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intratumoral chemotherapy

Elena Piretto, Marcello Delitala, Mario Ferraro
Drug resistance is one of the major obstacles to a successful treatment of cancer and, in turn, has been recognized to be linked to intratumoral heterogeneity, which increases the probability of the emergence of a cancer clones refractory to treatment. Combination therapies have been introduced to overcome resistance, but the design of successful combined protocols is still an open problem. In order to provide some indications on the effectiveness of medical treatments, a mathematical model is proposed, comprising two cancer populations competing for resources and with different susceptibilities to the action of immune system cells and therapies: the focus is on the effects of chemotherapy and immunotherapy, used singularly or in combination...
March 13, 2018: Journal of Theoretical Biology
Ornella Franzese, Fiorenzo Battaini, Grazia Graziani, Lucio Tentori, Maria Luisa Barbaccia, Angelo Aquino, Mario Roselli, Maria Pia Fuggetta, Enzo Bonmassar, Francesco Torino
In recent years, immune checkpoint inhibitors (ICpI) have provided the ground to bring tumor immunity back to life thanks to their capacity to afford a real clinical benefit in terms of patient's survival. Essential to ICpI success is the presence of tumor-associated neoantigens generated by non-synonymous mutations, since a direct relationship between mutation load of malignant cells and susceptibility to ICpI has been confidently established. However, it has been also suggested that high intratumor heterogeneity (ITH) associated with subclonal neoantigens could not elicit adequate immune responses...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Yang Cao, Yuli Chen, Tao Yu, Yuan Guo, Fengqiu Liu, Yuanzhi Yao, Pan Li, Dong Wang, Zhigang Wang, Yu Chen, Haitao Ran
Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery. Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets...
2018: Theranostics
Zhoujiang Chen, Weiping Liu, Long Zhao, Songzhi Xie, Maohua Chen, Tao Wang, Xiaohong Li
Cancer chemotherapy is confronted with difficulties enhancing the tumor accumulation, improving the bioavailability and relieving the adverse effect of chemotherapeutic agents. To address the challenges, this study proposes a feasible strategy to realize a sustained release of drug-loaded micelles from fiber fragments after intratumoral injection. Camptothecin (CPT) is grafted on hyaluronic acid (HA) via 3,3'-dithiodipropionic acid to obtain reduction-sensitive promicelle polymers (PMCPT), which are conjugated with poly(DL-lactide) via 2-propionic-3-methylmaleic anhydride (CDM) to obtain acid-labile copolymers for the preparation of injectable fiber fragments...
March 2, 2018: Biomacromolecules
Denis Soulières, Lisa Lictira, Ricard Mesía, Éva Remenár, Shau-Hsuan Li, Andrey Karpenko, Marie Chol, Ying A Wang, Nadia Solovieff, Laurence Bourdeau, Dalila Sellami, Sandrine Faivre
PURPOSE: The preplanned exploratory analysis of the BERIL-1 trial presented here aimed to identify biomarkers of response to the combination of buparlisib and paclitaxel. PATIENTS AND METHODS: BERIL-1 was a multicenter, randomized, double-blind, placebo-controlled phase 2 study. Patients with recurrent or metastatic SCCHN progressing on/after one previous platinum-based chemotherapy regimen in the recurrent or metastatic setting were treated with either buparlisib plus paclitaxel or placebo plus paclitaxel...
February 28, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Xi Liu, Ping Du, Lei Han, Anling Zhang, Kui Jiang, Qingyu Zhang
Gastric cancer is one of the most common cancers in the world; taxol displayed modest efficacy as first-line chemotherapy for gastric cancer, conversely, it has limitations used alone. β-catenin is a multifunctional oncogenic protein and the elevation in expression and activity of β-catenin has been implicated in many cancers. Therefore, we assume that the inhibition of β-catenin can enhanced the efficacy of taxol. The purpose of this study was to investigate the inhibitory effect of miR-200a mimics, FH535 combined with taxol on proliferation and invasion of human gastric cancer cell lines SGC-7901 and BGC-823...
December 6, 2017: Pathology, Research and Practice
Chia-En Chang, Chien-Ming Hsieh, Ling-Chun Chen, Chia-Yu Su, Der-Zen Liu, Hua-Jing Jhan, Hsiu-O Ho, Ming-Thau Sheu
The synergistic combination of docetaxel (DTX) and cisplatin (CIS) by local drug delivery with a pluronic lecithin organogel (PLO) to facilitate high drug concentrations at tumor sites and less nonspecific distribution to normal organs is thought to be beneficial in chemotherapy. In this study, using Capryol-90 (C90) with the addition of lecithin as the oil phase was developed to carry DTX, which was then incorporated into a PLO-containing CIS to formulate a dual-drug injectable PLO for local delivery. An optimal PLO composite, P13 L0...
November 2018: Drug Delivery
Qingshuo Meng, Jia Meng, Wei Ran, Junyang Wang, Yihui Zhai, Pengcheng Zhang, Yaping Li
Triple-negative breast cancer (TNBC) tumors are heterogeneous, with mesenchymal-like cells at their core and fast proliferating cells on the periphery. It is desirable and beneficial to treat TNBC cells of different phenotypes with the most appropriate drugs. Here, we report a 78 nm, chlorin e6-, docetaxel-, and anti-Twist siRNA-containing polymeric nanoparticle (CDTN) with spatiotemporally specific activity when irradiated by light. Under conditions mimicking superficial tumor tissue with sufficient light input, TNBC cells are mainly killed by the photodynamic therapy (PDT) function of CDTNs...
February 22, 2018: ACS Nano
Irina Mitrofanova, Marina Zavyalova, Vladimir Riabov, Nadezhda Cherdyntseva, Julia Kzhyshkowska
Angiogenesis and lymphangiogenesis play a crucial role in tumor growth, invasion and metastasis. Tumor-associated macrophages (TAM) induce both angiogenesis and lymphangiogenesis in mouse breast cancer models and positively correlate with these processes in human breast cancer patients. Neoadjuvant chemotherapy (NAC) is a widely used therapeutic option for cancer treatment. However, the effect of NAC on the distribution of TAM within intratumoral compartments and their correlation with angiogenesis and lymphangiogenesis remained unknown...
October 31, 2017: Immunobiology
Niranjan Awasthi, Sheena Monahan, Alexis Stefaniak, Margaret A Schwarz, Roderich E Schwarz
Nab-paclitaxel (NPT) combination with gemcitabine (Gem) represents the standard chemotherapy for pancreatic ductal adenocarcinoma (PDAC). Genetic alterations of the RAS/RAF/MEK/ERK (MAPK) signaling pathway yielding constitutive activation of the ERK cascade have been implicated as drivers of PDAC. Inhibition of downstream targets in the RAS-MAPK cascade such as MEK remains a promising therapeutic strategy. The efficacy of trametinib (Tra), a small molecule inhibitor of MEK1/2 kinase activity, in combination with nab-paclitaxel-based chemotherapy was evaluated in preclinical models of PDAC...
January 12, 2018: Oncotarget
Semra Bilaçeroğlu
Endobronchial ablative therapies, such as mechanical debulking, laser therapy, electrocautery, argon plasma coagulation, cryotherapy, brachytherapy, photodynamic therapy, microdebrider bronchoscopy, resector balloon deobstruction, and intratumoral chemotherapy, are performed through a rigid or flexible bronchoscope in palliating or curing symptomatic malignant and benign airway lesions to improve symptoms, quality of life, and survival. Technical factors together with patient- and lesion-specific features determine the therapy of choice, as each therapy is different in capacity, limitation, and complications...
March 2018: Clinics in Chest Medicine
J Benzaquen, C-H Marquette, N Glaichenhaus, S Leroy, P Hofman, M Ilié
INTRODUCTION: Immunotherapy aims to promote the immune system's activity against malignant cells by stimulating the response to several tumor antigens. STATE OF THE ART: Immunosurveillance may adjust the immunogenicity of tumors. To be effective, immunity must induce the specific activation of CD4+ and CD8+ T lymphocytes, as well as activation of innate immunity. Activator and inhibitory costimulatory molecules regulate T lymphocyte activation at immunity checkpoints such as PD-1/PD-L1 and CTLA-4...
February 7, 2018: Revue des Maladies Respiratoires
Yoshiki Hirooka, Hiroki Kawashima, Eizaburo Ohno, Takuya Ishikawa, Takashi Kamigaki, Shigenori Goto, Masashi Takahara, Hidemi Goto
Dendritic cell (DC)-based vaccines prepared using various antigen loading methods have been studied for cancer immunotherapy. The in vivo provocation of immunity by the direct injection of DCs without using tumor-specific antigens into tumors after apoptosis-inducing chemotherapy is more applicable. We previously reported that zoledronate-pulsed DCs (Zol-DCs) may induce tumor-antigen-specific CD8+ T cells by activating Vγ9γδT cells. In this report, we studied the feasibility, safety, and efficacy of a comprehensive immunotherapy involving the combined intratumoral injection of Zol-DC, gemcitabine (GEM) and αβT cells in locally advanced pancreatic carcinoma...
January 5, 2018: Oncotarget
Xinyue Zhang, Jie Yao, Kai Guo, Hu Huang, Siyuan Huai, Rui Ye, Baolong Niu, Tiannan Ji, Weidong Han, Jianxiong Li
Numerous studies have shown drug resistance of gastric cancer cells could be modulated by abnormal expression of microRNAs. Cisplatin (DDP) is one of the most commonly used drugs for chemotherapy of gastric cancer. In this study, the potential function of miR-125b on DDP resistance in gastric cancer cells was investigated. Sixteen miRNAs significantly differential expressed in gastric tumor tissues and adjacent tissues were characterized and their corresponding putative target genes were also screened. MiR-125b was selected as our focus for its evident down-regulated expression among candidate genes...
January 5, 2018: Oncotarget
Oliver D Mrowczynski, Sara T Langan, Elias B Rizk
Cushing once described craniopharyngiomas as the most forbidding tumor; and, despite surgical advances decades later, craniopharyngioma resection is still extremely complex due to its location and infiltration into local structures, making gross total resection challenging. Adjuvant treatments include radiation and chemotherapy, but intratumoral therapy may emerge as an adjuvant treatment for craniopharyngiomas. Here, we present a review of the literature on this treatment modality; and, summarize the available reported cases to underline usefulness and effectiveness of this treatment method...
March 2018: Clinical Neurology and Neurosurgery
Sipeng Shen, Yongyue Wei, Ruyang Zhang, Mulong Du, Weiwei Duan, Sheng Yang, Yang Zhao, David C Christiani, Feng Chen
Genetic intratumor heterogeneity is associated with tumor occurrence, development and overall outcome. The present study aims to explore the association between mutant-allele fraction (MAF) heterogeneity and patient overall survival in lung cancer. Somatic mutation data of 939 non-small cell lung cancer (NSCLC) cases were obtained from The Cancer Genome Atlas. Entropy-based mutation allele fraction (EMAF) score was used to describe the uncertainty of individual somatic mutation patterns and to further analyze the association with patient overall survival...
January 2018: Oncology Letters
Takeshi Azuma, Yukihide Matayoshi, Yujiro Sato, Yasuhi Nagase
It has previously been demonstrated that the intratumoral generation of the potent androgen dihydrotestosterone (DHT), contributes critically to the progression of prostate cancer and its castration-resistant form, castration-resistant prostate cancer (CRPC). Circulating testosterone is converted into DHT by 5α-reductase (SRD5A). Dutasteride is a dual inhibitor of type I and II SRD5A. The present study assessed the effectiveness of dutasteride in the treatment of CRPC. Between 2010 and 2013, CRPC was diagnosed in 41 patients at the Tokyo Metropolitan Tama Medical Center...
January 2018: Molecular and Clinical Oncology
Hyejin Kim, Van Phuc Nguyen, Panchanathan Manivasagan, Min Jung Jung, Sung Won Kim, Junghwan Oh, Hyun Wook Kang
The current research demonstrates the feasible biomedical application of AuNPs coated with doxorubicin (Dox)-loaded fucoidan (Fu) for dual-chemotherapy and photothermal treatment (PTT) on eye tumors in vitro and in vivo. Marine-derived Fu was used as a capping agent to achieve high photostability for AuNPs, and Dox as a FDA-approved anti-cancer drug was added to induce chemotherapy. The synthesized Dox-Fu@AuNPs exhibited high cytotoxicity on the tumor cells and strong light absorption for temperature increase in vitro...
December 26, 2017: Oncotarget
Debangshu Samanta, Youngrok Park, Xuhao Ni, Huili Li, Cynthia A Zahnow, Edward Gabrielson, Fan Pan, Gregg L Semenza
Triple-negative breast cancer (TNBC) is treated with cytotoxic chemotherapy and is often characterized by early relapse and metastasis. To form a secondary (recurrent and/or metastatic) tumor, a breast cancer cell must evade the innate and adaptive immune systems. CD47 enables cancer cells to evade killing by macrophages, whereas CD73 and PDL1 mediate independent mechanisms of evasion of cytotoxic T lymphocytes. Here, we report that treatment of human or murine TNBC cells with carboplatin, doxorubicin, gemcitabine, or paclitaxel induces the coordinate transcriptional induction of CD47, CD73, and PDL1 mRNA and protein expression, leading to a marked increase in the percentage of CD47+CD73+PDL1+ breast cancer cells...
January 24, 2018: Proceedings of the National Academy of Sciences of the United States of America
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
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