Cisplatin continues to be one of the most commonly used cytotoxic agent. Problems of drug resistance and nephrotoxicity have generated interest in new platinum derivatives. In this study, we used flow cytometry to study their effects on cell kinetics and to see if the extent of cell cycle perturbations can be used to determine relative potency. The following four platinum derivatives were tested: cisplatin, carboplatin, 254S, and NK121 on two human ovarian cancer cell lines: BG1 and CAOV3. Flow cytometric analysis revealed a dynamic spectrum of cell kinetic perturbations, which included sequential S-G2 block, concomitant S-G2 block, and a dominant S block with abolition of G2 block. Platinum derivatives NK121, 254S, and CARBO induced an average of 54.5 +/- 5.6, 21.2 +/- 5.5, and 2.5 +/- 2.8% more S-G2 blocks than cisplatin, respectively. When comparing the severity of S-G2 blocks and requiring a p-value of 0.05, the order of increasing potency was: cisplatin, carboplatin, 254S, and NK121.
The objective of this study was to determine the impact of conservative surgical trends in vulvar cancer related to morbidity, adequacy of surgical resection, recurrence rates and survival. A retrospective analyses of 160 patients treated surgically for vulvar cancer at the University of Miami/Jackson Memorial Medical Center from January 1, 1973 to December 31, 1991 was performed. Patients were divided into two groups based on the date of surgery. Group 1 patients (82) had surgery between January 1, 1973 to December 31, 1982. Group 2 patients (78) had surgery between January 1, 1983 and December 31, 1991. Patient demographics, stage, T N M classification and grade were not statistically different between groups. There was a significant trend away from curvilinear en bloc resection toward the use of a separate triple incision (P = 0.0001). Decreases in exenterative surgery and radical vulvectomy and concurrent increases in radical local excision and hemivulvectomy occurred (P = 0.014). In addition, deep pelvic node dissection was abandoned and an increase in unilateral vs bilateral inguinal node dissection also occurred, yet this did not reach significance (P = 0.09). No difference in the mean number of total nodes, number of groin nodes obtained and percentage of patients with positive nodes or positive margins was found. With the trend toward more conservative surgery, statistically significant decreases in mean estimated blood loss (1 334 ml to 834 ml; P = 0.009), length of days hospitalized (31.5 to 19.7; P = 0.001) and operative times (5.3 h to 4.1 h; P = 0.002) occurred. No difference was noted in minor wound breakdown rates; however, there were significantly fewer major wound breakdowns in the conservatively treated group (43.2% vs 16.6%) (P = 0.0003). Major wound breakdowns occurred more frequently in the abdomen/groin region in group 1 vs 2 (24.7% vs 7.7%; P = 0.004). Frequencies of wound breakdown in relation to the number of clinical risk factors (smoking, hypertension, diabetes, obesity, other) for all patients was found to be highly statistically significant (P = 0.006). When evaluating patients with squamous carcinoma only, recurrence rates and 5‐year survivals were not statistically different (P = 0.45). The trend toward conservative surgical management of vulvar carcinoma significantly reduced morbidity with no impact on recurrence rates or 5‐year survival.
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