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Liver cancer immunotherapy

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https://www.readbyqxmd.com/read/28098909/biology-and-function-of-glypican-3-as-a-candidate-for-early-cancerous-transformation-of-hepatocytes-in-hepatocellular-carcinoma-review
#1
Mauro Montalbano, Jeremias Georgiadis, Ashlyn L Masterson, Joshua T McGuire, Janika Prajapati, Ali Shirafkan, Cristiana Rastellini, Luca Cicalese
Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome...
January 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28075526/cetuximab-strongly-enhances-immune-cell-infiltration-into-liver-metastatic-sites-in-colorectal-cancer
#2
Yuka Inoue, Shoichi Hazama, Nobuaki Suzuki, Yukio Tokumitsu, Shinsuke Kanekiyo, Shinobu Tomochika, Ryouichi Tsunedomi, Yoshihiro Tokuhisa, Michihisa Iida, Kazuhiko Sakamoto, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Hiroaki Nagano
Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28074124/involvement-of-blood-mononuclear-cells-in-the-infertility-age-associated-diseases-and-cancer-treatment
#3
REVIEW
Antonin Bukovsky
Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system (TCS), where they exhibit morphostatic function by stimulating proliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system (IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo...
December 26, 2016: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28035433/development-of-t-cells-carrying-two-complementary-chimeric-antigen-receptors-against-glypican-3-and-asialoglycoprotein-receptor-1-for-the-treatment-of-hepatocellular-carcinoma
#4
Cheng Chen, Kesang Li, Hua Jiang, Fei Song, Huiping Gao, Xiaorong Pan, Bizhi Shi, Yanyu Bi, Huamao Wang, Hongyang Wang, Zonghai Li
Adoptive immunotherapy leveraging chimeric antigen receptor-modified T (CAR-T) cells holds great promise for the treatment of cancer. However, tumor-associated antigens often have low expression levels in normal tissues, which can cause on-target, off-tumor toxicity. Recently, we reported that GPC3-targeted CAR-T cells could eradicate hepatocellular carcinoma (HCC) xenografts in mice. However, it remains unknown whether on-target, off-tumor toxicity can occur. Therefore, we proposed that dual-targeted CAR-T cells co-expressing glypican-3 (GPC3) and asialoglycoprotein receptor 1 (ASGR1) (a liver tissue-specific protein)-targeted CARs featuring CD3ζ and 28BB (containing both CD28 and 4-1BB signaling domains), respectively, may have reduced on-target, off-tumor toxicity...
December 29, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28008250/a-polyethylenimine-modified-carboxyl-poly-styrene-acrylamide-copolymer-nanosphere-for-co-delivering-of-cpg-and-tgf-%C3%AE-receptor-i-inhibitor-with-remarkable-additive-tumor-regression-effect-against-liver-cancer-in-mice
#5
Shuyan Liang, Jun Hu, Yuanyuan Xie, Qing Zhou, Yanhong Zhu, Xiangliang Yang
Cancer immunotherapy based on nanodelivery systems has shown potential for treatment of various malignancies, owing to the benefits of tumor targeting of nanoparticles. However, induction of a potent T-cell immune response against tumors still remains a challenge. In this study, polyethylenimine-modified carboxyl-styrene/acrylamide (PS) copolymer nano-spheres were developed as a delivery system of unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides and transforming growth factor-beta (TGF-β) receptor I inhibitors for cancer immunotherapy...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27987156/immunotherapy-of-uveal-melanoma-vaccination-against-cancer
#6
Mirko Kummer, Beatrice Schuler-Thurner
Uveal melanoma is the most frequently occurring primary intraocular tumor in adults, with an incidence of about 5 out of 100,000 per year, the incidence rising with increasing age (Lipski, Klin Monbl Augenheilkd 230:1005-1019, 2013; Metz et al., Klin Monbl Augenheilkd 230:686-691, 2013; Singh and Topham, Ophthalmology 110:956-961, 2003). Often diagnosed late due to a lack of early symptoms, this kind of melanoma is associated with a poor prognosis. Approximately 50 % of the patients develop distant metastases (Lipski, Klin Monbl Augenheilkd 230:1005-1019, 2013; Metz et al...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27980102/blocking-the-ccl2-ccr2-axis-using-ccl2-neutralizing-antibody-is-an-effective-therapy-for-hepatocellular-cancer-in-a-mouse-model
#7
Kun-Yu Teng, Jianfeng Han, Xiaoli Zhang, Shu-Hao Hsu, Shun He, Nissar Wani, Juan Barajas, Linda A Snyder, Wendy L Frankel, Michael A Caligiuri, Samson T Jacob, Jianhua Yu, Kalpana Ghoshal
Hepatocellular carcinoma (HCC), a deadly disease, commonly arises in the setting of chronic inflammation. C-C motif chemokine ligand2 (CCL2/MCP1), a chemokine that recruits CCR2-positive immune cells to promote inflammation, is highly upregulated in HCC patients. Here, we examined the therapeutic efficacy of CCL2-CCR2 axis inhibitors against hepatitis and HCC in the miR-122 knockout (aka KO) mouse model. This mouse model displays upregulation of hepatic CCL2 expression, which correlates with hepatitis that progress to HCC with age...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27965307/dual-specific-chimeric-antigen-receptor-t-cells-and-an-indirect-vaccine-eradicate-a-variety-of-large-solid-tumors-in-an-immunocompetent-self-antigen-setting
#8
Clare Y Slaney, Bianca von Scheidt, Alexander J Davenport, Paul Beavis, Jennifer A Westwood, Sherly Mardiana, David Tscharke, Sarah Ellis, H Miles Prince, Joseph A Trapani, Ricky W Johnstone, Mark J Smyth, Michele W L Teng, Aesha Ali, Zhiya Yu, Steven A Rosenberg, Nicholas P Restifo, Paul J Neeson, Phillip K Darcy, Michael H Kershaw
PURPOSE: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. EXPERIMENTAL DESIGN: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100)...
December 13, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27959341/a-novel-pd-l1-targeting-antagonistic-dna-aptamer-with-antitumor-effects
#9
Wei-Yun Lai, Bo-Tsang Huang, Jen-Wei Wang, Pei-Ying Lin, Pan-Chyr Yang
The PD-1/PD-L1 axis is a major pathway involved in tumor immune evasion. Here, we report the novel PD-L1 antagonizing DNA aptamer (aptPD-L1) and demonstrate an integrated pipeline that expedites therapeutic aptamer development. Aptamer can exert antibody-mimic functions and is advantageous over antibody for its chemically synthetic nature, low immunogenicity, and efficient tissue penetration. Our results showed that aptPD-L1 blocked the binding between human PD-1 and PD-L1. Experiments using murine models showed that aptPD-L1 promoted in vitro lymphocyte proliferation and suppressed in vivo tumor growth without the induction of observable liver or renal toxicity...
December 13, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27910858/immunosuppression-in-liver-tumors-opening-the-portal-to-effective-immunotherapy
#10
REVIEW
P Guha, J Reha, S C Katz
We have recently witnessed substantial progress with immunotherapy for selected diseases. Checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cells are among the most promising agents. Whereas much of the early success with CAR-T cells has been demonstrated with hematological malignancies, important barriers remain for the application of CAR-T cell therapies for the management of metastatic solid tumors. The challenges are particularly apparent when considering primary and metastatic tumors in the liver...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27870680/liver-metastases-from-noncolorectal-malignancies-neuroendocrine-tumor-sarcoma-melanoma-breast
#11
Erica S Alexander, Michael C Soulen
Patients with noncolorectal hepatic metastases often face limited treatment options and a dismal prognosis. Over the last decade, the advent of targeted immunotherapies has transformed the treatment of certain metastatic cancers, such as sarcoma and melanoma; however, these patients eventually develop resistance. Metastatic sarcoma, melanoma, and breast and neuroendocrine tumors are notoriously treatment resistant once they have metastasized to the liver. For these cancers, minimally invasive transarterial and ablation therapies have emerged as safe, palliative therapies that can provide symptom control and even prolong survival...
November 2016: Cancer Journal
https://www.readbyqxmd.com/read/27835865/il-15-enhances-the-anti-tumor-activity-of-trastuzumab-against-breast-cancer-cells-but-causes-fatal-side-effects-in-humanized-tumor-mice-htm
#12
Anja K Wege, Florian Weber, Alexander Kroemer, Olaf Ortmann, Falk Nimmerjahn, Gero Brockhoff
Cancer immunotherapy has been shown to enhance established treatment regimens. We evaluated the potential reinforcing effect of IL-15 in trastuzumab treated humanized tumor mice (HTM) which were generated by concurrent transplantation of neonatal NOD-scid IL2Rγnull mice with human hematopoietic stem cells (HSC) and HER2 positive breast cancer cells (metastasizing SK-BR-3, solid tumor forming BT474). We found that trastuzumab treatment efficacy mainly depends on the immediate anti-tumorigenic cellular effect which is significantly enhanced by tumor interacting immune cells upon cotransplantion of HSC...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27814619/novel-strategies-to-target-cancer-stem-cells-by-nk-cells-studies-in-humanized-mice
#13
Anna K Kozlowska, Kawaljit Kaur, Paytsar Topchyan, Anahid Jewett
We have previously shown that following selection, Natural Killer (NK) cells, differentiate Cancer stem cells (CSCs)/undifferentiated or poorly differentiated tumors via secreted and membrane bound IFN-gamma and TNF-alpha, leading to prevention of tumor growth and remodeling of the tumor microenvironment. Since conventional therapeutic strategies including chemotherapy and radiotherapy remain unsuccessful in treating stem-like tumors, there has been an increasing interest in NK cell based immunotherapy for the treatment of resistant tumors...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27807108/development-of-a-prognostic-survival-algorithm-for-patients-with-metastatic-spine-disease
#14
Nuno Rui Paulino Pereira, Stein J Janssen, Eva van Dijk, Mitchel B Harris, Francis J Hornicek, Marco L Ferrone, Joseph H Schwab
BACKGROUND: Current prognostication models for survival estimation in patients with metastatic spine disease lack accuracy. Identifying new risk factors could improve existing models. We assessed factors associated with survival in patients surgically treated for spine metastases, created a classic scoring algorithm, nomogram, and boosting algorithm, and tested the predictive accuracy of the three created algorithms at estimating survival. METHODS: We included 649 patients from two tertiary care referral centers in this retrospective study (2002 to 2014)...
November 2, 2016: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/27802782/treatment-of-human-b-cell-lymphomas-using-minicircle-dna-vector-expressing-anti-cd3-cd20-in-a-mouse-model
#15
Xiaojuan Pang, Fei Ma, Peifa Zhang, Yujian Zhong, Jing Zhang, Tianyan Wang, Gang Zheng, Xiaohu Hou, Jing Zhao, Chengyi He, Zhi-Ying Chen
Bispecific antibodies (BsAbs), capable of directing T cells to kill specific cancer cells by transiently binding the two cell types, have emerged as one class of promising cancer immunotherapies. However, their wide clinical application might be hampered by two deficiencies: high cost and inconvenience in drug administration. This study presents concept-proving data that these problems could be bypassed by using an enhanced nonviral DNA vector minicircle (MC) to produce BsAb in vivo. It was found that the anti-CD3/CD20 produced from the minicircle (MC...
November 1, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27746013/cytokine-induced-killer-cell-infusion-combined-with-conventional-treatments-produced-better-prognosis-for-hepatocellular-carcinoma-patients-with-barcelona-clinic-liver-cancer-b-or-earlier-stage-a-systematic-review-and-meta-analysis
#16
Yun-Chen Li, Lin Zhao, Jiang-Ping Wu, Chen-Xu Qu, Qing-Kun Song, Rui-Bin Wang
BACKGROUND AIMS: To investigate the clinical benefits of cytokine-induced killer (CIK) cell infusions on hepatocellular carcinoma (HCC) patients, combined with other conventional treatments. METHODS: This was a systematic review and meta-analysis conducted among phase II and III randomized control trials worldwide. Review manager 5.2 version was used to pool the effect size across studies. Sensitivity analyses and risk of bias were estimated among included studies...
October 13, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27742386/the-bad-and-the-good-news-on-cancer-immunotherapy-implications-for-organ-transplant-recipients
#17
REVIEW
Umberto Maggiore, Julio Pascual
Cancer immunotherapy, especially the use of checkpoint inhibitors, is expanding and can be efficacious in organ transplant recipients with malignant neoplasia. In this review, we summarize clinical findings and evolution of several patients treated with CTL4-4 or PD-1 inhibitors reported in the literature. The CTL-4 inhibitor ipilimumab has been safely used in several liver and kidney allograft recipients. PD1-inhibitors look promising for tumor shrinking, but acute rejection is the rule, so they should be avoided in recipients of life-saving organs...
September 2016: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/27713136/the-role-of-extracellular-vesicles-in-mediating-progression-metastasis-and-potential-treatment-of-hepatocellular-carcinoma
#18
Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu, Mingqin Lu
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27699275/synergy-of-radiotherapy-and-pd-1-blockade-in-kras-mutant-lung-cancer
#19
Grit S Herter-Sprie, Shohei Koyama, Houari Korideck, Josephine Hai, Jiehui Deng, Yvonne Y Li, Kevin A Buczkowski, Aaron K Grant, Soumya Ullas, Kevin Rhee, Jillian D Cavanaugh, Neermala Poudel Neupane, Camilla L Christensen, Jan M Herter, G Mike Makrigiorgos, F Stephen Hodi, Gordon J Freeman, Glenn Dranoff, Peter S Hammerman, Alec C Kimmelman, Kwok-Kin Wong
Radiation therapy (RT), a critical modality in the treatment of lung cancer, induces direct tumor cell death and augments tumor-specific immunity. However, despite initial tumor control, most patients suffer from locoregional relapse and/or metastatic disease following RT. The use of immunotherapy in non-small-cell lung cancer (NSCLC) could potentially change this outcome by enhancing the effects of RT. Here, we report significant (up to 70% volume reduction of the target lesion) and durable (up to 12 weeks) tumor regressions in conditional Kras-driven genetically engineered mouse models (GEMMs) of NSCLC treated with radiotherapy and a programmed cell death 1 antibody (αPD-1)...
June 16, 2016: JCI Insight
https://www.readbyqxmd.com/read/27668795/iron-oxide-nanoparticles-inhibit-tumour-growth-by-inducing-pro-inflammatory-macrophage-polarization-in-tumour-tissues
#20
Saeid Zanganeh, Gregor Hutter, Ryan Spitler, Olga Lenkov, Morteza Mahmoudi, Aubie Shaw, Jukka Sakari Pajarinen, Hossein Nejadnik, Stuart Goodman, Michael Moseley, Lisa Marie Coussens, Heike Elisabeth Daldrup-Link
Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses...
November 2016: Nature Nanotechnology
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