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intratumoral chemotherapy

Triantafyllos Stylianopoulos
Tumor progression and response to treatment is determined in large part by the generation of mechanical stresses that stem from both the solid and the fluid phase of the tumor. Furthermore, elevated solid stress levels can regulate fluid stresses by compressing intratumoral blood and lymphatic vessels. Blood vessel compression reduces tumor perfusion, while compression of lymphatic vessels hinders the ability of the tumor to drain excessive fluid from its interstitial space contributing to the uniform elevation of the interstitial fluid pressure...
October 19, 2016: Journal of Biomechanical Engineering
Joo Hwa Lee, Nam Jin Yoo, Min Sung Kim, Sug Hyung Lee
Alterations of genes involved in histone modification are common in cancers. A histone demethylase-encoding gene PHF2 is considered a putative tumor suppressor gene (TSG). PHF2 is essential for p53-mediated TSG functions such as chemotherapy-mediated cancer cell killing. However, inactivating mutations of PHF2 that could inactivate its functions are not reported in cancers. In a genome database, we observed that the PHF2 gene possessed mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H)...
October 15, 2016: Pathology Oncology Research: POR
T Kunicka, P Prochazka, I Krus, P Bendova, M Protivova, S Susova, V Hlavac, V Liska, P Novak, M Schneiderova, P Pitule, J Bruha, O Vycital, P Vodicka, P Soucek
BACKGROUND: This study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis of colorectal carcinoma patients. METHODS: Testing set and two validation sets comprising paired tumor and adjacent mucosa tissue samples from 151 patients were used for transcript profiling of 15 5-FU pathway genes by quantitative real-time PCR and DNA methylation profiling by high resolution melting analysis. Intratumoral molecular profiles were correlated with clinical data of patients...
October 12, 2016: BMC Cancer
Katarina Kalavska, Michal Chovanec, Miriam Zatovicova, Martina Takacova, Paulina Gronesova, Daniela Svetlovska, Magdalena Baratova, Vera Miskovska, Jana Obertova, Patrik Palacka, Jan Rajec, Zuzana Sycova-Mila, Zuzana Cierna, Karol Kajo, Stanislav Spanik, Pavel Babal, Jozef Mardiak, Silvia Pastorekova, Michal Mego
Despite the fact that testicular germ cell tumors (TGCTs) are one of the most chemosensitive solid tumors, a small proportion of patients fail to be cured following cisplatin-based first line chemotherapy. Upregulation of carbonic anhydrase IX (CA IX) in various solid tumors is associated with poor outcome. The current prospective study investigated the prognostic value of serum CA IX level in TGCTs. In total, 83 patients (16 non-metastatic following orchiectomy with no evidence of disease, 57 metastatic chemotherapy-naïve and 10 metastatic relapsed chemotherapy-pretreated) starting adjuvant and/or new line of chemotherapy and 35 healthy controls were enrolled in the study...
October 2016: Oncology Letters
Ahitagni Biswas, Lakhan Kashyap, Aanchal Kakkar, Chitra Sarkar, Pramod Kumar Julka
Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal central nervous system tumor commonly affecting children <3 years of age. It roughly constitutes 1%-2% of all pediatric central nervous system tumors. Recent data show that it is the most common malignant central nervous system tumor in children <6 months of age. Management of this aggressive tumor is associated with a myriad of diagnostic and therapeutic challenges. On the basis of radiology and histopathology alone, distinction of AT/RT from medulloblastoma or primitive neuroectodermal tumor is difficult, and hence this tumor has been commonly misdiagnosed as primitive neuroectodermal tumor for decades...
2016: Cancer Management and Research
Laetitia Cicchelero, Sofie Denies, Katrien Vanderperren, Emmelie Stock, Leen Van Brantegem, Hilde de Rooster, Niek N Sanders
The immunological, anti-angiogenic and clinical effects of metronomic cyclophosphamide and 3 consecutive intratumoral interleukin (IL)-12 gene therapy (electrogene therapy (EGT)) treatments were evaluated in 6 dogs with spontaneous cancer. In all dogs, a decrease in peripheral leukocytes 2 days after IL-12 EGT coincided with erythema and swelling of the tumor. In the tumor, a transient increase in IL-12 levels was measured, whereas a continuous increase in interferon γ (IFNγ) and thrombospondin 1 (TSP-1) were determined in contrast to a continuous decrease in vascular endothelial growth factor (VEGF)...
September 28, 2016: Cancer Letters
Zhibin Bai, Yaoping Shi, Jianfeng Wang, Longhua Qiu, Eric J Monroe, Gaojun Teng, Feng Zhang, Xiaoming Yang
PURPOSE: To investigate the technical feasibility of using ultrasound-guided intratumoral radiofrequency hyperthermia (RFH) to enhance local chemotherapy of rat orthotopic pancreatic cancers. MATERIALS AND METHODS: Orthotopic pancreatic cancer masses were established by inoculating luciferase/mCherry labeled-pancreatic cancer cells into the pancreatic tails of Lewis model rats via a laparotomy approach. Twenty-four rats with pancreatic cancer and 24 mice with subcutaneous pancreatic cancer xenografts in four study groups (n = 6/group) received various treatments: i) combination therapy of intratumoral MR imaging-heating-guidewire-mediated RFH (42oC) plus local chemotherapy (gemcitabine); ii) intratumoral chemotherapy alone; iii) RFH alone; and (iv)phosphate-buffered saline (PBS)...
September 27, 2016: Oncotarget
Jamie C Harris, Jeannine M Coburn, Andre Kajdacsy-Balla, David L Kaplan, Bill Chiu
BACKGROUND: Sarcoma accounts for 20% of solid tumors in children. Surgery has significant morbidity. We hypothesized that delivering chemotherapy directly into tumors through sustained release silk systems could slow tumor growth. METHODS: Human Ewing sarcoma cells A673 were cultured with vincristine and doxorubicin to determine half maximal inhibitory concentration (IC50). Cells were injected into mouse hind leg to create orthotopic tumors. Tumor volumes were measured using ultrasound...
September 16, 2016: Journal of Pediatric Surgery
Shan Liu, Wei Wei, Bo Xie, Hua Yue, Dezhi Ni, Yali Bao, Guanghui Ma, Zhiguo G Su
In contrast to traditional strategies based on external driving forces, an internal path for intratumoral delivery is explored by degrading the tumor microenvironment component hyaluronan. Natural hyaluronidase PH20 and constructed long-acting PH20-Fc have been used to achieve this objective. It has been then evaluated how these agents facilitate the diffusion of the following typical therapeutic agents varying in nanoscales: doxorubicin (≈1.5 × 1.0 × 0.7 nm) chemotherapy, trastuzumab (10-15 nm) biotherapy, and gold nanorod (≈100 × 35 nm) thermotherapy...
September 27, 2016: Advanced Healthcare Materials
Kenneth S Chen, Woo Sun Kwon, Jiwoong Kim, Su Jin Heo, Hyo Song Kim, Hyo Ki Kim, Soo Hee Kim, Won Suk Lee, Hyun Cheol Chung, Sun Young Rha, Tae Hyun Hwang
Osteosarcoma is the most common primary bone cancer. It can be cured by aggressive surgery and chemotherapy, but outcomes for metastatic or chemoresistant disease remain dismal. Cancer sequencing studies have shown that the p53 pathway is dysregulated in nearly every case, often by translocation; however, no studies of osteosarcoma evolution or intratumor heterogeneity have been done to date. We studied a patient with chemoresistant, metastatic disease over the course of 3 years. We performed exome sequencing on germline DNA and DNA collected from tumor at three separate time points...
September 2016: Cold Spring Harbor Molecular Case Studies
He-Lin Xu, Kai-Li Mao, Cui-Tao Lu, Zi-Liang Fan, Jing-Jing Yang, Jie Xu, Pian-Pian Chen, De-Li ZhuGe, Bi-Xin Shen, Bing-Hui Jin, Jian Xiao, Ying-Zheng Zhao
Intratumoral drug delivery (IT) is an inherently appealing approach for concentrating toxic chemotherapies at the site of action. However, for most chemotherapies, poor tumor penetration and short retention at the administration site limit their anti-tumor effects. In this work, we describe permeable nanoparticles (NPs) prepared with a novel amphiphilic polymer, RRR-α-tocopheryl succinate-grafted-ε-polylysine conjugate (VES-g-ε-PLL). The nanoparticles (NPs) of VES-g-ε-PLL exhibited an ultra-small hydrodynamic diameter (20...
November 2016: Biomaterials
Yun-Long Wu, Han Wang, Ying-Kun Qiu, Sing Shy Liow, Zibiao Li, Xian Jun Loh
Injectable thermogel to deliver chemotherapeutics in a minimally invasive manner and to achieve their long term sustained release at tumor sites to minimize side effects is attractive for chemotherapy and precision medicine, but its rational design remains a challenge. In this work, a copolymer with natural biodegradable poly[(R)-3-hydroxybutyrate] (PHB), hydrophilic poly(ethylene glycol), and temperature sensitive poly(propylene glycol) blocks linked by urethane linkages is designed to show thermogelling characteristics which are beneficial for minimally invasive injection and safe degradation...
September 5, 2016: Advanced Healthcare Materials
Ying Zhang, Jinyan Li, Tinghe Yu
INTRODUCTION: Sonochemotherapy is a promising strategy for the treatment of cancer, however, there is limited understaning of its pharmacokinetics (PK). AREA COVERED: The PK profile of sonochemotherapy is evaluated based on released data. Preclinical investigations suggest that the blood PK of sonochemotherapy is similar to chemotherapy when using free anticancer drugs. When using encapsulated drugs, a lower plasma level usually occurs; however, the ultrasonic release of drugs within a tumor may lead to drugs leaking into circulation, causing a rebound in the plasma drug level; a higher drug level is detected in certain healthy organs, however this depends mostly on the pharmaceutical formulation...
September 2, 2016: Expert Opinion on Drug Delivery
David B Page, Jianda Yuan, David Redmond, Y Hanna Wen, Jeremy C Durack, Ryan Emerson, Stephen Solomon, Zhiwan Dong, Phillip Wong, Christopher Comstock, Adi Diab, Janice Sung, Majid Maybody, Elizabeth Morris, Edi Brogi, Monica Morrow, Virgilio Sacchini, Olivier Elemento, Harlan Robins, Sujata Patil, James P Allison, Jedd D Wolchok, Clifford Hudis, Larry Norton, Heather L McArthur
In early-stage breast cancer, the degree of tumor-infiltrating lymphocytes (TIL) predicts response to chemotherapy and overall survival. Combination immunotherapy with immune checkpoint antibody plus tumor cryoablation can induce lymphocytic infiltrates and improve survival in mice. We used T-cell receptor (TCR) DNA sequencing to evaluate both the effect of cryoimmunotherapy in humans and the feasibility of TCR sequencing in early-stage breast cancer. In a pilot clinical trial, 18 women with early-stage breast cancer were treated preoperatively with cryoablation, single-dose anti-CTLA-4 (ipilimumab), or cryoablation + ipilimumab...
October 2016: Cancer Immunology Research
Yukiko Masaki, Yoichi Shimizu, Takeshi Yoshioka, Fei Feng, Songji Zhao, Kenichi Higashino, Yoshito Numata, Yuji Kuge
Hypoxia, or low oxygen concentration, is a key factor promoting tumor progression and angiogenesis and resistance of cancer to radiotherapy and chemotherapy. 2-Nitroimidazole-based agents have been widely used in pathological and nuclear medicine examinations to detect hypoxic regions in tumors; in particular, pimonidazole is used for histochemical staining of hypoxic regions. It is considered to accumulate in hypoxic cells via covalent binding with macromolecules or by forming reductive metabolites after reduction of its nitro group...
2016: PloS One
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...
August 28, 2016: Seminars in Cell & Developmental Biology
Justinas Besusparis, Benoit Plancoulaine, Allan Rasmusson, Renaldas Augulis, Andrew R Green, Ian O Ellis, Aida Laurinaviciene, Paulette Herlin, Arvydas Laurinavicius
BACKGROUND: Gene expression studies have identified molecular subtypes of breast cancer with implications to chemotherapy recommendations. For distinction of these types, a combination of immunohistochemistry (IHC) markers, including proliferative activity of tumor cells, estimated by Ki67 labeling index is used. Clinical studies are frequently based on IHC performed on tissue microarrays (TMA) with variable tissue sampling. This raises the need for evidence-based sampling criteria for individual IHC biomarker studies...
2016: Diagnostic Pathology
Jian-Ping Liu, Ting-Ting Wang, Dang-Ge Wang, An-Jie Dong, Ya-Ping Li, Hai-Jun Yu
The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have several advantages over the free drug forms, including reduced cytotoxicity, prolonged circulation in the blood and increased accumulation in tumors. Currently, however, nanoparticulate drugs have only marginally improved the overall survival rate in clinical trials because of the various pathophysiological barriers that exist in the tumor microenvironment, such as intratumoral distribution, penetration and intracellular trafficking, etc...
August 29, 2016: Acta Pharmacologica Sinica
Yaqin Zhu, Xiuxiu Wang, Jing Chen, Jian Zhang, Fenghua Meng, Chao Deng, Ru Cheng, Jan Feijen, Zhiyuan Zhong
Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of 'personalized medicine'. Here, we designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction...
August 25, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ji Wang, Chengchu Zhu
Hypercoagulable state and disorganized angiogenesis are two conspicuous characteristics during tumor progression. There are a considerable number of clinical trials focusing on the effects of anticoagulant and antiangiogenic drugs on the survival of cancer patients. Favorable outcomes have been observed. Excessive blood coagulation not only causes cancer-associated thrombosis, which is a common complication and is the second leading cause of death in patients, but also decreases intratumoral perfusion rates and drug delivery by reducing the effective cross-sectional area of blood vessels...
2016: OncoTargets and Therapy
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