Mouse Anti-Human CR1 Hybridoma [mAb 654]

Purpose of Investigation: When carbonyl reductase 1 (CR1) is highly expressed in human ovarian cancer cells in vivo, tumor growth is reported to be inhibited. Conversely, when expression of CR1 decreases, tumor growth, invasion, and metastasis are reported to increase. Thus, the aim of the current study was to examine dynamic changes in ovarian cancer cells under different CR1 expression levels in artificial human peritoneal tissue (AHPT). Materials and Methods: Serous ovarian cancer cells with different levels of CR1 expression were produced by transfection of BRA human ovarian carcinoma cells with CR1 DNA or CR1 siRNA. The transfected cells were seeded in AHPT and observed over time until peritoneal development of carcinomatosis. Apoptotic cells in the AHPT were compared using TUNEL staining and fluorescence-based flow cytometry. Results: Cells transfected with CR1 DNA or CR1 siRNA did not differ from control cells in terms of their adherence to the mesothelium. After 24 hours, when cells had invaded the tissue below the mesothelium, proliferation of CR1-overexpressing cells was inhibited while proliferation of CR1-suppressing cells increased. At 72 hours, CR1-suppressing cells had invaded the stroma. CR1-overexpressing cells had a markedly higher rate of apoptosis than control or CR1-suppressing cells. Moreover, electron microscopy revealed apoptotic bodies in cells overexpressing CR1. Differences in tumor growth depending on the extent of CR1 expression have been noted in vivo, and similar results were obtained in the present in vitro model of AHPT. High and low levels of CR1 expression did not affect cell adherence to the mesothelium, but low levels did result in cells invading and proliferating below the mesothelium. Conclusion: The present results have also demonstrated that tumor inhibition by CR1 involves an increase in apoptosis.

We explored the prognostic factors for children with very high-risk (VHR) Philadelphia chromosome (Ph) negative B-cell acute lymphoblastic leukaemia (B-ALL) and compared the therapeutic effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo-HSCT) as post-remission treatment in these patients undergoing first complete remission (CR1). A total of 104 paediatric patients with VHR B-ALL in CR1 were retrospectively enrolled in this study, including 42 receiving unmanipulated haplo-HSCT (Group A) and 62 receiving ongoing chemotherapy (Group B). Estimated 3-year overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) at 36 center dot 2 months median follow-up were 69 center dot 5 +/- 4 center dot 7%, 63 center dot 5 +/- 4 center dot 8% and 32 center dot 4 +/- 4 center dot 7%, respectively. Maintenance of persistent positive or conversion from negative to positive of measurable residual disease (MRD) and chemotherapy were independent risk factors associated with inferior long-term survival and higher CIR. OS, DFS, and CIR differed significantly between the groups in patients with persistent positive or negative-to-positive MRD. Haplo-HSCT may be an option for children with VHR Ph-negative B-ALL in CR1, especially for patients with persistent positive or negative-to-positive MRD, and could achieve better survival than intensive chemotherapy as post-remission treatment.