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https://www.readbyqxmd.com/read/27932068/rovalpituzumab-tesirine-a-dll3-targeted-antibody-drug-conjugate-in-recurrent-small-cell-lung-cancer-a-first-in-human-first-in-class-open-label-phase-1-study
#1
Charles M Rudin, M Catherine Pietanza, Todd M Bauer, Neal Ready, Daniel Morgensztern, Bonnie S Glisson, Lauren A Byers, Melissa L Johnson, Howard A Burris, Francisco Robert, Tae H Han, Sheila Bheddah, Noah Theiss, Sky Watson, Deepan Mathur, Bharathi Vennapusa, Hany Zayed, Satwant Lally, Donald K Strickland, Ramaswamy Govindan, Scott J Dylla, Stanford L Peng, David R Spigel
BACKGROUND: Rovalpituzumab tesirine is a first-in-class antibody-drug conjugate directed against delta-like protein 3 (DLL3), a novel target identified in tumour-initiating cells and expressed in more than 80% of patients with small-cell lung cancer. We aimed to assess the safety and activity of rovalpituzumab tesirine in patients who progressed after one or more previous regimen. METHODS: We conducted a phase 1 open-label study at ten cancer centres in the USA...
December 2, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27932046/stereotactic-ablative-body-radiosurgery-sabr-or-stereotactic-body-radiation-therapy-sbrt
#2
REVIEW
Michael R Folkert, Robert D Timmerman
While conventional treatment relies on protracted courses of therapy using relatively small dose-per-fraction sizes of 1.8-2Gy, there is substantial evidence gathered over decades that this may not be the optimal approach for all targetable disease. Stereotactic ablative body radiosurgery (SABR) or stereotactic body radiation therapy (SBRT) is a technique which uses precise targeting to deliver high doses of radiation capable of ablating tumors directly. In this review, we will discuss the justification for and techniques used to deliver ablative doses to improve treatment outcomes, interactions with biological and immunologic therapy, and special procedures to spare normal tissue, which have facilitated the expanding role for these techniques in the management of a wide range of malignant histologies and disease states...
December 5, 2016: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/27931239/mcl-1-inhibition-provides-a-new-way-to-suppress-breast-cancer-metastasis-and-increase-sensitivity-to-dasatinib
#3
Adelaide I J Young, Andrew M K Law, Lesley Castillo, Sabrina Chong, Hayley D Cullen, Martin Koehler, Sebastian Herzog, Tilman Brummer, Erinna F Lee, Walter D Fairlie, Morghan C Lucas, David Herrmann, Amr Allam, Paul Timpson, D Neil Watkins, Ewan K A Millar, Sandra A O'Toole, David Gallego-Ortega, Christopher J Ormandy, Samantha R Oakes
BACKGROUND: Metastatic disease is largely resistant to therapy and accounts for almost all cancer deaths. Myeloid cell leukemia-1 (MCL-1) is an important regulator of cell survival and chemo-resistance in a wide range of malignancies, and thus its inhibition may prove to be therapeutically useful. METHODS: To examine whether targeting MCL-1 may provide an effective treatment for breast cancer, we constructed inducible models of BIMs2A expression (a specific MCL-1 inhibitor) in MDA-MB-468 (MDA-MB-468-2A) and MDA-MB-231 (MDA-MB-231-2A) cells...
December 8, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27931134/constitutive-activation-of-alternative-nuclear-factor-kappa-b-pathway-in-canine-diffuse-large-b-cell-lymphoma-contributes-to-tumor-cell-survival-and-is-a-target-of-new-adjuvant-therapies
#4
Davis M Seelig, Daisuke Ito, Colleen L Forster, Una A Yoon, Matthew Breen, Linda J Burns, Veronika Bachanova, Kerstin Lindblad-Toh, Timothy D O'Brien, Stephen C Schmechel, Anthony E Rizzardi, Jaime F Modiano, Michael A Linden
Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1)...
December 8, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27930982/targeted-osteosarcoma-chemotherapy-using-rgd-peptide-installed-doxorubicin-loaded-biodegradable-polymeric-micelle
#5
Zhenhua Fang, Yanpeng Sun, Hong Xiao, Peng Li, Ming Liu, Fan Ding, Wusheng Kan, Runsheng Miao
Osteosarcoma is the most common primary malignant bone tumor in the pediatric age group, and chemotherapy directed by targeted nanoparticulate drug delivery system represents a promising approach for osteosarcoma treatment recently. Here, we designed and developed a novel DOX-loaded targeted polymeric micelle self-assembled from RGD-terminated poly(ethylene glycol)-block-poly (trimethylene carbonate) (RGD-PEG-PTMC) amphiphilic biodegradable block copolymer, for high-efficiency targeted chemotherapy of osteosarcoma...
December 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27930644/immunotherapy-for-the-treatment-of-breast-cancer-checkpoint-blockade-cancer-vaccines-and-future-directions-in-combination-immunotherapy
#6
Heather L McArthur, David B Page
Immunotherapy encompasses both vaccines that direct immune responses to tumor-associated antigens, and checkpoint blocking antibodies that inhibit immune system suppression by targeting key pathways mediated by cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1). Both of these approaches currently are being explored as potential strategies for the treatment of breast cancer. Recent studies suggest that immunotherapy is poised to change the therapeutic landscape for some breast cancers...
November 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27930631/cd19-targeted-car-t-cells-as-novel-cancer-immunotherapy-for-relapsed-or-refractory-b-cell-acute-lymphoblastic-leukemia
#7
Marco L Davila, Renier J Brentjens
Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable...
October 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27930339/growth-hormone-releasing-hormone-receptor-antagonists-inhibit-human-gastric-cancer-through-downregulation-of-pak1-stat3-nf-%C3%AE%C2%BAb-signaling
#8
Jinfeng Gan, Xiurong Ke, Jiali Jiang, Hongmei Dong, Zhimeng Yao, Yusheng Lin, Wan Lin, Xiao Wu, Shumei Yan, Yixuan Zhuang, Wai Kit Chu, Renzhi Cai, Xianyang Zhang, Herman S Cheung, Norman L Block, Chi Pui Pang, Andrew V Schally, Hao Zhang
Gastric cancer (GC) ranks as the fourth most frequent in incidence and second in mortality among all cancers worldwide. The development of effective treatment approaches is an urgent requirement. Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) have been found to be present in a variety of tumoral tissues and cell lines. Therefore the inhibition of GHRH-R was proposed as a promising approach for the treatment of these cancers. However, little is known about GHRH-R and the relevant therapy in human GC...
December 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27930095/multi-omics-data-integration-and-mapping-of-altered-kinases-to-pathways-reveal-gonadotropin-hormone-signaling-in-glioblastoma
#9
Savita Jayaram, Manoj Kumar Gupta, Rajesh Raju, Poonam Gautam, Ravi Sirdeshmukh
Glioblastoma multiforme (GBM) is one of the most lethal brain tumors with an inadequately understood pathophysiology. Biomarkers that guide accurate diagnosis and treatment decisions would greatly support precision medicine for GBM. Previous studies of GBM have focused on signaling pathways such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptors (PDGFRs), notch, wnt, and others, identified with single omics technology platforms (genomics, transcriptomics, or proteomics), but not with their integrated use...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27929800/harnessing-benefit-from-targeting-tumor-associated-carbohydrate-antigens
#10
Thomas Kieber-Emmons, Bejatohlah Monzavi-Karbassi, Laura F Hutchins, Angela Pennisi, Issam Makhoul
Integrating additive or synergistic antitumor effects that focus on distinct elements of tumor biology are the most rational strategies for cancer treatment. Treatments for breast cancer have increased overall survival, but remain limited by lack of efficacy in a subset of breast cancer patients. The real challenge is to define what elements of tumor biology make the most sense to be integrated. An emerging strategy is to consider a systems biology approach to impact multiple interactions in networks as compared to hitting a specific protein-protein interaction target...
December 8, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27929501/volumetric-modulated-arc-therapy-using-multicriteria-optimization-for-body-and-extremity-sarcoma
#11
Michael R Young, David L Craft, Caroline M Colbert, Kyla Remillard, Liam Vanbenthuysen, Yi Wang
This study evaluates the implementation of volumetric-modulated arc therapy (VMAT) using multicriteria optimization (MCO) in the RayStation treatment planning system (TPS) for complex sites, namely extremity and body sarcoma. The VMAT-MCO algorithm implemented in RayStation is newly developed and requires an integrated, comprehensive analysis of plan generation, delivery, and treatment efficiency. Ten patients previously treated by intensity-modulated radiation therapy (IMRT) with MCO were randomly selected and replanned using VMAT-MCO...
November 8, 2016: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/27929499/development-and-evaluation-of-a-clinical-model-for-lung-cancer-patients-using-stereotactic-body-radiotherapy-sbrt-within-a-knowledge-based-algorithm-for-treatment-planning
#12
Karen Chin Snyder, Jinkoo Kim, Anne Reding, Corey Fraser, James Gordon, Munther Ajlouni, Benjamin Movsas, Indrin J Chetty
The purpose of this study was to describe the development of a clinical model for lung cancer patients treated with stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning, and to evaluate the model performance and applicability to different planning techniques, tumor locations, and beam arrangements. 105 SBRT plans for lung cancer patients previously treated at our institution were included in the development of the knowledge-based model (KBM). The KBM was trained with a combination of IMRT, VMAT, and 3D CRT techniques...
November 8, 2016: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/27929482/anatomy-based-definition-of-point-a-utilizing-three-dimensional-volumetric-imaging-approach-for-high-dose-rate-hdr-intracavitary-brachytherapy-dose-prescription-when-treating-cervical-cancer-using-limited-resources
#13
Manish K Goyal, D V Rai, Than S Kehwar, Jayanand Manjhi, Bret H Heintz, Kathleen L Shide, Jerry L Barker
This study was designed to determine whether volumetric imaging could identify consistent alternative prescription methods to Manchester/point A when prescribing radiation dose in the treatment of cervical cancer using HDR intracavitary brachy-therapy (ICBT). One hundred and twenty-five treatment plans of 25 patients treated for carcinoma of the cervix were reviewed retrospectively. Each patient received 5 fractions of HDR ICBT following initial cisplatin-based pelvic chemoradiation, and radiation dose was originally prescribed to point A (ICRU-38)...
July 16, 2016: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/27929475/anticancer-efficacy-of-photodynamic-therapy-with-lung-cancer-targeted-nanoparticles
#14
Ji-Eun Chang, Hyun-Jong Cho, Sanghoon Jheon
Photodynamic therapy (PDT) is a non-invasive and non-surgical method representing an attractive alternative choice for lung cancer treatment. Photosensitizers selectively accumulate in tumor tissue and lead to tumor cell death in the presence of oxygen and the proper wavelength of light. To increase the therapeutic effect of PDT, we developed both photosensitizer- and anticancer agent-loaded lung cancer-targeted nanoparticles. Both enhanced permeability and retention (EPR) effect-based passive targeting and hyaluronic-acid-CD44 interaction-based active targeting were applied...
December 1, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27928945/jak-stat-signal-transduction-promising-attractive-targets-for-immune-inflammatory-and-hematopoietic-diseases
#15
Qianwen Gao, Xuewu Liang, Abdul Sami Shaikh, Jie Zang, Wenfang Xu, Yingjie Zhang
JAKs, a key family of cytoplasmic tyrosine kinases acting as a requisite part in the signaling process of growth factors and cytokines, important for immunity responses and hematopoiesis have become attractive targets for a considerable number of immune, inflammatory and hematopoietic diseases. Moreover, the JAK signal system has drawn significant attention in recent years as therapeutic targets including JAKs, STATs and JAK/STAT signal pathway. Herein, we present a review of the JAK/STAT signal pathway, the structure, biological function, mechanism of the JAKs and STATs along with a summary of the up-to-date clinical or approved JAK inhibitors which are involved in the treatment of various kinds of tumors and other immunity indications...
December 7, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27928804/-treatment-and-prognosis-of-108-patients-with-high-risk-gastrointestinal-stromal-tumor
#16
Cheng Lei, Lin Liu, Qisan Wang, Haijiang Wang
OBJECTIVE: To investigate the treatment methods and prognostic factors of high-risk gastrointestinal stromal tumor (GIST). METHODS: Clinicopathological date and follow-up data of 108 patients with high-risk GIST from January 2002 to February 2016 treated at our department were retrospectively reviewed. The patients were divided into two groups according to whether they received adjuvant therapy after surgery. A group of patients received imatinib adjuvant therapy(adjuvant therapy group, 69 cases)...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27928802/-clinical-characteristics-and-prognosis-analysis-of-119-cases-with-giant-gastrointestinal-stromal-tumor
#17
Peng Zhang, Xiangyu Zeng, Jinbo Gao, Weizhen Liu, Xiaoming Shuai, Ke Liu, Xinghua Liu, Ming Cai, Kailin Cai, Guobin Wang, Kaixiong Tao
OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment as well as prognostic factors of the giant gastrointestinal stromal tumor (GIST). METHODS: Clinical data of 235 patients with high risk GIST treated in the Union Hospital, Tongi Medical College, Huazhong University of Science and Technology between January 2005 and July 2015 were retrospectively analyzed. Patients were divided into giant GIST group (diameter equal to or larger than 10 cm, 119 cases) and high risk group (diameter less than 10 cm, 116 cases) according to tumor size...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27928800/-efficacy-analysis-of-targeted-therapy-combined-with-surgery-in-the-treatment-of-recurrent-and-metastatic-gastrointestinal-stromal-tumor
#18
Xiaodong Gao, Anwei Xue, Yong Fang, Ping Shu, He Li, Jiaqian Ling, Li Wang, Yingyong Hou, Kuntang Shen, Jing Qin, Yihong Sun, Xinyu Qin
OBJECTIVE: To investigate the efficacy of targeted therapy combined with surgery in the treatment of recurrent and metastatic gastrointestinal stromal tumor(GIST). METHODS: Clinicopathological and followed-up data of 318 patients with recurrent and metastatic GIST admitted in Zhongshan Hospital between January 2000 and December 2015 were analyzed retrospectively. According to different treatment methods, the patients were divided into four groups: surgery group (operation alone, 44 cases), target therapy group (imatinib alone, 108 cases), target therapy combined with surgery group (imatinib plus operation, 139 cases), other therapy group (chemotherapy, Chinese medicine and others, 27 cases)...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27928790/-preliminary-understanding-of-gastrointestinal-stromal-tumor-with-the-highest-risk
#19
Chaoyong Shen, Bo Zhang
Nowadays, surgery still remains the mainstay treatment for gastrointestinal stromal tumor (GIST). Nevertheless, some GIST patients have also experienced tumor recurrence/metastasis even with R0 resection. Meanwhile, the prognosis of GIST has been dramatically improved after targeted drug imatinib used in clinical practice for GIST, but tumor recurrence/metastasis still occurred in some patients with high-risk when adjuvant treatment course ended, as such, the 2008 modified NIH criterion, which is used to guide the adjuvant treatment of GIST, still has shortcomings...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27928785/-interpretation-of-the-latest-guidelines-in-the-treatment-of-gastrointestinal-neuroendocrine-neoplasms
#20
Luohai Chen, Jie Chen, Zhiwei Zhou
Neuroendocrine neoplasms(NEN) is a rare group of tumors with gastrointestinal tract as one of the most common primary locations. The most commonly used guidelines are proposed by European Neuroendocrine Tumor Society (ENETS) and National Comprehensive Cancer Network(NCCN) respectively, while the management of gastrointestinal NEN is generally identical in these two guidelines. Surgery is still the sole curative method which should be considered as the first choice of locoregional NEN. Otherwise, 40% to 50% of patients manifests metastatic disease when diagnosed...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
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