBM treatment by exploiting innate vulnerabilities of cancer cells to low intensity electric fields. This report describes the preclinical outcomes of a novel electrotherapeutic strategy called Intratumoral Modulation Therapy (IMT) that uses an implanted stimulation system to deliver sustained, titratable, low intensity electric fields directly across GBM-affected brain regions...
May 8, 2018: Scientific Reports
Rosario Mazzola, Umberto Tebano, Dario Aiello, Gioacchino Di Paola, Niccolò Giaj-Levra, Francesco Ricchetti, Sergio Fersino, Alba Fiorentino, Ruggero Ruggieri, Filippo Alongi
Aim Metastases from colorectal cancer are poorly responsive to stereotactic ablative radiation therapy (SABR) due to intratumoral hypoxia. Intratumoral oxygenation is improved by administration of angiogenesis inhibitors. Thus, there could be a clinical synergistic effect of SABR with bevacizumab on metastases from colorectal cancer. The aim of this study was to evaluate the feasibility and efficacy of SABR after bevacizumab in lung oligometastases from colon cancer. Methods The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon cancer in patients who underwent SABR; patients receiving previous chemotherapy alone or in combination with bevacizumab; Karnofsky performance status >80; life expectancy >6 months; at least 6 months' follow-up after SABR; presence of KRAS mutation...
December 1, 2017: Tumori
E M Rutter, H T Banks, K B Flores
Glioblastoma multiforme (GBM) is a malignant brain cancer with a tendency to both migrate and proliferate. We propose modeling GBM with heterogeneity in cell phenotypes using a random differential equation version of the reaction-diffusion equation, where the parameters describing diffusion (D) and proliferation ([Formula: see text]) are random variables. We investigate the ability to perform the inverse problem to recover the probability distributions of D and [Formula: see text] using the Prohorov metric, for a variety of probability distribution functions...
May 8, 2018: Journal of Mathematical Biology
Xiu-Li Wu, Tao Guo, Hua-Wei Cai
OBJECTIVE: To induce cisplatin-resistant cervical squamous carcinoma cell line and investigate the drug resistant mechanisms and adenovirus trans-gene therapeutical treatment. METHODS: The cisplatin-resistant subline,designated C-33A/cis,was originated by growing parental C-33A cells with gradually increasing doses of cisplatin. The cytotoxicity of cisplatin was determined by CCK-8 assay,and the CTR1 expression was measured by Western blot. Subcutaneous xenograft cervical tumor model was established by cisplatin-resistant C-33A/cis cell line...
January 2018: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Siang-Boon Koh, Yann Wallez, Charles R Dunlop, Sandra Bernaldo de Quirós Fernández, Tashinga E Bapiro, Frances M Richards, Duncan I Jodrell
Combination of cytotoxic therapy with emerging DNA damage response inhibitors (DDRi) has been limited by tolerability issues. However, the goal of most combination trials has been to administer DDRi with standard-of-care doses of chemotherapy. We hypothesised that mechanism-guided treatment scheduling could reduce the incidence of dose-limiting toxicities and enable tolerable multitherapeutic regimens. Integrative analyses of mathematical modelling and single-cell assays distinguished the synergy kinetics of WEE1i from CHK1i by potency, spatiotemporal perturbation, and mitotic effects when combined with gemcitabine...
May 7, 2018: Cancer Research
Binghao Li, Zhan Wang, Hao Wu, Mingfeng Xue, Peng Lin, Shengdong Wang, Nong Lin, Xin Huang, Weibo Pan, Meng Liu, Xiaobo Yan, Hao Qu, Lingling Sun, Hengyuan Li, Yan Wu, Wangsiyuan Teng, Zenan Wang, Xingzhi Zhou, Huabiao Chen, Mark C Poznansky, Zhaoming Ye
The mechanism by which osteosarcomas metastasize is elusive, and challenges remain regarding its treatment with modalities including immunotherapy. CXCL12 is deeply involved in the process of tumor metastasis and T-cell homing, which is driven by a chemokine gradient, but healthy bones are supposed to preferentially express CXCL12. Here we show for the first time that osteosarcomas epigenetically downregulate CXCL12 expression via DNA methyltransferase 1 (DNMT1) and consequently acquire the ability to metastasize and impair cytotoxic T-cell homing to the tumor site...
May 7, 2018: Cancer Research
Alexander E Davies, John G Albeck
Intra-tumor cellular heterogeneity is a major challenge in cancer therapy. Tumors are composed of multiple phenotypic subpopulations that vary in their ability to initiate metastatic tumors and in their sensitivity to chemotherapy. In many cases, cells can transition between these subpopulations, not by genetic mutation, but instead through reversible changes in signal transduction or gene expression programs. This plasticity begins at the level of the microenvironment where local autocrine and paracrine signals, exosomes, tumor-stroma interactions, and extracellular matrix (ECM) composition create a signaling landscape that varies over space and time...
2018: Frontiers in Cell and Developmental Biology
Ko Oshita, Toshiyuki Itamoto, Akihiko Oshita, Hideki Nakahara, Takashi Nishisaka
BACKGROUND: Although secondary liver involvement of the lymphoma is common and occurs in 50% of patients with non-Hodgkin's lymphoma, liver tumor rupture in malignant lymphoma is extremely rare. We report a case of a spontaneously ruptured secondary liver involvement of non-Hodgkin's lymphoma that was successfully treated with transcatheter arterial embolization (TAE) to obtain hemostasis, and subsequent hepatectomy and systemic chemotherapy. To the best of our knowledge, this is only the second reported case of a ruptured hepatic lymphoma...
May 3, 2018: Surgical Case Reports
Amanda O Salzwedel, Joohee Han, Christopher J LaRocca, Ryan Shanley, Masato Yamamoto, Julia Davydova
Recent clinical trials utilizing Interferon-alpha (IFN) in combination with chemoradiation have demonstrated significant improvements in the survival of patients with pancreatic cancer. However, efficacy was limited by the systemic toxicity of IFN and low intratumoral levels of the cytokine. We sought to address these drawbacks by using an Oncolytic Adenovirus expressing IFN (OAd-hamIFN) in combination with chemotherapy and/or radiation in regimens mimicking the IFN-based therapies used in clinical trials. IFN expressed from OAd-hamIFN potentiated the cytotoxicity of radiation and chemotherapy (5-FU, Gemcitabine, and Cisplatin), and enhanced pancreatic cancer cell death in both in vitro and in vivo experimental settings...
April 6, 2018: Oncotarget
Haijun Shen, Fang Li, Dongxia Wang, Zhihan Yang, Chunfang Yao, Yang Ye, Xiaona Wang
Background and object: Polyelectrolyte microcapsule is a promising candidate for multifunctional drug delivery system. However, the lack of reports about animal experiments have greatly slowed down their development for drug delivery. We engineered biodegradable chitosan-alginate polyelectrolyte multilayer capsule filled with bovine serum albumin gel (BSA-gel-capsule). Herein, we demonstrated their applicability for local chemotherapy, a means of treating local or regional malignancies by direct administration of anti-tumor agents to tumor sites...
2018: Drug Design, Development and Therapy
Je Hun Jang, Young San Ko, Eun Kyeong Hong, Ho Shin Gwak
Surgery, anticoagulation therapy, pregnancy, and hormone treatments, such as bromocriptine, are well-characterized precipitating factors for pituitary apoplexy. However, whether cytotoxic chemotherapy for systemic cancer could cause pituitary apoplexy has not been investigated. Here, we present a case of a 41-year-old woman who developed a severe headache with decreased visual acuity after intravenous cytotoxic chemotherapy to treat metastatic breast cancer. Preoperative neuroimaging revealed pituitary adenoma with necrosis...
April 2018: Brain Tumor Research and Treatment
Jia Wu, Guohong Cao, Xiaoli Sun, Juheon Lee, Daniel L Rubin, Sandy Napel, Allison W Kurian, Bruce L Daniel, Ruijiang Li
Purpose To characterize intratumoral spatial heterogeneity at perfusion magnetic resonance (MR) imaging and investigate intratumoral heterogeneity as a predictor of recurrence-free survival (RFS) in breast cancer. Materials and Methods In this retrospective study, a discovery cohort (n = 60) and a multicenter validation cohort (n = 186) were analyzed. Each tumor was divided into multiple spatially segregated, phenotypically consistent subregions on the basis of perfusion MR imaging parameters. The authors first defined a multiregional spatial interaction (MSI) matrix and then, based on this matrix, calculated 22 image features...
April 27, 2018: Radiology
Lucia Sommerová, Eva Michalová, Roman Hrstka
BACKGROUND: Due to the irreplaceable role of chemotherapy in cancer treatment, research has focused on improving the efficacies of individual drugs and minimizing, or completely suppressing, their negative side effects. Based on long-term experience and the results of clinical trials, the selection of appropriate treatment is currently based on classical clinical diagnostic criteria, such as tumor size, grade, and the presence or absence of standard markers. However, complications arise due to variability between patients and tumor heterogeneity...
2018: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Dora Molina-Ortiz, Carmen Torres-Zárate, Rocío Cárdenas-Cardós, José Martin Palacios-Acosta, Daniel Hernández-Arrazola, Jaime Shalkow-Klincovstein, Erick Díaz-Díaz, Araceli Vences-Mejía
BACKGROUND: Intratumoral up-regulation of genes coding for drug transporters and metabolizing enzymes, such as MDR1 and CYP3A4, after chemotherapy are linked to cancer drug resistance. However their expression in primary soft tissue sarcomas (STS) prior to drug treatment and their role in innate resistance remain unclear. OBJECTIVE: The aim of this study was characterize MDR1 and CYP3A4 expression pattern before to chemotherapy and its clinical implication in pediatric STS...
April 13, 2018: Cancer Biomarkers: Section A of Disease Markers
R Andersen, T H Borch, A Draghi, A Gokuldass, M A H Rana, M Pedersen, M Nielsen, P Kongsted, J W Kjeldsen, M C W Westergaard, H D Radic, C A Chamberlain, L R Hölmich, H W Hendel, M S Larsen, Ö Met, I M Svane, M Donia
Background: The majority of patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing following CPI treatment was able to generate functional tumor-specific immune responses. Materials and methods: Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which progressed during or after anti-PD-1 and anti-CTLA-4 treatment...
April 24, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Raimund Bauer, Florian Udonta, Mark Wroblewski, Isabel Ben-Batalla, Ines Miranda Santos, Federico Taverna, Meike Kuhlencord, Victoria Gensch, Sarina Päsler, Stefan Vinckier, Johanna M Brandner, Klaus Pantel, Carsten Bokemeyer, Thomas Vogl, Johannes Roth, Peter Carmeliet, Sonja Loges
Intrinsic and adaptive resistance hamper the success of anti-angiogenic therapies (AAT), especially in breast cancer where this treatment modality has proven largely ineffective. Therefore, novel strategies to improve the efficacy of AAT are warranted. Solid tumors such as breast cancer are characterized by a high infiltration of myeloid-derived suppressor cells (MDSC) which are key drivers of resistance to AAT. Therefore, we hypothesized that all-trans retinoic acid (ATRA), which induces differentiation of MDSC into mature cells, could improve the therapeutic effect of AAT...
April 19, 2018: Cancer Research
Li-Jun Di, Dapeng Hao, Jie Liu, Meng Chen, Jingjing Li, Li Wang, Guangyu Wang, Qi Zhao
PURPOSE: Ovarian cancer is one of the first human cancers for which in situ immune response was reported to be important for the clinical outcome. To elucidate the mechanistic relationship between immune repertoire and cancer genotype in ovarian cancer, the development of a well-defined immune score for ovarian cancer is required. EXPERIMENTAL DESIGN: From a collection of 2,203 patient samples of advanced ovarian cancer from public available resources, we evaluated the prognostic values for a compendium of immune marker genes and proposed an immune score...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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