The effects of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on N-acetyltransferase (NAT) activity were examined using a human colon tumor cell line (colo 205). BHA or BHT were added to the cytosols or to the medium of human colon tumor cells: The NAT activity was measured by high performance liquid chromatography, assaying the amounts of acetylated 2-aminoflluorene (AAF), p aminobenzoic acid (N-Ac-PABA), nonacetylated 2 aminofluorene (AF) and p-aminobenzoic acid (PABA). The NAT activity in the human colon tumor cells and cytosols was suppressed by BHA or BHT in a dose-dependent manner. The apparent values of Km and Vmax of NAT of human colon tumor cells were also decreased by BHA or BHT in cytosols and in intact cells. BHA or BHT may act as a noncompetitive inhibitor. After the incubation of human colon tumor cells with AF in the presence of BHA or BHT, the cells were recovered and DNA was prepared and hydrolysed to nucleotides. Adducted nucleotides were extracted into butanol and AF-DNA adducts were analysed by HPLC. The results also demonstrated that when BHA or BHT was added to the media, a decrease in AF-DNA adduct formation was seen in the human colon tumor cells. The finding of AF-DNA adduct formation in cultured human colon tumor cells suggest the possibility of using cultured cells for assessing arylamine-induced DNA damage.
We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced by Solanum lyratum extracts (SLE) or diosgenin in WEHI-3 murine leukemia cells in vitro and antitumor activity in vivo. Diosgenin is one of the components of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells and induced G(0)/G(1) phase arrest and apoptosis in concentration- or time-dependent manners. Both reagents increased the levels of ROS production and decreased the mitochondrial membrane potential (ΔΨ(m)). SLE- and diosgenin-triggered apoptosis is mediated through modulating the extrinsic and intrinsic signaling pathways. Intriguingly, the p53 inhibitor (pifithrin-α), anti-Fas ligand (FasL) mAb, and specific inhibitors of caspase-8 (z-IETD-fmk), caspase-9 (z-LEHD-fmk), and caspase-3 (z-DEVD-fmk) blocked SLE- and diosgenin-reduced cell viability of WEHI-3 cells. The in vivo study demonstrated that SLE has marked antitumor efficacy against tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and diosgenin-induced G(0)/G(1) phase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activity in vivo. Our findings showed that SLE may be potentially efficacious in the treatment of leukemia in the future.
Nephrologists commonly recommend continuous ambulatory peritoneal dialysis (CAPD) with break-in periods of at least 2 weeks. We investigated the safety and feasibility of shorter break-in periods following surgical implantation of Tenckhoff catheters.We retrospectively examined 310 patients that underwent Tenckhoff catheter implantation for the first time. The early group comprised 226 patients that started CAPD ≤ 14 days after implantation; the late group comprised 84 patients that started CAPD > 14 days after implantation. Catheter-related complications within 6 months were analyzed.A total of 310 patients were enrolled. Time to CAPD initiation was shorter in the early group (2.0 ± 2.7 days) than in the late group (40.6 ± 42.8 days) (p < 0.001). The bridge hemodialysis rate was higher in the late group (57.1%) than in the early group (31.4%) (p < 0.001). Overall, 33 early-group (14.6%) and 11 late-group patients (13.1%) developed catheter-related complications within 6 months. The early-group complications were leakage (n = 5), diminished outflow volume (n = 7), migration (n = 7), pericatheter hernia (n = 1), hemoperitoneum (n = 1), pericatheter infection (n = 3), and peritonitis (n = 9). The late-group complications were leakage (n = 2), diminished outflow volume (n = 5), migration (n = 2), and peritonitis (n = 2). Actuarial freedom from catheter-related complications was similar in both groups (log rank, p = 0.76).Early initiation of CAPD with surgically implanted Tenckhoff catheters is feasible and safe. Shorter break-in periods are not associated with more catheter-related complications. The data from our peritoneal dialysis population suggest that early initiation is not associated with an increased number of complications. This needs to be confirmed in a randomized trial.
Metastatic castration-resistant prostate cancer (mCRPC) is a progressive stage of prostate cancer that often spreads to the bone. Radium-223, a bone-targeting radiopharmaceutical, has been shown to improve the overall survival in mCRPC in patients without visceral metastasis. However, the impact of prior systemic therapy on the treatment outcome of mCRPC patients receiving radium-223 remains unclear. This study aimed to investigate the optimal choice of systemic therapy before radium-223 in mCRPC patients. The study included 41 mCRPC patients who received radium-223 therapy, with 22 receiving prior enzalutamide and 19 receiving prior abiraterone. The results showed that the median overall survival was significantly longer in the enzalutamide group than in the abiraterone group (25.1 months vs. 14.8 months, p = 0.049). Moreover, the number of patients requiring blood transfusion was higher in the abiraterone group than in the enzalutamide group (9.1% vs. 26.3%, p = 0.16). The study also found that the number of doses of Radium-223 received was significantly associated with overall survival (≥5 vs. <5, HR 0.028, 95%CI 0.003–0.231, p = 0.001). Our study provides insights into the optimal treatment choice for mCRPC prior to radium-223, indicating that enzalutamide prior to radium-223 administration may have better outcomes compared to abiraterone in mCRPC patients without visceral metastasis.
Objective: The study was performed to know if the possibility of tumor growth around a stone can be diagnosed immediately following the procedure of endourological surgery.
e16139 Background: The benefit of adjuvant chemotherapy (AC) for upper tract urothelial cancer (UTUC) is controversial. Pathologic characteristics such as lymphovascular invasion (LVI) and squamous differentiation (SD) are prognostic and may help decision-making in selecting patients who need adjuvant chemotherapy. We evaluated the impact of pathologic characteristics on the efficacy of adjuvant chemotherapy in UTUC Methods: We retrospectively reviewed records on 200 consecutive patients with UTUC (pathologic stage II, III, and non-metastasis IV) treated with radical nephroureterectomy between January 2004 and September 2014 and obtained free surgical margins. Adjuvant chemotherapy of gemcitabine and cisplatin was given. Overall survival (OS), recurrence-free survival, local-regional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method. The values of prognostic factors were evaluated by Cox regression analysis. Results: The median follow up is 19.5 months. LVI was found in 74 (37.0%) patients and SD in 57 patients (28.5%). AC was administered in 60 (30%) patients. Multivariate analysis showed LVI, SD and AC were independent prognostic factors in terms of OS and DMFS but not in LRFS. For patients with LVI, AC improved OS and DMFS, but the benefit of AC was not observed in patients without LVI. In contrast, there was no improvement of OS and DMFS in patients with squamous differentiation when AC was administered, but AC significantly improved OS and DMFS in patients without squamous differentiation. Conclusions: Lymphovascular invasion and squamous differentiation had differential impact on the efficacy of adjuvant chemotherapy in UTUC. The design of chemotherapy for UTUC should consider pathologic characteristics. OS (%) P DMFS (%) P With LVI (with vs without AC) 83.3 vs 21 < 0.001 85.1 vs 32.4 < 0.001 Without LVI (with vs without AC) 65.2 vs 63.2 0.832 77.8 vs 82.4 0.692 With SD (with vs without AC) 44.9 vs 39.3 0.268 67.6 vs 49.3 0.250 Without SD (with vs without AC) 85.9 vs 55.7 0.005 86.7 vs 72.6 0.039
Aspirin (acetylsalicylic acid) was used to determine the inhibition of arylamine N-acetyltransferase (NAT) activity and DNA adduct formation in a human bladder tumour cell line (T24). The activity of NAT was measured by high-performance liquid chromatography, assaying for the amounts of N-acetyl-2-aminofluorene and N-acetyl-p-aminobenzoic acid and remaining 2-aminofluorene and p-aminobenzoic acid. Two assay systems were used: one with cytosol and the other with intact cells. High-performance liquid chromatography was also used to analyse for the 2-aminofluorene-DNA adducts. Intact bladder tumour cells were used. The results demonstrated that NAT activity and 2-aminofluorene-DNA adduct formation in human bladder tumour cells were inhibited by acetylsalicylic acid in a dose-dependent manner. The effects of acetylsalicylic acid on the values of the apparent K(m) and V(max) were also determined in both examined systems. The data also indicated that acetylsalicylic acid decreased the apparent values of K(m) and V(max) from human bladder tumour cells in both cytosol and intact cells.
Extracorporeal shock-wave lithotripsy (ESWL) is a safe and widespread modality for the treatment of renal stones. Although rarely used for treatment of subcapsular hematoma of the kidney, this procedure may sometimes be required in critical case for possible renal loss. This study investigated 10 subcapsular hematomas that were encountered during a 10-year period using ESWL treatment in patients with renal stones. This history revealed eight with hypertension, four with urinary tract infection (UTI), two with diabetes mellitus (DM) and 1 with peptic ulcer. None of the patients died. One Dm patient with coexisting UTI underwent nephrectomy due to the occurrence of perirenal abscess. Age older than 50 years and multiple stones might be risk fac-tors of the occurrence of perirenal hematoma after ESWL.(J Urol R.O.C., 10:164-167,1999)
Berberine, an isoquinoline alkaloid, has been shown to possess anticancer properties in some cancer cell lines. Here, we report that in vitro treatment of cervical cancer Ca Ski cells with berberine decreased the percentage of viable Ca Ski cells in a dose-dependent and time-dependent manner. Berberine enhanced the apoptosis of Ca Ski cells with the induction of a higher ratio of p53 and Bax/Bcl-2 proteins, increased levels of reactive oxygen species (ROS) and Ca2+, disruption of the mitochondrial membrane potential, and promotion of caspase-3 activity. In CaSki cells pretreated with the pan-caspase inhibitor zVAD-fmk, the berberine-induced caspase-3 activity and apoptosis were significantly blocked as confirmed by flow cytometric analysis. Western blot also showed that berberine induced the expression of GADD153, a transcription factor involved in apoptosis. Thus berberine increased ROS levels leading to endoplasmic reticulum (ER) stress based on the increase of GADD153 and shown by Ca2+ release from the ER. When the Ca Ski cells were pretreated with catalase, GADD153 production was abrogated and apoptosis was significantly reduced.
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