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Michail Ignatiadis, Gert Van den Eynden, Salgado Roberto, Marco Fornili, Yacine Bareche, Christine Desmedt, Françoise Rothé, Marion Maetens, David Venet, Esther Holgado, Virginia McNally, Astrid Kiermaier, Heidi M Savage, Timothy R Wilson, Javier Cortes, Andreas Schneeweiss, Karen Willard-Gallo, Elia Biganzoli, Christos Sotiriou
Background: There is an urgent requirement to identify biomarkers to tailor treatment in human epidermal growth factor receptor 2 (HER2)-amplified early breast cancer treated with trastuzumab/pertuzumab-based chemotherapy. Methods: Among the 225 patients randomly assigned to trastuzumab/pertuzumab concurrently or sequentially with an anthracycline-containing regimen or concurrently with an anthracycline-free regimen in the Tryphaena trial, we determined the percentage of tumor-infiltrating lymphocytes (TILs) at baseline in 213 patients, of which 126 demonstrated a pathological complete response (pCR; ypT0/is ypN0), with 28 demonstrating event-free survival (EFS) events...
May 18, 2018: Journal of the National Cancer Institute
Hao Li, Lei-Lei Yang, Yao Xiao, Wei-Wei Deng, Lei Chen, Lei Wu, Wen-Feng Zhang, Zhi-Jun Sun
Objectives: The aims of this study were to investigate the relationship between Golgi phosphoprotein 2 (GOLPH2) and oral squamous cell carcinoma (OSCC) and explore the clinical significance of GOLPH2 in OSCC. Methods: Tissue microarrays from human OSCC samples were stained for GOLPH2 expression and clinicopathologic features. Kaplan-Meier analysis was used to compare the survival of patients with high GOLPH2 expression and patients with low GOLPH2 expression. Results: We found GOLPH2 is highly expressed in OSCC tissue, and the GOLPH2 expression in metastatic lymph nodes is higher than in tumor tissue...
May 16, 2018: American Journal of Clinical Pathology
Melina E Marmarelis, Charu Aggarwal
PURPOSE OF REVIEW: Checkpoint blockade has changed the treatment landscape in non-small cell lung cancer (NSCLC), but single-agent approaches are effective for only a select subset of patients. Here, we will review the evidence for combination immunotherapies in NSCLC and the clinical data evaluating the efficacy of this approach. RECENT FINDINGS: Clinical trials evaluating combination PD-1 and CTLA-4 blockade as well as PD-1 in combination with agents targeting IDO1, B7-H3, VEGF, and EGFR show promising results...
May 8, 2018: Current Oncology Reports
Zhili Xu, Ling Wang, Jianhua Tian, Hongwei Man, Pengfei Li, Baoen Shan
The objective of the present study was to investigate the association of B7-H3 expression and cluster of differentiation (CD)163+ tumor-associated macrophage (TAM) infiltration with clinicopathological parameters in urothelial cell carcinoma of the bladder (UCB), and to investigate their potential conjoint effects on progression of UCB. B7-H3 expression and CD163+ TAM infiltration in tumor specimens from 134 consecutive patients that underwent radical cystectomy for UCB were tested using immunohistochemistry, followed by statistical analysis...
May 2018: Oncology Letters
Katheryne E Wilson, Sunitha V Bachawal, Juergen K Willmann
PURPOSE: Breast cancer often requires surgical treatment including breast-conserving surgical resection. However, with current post-surgical histological margin analysis, one-quarter of breast cancer patients undergo re-excision to achieve negative margins corresponding to decreased local recurrence and better outcomes. Therefore, a method with high resolution and specificity for intraoperative margin assessment is needed. EXPERIMENTAL DESIGN: First, quantitative immunofluorescence staining of B7-H3 expression was assessed in four pathological stages of breast cancer progression of the MMTV-PyMT transgenic murine model...
April 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Shuxia Wang, Jianguo Mou, Lansong Cui, Xingong Wang, Zhiqing Zhang
Astragaloside IV showed a pivotal anti-cancer efficacy in multiple types of cancers and reversed chemoresistance in colorectal cancer (CRC). However, it remained unknown whether and how Astragaloside IV suppressed the progression of CRC. In the present study, we found that Astragaloside IV treatment significantly and dose-dependently reduced cell proliferation of CRC cell lines (SW620 and HCT116), whereas it showed no significant influence on the cell proliferation of normal colonic cells (FHC). Flow cytometry (FCM) analysis indicated that there was a significant cell cycle arrest in G0/G1 phase of SW620 cells and HCT116 cells which were treated with Astragaloside IV...
April 3, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Benjamin B Kasten, Abhishek Gangrade, Harrison Kim, Jinda Fan, Soldano Ferrone, Cristina R Ferrone, Kurt R Zinn, Donald J Buchsbaum
No abstract text is available yet for this article.
April 25, 2018: Nuclear Medicine and Biology
Rui Cheng, Yongqin Chen, Haohui Zhou, Bi Wang, Qiang Du, Yanling Chen
This study was designed to explore the expression of B7-H3 in human intrahepatic cholangiocarcinoma (ICC) and its association with the clinicopathologic factors. In the current study, the expression of B7-H3 in 45 patients with intrahepatic cholangiocarcinoma and 8 patients with hepatolithiasis was analyzed by immunohistochemistry, which revealed that B7-H3 was not expressed in hepatolithiatic tissues, but positively expressed in 57.8% (26/45) of the ICC cases. The expression of B7-H3 was significantly associated with lymph node metastases and venous invasion...
May 2018: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
Kimio Yonesaka, Koji Haratani, Shiki Takamura, Hitomi Sakai, Ryoji Kato, Naoki Takegawa, Takayuki Takahama, Kaoru Tanaka, Hidetoshi Hayashi, Masayuki Takeda, Sigeki Kato, Osamu Maenishi, Kazuko Sakai, Yasutaka Chiba, Takafumi Okabe, Keita Kudo, Yoshikazu Hasegawa, Hiroyasu Kaneda, Michiko Yamato, Kenji Hirotani, Masaaki Miyazawa, Kazuto Nishio, Kazuhiko Nakagawa
Purpose: Anti-programmed-death-1 (PD-1) immunotherapy improves survival in non-small cell lung cancer (NSCLC), but some cases are refractory to treatment, thereby requiring alternative strategies. B7-H3, an immune-checkpoint molecule, is expressed in various malignancies. To our knowledge, this study is the first to evaluate B7-H3 expression in NSCLCs treated with anti-PD-1 therapy and the therapeutic potential of a combination of anti-PD-1 therapy and B7-H3 targeting. Experimental Design: B7-H3 expression was evaluated immunohistochemically in patients with NSCLC ( n = 82), and its relationship with responsiveness to anti-PD-1 therapy and CD8+ tumor-infiltrating lymphocytes (TILs) was analyzed...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Edwin Roger Parra, Pamela Villalobos, Jiexin Zhang, Carmen Behrens, Barbara Mino, Stephen Swisher, Boris Sepesi, Annika Weissferdt, Neda Kalhor, John Victor Heymach, Cesar Moran, Jianjun Zhang, Jack Lee, Jaime Rodriguez-Canales, Don Gibbons, Ignacio I Wistuba
INTRODUCTION: The understanding of immune checkpoint molecules' co-expression in non-small cell lung carcinoma (NCLC) is important to potentially design combinatorial immunotherapy approaches. METHODS: We studied 225 formalin-fixed, paraffin-embedded tumor tissues from stage I-III NCLCs - 142 adenocarcinomas (ADCs) and 83 squamous cell carcinomas (SCCs) - placed in tissue microarrays. Nine immune checkpoint markers were evaluated; four (programmed death ligand 1 [PD-L1], B7-H3, B7-H4, and indoleamine 2,3-dioxygenase 1 [IDO-1]) expressed predominantly in malignant cells (MCs) and five (inducible T cell costimulator, V-set immunoregulatory receptor, T-cell immunoglobulin mucin family member 3, lymphocyte activating 3, and OX40) expressed mostly in stromal tumor-associated inflammatory cells (TAICs)...
June 2018: Journal of Thoracic Oncology
L-L Yang, L Wu, G-T Yu, W-F Zhang, B Liu, Z-J Sun
Targeted therapy using monoclonal antibodies (mAbs) has emerged as a widely used form of immunotherapy in head and neck squamous cell carcinoma (HNSCC). Membrane-associated glycoprotein CD317 has been preferentially overexpressed by multiple myeloma cells, and its humanized mAb has been previously used in clinical trials. However, overexpression of CD317 in HNSCC and its correlation with tumor immunity is still uncertain. Here, the immunoreactivity of CD317 was detected in human HNSCC tissue microarrays, which contained 43 oral mucosa samples, 48 dysplasia samples, and 165 primary HNSCC...
February 1, 2018: Journal of Dental Research
Vinod Varki, Olga B Ioffe, Soren M Bentzen, Jon Heath, Ashley Cellini, Josephine Feliciano, Dan P Zandberg
BACKGROUND: To characterize the expression of co-signaling molecules PD-L1, PD-1, and B7-H3 in cutaneous squamous cell carcinoma (cSCC) by immune status. METHODS: We retrospectively analyzed 66 cases of cSCC treated with surgical resection from 2012 to 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (Tum-PD-L1%), B7-H3 (Tum-B7-H3%), density of peri and intratumoral CD8 T cells (CD8 density), proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) and of tumor-infiltrating immune cells (TII) expressing PD-L1 (TII-PD-L1%)...
May 2018: Cancer Immunology, Immunotherapy: CII
Xuedong Wei, Kai Li, Guangbo Zhang, Yuhua Huang, Jinxing Lv, Miao Li, Lun Zhao, Caibin Fan, Jinxian Pu, Jianquan Hou, Hexing Yuan
Objective: We found seminal B7-H3 was associated with human sperm concentration. However, the mechanism is unclear. The purpose of this study was to investigate the expression of B7-H3 in mouse testis and determine the effects of B7-H3 on the proliferation of mouse spermatogonial stem cells (SSCs) and the underlying mechanisms. Methods: B7-H3 expression in the testis of mice at different ages (3 weeks, 8 weeks, 4 months and 9 months) was detected by western blot and immunohistochemistry...
January 5, 2018: Oncotarget
Benjamin B Kasten, Abhishek Gangrade, Harrison Kim, Jinda Fan, Soldano Ferrone, Cristina R Ferrone, Kurt R Zinn, Donald J Buchsbaum
INTRODUCTION: We recently validated monoclonal antibody (mAb) 376.96 as an effective carrier for targeted α-particle radioimmunotherapy (RIT) with 212 Pb in ovarian cancer mouse models. In this study, we tested the binding of radiolabeled mAb 376.96 to human pancreatic ductal adenocarcinoma (PDAC) cells and localization in xenografts in immune-deficient mice and evaluated 212 Pb-labeled 376.96 (212 Pb-376.96) for PDAC therapy. METHODS: In vitro Scatchard assays assessed the specific binding of 212 Pb-376...
March 2018: Nuclear Medicine and Biology
Fenghuang Xu, Junzhu Yi, Feifei Wang, Weiwei Wang, Zhuoya Wang, Jiangnan Xue, Xiying Luan
Previous studies have demonstrated that B7-H3, and the inflammatory cytokines interleukin (IL)-17, IL-8 and IL-6, are involved in the development of a variety of tumors. The objectives of the present study were: i) To investigate the association between soluble B7-H3 (sB7-H3) and cytokine levels of IL-17, IL-8 and IL-6 in the serum of patients with hepatocellular carcinoma (HCC); and ii) to determine their potential value for use in HCC diagnosis. Serum sB7-H3, IL-17, IL-8 and IL-6 levels in the HCC patients and healthy control subjects were measured using ELISA...
December 2017: Oncology Letters
Fang Cong, Haitao Yu, Xiuhua Gao
This study aimed to investigate the correlation between the expression of CD24 and B7-H3 in breast cancer tissues and the clinical significance. Expression of CD24 and B7-H3 in breast cancer and adjacent tissues were detected by immunohistochemistry. Quantitative PCR was used to detect the expression of CD24 and B7-H3 mRNA in breast cancer and adjacent tissues. The expression of CD24 and B7-H3 protein in breast cancer and adjacent tissues was detected by immunoblotting. The correlation between the expression levels of the two proteins was analyzed and the relationship between the expression of two proteins and the 5-year survival of breast cancer patients was investigated...
December 2017: Oncology Letters
Gen Li, Yanchun Quan, Fengyuan Che, Lijuan Wang
B7-H3 is a type I transmembrane co-stimulatory molecule of the B7 family. B7-H3 mRNA is widely distributed in most tissues; however, B7-H3 protein is not constitutively expressed. Few molecules have been shown to mediate the regulation of B7-H3 expression, and their regulatory mechanisms remain unexplored. Recently, TREM-like transcript 2 (TLT-2) has been identified as a potential receptor of B7-H3. However, TLT-2 may not be the only receptor of B7-H3, as B7-H3 has many contradictory roles. As a co-stimulatory molecule, B7-H3 increases the proliferation of both CD4+ and CD8+ T-cells and enhances cytotoxic T-cell activity...
February 2018: Cancer Chemotherapy and Pharmacology
Xinmeng Qi, Bo Jia, Xue Zhao, Dan Yu
Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells "immune checkpoint" has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc)...
2017: OncoTargets and Therapy
Xianyun Zhang, Chuntao Fang, Guangbo Zhang, Fujin Jiang, Lei Wang, Jianquan Hou
Increasing evidence suggests B7-H3 is aberrantly expressed in various cancers, though its prognostic significance in solid tumors remains controversial. We therefore performed a meta-analysis to clarify the prognostic value of B7-H3 expression in human solid tumors. The PubMed and Embase databases were searched, and 28 studies involving 4623 patients were ultimately included in the analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized as effect estimates to evaluate the association between B7-H3 expression and overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS)...
November 3, 2017: Oncotarget
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