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https://www.readbyqxmd.com/read/29232552/therapeutic-antibody-targeting-tumor-and-osteoblastic-niche-derived-jagged1-sensitizes-bone-metastasis-to-chemotherapy
#1
Hanqiu Zheng, Yangjin Bae, Sabine Kasimir-Bauer, Rebecca Tang, Jin Chen, Guangwen Ren, Min Yuan, Mark Esposito, Wenyang Li, Yong Wei, Minhong Shen, Lanjing Zhang, Nikolai Tupitsyn, Klaus Pantel, Chadwick King, Jan Sun, Jodi Moriguchi, Helen Toni Jun, Angela Coxon, Brendan Lee, Yibin Kang
Bone metastasis is a major health threat to breast cancer patients. Tumor-derived Jagged1 represents a central node in mediating tumor-stromal interactions that promote osteolytic bone metastasis. Here, we report the development of a highly effective fully human monoclonal antibody against Jagged1 (clone 15D11). In addition to its inhibitory effect on bone metastasis of Jagged1-expressing tumor cells, 15D11 dramatically sensitizes bone metastasis to chemotherapy, which induces Jagged1 expression in osteoblasts to provide a survival niche for cancer cells...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29232474/is-intraperitoneal-chemotherapy-still-an-acceptable-option-in-primary-adjuvant-chemotherapy-for-advanced-ovarian-cancer
#2
B J Monk, J K Chan
The role of intraperitoneal (i.p.) chemotherapy in treating newly diagnosed advanced epithelial ovarian cancer (EOC) has been the subject of controversy for almost three decades. Three large intergroup phase III trials (GOG 104, 114, 172) have demonstrated a survival benefit associated with i.p. over intravenous (i.v.) therapy in advanced, low-volume EOC. Despite the positive clinical trial results and a subsequent National Cancer Institute alert in 2006, i.p. treatment has not been widely accepted as the standard of care in the United States and is infrequently used in Europe...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29232470/how-can-molecular-abnormalities-influence-our-clinical-approach
#3
W Wei, F Giulia, S Luffer, R Kumar, B Wu, M Tavallai, R T Bekele, M J Birrer
Background: Despite improvements in diagnostics and treatment, the clinical outcome of epithelial ovarian cancer remains poor over the last three decades. Recent high-throughput genomic studies have demonstrated ovarian cancer as a highly heterogeneous entity with distinctive molecular signatures among different or even within the same histotype. In this article, we review the molecular genetics of epithelial ovarian cancer and how they have been translated into modern clinical trials, as well as their implications in patient stratification for more targeted and personalized approaches...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29232467/immunotherapy-in-ovarian-cancer
#4
K Odunsi
Immunological destruction of tumors is a multistep, coordinated process that can be modulated or targeted at several critical points to elicit tumor rejection. These steps in the cancer immunity cycle include: (i) generation of sufficient numbers of effector T cells with high avidity recognition of tumor antigens in vivo; (ii) trafficking and infiltration into the tumor; (iii) overcoming inhibitory networks in the tumor microenvironment; (iv) direct recognition of tumor antigens and generation of an effector anti-tumor response; and (v) persistence of the anti-tumor T cells...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29232465/new-treatments-in-ovarian-cancer
#5
E Pujade-Lauraine
In targeting DNA repair pathways of the most genomic instable cancer, poly-(adenosine diphosphate [ADP])-ribose polymerase inhibitors (PARPi) have been demonstrated as the most effective drug since platinum in high grade serous or endometrioid ovarian cancer. Immunotherapy is strongly pushing the door of ovarian cancer and has the ambition to change the fate of this deadly disease when combined with chemotherapy, vascular endothelial growth factor inhibitor or PARPi. The activity of PARPi could also be improved by modulators of the cell cycle, which are required to give time enough for DNA repair...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29232409/lupeol-and-stigmasterol-suppress-tumor-angiogenesis-and-inhibit-cholangiocarcinoma-growth-in-mice-via-downregulation-of-tumor-necrosis-factor-%C3%AE
#6
Thaned Kangsamaksin, Supattra Chaithongyot, Chanida Wootthichairangsan, Rattanavinan Hanchaina, Chayada Tangshewinsirikul, Jisnuson Svasti
Lupeol and stigmasterol, major phytosterols in various herbal plants, possess anti-inflammatory activities and have been proposed as candidates for anti-cancer agents, but their molecular mechanisms are still unclear. Here, we investigated the effects of lupeol and stigmasterol on tumor and endothelial cells in vitro and their anti-cancer activities in vivo. Our results demonstrated that lupeol and stigmasterol suppressed cell viability, migration, and morphogenesis of human umbilical vein endothelial cells (HUVECs) but not cholangiocarcinoma (CCA) cells...
2017: PloS One
https://www.readbyqxmd.com/read/29232269/mr-guided-biopsy-and-focal-therapy-new-options-for-prostate-cancer-management
#7
Fuad F Elkhoury, Demetrios N Simopoulos, Leonard S Marks
PURPOSE OF REVIEW: Options for prostate cancer management are rapidly expanding. The recent advent of MRI technology has led to guided prostate biopsies by radiologists working in-bore or by urologists using MR/US fusion technology. The resulting tumor visualization now provides the option of focal therapy. Currently available are highly directed energies - focused ultrasound (HIFU), cryotherapy, and laser - all offering the hope of curing prostate cancer with few side effects. RECENT FINDINGS: MRI now enables visualization of many prostate cancers...
December 11, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/29231907/activated-hgf-c-met-axis-in-head-and-neck-cancer
#8
REVIEW
Levi Arnold, Jonathan Enders, Sufi Mary Thomas
Head and neck squamous cell carcinoma (HNSCC) is a highly morbid disease. Recent developments including Food and Drug Administration (FDA) approved molecular targeted agent's pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal-epithelial transition factor (c-Met) and its ligand hepatocyte growth factor (HGF) are overexpressed in head and neck squamous cell carcinoma (HNSCC); and regulates tumor progression and response to therapy...
December 12, 2017: Cancers
https://www.readbyqxmd.com/read/29231244/sirt7-depletion-inhibits-cell-proliferation-migration-and-increases-drug-sensitivity-by-activating-p38mapk-in-breast-cancer-cells
#9
Kun-Lin Chen, Lian Li, Fang-Xiao Yang, Cheng-Min Li, Yi-Ru Wang, Gen-Lin Wang
SIRT7 is a member of the sirtuin family of proteins that are known to be associated with tumor development. However, the functional roles and molecular mechanisms underlying the function of SIRT7 in breast cancer cell survival and tumor development remain unclear. Recent studies demonstrated that SIRT7 is upregulated in breast cancer cells and tissues. In the present study, we systematically explored the roles of SIRT7 in the growth of breast cancer cells and tumors both in vitro and in vivo. Our results showed that SIRT7 plays a major role in facilitating cell survival by promoting cell proliferation and inhibiting apoptosis...
December 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29231057/a-critical-review-on-ramucirumab-in-the-treatment-of-advanced-urothelial-cancer
#10
Panagiotis J Vlachostergios, Aileen Lee, Charlene Thomas, Ryan Walsh, Scott T Tagawa
Advanced urothelial cancer (UC) is a lethal disease despite current advances in systemic therapy, including platinum chemotherapy combinations and immune checkpoint inhibition. Tumor angiogenesis is involved in UC growth and metastatic progression. Proangiogenic signaling through the VEGFR is a key process in UC with prognostic significance. Targeting of VEGFR2 with the monoclonal antibody ramucirumab has been tested in various different tumor types. In this review, we discuss the development of the drug in the context of its preclinical and clinical use with a focus on UC...
December 12, 2017: Future Oncology
https://www.readbyqxmd.com/read/29230175/the-combined-use-of-in-silico-in-vitro-and-in-vivo-analyses-to-assess-anti-cancerous-potential-of-a-bioactive-compound-from-cyanobacterium-nostoc-sp-mgl001
#11
Niveshika, Ekta Verma, Shashank K Maurya, Rajnikant Mishra, Arun K Mishra
Escalating incidences of cancer, especially in developed and developing countries, demand evaluation of potential unexplored natural drug resources. Here, anticancer potential of 9-Ethyliminomethyl-12-(morpholin-4-ylmethoxy)-5,8,13,16-tetraaza -hexacene-2,3-dicarboxylic acid (EMTAHDCA) isolated from fresh water cyanobacterium Nostoc sp. MGL001 was screened through in silico, in vitro, and in vivo studies. For in silico analysis, EMTAHDCA was selected as ligand and 11 cancer related proteins (Protein Data Bank ID: 1BIX, 1NOW, 1TE6, 2RCW, 2UVL, 2VCJ, 3CRY, 3HQU, 3NMQ, 5P21, and 4B7P) which are common targets of various anticancer drugs were selected as receptors...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29230121/leptomeningeal-disease-and-the-evolving-role-of-molecular-targeted-therapy-and-immunotherapy
#12
REVIEW
Katharine Hall Thomas, Robert A Ramirez
Background: Leptomeningeal disease (LMD) is a complication that results from solid tumor metastasis. Prognosis is extremely poor. As therapeutic options for solid tumors improve, the rate of LMD continues to increase. Until recently, treatment has been limited to radiation therapy, intrathecal chemotherapy, and systemic chemotherapy, with an overall survival of 2-3 months. Targeted molecular therapy and immunotherapies are promising new options for increasing overall survival and clinical improvement; however, optimal clinical management remains unknown...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29230082/recent-advances-in-adam17-research-a-promising-target-for-cancer-and-inflammation
#13
REVIEW
Marcia L Moss, Dmitry Minond
Since its discovery, ADAM17, also known as TNFα converting enzyme or TACE, is now known to process over 80 different substrates. Many of these substrates are mediators of cancer and inflammation. The field of ADAM metalloproteinases is at a crossroad with many of the new potential therapeutic agents for ADAM17 advancing into the clinic. Researchers have now developed potential drugs for ADAM17 that are selective and do not have the side effects which were seen in earlier chemical entities that targeted this enzyme...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29229995/lysyl-oxidase-like-3-is-required-for-melanoma-cell-survival-by-maintaining-genomic-stability
#14
Patricia G Santamaría, Alfredo Floristán, Bárbara Fontanals-Cirera, Alberto Vázquez-Naharro, Vanesa Santos, Saleta Morales, Lourdes Yuste, Héctor Peinado, Antonio García-Gómez, Francisco Portillo, Eva Hernando, Amparo Cano
Lysyl oxidase-like 3 (LOXL3) is a member of the lysyl oxidase family comprising multifunctional enzymes with depicted roles in extracellular matrix maturation, tumorigenesis, and metastasis. In silico expression analyses followed by experimental validation in a comprehensive cohort of human cell lines revealed a significant upregulation of LOXL3 in human melanoma. We show that LOXL3 silencing impairs cell proliferation and triggers apoptosis in various melanoma cell lines. Further supporting a pro-oncogenic role in melanoma, LOXL3 favors tumor growth in vivo and cooperates with oncogenic BRAF in melanocyte transformation...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229854/interferon-beta-represses-cancer-stem-cell-properties-in-triple-negative-breast-cancer
#15
Mary R Doherty, HyeonJoo Cheon, Damian J Junk, Shaveta Vinayak, Vinay Varadan, Melinda L Telli, James M Ford, George R Stark, Mark W Jackson
Triple-negative breast cancer (TNBC), the deadliest form of this disease, lacks a targeted therapy. TNBC tumors that fail to respond to chemotherapy are characterized by a repressed IFN/signal transducer and activator of transcription (IFN/STAT) gene signature and are often enriched for cancer stem cells (CSCs). We have found that human mammary epithelial cells that undergo an epithelial-to-mesenchymal transition (EMT) following transformation acquire CSC properties. These mesenchymal/CSCs have a significantly repressed IFN/STAT gene expression signature and an enhanced ability to migrate and form tumor spheres...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229829/psma-targeted-polyinosine-polycytosine-vector-induces-prostate-tumor-regression-and-invokes-an-antitumor-immune-response-in-mice
#16
Yael Langut, Alaa Talhami, Samarasimhareddy Mamidi, Alexei Shir, Maya Zigler, Salim Joubran, Anna Sagalov, Efrat Flashner-Abramson, Nufar Edinger, Shoshana Klein, Alexander Levitzki
There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine-polyethyleneglycol (PEI-PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229675/evaluation-of-metase-pemetrexed-loaded-peg-plga-nanoparticles-modified-with-anti-cd133-scfv-for-treatment-of-gastric-carcinoma
#17
Lin Xin, Hou-Ting Zhang, Wei-Feng Yang, Yi-Fan Li, Chuan Liu
PEG-PLGA nanoparticles (NPs) modified with anti-CD133 and tumor-targeting single-chain antibody fragment (scFV-NPs) for systemic delivery of methioninase (METase) and pemetrexed for gastric carcinoma were successfully formulated. The structure characterization and biological functions of METase-pemetrexed-loaded scFV-PEG-PLGA NPs (scFV-METase/pemetrexed-NPs) in vitro were investigated. Functional scFV-PEG-PLGA NPs or PEG-PLGA NPs presents low cell cytoxicity in CD133+ SGC7901 cells. scFV-METase/pemetrexed-NPs (scFv-M/P-NP) was more effective in inhibiting tumor growth (including cell growth and migration ability) in CD133 positive expressed gastric cancer cells than METase/pemetrexed-NPs (M/P-NP)...
December 11, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29229673/lncrna-gas5-suppresses-ovarian-cancer-by-inducing-inflammasome-formation
#18
Jie Li, Chen Yang, Yinguang Li, Aiyue Chen, Li Li, Zeshan You
OBJECTIVE: Long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is involved in various kinds of cancer. However, the role of lncGAS5 in the development of ovarian cancer remains unclear. In the current study, we explored the cellular mechanism and clinical value of lncRNA GAS5 in ovarian cancer. METHODS: Quantitative real-time PCR was used to detect mRNA level of LncRNA GAS5 in 20 ovarian cancer tissues. The effect of lncRNA GAS5 on cell proliferation was performed using CCK-8 assay...
December 11, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29229597/nkx2-2as-suppression-contributes-to-the-pathogenesis-of-sonic-hedgehog-medulloblastoma
#19
Yimeng Zhang, Ting Wang, Shan Wang, Yanlu Xiong, Rui Zhang, Xiang Zhang, Jing Zhao, An-Gang Yang, Lei Wang, Lintao Jia
Aberrant Hedgehog signaling and excessive activation of the Gli family of transcriptional activators are key drivers of medulloblastoma (MB), the most common human pediatric brain malignancy. MB originates mainly from cerebellar granule neuron progenitors (CGNP), but the mechanisms underlying CGNP transformation remain largely obscure. In this study, we found that suppression of the non-coding RNA Nkx2-2as promotes Sonic Hedgehog (Shh)-potentiated MB development. Nkx2-2as functioned as a competing endogenous RNA (ceRNA) against miR-103 and miR-107, sequestering them and thereby de-repressing their tumor suppressive targets BTG2 and LATS1 and impeding cell division and migration...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29229426/cbx4-exhibits-oncogenic-activities-in-breast-cancer-via-notch1-signaling
#20
Jing-Sheng Zeng, Zhen-Dong Zhang, Li Pei, Zhi-Zhu Bai, Yong Yang, Hong Yang, Qiu-Hong Tian
Polycomb chromobox (CBX) proteins are involved in gene silencing to function as oncogenes or tumor suppressors through the polycomb repressive complex (PRC1). CBX4 has been implicated in the progression of human cancers, but its role and clinical significance in breast cancer remain unclear. Here, we show that CBX4 is up-regulated in breast cancer and exerts oncogenic activities via miR-137-mediated activation of Notch1 signaling pathway. CBX4 expression was increased in breast cancer, compared with the nontumorous tissues...
December 8, 2017: International Journal of Biochemistry & Cell Biology
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