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https://www.readbyqxmd.com/read/29352488/understanding-intratumor-heterogeneity-by-combining-genome-analysis-and-mathematical-modeling
#1
REVIEW
Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy...
January 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29352443/baculovirus-based-gene-silencing-of-humanin-for-the-treatment-of-pituitary-tumors
#2
María Florencia Gottardo, Matías L Pidre, Camila Zuccato, Antonela S Asad, Mercedes Imsen, Gabriela Jaita, Marianela Candolfi, Víctor Romanowski, Adriana Seilicovich
Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells...
January 19, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29350351/convection-enhanced-delivery-of-cetuximab-conjugated-iron-oxide-nanoparticles-for-treatment-of-spontaneous-canine-intracranial-gliomas
#3
A Courtenay Freeman, Simon R Platt, Shannon Holmes, M Kent, Kelsey Robinson, Elizabeth Howerth, Joe Eagleson, Alexandros Bouras, Milota Kaluzova, Constantinos G Hadjipanayis
Cetuximab conjugated iron-oxide nanoparticles (cetuximab-IONPs) have shown both in-vitro and in-vivo anti-tumor efficacy against gliomas. The purpose of this pilot study was to evaluate the safety and potential efficacy of cetuximab-IONPs for treatment of spontaneously occurring intracranial gliomas in canines after convection-enhanced delivery (CED). The use of CED allowed for direct infusion of the cetuximab-IONPs both intratumorally and peritumorally avoiding the blood brain barrier (BBB) and limiting systemic effects...
January 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29348457/ltbp3-promotes-early-metastatic-events-during-cancer-cell-dissemination
#4
Elena I Deryugina, Ewa Zajac, Lior Zilberberg, Tomoki Muramatsu, Grishma Joshi, Branka Dabovic, Daniel Rifkin, James P Quigley
Latent transforming growth factor β (TGFβ)-binding proteins (LTBPs) are important for the secretion, activation, and function of mature TGFβ, especially so in cancer cell physiology. However, specific roles of the LTBPs remain understudied in the context of the primary tumor microenvironment. Herein, we investigated the role of LTBP3 in the distinct processes involved in cancer metastasis. By using three human tumor cell lines of different tissue origin (epidermoid HEp-3 and prostate PC-3 carcinomas and HT-1080 fibrosarcoma) and several metastasis models conducted in both mammalian and avian settings, we show that LTBP3 is involved in the early dissemination of primary cancer cells, namely in the intravasation step of the metastatic cascade...
January 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29348271/intratumoral-payload-concentration-correlates-with-the-activity-of-antibody-drug-conjugates
#5
Donglu Zhang, Shang-Fan Yu, S Cyrus Khojasteh, Yong Ma, Thomas H Pillow, Jack D Sadowsky, Dian Su, Katherine R Kozak, Keyang Xu, Andrew G Polson, Peter Dragovich, Cornelis Eca Hop
Antibody-drug conjugates (ADCs) have become important scaffolds for targeted cancer therapies. However, ADC exposure - response correlation is not well characterized. We demonstrated that intratumor payload exposures correlated well with the corresponding efficacies of several disulfide-linked ADCs bearing an DNA alkylating agent, pyrrolo[2,1-c][1,4]benzodiazepine-dimer (PBD), in HER2-expressing xenograft models. The correlation suggests that a threshold concentration of intratumor payload is required to support sustained efficacy and an ADC can deliver an excessive level of payload to tumors that does not enhance efficacy ('Plateau' effect)...
January 18, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29347918/somatic-evolutionary-timings-of-driver-mutations
#6
Karen Gomez, Sayaka Miura, Louise A Huuki, Brianna S Spell, Jeffrey P Townsend, Sudhir Kumar
BACKGROUND: A unified analysis of DNA sequences from hundreds of tumors concluded that the driver mutations primarily occur in the earliest stages of cancer formation, with relatively few driver mutation events detected in the late-arising subclones. However, emerging evidence from the sequencing of multiple tumors and tumor regions per individual suggests that late-arising subclones with additional driver mutations are underestimated in single-sample analyses. METHODS: To test whether driver mutations generally map to early tumor development, we examined multi-regional tumor sequencing data from 101 individuals reported in 11 published studies...
January 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29347887/cryo-assisted-resection-en-bloc-and-cryoablation-in-situ-of-primary-breast-cancer-coupled-with-intraoperative-ultrasound-guided-tracer-injection-a-preliminary-clinical-study
#7
Nikolai N Korpan, Kecheng Xu, Philipp Schwarzinger, Masashi Watanabe, Gerhard Breitenecker, Le Pivert Patrick
The aim of the study was to perform cryosurgery on a primary breast tumor, coupled with simultaneous peritumoral and intratumoral tracer injection of a blue dye, to evaluate lymphatic mapping. We explored the ability of our strategy to prevent tumor cells, but not that of injected tracers, to migrate to the lymphovascular drainage during conventional resection of frozen breast malignancies. Seventeen patients aged 51 (14) years (mean [standard deviation]), presenting primary breast cancer with stage I to IV, were randomly selected and treated in The Rudolfinerhaus Private Clinic in Vienna, Austria, and included in this preliminary clinical study...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29346317/liposomal-tricurin-a-synergistic-combination-of-curcumin-epicatechin-gallate-and-resveratrol-repolarizes-tumor-associated-microglia-macrophages-and-eliminates-glioblastoma-gbm-and-gbm-stem-cells
#8
Sumit Mukherjee, Juliet N E Baidoo, Samay Sampat, Andrew Mancuso, Lovena David, Leah S Cohen, Shuiqin Zhou, Probal Banerjee
Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin)...
January 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29345636/promoting-the-accumulation-of-tumor-specific-t-cells-in-tumor-tissues-by-dendritic-cell-vaccines-and-chemokine-modulating-agents
#9
Nataša Obermajer, Julie Urban, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, David L Bartlett, Pawel Kalinski
This protocol describes how to induce large numbers of tumor-specific cytotoxic T cells (CTLs) in the spleens and lymph nodes of mice receiving dendritic cell (DC) vaccines and how to modulate tumor microenvironments (TMEs) to ensure effective homing of the vaccination-induced CTLs to tumor tissues. We also describe how to evaluate the numbers of tumor-specific CTLs within tumors. The protocol contains detailed information describing how to generate a specialized DC vaccine with augmented ability to induce tumor-specific CTLs...
February 2018: Nature Protocols
https://www.readbyqxmd.com/read/29344137/the-association-between-aquaporin-1-expression-microvessel-density-and-the-clinicopathological-features-of-hepatocellular-carcinoma
#10
Li-Min Luo, Hu Xia, Rong Shi, Jun Zeng, Xin-Rui Liu, Min Wei
The present study aimed to evaluate the effects of aquaporin-1 (AQP1) level and intratumoral microvessel density (IMD) on the clinicopathological features of patients with hepatocellular carcinoma (HCC). The AQP1 expression levels, IMD and AQP1/IMD ratios in patients with HCC were measured using a semi-quantitative immunohistochemical technique. The association between these features and clinicopathological variables were evaluated. The prognostic impact of AQP1 and IMD on overall survival (OS), and 5-year disease-free survival (DFS) of HCC patients was investigated retrospectively...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29341153/circulating-tumour-cells-and-dna-as-liquid-biopsies-in-gastrointestinal-cancer
#11
REVIEW
O Nordgård, K Tjensvoll, B Gilje, K Søreide
BACKGROUND: Blood is the most extensively studied body fluid and, because it contains circulating tumour cells (CTCs) and circulating tumour-derived cell-free DNA (ctDNA), it may represent a liquid biopsy for cancer. Methods for enrichment and detection of CTCs and ctDNA, their clinical applications and future opportunities in gastrointestinal cancers were the focus of this review. METHODS: The PubMed database was searched for literature up to 24 June 2017, with a focus on the past 10 years...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29339376/tumor-immunity-and-survival-as-a-function-of-alternative-neopeptides-in-human-cancer
#12
Andrew J Rech, David Balli, Alejandro Mantero, Hemant Ishwaran, Katherine L Nathanson, Ben Z Stanger, Robert H Vonderheide
The immune system exerts antitumor activity via T cell-dependent recognition of tumor-specific antigens. Although the number of tumor neopeptides - peptides derived from somatic mutations - often correlates with immune activity and survival, most classically defined high-affinity neopeptides (CDNs) are not immunogenic, and only rare CDNs have been linked to tumor rejection. Thus, the rules of tumor antigen recognition remain incompletely understood. Here, we analyzed neopeptides, immune activity, and clinical outcome from 6,324 patients across 27 tumor types...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29338444/adp53-gendicine-12-years-in-clinic-the-first-approved-gene-therapy-product-for-cancer
#13
Wei-Wei Zhang, Jianglong Li, Dinggang Li, Jiliang Liu, Xiuqin Li, Wei Li, Xiaolong Xu, Michael J Zhang, Lois Chandler, Hong Lin, Aiguo Hu, Wei Xu, Dominic Man-Kit Lam
Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech Company, was approved by CFDA in 2003. It has been used in clinical oncology for 12 years since it entered the market in 2004. As the first-in-class product for cancer gene therapy, Gendicine met its expectation and demonstrated with ample clinical data that it is safe and effective for treating cancer. SiBiono manufactured 41 batches in compliant with CFDA QC/QA requirements. Total 169,571 vials (1.0x1012 vector particles per vial) were used in more than 50,000 patients, among them about 5,000 were international form over 50 nations outside China...
January 16, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29337243/intratumoral-morphological-heterogeneity-can-be-an-indicator-of-genetic-heterogeneity-in-colorectal-cancer
#14
Juliane Büttner, Korinna Jöhrens, Frederick Klauschen, Michael Hummel, Dido Lenze, Wolfgang Saeger, Annika Lehmann
Anti-EGFR-targeted therapy is used to treat metastatic colorectal cancers with RAS wild-type. However, resistance to targeted therapy is often observed and can be primary or acquired. One reason for primary resistance is the presence of mutations that are undetected due to genetic heterogeneity, which can be expressed by differences present in primary tumor and distant metastasis or recurrence or by an intratumoral heterogeneity (presence of different subclones in the investigated tumor sample). The aim of our study was to investigate if morphological heterogeneity can be an indicator of intratumoral heterogeneity...
January 11, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29336030/the-aryl-hydrocarbon-receptor-modulates-the-function-of-human-cd56bright-nk-cells
#15
Uriel Y Moreno-Nieves, David C Mundy, June Ho Shin, Kenric Tam, John B Sunwoo
Human natural killer (NK) cells are divided into two subsets: CD56bright and CD56dim NK cells, which differ in maturation, function and distribution. Mechanisms regulating NK cell functions are not completely understood. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds to a variety of endogenous and exogenous molecules, and that has recently been shown to modulate the function and differentiation of immune cells. Here, we studied the expression of AhR and its involvement in the regulation of NK cell functions...
January 16, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29334772/spontaneous-regression-of-a-large-skull-base-meningioma-case-report
#16
Ashwin Kumaria, Harshal A Ingale, Donald C Macarthur
We present the case of a 58 year old lady with a large middle cranial fossa meningioma (5 cm × 4 cm in maximal dimensions) which has considerably regressed without any treatment during seven years of follow up. While the tumour had remained radiologically static for the first three years, scans from year five post-diagnosis onwards have shown shrinkage of the meningioma from a calculated volume of 36 cm3 to 11.2 cm3. There has been no intratumoral haemorrhage or infarction and no medication or exogenous hormonal effect that could account for this effect...
January 15, 2018: British Journal of Neurosurgery
https://www.readbyqxmd.com/read/29334371/cooperative-targeting-of-melanoma-heterogeneity-with-an-axl-antibody-drug-conjugate-and-braf-mek-inhibitors
#17
Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334186/natural-humic-acid-based-phototheranostic-agent
#18
Zhao-Hua Miao, Kai Li, Pei-Ying Liu, Zhenglin Li, Huanjie Yang, Qingliang Zhao, Manli Chang, Qingzhu Yang, Liang Zhen, Cheng-Yan Xu
Humic acids, a major constituent of natural organic carbon resources, are naturally formed through the microbial biodegradation of animal and plant residues. Due to numerous physiologically active groups (phenol, carboxyl, and quinone), the biomedical applications of humic acid have been already investigated across different cultures for several centuries or even longer. In this work, sodium humate, the sodium salt of humic acid, is explored as phototheranostic agent for light-induced photoacoustic imaging and photothermal therapy based on intrinsic absorption in the near-infrared region...
January 15, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29331808/simultaneous-inhibition-of-hedgehog-signaling-and-tumor-proliferation-remodels-stroma-and-enhances-pancreatic-cancer-therapy
#19
Jun Zhao, Huamin Wang, Cheng-Hui Hsiao, Diana S-L Chow, Eugene J Koay, Yaan Kang, Xiaoxia Wen, Qian Huang, Ying Ma, James A Bankson, Stephen E Ullrich, Willem Overwijk, Anirban Maitra, David Piwnica-Worms, Jason B Fleming, Chun Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has an excessive desmoplastic stroma that can limit the intratumoral delivery of chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both stromal and tumor compartments need to be addressed in order to effectively treat PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation (M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts (CAFs), while PTX can inhibit tumor proliferation...
January 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29331106/kbtbd2-inhibits-the-cytotoxic-activity-of-immortalized-nk-cells-through-down-regulating-mtor-signaling-in-a-mouse-hepatocellular-carcinoma-model
#20
Kai Dai, Yabing Huang, Zubing Chen, Xiaomei Sun, Lihua Yang, Yingan Jiang
Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C...
January 13, 2018: European Journal of Immunology
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