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Biomedical subjects

H Averette

Publications and source records attributed to H Averette.

13 recordsLinked to original sources
PubMed1992

In vitro evaluation of a novel chemotherapeutic agent, Adozelesin, in gynecologic-cancer cell lines.

Adozelesin is a derivative of an extremely cytotoxic compound, CC1065. This entirely new class of drug binds preferentially to DNA and facilitates alkylation reaction. In the present study, we used the adenosine triphosphate (ATP) chemosensitivity assay to compare the cytotoxic potency of Adozelesin with that of common chemotherapeutic agents in ten gynecologic-cancer cell lines. Flow cytometry was also used to study its effects on cell-cycle kinetics. The mean drug concentrations required to produce a 50% reduction in ATP levels as compared with controls [IC50] were: Adriamycin, 0.17 +/- 0.06 microM; 4OH-Cytoxan, 18 +/- 3 microM; cisplatin, 17 +/- 7 microM; 5-fluorouracil, 183 +/- 116 microM; and Adozelesin, 11.0 +/- 5.4 pM. Thus, Adozelesin was 10(4) - 10(7) times more potent than Adriamycin, cisplatin, 5-fluorouracil, and Cytoxan. Cell kinetics studies revealed significant S and G2 blocks such as those previously reported for other alkylating agents.

Adenocarcinoma↗
PubMed1992

Spectrum of cell-cycle kinetics of alkylating agent adolezesin in gynecological cancer cell lines: correlation with drug-induced cytotoxicity.

Adolezesin is an analog of CC-1065. These compounds are among the most potent alkylating agents known to date. Currently Adolezesin is undergoing phase I clinical trials at several cancer centers in the USA. While the cytotoxic effects of Adolezesin have been addressed elsewhere, its effects on cell-cycle kinetics have not been reported. Flow cytometry was performed on five human gynecological cancer cell lines: AN3, AE7, BG1, HEC1A, and SKUT1B. Exposure to Adolezesin (U73975, Upjohn Co.) was done at near confluency at 0, 0.1, 0.2, 0.5, 1 and 5x, with x = 10 pg/ml as reference concentration, for 90 min. Cell samples were taken by trypsinization at 0, 24, 48, 72, 96, and 168 h for flow cytometry. The ATP chemosensitivity assays were performed on the above cell lines to establish dose/response curves. Flow-cytometric analyses revealed that there was a spectrum of cell-cycle perturbations, which included biphasic S and G2 blocks, reverse dose-dependent G2 blocks, and a sequential relationship of S and G2 blocks. This study demonstrated that the cell kinetic response to Adolezesin depended on several variables such as cell lines, drug sensitivity, concentrations, and sampling time. Because of this multivariable dependence and the lack of correlation with cytotoxicity, it would be difficult to use cell kinetic pertubations to predict chemotherapeutic response.

Adenosine Triphosphate↗
PubMed1992

Infectious complications after gastrointestinal surgery in patients with ovarian carcinoma and malignant ascites.

One hundred four patients with ovarian cancer underwent intestinal reconstruction as part of a cytoreductive effort or for relief of intestinal obstruction from July 1980 to June 1990. Twenty-four percent of patients were obstructed preoperatively, while the remaining seventy-six percent had bowel resections performed in concert with a debulking procedure. The overall infectious complication rate was 14.4%. No statistical association was found between the presence of ascites at the time of laparotomy and infectious morbidity (P = 0.58). The use of a preoperative mechanical bowel preparation was associated with a significant reduction in infectious morbidity (P = 0.01). Additionally, patients considered in adequate nutritional condition experienced significantly less infectious complications than those patients in poor nutritional condition (P = 0.03). Intestinal procedures involving the large bowel were marginally associated with increased infectious complications (P = 0.13). Neither preoperative radiotherapy, the presence of preoperative obstruction, disease presence, extent of debulking, number of intestinal procedures, or hand versus stapled anastomosis was found to be significantly associated with infectious complications. It is concluded that the presence of ascites does not increase the infectious complication rate in ovarian cancer patients who undergo small or large bowel reconstructive procedures. Additionally, patients with preoperative bowel obstruction or previous abdominal radiation therapy were not found to experience a significant increase in the infectious complication rate in the current series.

Anti-Bacterial Agents↗
PubMed1992

Comparison of U-73,975 and cisplatin cytotoxicity in fresh cervical and ovarian carcinoma specimens with the ATP-chemosensitivity assay.

U-73,975 (U-73), a closely related synthetic analogue of the antitumor agent CC-1065, acts by binding tightly in the minor groove of DNA. A comparison was made between the cytotoxicity of U-73 and cisplatin (DDP) on 11 fresh cervical and 7 fresh ovarian carcinoma specimens. The ATP-chemosensitivity assay as previously described (Sevin et al. Gynecol. Oncol. 31, 191-204, 1988) was used to determine the cytotoxic effect of U-73 and DDP. IC 50s were calculated using regression analysis. The mean IC 50s for U-73 and DDP were 519 pg/ml and 2918 ng/ml, respectively, for the cervical carcinoma specimens and 324 pg/ml and 2649 ng/ml, respectively, for the ovarian carcinoma specimens. Significance comparing U-73 and DDP for cervical and ovarian tissue was demonstrated with P < 0.001. U-73 was 4000 times as cytotoxic per unit of mass as DDP on cervical carcinoma compared to over 8000 times for ovarian carcinoma. Based on these in vitro data, U-73 appears to be a very promising antitumor agent for cervical and ovarian carcinoma.

Adenosine Triphosphate↗
PubMed1992

Comparative evaluation of pirarubicin and adriamycin in gynecologic cancer cell lines.

Pirarubicin (PIRA) has been shown to have improved potency with less cardiac toxicity in several phase I and II clinical trials in Japan and Europe. Since Adriamycin (DXR) remains one of the most potent drugs in treatment of gynecologic cancers, this derivative has the potential to become an important chemotherapeutic agent. In this study, we compared the performance of these two drugs against a panel of 10 gynecologic cancer cell lines. The ATP chemosensitivity assays were used to determine dose-response curves. Flow cytometry was used to study cell kinetic response to both drugs. Using an IC50 value of 0.2 micrograms/ml as a cutoff for drug sensitivity, 4 cell lines, ECC1, HEC1B, BG1, and SKOV3, were considered resistant to DXR. By comparing IC50s, PIRA was 3.4 +/- 0.4 times more potent than DXR (P = 0.05). The other 6 cell lines, AN3, AE7, HEC1A, CAOV3, SKUT1B, and ME180, were considered sensitive to DXR. In this group of cell lines, PIRA was 1.6 +/- 0.3 times more potent than DXR (P = 0.5). Both PIRA and DXR elicited a spectrum of cell kinetics. By comparing the magnitude of G2 blocks at 0.1 micrograms/ml, PIRA was approximately 2-5 times more potent than DXR in SKUT1B, HEC1A, and BG1 cell lines. PIRA also displayed a reverse dose-response pattern of G2 block so that at high dose, cell cycle kinetics would mirror those of untreated controls. This observation supports the presence of a resistant tumor subpopulation and the concept of tumor heterogeneity.

Antibiotics, Antineoplastic↗
PubMed1988

Reconstructive techniques in gynecologic oncology: the use of human dura mater allografts.

Human dura mater has been utilized in various reconstructive procedures following radical pelvic surgery at the Division of Gynecologic Oncology, University of Miami School of Medicine. Our preliminary results indicate that this allograft is strong, durable, and acts as a good biological barrier. However, it does not seem to prevent the development of enteropelvic fistulae in patients who undergo total pelvic exenteration following radiotherapy. Dura mater has also been employed in abdominal hernia repairs, repair of wound dehiscenses, and in the coverage of the femoral vessels after groin dissection. Provisional results with these reconstructive techniques appear promising. These results are discussed, and suggestions regarding the use of this allograft are delineated.

Carcinoma, Squamous Cell↗
PubMed1987

Gastrointestinal surgery in gynecologic oncology: evaluation of surgical techniques.

In recent years, the use of surgical staples has become popular in all subspecialties of surgery. The advantages proposed have been a decrease in operative time and morbidity. This paper reviews the University of Miami/Jackson Memorial Medical Center, Division of Gynecologic Oncology experience with the use of surgical staples in gastrointestinal surgery on patients with a diagnosis of a gynecologic malignancy. Between January 1, 1979 and July 1, 1985, a total of 152 procedures were done, 81 by stapler and 71 by suture anastomosis. Ninety-one patients had received previous radiation or chemotherapy. The average age of the patients was 52 years. The results show a decrease in operating time, blood loss, and postoperative hospital stay in those patients where the stapler anastomosis was used. The postoperative morbidity and mortality were not increased. Twenty-seven total pelvic exenterations were performed during the period of study and they were evaluated separately. The hospital stay and blood loss as well as the operative time were significantly less using staplers. This report includes a detailed evaluation of the results. From this study, we concluded that surgical staples are a safe alternative in gastrointestinal surgery in patients with a gynecologic malignancy.

Adult↗
PubMed1986

Small bowel complications after supravesical urinary diversion in pelvic exenteration.

Between June, 1966, and June, 1984, 102 pelvic exenterations were performed at Jackson Memorial Hospital/University of Miami Medical Center and all patients had some type of supravesical urinary diversion. Of these patients, 23 were reexplored for a gastrointestinal complication and 15 of those had a small bowel complication. Small bowel fistula occurred in 15 instances and 9 patients were reexplored. The fistula associated mortality was 53.3%. All the fistulas occurred in previously radiated patients who had undergone an enteroenteroanastomosis. The recent use of enterocolostomies after the construction of an ileal conduit in 21 patients has not produced any postoperative small bowel fistula, while in 43 patients who underwent enteroenterostomies, 13 fistulas occurred (P less than 0.01). Patients who did not undergo pelvic floor closure had a higher incidence of fistula and small bowel obstruction, while there were no fistulas in patients with previous enterocolostomies, regardless of the pelvic closure.

Colon, Sigmoid↗
PubMed1986

Major surgical procedures for gynecologic malignancy in elderly women.

We review 89 patients more than 75 years old who had major operations for various gynecologic malignancies. The recent routine use of perioperative intensive care decreased hospital mortality from 8.9% to 3.2%, and helped in decreasing and anticipating intraoperative and postoperative cardiorespiratory complications. Availability of visiting nurses since 1980 decreased the mean hospital stay from 30.2 to 24.4 days in patients who had radical vulvectomy. There were no deaths among 11 patients who subsequently had surgical reexploration for recurrent or new disease. Fifty-two of the 89 patients survived more than three years with no limitations resulting from the operations. When indicated, major surgical procedures for gynecologic malignancy in elderly women can be done safely, especially when the patient is evaluated and managed in a well staffed surgical intensive care unit.

Aged↗
PubMed1986

Genital rhabdomyosarcoma: current management and review of the literature.

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and 20 per cent of these cancers involve the pelvis or genitourinary system. Radical pelvic surgery, such as exenteration, was considered at one time to be the standard treatment for this cancer which carried a very poor prognosis. Over the past 15 years, a combined modality approach to treating rhabdomyosarcoma, using chemotherapy, radiotherapy, and less radical surgery, has evolved and survival rates have improved. This paper presents a case of rhabdomyosarcoma involving the perineum which was treated by combination chemotherapy of Vincristine, Actinomycin-D, and Cytoxan, followed by wide local excision, interstitial and external beam radiotherapy, and postoperative chemotherapy. The literature on pelvic rhabdomyosarcoma is reviewed and the current approach to treating this cancer using multimodal therapy is discussed.

Adolescent↗