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intratumoral chemotherapy lung cancer

Daniela Adua, Francesca Di Fabio, Giorgio Ercolani, Michelangelo Fiorentino, Elisa Gruppioni, Annalisa Altimari, Fabiola Lorena Rojas Limpe, Nicola Normanno, Antonio Daniele Pinna, Carmine Pinto
Molecular heterogeneity between primary tumors (PTs) and synchronous resected liver metastasis in colorectal cancer (CRC) has potential relevance in treatment strategies. Next-generation sequencing (NGS) may be able to increase the chances of identifying multiple molecular driver alterations, calling for therapy. The aim of the present study was to evaluate mutations in PT and synchronous resected liver metastases for patients with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) exon 2 wild-type metastatic (m)CRC who underwent chemotherapy (CT) featuring an anti-epidermal growth factor receptor (EGFR) monoclonal antibody...
July 2017: Molecular and Clinical Oncology
(no author information available yet)
To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 9 more questions are presented as follows. Question 31: How does aging process inhibit the formation of sarcoma? Question 32: Is intratumoral morphological heterogeneity the consequence of tumor genomic instability or the cause of aggressive tumor behavior? Can we identify more aggressive tumors by computationally analyzing the morphological heterogeneity of the tumor tissues? Question 33: How to pre-surgically differentiate irradiation-induced ulceration from cancerous ulceration? Question 34: Why is epidermal growth factor receptor (EGFR) 19 Del-positive tumor more sensitive to targeted therapy than EGFR 21 L858R-positive tumor in patients with non-small cell lung cancer? Question 35: Can an Epstein-Barr virus vaccine be developed to reduce the incidence of EBV-related malignancies? Question 36: What is the unique feature in sarcoma vasculature that causes the intrinsic resistance of sarcoma against anti-angiogenic therapy? Question 37: How many ways can sarcoma cells protect themselves from the attacks of cytotoxic drugs? Question 38: How stable does the tumor heterogeneity remain along with cytotoxic chemotherapy? Question 39: How to generate a prognostic classifier for diffuse low-grade gliomas by integrating genetic and epigenetic signatures with histological features?...
June 2, 2017: Chinese Journal of Cancer
Gautier Stoll, Yuting Ma, Heng Yang, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer...
2017: Oncoimmunology
Li Gao, Chuanqi Xie, Yuzhi Du, Xiaodong Wang, Erkang Xuan, Xiuxiu Liu, Yang Zhao, Jianjian Xu, Lan Luo
Etoposide is widely used in the chemotherapy of a variety of malignancies. But the strong lipophilicity, poor bioavailability, and severe side effects of etoposide limit its clinical application. The aim of this study was to develop sustained-release etoposide-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. We prepared the implants containing etoposide, poly(L-lactid acid) and polyethylene glycol 4000 by the direct compression method. The implants were characterized regarding drug-excipient compatibility, content uniformity, morphology, sterility, in vitro, and in vivo release profiles...
November 2017: Drug Delivery
Min Sil Kang, Rajendra K Singh, Tae-Hyun Kim, Joong-Hyun Kim, Kapil D Patel, Hae-Won Kim
Multifunctional nanocarrier-based theranostics is currently considered to solve some key unmet challenges in cancer treatment. Here we report a nanocarrier platform, named carbon dot (CD) created mesoporous hollow organosilica (C-hMOS) nanoparticles, to deliver anticancer drug and to enable optical imaging. The hollow structure was formed by the removal of a nanorod core template, and at the same time, the fluorescent signal was endowed from the heat-treated organosilica network. Thanks to the hollow and mesoporous structure, the C-hMOS effectively loaded doxorubicin (DOX) for cancer chemotherapy...
April 1, 2017: Acta Biomaterialia
Hiren J Mehta, Michael A Jantz
Isolated hilar and mediastinal recurrence (IMHR) following external beam radiation therapy (EBRT) in patients with lung cancer is common. These patients do not have many treatment options and are usually offered palliative chemotherapy or best supportive care. Endobronchial ultrasound (EBUS)-guided intratumoral injection of cisplatin (ITC) is a novel approach for these patients. The procedure is performed under conscious sedation. The lesion is located with a bronchoscopy using EBUS, and a 22-gauge EBUS needle is advanced through the working channel of the scope and locked in position...
February 12, 2017: Journal of Visualized Experiments: JoVE
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...
January 23, 2017: Vaccine
Venkatesan Kathiresan, Swathika Subburaman, Arun Venkatesh Krishna, Mathivanan Natarajan, Gandhidasan Rathinasamy, Kumaresan Ganesan, Murugesan Ramachandran
Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2...
2016: Journal of Environmental Pathology, Toxicology and Oncology
Lin Shi, Xiangdong Wang
Patients with lung cancer still have high mortality, recurrence rate after adjuvant treatment, and poor five-year survival rates, despite of advances in multidisciplinary anti-cancer therapies, e.g. chemotherapy, radiotherapy and targeted therapies, It depends upon the presence of intratumoral heterogeneity and complexity of lung cancer. There is growing evidence to suggest that osteopontin (OPN) may play a critical role in tumor progression and metastasis. The present review briefly describes the structure and molecular biology of OPN, highlights the role of OPN in the development and metastasis of lung cancer, and summarizes potential mechanisms of OPN heterogeneity in tumor to underline some of these inconsistencies...
April 2017: Seminars in Cell & Developmental Biology
Jun-Jie Ma, Hui-Ping Liu
OBJECTIVE: To investigate the efficacy of Aidi Injection () on overexpression of P-glycoprotein (P-gp) induced by vinorelbine and cisplatin (NP) regimen in patients with non-small cell lung cancer (NSCLC), and study the difference between intravenous administration and targeting intratumor administration of Aidi Injection with thoracoscope. METHODS: Totally 150 patients with NSCLC were randomly assigned to the control group, the intravenous group and the intratumor group by the random envelope method, 50 cases in each group...
August 2, 2016: Chinese Journal of Integrative Medicine
Jarrod D Predina, Jane Keating, Ollin Venegas, Sarah Nims, Sunil Singhal
Non-small Cell Lung Cancer (NSCLC) remains a deadly disease despite aggressive treatment protocols which incorporate chemotherapy, radiation and surgery. These traditional approaches have reached a plateau in therapeutic benefit. There is emerging evidence suggesting that immunotherapy can serve as an alternative treatment modality for NSCLC. Our group has nearly two decades of experience involving immuno-gene therapy with Ad.hIFN-α and Ad.hIFN-β in human mesothelioma trials, and has observed both safety and efficacy in treatment of Thoracic malignancies...
April 2016: Discovery Medicine
Weijian Feng, Jin Li, Suhong Han, Jinfeng Tang, Jie Yao, Yuqing Cui, Chuntang Wang, Zhongcheng Chen, Xiaoguang Li, Xiuyi Zhi
BACKGROUND: Radiofrequency ablation (RFA) has become one of the local treatment for inoperable early stage non-small cell lung cancer (NSCLC). This study observes effectiveness and safety of computed tomography (CT) guided RFA followed intratumoral chemotherapy (RFA-ITC). METHODS: From 2005 to 2015, our group perspectively enrolled inoperable early stage NSCLC underwent RFA-ITC duo to poor cardiopulmonary function or with other diseases or patient can't tolerate or reject surgery...
May 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Elizabeth A Guancial, Deepak Kilari, Guang-Qian Xiao, Sohaib H Abu-Farsakh, Andrea Baran, Edward M Messing, Eric S Kim
BACKGROUND: Platinum (Pt)-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC). However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC) in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC) specimens would correlate with improved pathologic response to Pt-based NAC in MIBC...
2016: PloS One
Xiaoming Luo, Guisen Xu, Jiaojun Wei, Maohua Chen, Hong Zhang, Xiaohong Li
Cancer progression and metastasis relies much on vasculature networks in tumor microenvironment, and the combination treatment with chemotherapeutic drugs and vascular disrupting agents represents apparent clinical benefits. In the current study, fiber fragments with loadings of hydroxycamptothecin (HCPT) or combretastatin A-4 (CA4) were proposed for tumor inhibition and blood vessel disruption after local administration in tumors. To address challenges in balancing the disruption of tumor vessels and intratumoral uptake of chemotherapeutic agents, this study is focus on release tuning of HCPT and CA4 from the fiber fragment mixtures...
June 15, 2016: International Journal of Pharmaceutics
Gerald S M A Kerner, Vikram R Bollineni, Thijo J N Hiltermann, Nanna M Sijtsema, Alexander Fischer, Alphons H H Bongaerts, Jan Pruim, Harry J M Groen
BACKGROUND: Hypoxia is associated with resistance to chemotherapy and radiotherapy and is randomly distributed within malignancies. Characterization of changes in intratumoral hypoxic regions is possible with specially developed PET tracers such as (18)F-fluoroazomycin arabinoside ((18)F-FAZA) while tumor metabolism can be measured with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG). The purpose of this study was to study the effects of chemotherapy on (18)F-FAZA and (18)F-FDG uptake simultaneously in non-small-cell lung cancer (NSCLC) patients METHODS: At baseline and after the second chemotherapy cycle, both PET/CT with (18)F-FDG and (18)F-FAZA was performed in seven patients with metastasized NSCLC...
December 2016: EJNMMI Research
Karen Foguer, Marina de Souza Braga, Jean Pierre Schatzmann Peron, Karina Ramalho Bortoluci, Maria Helena Bellini
BACKGROUND: Renal cell carcinoma (RCC) is a highly vascularized cancer resistant to chemotherapy and radiotherapy. RCC is frequently infiltrated with immune cells, with macrophages being the most abundant cell type. Alternatively activated M2 macrophages are known to contribute to tumor progression. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we investigated the impact of ES gene therapy on the polarization of tumor-associated macrophages (TAMs) in lung metastases from tumor-bearing mice...
April 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Farshad Ramazani, Cornelis F van Nostrum, Gert Storm, Fabian Kiessling, Twan Lammers, Wim E Hennink, Robbert J Kok
Locoregional delivery of anticancer drugs is an attractive approach to minimize adverse effects associated with intravenous chemotherapy. Polymer-based drug depots injected or implanted intratumorally or adjacent to the tumor can provide long-term local drug exposure. This review highlights studies in which drug-eluting depots have been applied locally in the treatment of cancer. In many cases such drug depots are used for prevention of tumor recurrence after surgery to eradicate remaining tumor cells. Clinical success has been reported for the treatment of brain cancer and liver cancer, and preclinical studies showed proof-of-concept for inhaled drug depots in lung cancer and intraperitoneally injected depots for the treatment of abdominal cancer...
April 2016: Drug Discovery Today
Nicholas McGranahan, Andrew J S Furness, Rachel Rosenthal, Sofie Ramskov, Rikke Lyngaa, Sunil Kumar Saini, Mariam Jamal-Hanjani, Gareth A Wilson, Nicolai J Birkbak, Crispin T Hiley, Thomas B K Watkins, Seema Shafi, Nirupa Murugaesu, Richard Mitter, Ayse U Akarca, Joseph Linares, Teresa Marafioti, Jake Y Henry, Eliezer M Van Allen, Diana Miao, Bastian Schilling, Dirk Schadendorf, Levi A Garraway, Vladimir Makarov, Naiyer A Rizvi, Alexandra Snyder, Matthew D Hellmann, Taha Merghoub, Jedd D Wolchok, Sachet A Shukla, Catherine J Wu, Karl S Peggs, Timothy A Chan, Sine R Hadrup, Sergio A Quezada, Charles Swanton
As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+)tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non-small cell lung cancer and expressed high levels of PD-1...
March 25, 2016: Science
Andrea Casadei Gardini, Marita Mariotti, Alessandro Lucchesi, Sara Pini, Martina Valgiusti, Sara Bravaccini, Angelo Del Monte, Marco Angelo Burgio, Giorgia Marisi, Dino Amadori, Giovanni Luca Frassineti
BACKGROUND: Small-cell lung cancer (SCLC) is known to express antigens of both the neural crest and epithelium, and to secrete polypeptide hormones and enzymes. Anecdotal reports correlate lung cancer with marked hyperamylasemia, and a review of the literature reveals only one case of metastatic SCLC linked to high paraneoplastic lipase production. CASE PRESENTATION: We present the case of a patient with metastatic SCLC who showed both lipase and pancreatic isoamylase elevation in the absence of acute pancreatitis...
February 17, 2016: BMC Cancer
Chun Huang, Xuan Wang, Jing Wang, Li Lin, Zhujun Liu, Wenjing Xu, Liuchun Wang, Jianyu Xiao, Kai Li
BACKGROUND: Antiangiogenesis plays a key role in the treatment of non-small lung cancer (NSCLC). We observed the cavitation of lesions in patients with stage IIIB/IV NSCLC treated with Endostar and vinorelbine-cisplatin (NP) chemotherapy, and evaluated the imaging characteristics and clinical outcome of patients who developed tumor cavitation. METHODS: Our study included 105 untreated NSCLC patients who received Endostar in combination with NP chemotherapy at the Tianjin Lung Cancer Center...
September 2014: Thoracic Cancer
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