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intratumoral chemotherapy

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https://www.readbyqxmd.com/read/28319448/rationale-and-design-of-a-phase-1-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#1
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28302530/regorafenib-overcomes-chemotherapeutic-multidrug-resistance-mediated-by-abcb1-transporter-in-colorectal-cancer-in-vitro-and-in-vivo-study
#2
Yi-Jun Wang, Yun-Kai Zhang, Guan-Nan Zhang, Sweilem B Al Rihani, Meng-Ning Wei, Pranav Gupta, Xiao-Yu Zhang, Suneet Shukla, Suresh V Ambudkar, Amal Kaddoumi, Zhi Shi, Zhe-Sheng Chen
Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1...
March 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28289245/treatment-induced-mutagenesis-and-selective-pressures-sculpt-cancer-evolution
#3
Subramanian Venkatesan, Charles Swanton, Barry S Taylor, Joseph F Costello
Despite the great progress in our understanding of the molecular basis of human cancer, the heterogeneity of individual tumors and the evolutionary pressures imposed by therapy have hampered our ability to effectively eradicate and control this disease. How, therefore, do cancers evolve under the selective pressures of cancer therapy? Recent studies have linked both primary (or de novo) and acquired treatment resistance to intratumor heterogeneity and clonal evolution. Resistance to targeted therapies often includes mutation of the drug target itself and aberrations of pathways upstream of, downstream from, or parallel to the drug target...
March 13, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28287634/immune-microenvironment-of-gliomas
#4
Anna Gieryng, Dominika Pszczolkowska, Kacper A Walentynowicz, Wenson D Rajan, Bozena Kaminska
High-grade gliomas are rapidly progressing tumors of the central nervous system (CNS) with a very poor prognosis despite extensive resection combined with radiation and/or chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed heterogeneity of a tumor and its niche, composed of reactive astrocytes, endothelial cells, and numerous immune cells. Infiltrating immune cells consist of CNS resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells (MDSCs), and T lymphocytes...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28287519/endobronchial-ultrasound-guided-intratumoral-injection-of-cisplatin-for-the-treatment-of-isolated-mediastinal-recurrence-of-lung-cancer
#5
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
https://www.readbyqxmd.com/read/28280388/alternative-therapies-for-metastatic-breast-cancer-multimodal-approach-targeting-tumor-cell-heterogeneity
#6
REVIEW
Manpreet Sambi, Sabah Haq, Vanessa Samuel, Bessi Qorri, Fiona Haxho, Kelli Hill, William Harless, Myron R Szewczuk
One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse signals from the local microenvironment may also contribute to the induction of tumor growth and metastasis. Collectively, these factors must be strategically studied and targeted in order to develop an effective treatment protocol...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28270234/genetic-and-epigenetic-stability-of-oligodendrogliomas-at-recurrence
#7
Koki Aihara, Akitake Mukasa, Genta Nagae, Masashi Nomura, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Junji Shibahara, Miwako Takahashi, Toshimitsu Momose, Shota Tanaka, Shunsaku Takayanagi, Shunsuke Yanagisawa, Takahide Nejo, Satoshi Takahashi, Mayu Omata, Ryohei Otani, Kuniaki Saito, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Hiroyuki Aburatani, Nobuhito Saito
Among diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients...
March 7, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28266842/enhancing-doxorubicin-delivery-toward-tumor-by-hydroxyethyl-starch-g-polylactide-partner-nanocarriers
#8
Chan Yu, Qing Zhou, Fan Xiao, Yihui Li, Hang Hu, Ying Wan, Zifu Li, Xiangliang Yang
Doxorubicin (DOX), a kind of wide-spectrum chemotherapeutic drug, can cause severe side effects in clinical use. To enhance its antitumor efficacy while reducing the side effects, two kinds of nanoparticles with desirable compositions and properties were assembled using optimally synthesized hydroxyethyl starch-grafted-polylactide (HES-g-PLA) copolymers and utilized as partner nanocarriers. The large empty HES-g-PLA nanoparticles (mean size, ca. 700 nm), at an optimized dose of 400 mg/kg, were used to block up the reticuloendothelial system in tumor-bearing mice 1...
March 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28263422/correlation-between-fluorodeoxyglucose-hotspots-on-pretreatment-positron-emission-tomography-ct-and-preferential-sites-of-local-relapse-after-chemoradiotherapy-for-head-and-neck-squamous-cell-carcinoma
#9
Anne Chaput, Jérémie Calais, Philippe Robin, Sébastien Thureau, David Bourhis, Romain Modzelewski, Ulrike Schick, Pierre Vera, Pierre-Yves Salaün, Ronan Abgral
BACKGROUND: The potential benefits of (18) F-fluoro-2-deoxy-D-glucose-positron emission tomography/CT (FDG-PET/CT) imaging for radiotherapy (RT) treatment planning of head and neck squamous cell carcinoma (HNSCC) are increasingly being recognized. It has been suggested that intratumoral subvolumes with high FDG avidity ("hotspots") are potential targets for selected dose escalation. The purposes of this study were to demonstrate that pre-RT FDG-PET/CT can identify intratumoral sites at increased risk of local relapse after RT and to determine an optimal threshold to delineate smaller RT target volumes that would facilitate RT dose escalation without impaired tolerance...
March 6, 2017: Head & Neck
https://www.readbyqxmd.com/read/28255193/the-impact-of-the-expression-level-of-intratumoral-dihydropyrimidine-dehydrogenase-on-chemotherapy-sensitivity-and-survival-of-patients-in-gastric-cancer-a-meta-analysis
#10
REVIEW
Cong Zhang, Hongpeng Liu, Bin Ma, Yongxi Song, Peng Gao, Yingying Xu, Dehao Yu, Zhenning Wang
The potential impact that the intratumoral expression level of dihydropyrimidine dehydrogenase (DPD) has on chemotherapy sensitivity and long-term survival for gastric cancer (GC) patients remains controversial; therefore, this study seeks to clarify this issue. Our meta-analysis was performed using Review Manager (RevMan) 5.3 software. In vitro drug sensitivity tests, correlation coefficients between sensitivity to 5-fluorouracil (5-FU), and expression levels of intratumoral DPD were used as effective indexes to analyse...
2017: Disease Markers
https://www.readbyqxmd.com/read/28253733/rationale-and-design-of-a-phase-i-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#11
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy; and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor specific tropism and potential efficacy in the treatment of malignant brain tumors...
February 24, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28236180/supraorbital-subfrontal-trans-laminar-endoscope-assisted-approach-for-tumors-of-the-posterior-third-ventricle
#12
Maurizio Iacoangeli, Roberto Colasanti, Domenic Esposito, Alessandro Di Rienzo, Lucia di Somma, Mauro Dobran, Maurizio Gladi, Massimo Scerrati
BACKGROUND: Different surgical approaches have been developed for dealing with third ventricle lesions, all aimed at obtaining a safe removal minimizing brain manipulation. The supraorbital subfrontal trans-lamina terminalis route, commonly employed only for the anterior third ventricle, could represent, in selected cases with endoscopic assistance, an alternative approach to posterior third ventricular lesions. METHODS: Seven patients underwent a supraorbital subfrontal trans-laminar endoscope-assisted approach to posterior third ventricle tumors (two craniopharyngiomas, one papillary tumor of the pineal region, one pineocytoma, two neurocytomas, one glioblastoma)...
February 24, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28228084/the-development-of-oncoltyic-adenovirus-therapy-in-the-past-and-future-for-the-case-of-pancreatic-cancer
#13
Mizuho Sato-Dahlman, Masato Yamamoto
Pancreatic cancer is an aggressive malignant disease and the efficacy of current treatments for unresectable diseases is quite limited despite recent advances. Gene therapy /virotherapy strategies may provide new options for treatment of various cancers including pancreatic cancer. Oncolytic adenovirus shows an antitumoral effect via its intratumoral amplification and strong cytocidal effect in a variety of cancers and it has been employed for the development of potent oncolytic virotherapy agents for pancreatic cancer...
February 22, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28213783/high-pten-gene-expression-is-a-negative-prognostic-marker-in-human-primary-breast-cancers-with-preserved-p53-function
#14
Synnøve Yndestad, Eilin Austreid, Stian Knappskog, Ranjan Chrisanthar, Peer Kåre Lilleng, Per Eystein Lønning, Hans Petter Eikesdal
PURPOSE: PTEN is an important tumor suppressor in breast cancer. Here, we examined the prognostic and predictive value of PTEN and PTEN pseudogene (PTENP1) gene expression in patients with locally advanced breast cancer given neoadjuvant chemotherapy. METHODS: The association between pretreatment PTEN and PTENP1 gene expression, response to neoadjuvant chemotherapy, and recurrence-free and disease-specific survival was assessed in 364 patients with locally advanced breast cancer given doxorubicin, 5-fluorouracil/mitomycin, or epirubicin versus paclitaxel in three phase II prospective studies...
February 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28210996/quantitative-evaluation-of-oxygen-metabolism-in-the-intratumoral-hypoxia-18-f-fluoromisonidazole-and-15-o-labelled-gases-inhalation-pet
#15
Tadashi Watabe, Yasukazu Kanai, Hayato Ikeda, Genki Horitsugi, Keiko Matsunaga, Hiroki Kato, Kayako Isohashi, Kohji Abe, Eku Shimosegawa, Jun Hatazawa
BACKGROUND: Intratumoral hypoxia is one of the resistant factors in radiotherapy and chemotherapy for cancer. Although it is detected by (18)F-fluoromisonidazole (FMISO) PET, the relationship between intratumoral hypoxia and oxygen metabolism has not been studied. The purpose of this study was to evaluate the intratumoral perfusion and oxygen metabolism in hypoxic regions using the rat xenograft model. Ten male Fischer rats with C6 glioma (body weight = 220 ± 15 g) were investigated with (18)F-FMISO PET and steady-state inhalation method of (15)O-labelled gases PET...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28187033/prognostic-significance-of-stromal-versus-intratumoral-infiltrating-lymphocytes-in-different-subtypes-of-breast-cancer-treated-with-cytotoxic-neoadjuvant-chemotherapy
#16
Thaer Khoury, Vidya Nagrale, Mateusz Opyrchal, Xuan Peng, Dan Wang, Song Yao
BACKGROUND: The aim of the study was to investigate if there were differences in associations of stromal versus intratumoral tumor infiltrating lymphocytes (TILs) with pathology complete response (pCR) among breast cancer (BC) subtypes treated with neoadjuvant therapy. MATERIALS AND METHODS: The hematoxylin and eosin slides of BC-core biopsy consecutive cases (n=331) were reviewed from a single institution between 2000 and 2014. TIL-stroma (TIL-str) was scored from 0% to 100%...
February 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28181817/mathematical-modeling-of-intraperitoneal-drug-delivery-simulation-of-drug-distribution-in-a-single-tumor-nodule
#17
Margo Steuperaert, Giuseppe Falvo D'Urso Labate, Charlotte Debbaut, Olivier De Wever, Christian Vanhove, Wim Ceelen, Patrick Segers
The intraperitoneal (IP) administration of chemotherapy is an alternative treatment for peritoneal carcinomatosis, allowing for higher intratumor concentrations of the cytotoxic agent compared to intravenous administration. Nevertheless, drug penetration depths are still limited to a few millimeters. It is thus necessary to better understand the limiting factors behind this poor penetration in order to improve IP chemotherapy delivery. By developing a three-dimensional computational fluid dynamics (CFD) model for drug penetration in a tumor nodule, we investigated the impact of a number of key parameters on the drug transport and penetration depth during IP chemotherapy...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28181548/thiazole-valine-peptidomimetic-ttt-28-antagonizes-multidrug-resistance-in-vitro-and-in-vivo-by-selectively-inhibiting-the-efflux-activity-of-abcb1
#18
Yi-Jun Wang, Bhargav A Patel, Nagaraju Anreddy, Yun-Kai Zhang, Guan-Nan Zhang, Saeed Alqahtani, Satyakam Singh, Suneet Shukla, Amal Kaddoumi, Suresh V Ambudkar, Tanaji T Talele, Zhe-Sheng Chen
Multidrug resistance (MDR) attenuates the chemotherapy efficacy and increases the probability of cancer recurrence. The accelerated drug efflux mediated by ATP-binding cassette (ABC) transporters is one of the major MDR mechanisms. This study investigated if TTT-28, a newly synthesized thiazole-valine peptidomimetic, could reverse ABCB1-mediated MDR in vitro and in vivo. TTT-28 reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1 overexpressing cells by selectively blocking the efflux function of ABCB1, but not interfering with the expression level and localization of ABCB1...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181130/micrornas-mir-7-and-mir-340-predict-response-to-neoadjuvant-chemotherapy-in-breast-cancer
#19
Mithu Raychaudhuri, Holger Bronger, Theresa Buchner, Marion Kiechle, Wilko Weichert, Stefanie Avril
PURPOSE: miRNAs have been linked to chemosensitivity of breast cancer cells in vitro. In patients, however, there is no clinically validated method for predicting chemotherapy response. The aim of this study was to assess whether (I) a specific pattern of miRNA expression in pretherapeutic biopsies can predict response to neoadjuvant chemotherapy, and (II) differential miRNA expression in residual tumor after completion of chemotherapy allows further prognostic stratification of non-responding patients...
February 8, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28174262/role-of-vascular-normalization-in-benefit-from-metronomic-chemotherapy
#20
Fotios Mpekris, James W Baish, Triantafyllos Stylianopoulos, Rakesh K Jain
Metronomic dosing of chemotherapy-defined as frequent administration at lower doses-has been shown to be more efficacious than maximum tolerated dose treatment in preclinical studies, and is currently being tested in the clinic. Although multiple mechanisms of benefit from metronomic chemotherapy have been proposed, how these mechanisms are related to one another and which one is dominant for a given tumor-drug combination is not known. To this end, we have developed a mathematical model that incorporates various proposed mechanisms, and report here that improved function of tumor vessels is a key determinant of benefit from metronomic chemotherapy...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
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