We and other groups have previously shown that interleukin-5 (IL-5) maintained the viability of mature eosinophils in an in vitro liquid culture system. Mature eosinophils did not proliferate but their survival was maintained in the presence of IL-5. Using this culture system, we investigated the mechanism of IL-5-mediated survival. In the absence of human IL-5 (hIL-5) mature eosinophils succumbed after 4 days, while in the presence of hIL-5 they survived up to 10 days. When DNA extracts of cultured eosinophils were analyzed on an agar gel electrophoresis, marked DNA fragmentation was observed in the absence of hIL-5, while no significant DNA fragmentation was observed in the culture with hIL-5 for 48 hours. The DNA fragmentation appeared as early as 6 to 12 hours after hIL-5 deprivation. Concomitantly, IL-5 stimulated total RNA and protein synthesis, but did not induce DNA synthesis in mature eosinophils. Because cycloheximide or actinomycin D impeded the protection of apoptosis by hIL-5, some new RNA and protein synthesis appeared to be required in this phenomena. These findings indicate that IL-5 maintains survival of mature eosinophils with induction of new RNA and protein synthesis, thus leading to the inhibition of apoptosis.
GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) and is highly expressed in parts of tumor cells. The involvement of GPR56 in tumorigenesis has been reported. We generated agonistic monoclonal antibodies against human GPR56 and analyzed the action and signaling pathway of GPR56. The antibodies inhibited cell migration through the Gq and Rho pathway in human glioma U87-MG cells. Coimmunoprecipitation analysis indicated that the interaction between the GPR56 extracellular domain and transmembrane domain was potentiated by agonistic antibodies. These results demonstrated that functional antibodies are invaluable tools for GPCR research and should open a new avenue for therapeutic treatment of tumors.
Laparoscopic surgery for patients with a horseshoe kidney is challenging because of the location, aberrant vasculature, and difficulty with division of the isthmus with adequate hemostasis. We herein report performance of a laparoscopic heminephrectomy for left ureteral cancer in a patient with a horseshoe kidney under guidance from near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG). A 62-year-old male was referred to our hospital for treatment of left ureteral cancer associated with a horseshoe kidney. We performed a laparoscopic left nephroureterectomy and bladder resection in June 2017. During the operation, the NIRF imaging system was used to evaluate the border of the kidney parenchyma isthmus after ligation of the left kidney vasculature supply. Interestingly, the dominant region of the right kidney showed strong ICG fluorescence as compared to the left kidney region. With the assistance of ICG-based NIRF imaging, isthmus division was performed with monopolar scissors and adequate hemostasis was obtained by electrocautery coagulation. This is the first report of use of an ICG-based NIRF imaging system and this novel approach can help to demarcate the left moiety isthmus from right one with more certainty.
BackgroundThe significance of combination of docetaxel (DTX) with estramustine phosphate (EMP) in castration-resistant prostate cancer (CRPC) patients remains unclear. In this study, we aimed to retrospectively evaluate the efficacy and toxicity of DTX with or without EMP and to elucidate the significance of DTX and EMP combination therapy in Japanese EMP-refractory CRPC patients.MethodsTo compare the efficacy and toxicity of DTX and EMP, we divided CRPC patients, who were confirmed to be resistant to EMP, into the following two groups: group D (n = 28), which included patients treated with DTX (60 mg/m2, once in every four weeks) alone, and group DE (n = 33), which included patients treated with a combination of DTX (60 mg/m2, once in every four weeks) and EMP (twice daily oral administration at 280 mg).ResultsProstate specific antigen (PSA) response (> 50% decline in PSA) was observed in six patients (21%) in group D and eight patients (24%) in group DE. The median time to progression (TTP) was 12.0 months and 6.2 months and the median overall survival (OS) was 26.4 months and 24.3 months in group D and DE, respectively. There was no statistical difference between the two groups in terms of PSA response, TTP, and OS. The incidence of adverse events of grade 3/4 was low in both the groups, and there was no statistical difference between the two groups.ConclusionsAlthough treatment with DTX at 60 mg/m2 was effective and highly tolerated in EMP-refractory Japanese CRPC patients, the DTX and EMP combination therapy might not exhibit any survival benefit for CRPC patients.
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