During the course of our screening program for natural product drugs effective against multidrug resistant cells by using adriamycin resistant HL-60 cells, we have discovered a new 12 membered macrolide FD-895 in the fermentation broth of Streptomyces hygroscopicus A-9561 isolated from a soil sample collected at Iriomote Island, Okinawa prefecture, Japan. FD-895 showed stronger cytocidal activities against in vitro tumor cell lines than adriamycin. FD-895 had the same IC50values against parent and adriamycin resistant HL-60 cells.A major drawback to cancer chemotherapy is that many tumors are either intrinsically resistant to the compoundor develop resistance over the course of treatment. Treatment with chemotherapeutic agents generally results only in temporary remission of tumor disease in the clinic.It is also well knownexperimentally1 '2) that mammalian cells selected for resistance to a single cytotoxic natural product drug can becomenot only resistant to the agent used but also cross-resistant to a wide range of structurally and functionally unrelated antibiotics and alkaloids. For these reasons the developmentof chemotherapeutic agents equally effective against malignant and resistant cells has been desired world wide for overcoming tumor disease. From this standpoint, we have explored natural product drugs effective against multidrug resistant cells.In the course of our screening program using adriamycin resistant HL-60cells to discover low molecular compoundsproduced in microbial fermentation broths and capable of circumventing multidrug resistance, we have discovered a new 12-membered macrolide FD-895 (Fig. 1)
PurposeAbdominoperineal resection (APR) of advanced lower rectal cancer carries a high incidence of perineal wound infection. The aim of this study was to retrospectively evaluate risk factors for perineal wound infection after APR.MethodsThe study group comprised 154 patients who underwent APR for advanced lower rectal cancer in our department from January 1990 through December 2012. The following 15 variables were studied as potential risk factors for perineal wound infection: sex, age, body-mass index, American Society of Anesthesiologists score, diabetes mellitus, preoperative albumin level, preoperative hemoglobin level, neoadjuvant chemoradiotherapy(NCRT), surgical procedure (open surgery vs. laparoscopic surgery), operation time, bleeding volume, intraoperative transfusion, tumor diameter, invasion depth, and histopathological stage.ResultsAmong the 154 patients, 30 (19%) had perineal wound infection. Univariate analysis showed that a hemoglobin level of ≤11 g/dL (p = 0.001) and NCRT (p = 0.001) were significantly related to perineal wound infection. On multivariate analysis including the preoperative albumin level (≤3.5 g/dL) in addition to the above 2 variables, neoadjuvant chemoradiotherapy (NCRT) was the only independent risk factor for perineal wound infection. Perineal wound infection developed in 31% of patients who received NCRT, as compared with 10% of patients who did not receive NCRT. The relative risk of perineal infection in the former group was 4.092 as compared with the latter group (p = 0.0002).ConclusionsNCRT is a risk factor for perineal wound infection after APR in patients with advanced lower rectal cancer.
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