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Han L.,Nantong Tuomor Hospital | Jiang B.,Nantong Tuomor Hospital | Wu H.,Nantong University | Wang X.,Nantong University | And 4 more authors.
Medical Oncology | Year: 2012

The laryngeal squamous cell carcinoma (LSCC) is one of the most common cancers threatening people's life. CXC-chemokine receptor type 2 (CXCR2) was reported to play critical roles in angiogenesis, tumorigenesis, and metastasis of several cancers such as colon cancer, melanoma, lung cancer, and so on. However, the expression of CXCR2 in LSCC and its association with clinical characters of LSCC remain unclear. Quantitative real-time reverse transcription-PCR and immunohistochemistry were used, respectively, to analyze the mRNA level and protein level of CXCR2 in 109 cases of LSCC tissues and 28 cases of tumor-adjacent normal tissues. The expression of CXCR2 in LSCC was significantly higher than that in tumor-adjacent tissues. Moreover, the expression level of CXCR2 protein in LSCC was significantly related to lymph node metastasis (P = .022), histopathological grade (P = .038), and 5 years' survival (P = .007). Cox regression analysis revealed that CXCR2 expression (P = .031), as well as lymphatic metastasis (P = .026) and TNM classification (P = .042), is an independent prognostic marker of LSCC. High expression of CXCR2 is also associated with short survival of LSCC patients. Our data indicate that the expression of CXCR2 is associated with the development and progression of LSCC. CXCR2 expression may serve as an independent prognostic marker for LSCC patients. © 2012 Springer Science+Business Media, LLC.

Ding G.,Nanjing Medical University | Chen X.,Nanjing Medical University | Zhu J.,Huadong Medical Institute of Biotechniques | Duesbery N.S.,Van Andel Research Institute | And 2 more authors.
Clinical and Developmental Immunology | Year: 2013

Human anthrax infection caused by exposure to Bacillus anthracis cannot always be treated by antibiotics. This is mostly because of the effect of the remaining anthrax toxin in the body. Lethal factor (LF) is a component of lethal toxin (LeTx), which is the major virulence of anthrax toxin. A murine IgG monoclonal antibody (mAb) against LF with blocking activity (coded LF8) was produced in a previous study. In this report, a human/murine chimeric Fab mAb (coded LF8-Fab) was developed from LF8 by inserting murine variable regions into human constant regions using antibody engineering to reduce the incompatibility of the murine antibody for human use. The LF8-Fab expressed in Escherichia coli could specifically identify LF with an affinity of 3.46×107 L/mol and could neutralize LeTx with an ECof 85 g/mL. Even after LeTx challenge at various time points, the LF8-Fab demonstrated protection of J774A.1 cells in vitro. The results suggest that the LF8-Fab might be further characterized and potentially be used for clinical applications against anthrax infection. © 2013 Guipeng Ding et al.

Chen R.,Nanjing Medical University | Zhang D.,Nanjing Medical University | Mao Y.,Jiangsu Provincial Official Hospital | Zhu J.,Nanjing Medical University | And 9 more authors.
Molecular Cancer Therapeutics | Year: 2012

Nasopharyngeal carcinoma (NPC) is a major cause of cancer-related death in Southeast Asia and China. Metastasis and relapse are the primary cause of morbidity and mortality in NPC. Recent evidence suggests that the Epstein-Barr virus latent membrane protein 1 (LMP1) is exclusively expressed in most NPC and is a potential target for biotherapy. In this study, we successfully prepared a novel human antibody Fab (HLEAFab) against LMP1 extracellular domain, which was subsequently conjugated with mitomycin C (MMC), thus forming an immunoconjugate (HLEAFab-MMC). The effects of HLEAFab-MMC on proliferation and apoptosis inNPCcell lines HNE2/LMP1 and the inhibition rate of growth ofNPCxenografts in nude mice were examined. The inhibition rate of HNE2/LMP1 cell proliferation was the highest for HLEAFab-MMC (76%) compared with MMC (31%) and HLEAFab (22%) at a concentration of 200 nmol/L and showed dose-dependent fashion. The apoptosis rate of HNE2/LMP1 cell lines was 13.88% in HLEAFab-MMC group, 3.04% in MMC group, 2.78% in HLEAFab group, and 2.10% in negative control group at the same concentration, respectively. In vivo, the inhibition rate of growth of NPC xenografts in nude mice was 55.1% in HLEAFab-MMC group, 26.5% in MMC group, and 5.64% in HLEAFab group. In summary, our findings show that HLEAFab-MMC is a unique immunoconjugate with the potential as a novel therapeutic agent in the treatment of LMP1-expressing NPC. ©2011 AACR.

Zhang H.,Nanjing Medical University | Qiu J.,Nanjing Medical University | Ye C.,Nanjing Medical University | Yang D.,Nanjing Medical University | And 10 more authors.
Scientific Reports | Year: 2014

The receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is a transmembrane protein belongs to receptor tyrosine kinase (RTK) family. This study aimed to examine the expression of ROR1 in human ovarian cancer and investigate the relationship between its expression and the prognosis of ovarian cancer patients. In this present study, one-step quantitative reverse transcription-polymerase chain reaction (15 ovarian cancer samples of high FIGO stage, 15 ovarian cancer samples of low FIGO stage and nine normal ovary tissue samples) and immunohistochemistry by tissue microarrays (100 ovarian cancer samples and 50 normal ovary samples) were performed to characterize expression of the ROR1 gene in ovarian cancer. Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of ovarian cancer. The results of qPCR and IHC analysis showed that the expression of ROR1 in ovarian cancer was significantly higher than that in normal ovary tissues (all p < 0.05). Survival analysis showed that ROR1 protein expression was one of the independent prognostic factors for disease-free survival and overall survival (both p < 0.05). The data suggest that ROR1 expression is correlated with malignant attributes of ovarian cancer and it may serve as a novel prognostic marker in ovarian cancer.

Wu H.,Nantong University | Xu H.,Nantong University | Zhang S.,Nantong University | Wang X.,Nantong University | And 4 more authors.
Head and Neck | Year: 2013

Background: The human trophoblastic cell surface antigen 2 (TROP2) gene is associated with the development of malignancies, but its expression in laryngeal squamous cell carcinoma (SCC) and its relationship with clinical characteristics of the disease remain undetermined. Methods: Expression of TROP2 protein was detected by immunohistochemistry with a self-made anti-TROP2 antibody in laryngeal SCC tissue microarrays. Results: Elevated expression of TROP2 was detected in laryngeal SCC tissues compared with adjacent noncancerous tissues. TROP2 expression in laryngeal SCC was related to tumor differentiation (p =.0001) and lymph node metastasis (p =.0352). Cox regression analyses confirmed that TROP2 expression (p =.015), lymph node metastasis (p =.001), degree of differentiation (p =.002), tumor site (p =.021), and T classification (p =.003) were independent prognostic factors. Conclusions: TROP2 can be used as an independent prognostic indicator for laryngeal SCC. © 2012 Wiley Periodicals, Inc.

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