Development of orthotopic tumor xenograft models of esophageal squamous cell carcinoma for preclinical drug testing

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Tumor xenograft animal models for esophageal squamous cell carcinoma

Abstract Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer worldwide and highly prevalent in less developed regions. Management of ESCC is challenging and involves multimodal treatments. Patient prognosis is generally poor especially for those diagnosed in advanced disease stage. One factor contributing to this clinical dismal is the incomplete understanding of disease mechanism, for which this situation is further compounded by the presence of other limiting factors for disease diagnosis, patient prognosis and treatments. Tumor xenograft animal models including subcutaneous tumor xenograft model, orthotopic tumor xenograft model and patient-derived tumor xenograft model are vital tools for ESCC research. Establishment of tumor xenograft models involves the implantation of human ESCC cells/xenografts/tissues into immunodeficient animals, in which mice are most commonly used. Different tumor xenograft models have their own advantages and limitations, and these features serve as key factors to determine the use of these models at different stages of research. Apart from their routine use on basic research to understand disease mechanism of ESCC, tumor xenograft models are actively employed for undertaking preclinical drug screening project and biomedical imaging research

Correction of Combined Flexed and Stiff Knee Gait in Spastic Diplegic Cerebral Palsy by Double Tendon Transfers Around the Knee as Part of Multilevel Surgery

Background/Purpose: Flexed knee gait and stiff knee gait are common coexisting gait disturbances in children with cerebral palsy. We analyzed the effect of medial hamstring transfer and distal rectus transfer around the knee as part of multi-level surgery for this group of patient. Methods: Eleven lower limbs of six patients who received double transfer were retrospectively studied. Instrumented gait analysis were carried out before and a minimum of 2 years after operation. Results: Comparing the kinematic study before and after the operation, maximum knee extension in stance phase (MKES), total knee swing (TKS) and the time to maximum knee flexion in swing phase (TMKFS) showed statistically significant improvement (p <0.05). Hip extension in swing phase and hip extension power were maintained. The oxygen consumption during walking also decreased after operation (p <0.05). Conclusion: Double transfer around the knee can improve both flexed knee gait and stiff knee gait, without causing significant hip extension weakness

Overexpression of transferrin receptor CD71 and its tumorigenic properties in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in endemic Asian regions. In the present study, we investigated the clinical implication and role of transferrin receptor CD71 in ESCC. CD71 has a physiological role in cellular iron intake and is implicated in the carcinogenesis of various types of tumors. In our cohort, more than a 2-fold upregulation of the CD71 transcript was detected in 61.5% of patients using quantitative polymerase chain reaction. Immunohistochemical analysis also showed strong membranous and cytoplasmic localization of CD71 in paraffin-embedded tumors. Staining parallel tumor sections with the proliferative marker Ki-67 revealed that the pattern of Ki-67 staining was associated with CD71 expression. Analysis of clinicopathological data indicated that CD71 overexpression can be used as an indicator for advanced T4 stage (P=0.0307). These data suggested a strong link between CD71 and ESCC. Subsequent in vitro assays using short interfering RNA (siRNA) to suppress CD71 expression confirmed the tumorigenic properties of CD71 in ESCC; cell growth inhibition and cell cycle arrest at S phase were observed in CD71-suppressed cells. The underlying mechanism involved activation of the MEK/ERK pathway. In summary, the present study provides evidence showing the tumorigenic properties of CD71 in ESCC with clinical correlations and suggests targeting CD71 as a strategy for the treatment of ESCC.Link_to_subscribed_fulltex