Biomedical subjects

H N Nguyen

Publications and source records attributed to H N Nguyen.

At least 73 records · Page 4Linked to original sources

PubMed1993

National survey of ovarian carcinoma. I. A patient care evaluation study of the American College of Surgeons.

BACKGROUND: The Commission on Cancer of the American College of Surgeons recently finished a national survey of patients with ovarian cancer patients. The goal was to compare the patterns of care over a 5-year period. METHODS: Data were collected from 25 consecutive patients whose disease was diagnosed first at 904 hospitals with cancer programs in 1983 and 1988. RESULTS: There was a total of 12,316 patients, of whom 80% were 45-85 years old. Contrary to popular belief, only 8.2% of patients were nulliparous; 85% of patients had one to five children. Of significance, 18.2% of patients with ovarian cancer had undergone a previous hysterectomy with ovarian preservation. Primary surgical treatment was used in 94.9% of patients and consisted of: oophorectomy, 81.9%; hysterectomy, 55.1%; and omentectomy, 59.0%. However, only 12-25% of patients had biopsies of the diaphragm, paracolic gutters, colon, small bowel, pelvic and paraaortic lymph nodes, and cul-de-sac to permit adequate surgical staging. The primary surgeons were: gynecologic oncologists, 21%; obstetrician-gynecologists, 45%; general surgeons, 21%; and others, 13%. CONCLUSIONS: These data indicate that additional resources are needed to improve the care of patients with ovarian cancer.

Adult↗

PubMed1993

Preliminary experience with a modified Tenckhoff catheter for intraperitoneal chemotherapy.

This study reports our preliminary experience with a modified Tenckhoff catheter for intraperitoneal chemotherapy, primarily designed to be larger, longer, and have more perfusion holes. There were 137 catheters implanted in 125 ovarian cancer patients from June 1988 to December 1990, among which 116 were actually used for intraperitoneal chemotherapy. A total of 559 cycles of intraperitoneal chemotherapy was given with a range of 1 to 16 uses per catheter. There were seven infections (6.0%), four inflow obstructions (3.4%), three bowel perforations (2.6%), and one leakage (0.8%). Among patients with catheter infection, three had delayed bowel perforation. Although the incidence of inflow obstruction was reduced from 5.5 to 3.4%, the improvement did not reach statistical significance. The frequency of delayed bowel perforation and infection were similar to the literature experience of other catheters. An unused catheter should be removed to avoid this serious complication. Further study is needed to evaluate fully the performance of this catheter system.

Antineoplastic Agents↗

PubMed1993

Radiosensitization of uterine cancer cell lines by cytotoxic agents.

Radiotherapy remains an integral part of uterine cancer therapy. Overcoming radioresistant tumors by sensitizers continues to be a prime objective in radiotherapy research. In this study, the effects of five cytotoxic agents on two radiosensitive and four radioresistant uterine cancer cell lines were investigated. The ATP bioluminescence was used to measure surviving fractions. Data analysis was done using the linear quadratic model and radiosensitivity index D. Both AN3 and SKUT1B were radiosensitive with Ds of 1.73 and 1.72 Gy, respectively. The resistant cell lines had the following D values: AE7, 3.50; ECC, 6.61; HEC1A, 4.59; and HEC1B, 13.49 Gy. The average radiosensitization effects for various drugs were measured by reduction of D: DXR 45 +/- 7, DDP 40 +/- 9, 5FU 55 +/- 10, MITO 59 +/- 14, and HU 1.7 +/- 7%. Except for HU, Wilcoxon analyses revealed that these sensitizing effects were significant with P < 0.02. In summary, Adriamycin, 5-fluorouracil, cisplatin, and mitomycin-C have the potential to be radiosensitizers in uterine cancer cell lines.

Adenosine Triphosphate↗

PubMed1993

Radical hysterectomy for stage IB adenocarcinoma of the cervix: the University of Miami experience.

The treatment of adenocarcinoma of the cervix has traditionally followed that of squamous cancer. A 25-year review of 88 radical hysterectomies for Stage IB adenocarcinoma of the cervix at the University of Miami/Jackson Medical Center (UM) is compared to over 1600 cases reported in the literature. Adenocarcinoma represented 10.4% of 978 radical hysterectomies performed at UM from July 1965 to December 1990. In a survey of the literature, patients with Stage IB cervical adenocarcinoma treated by radical surgery alone had a statistically better 5-year survival than those treated by radiation alone (79% vs 67%, respectively; P < or = 0.05). Furthermore, no additional benefit was achieved by combining the two therapeutic modalities. The corrected 5-year survival at UM is 81% for Stage IB adenocarcinoma of the cervix treated with radical hysterectomy, a number consistent with the cumulative data base. Radical surgery is an acceptable primary therapy in Stage IB adenocarcinoma of the cervix.

Adenocarcinoma↗

PubMed1993

The role of DNA index as a prognostic factor in early cervical carcinoma.

The value of DNA index as a prognostic factor in early cervical cancers was investigated. A total of 124 patients who underwent radical hysterectomy for stages IB-IA cervical cancers from 1/1982 to 12/1985 were included. Paraffin blocks were available in only 98 patients for the analysis. After dewaxing, rehydrating, and enzyme disaggregation, cells were subjected to dual parameter flow cytometry. Tumor DNA index was calculated and the results were correlated with 5-year survival, stage, grade, tumor size, nodal metastasis, surgical margins, and lymphovascular invasion. There were 1% hypoploid, 7.3% diploid, 72.9% aneuploid, 16.7% tetraploid, and 2.1% hyperploid. At the end of 5 years, there were 69 alive and 27 dead patients with mean DNA indices of 1.50 +/- 0.3 and 1.70 +/- 0.3, respectively. t Test analysis revealed that mean DNA index of deceased patients was significantly higher than that of alive ones (P = 0.008). Survival analysis demonstrated the prognostic significance of DNA index 1.70 (P = 0.017). Median survival of patients with DNA index of 1.70 or greater was 36 months in contrast to 73.5 months for those with DNA index less than 1.70. Multivariate analysis subsequently confirmed DNA index of 1.70 as an independent prognostic indicator with a hazard ratio of 2.05.

Carcinoma↗

PubMed1993

Adenosquamous carcinoma of the cervix: prognosis in early stage disease treated by radical hysterectomy.

The prognosis of adenosquamous carcinoma of the cervix compared to the pure cell types of this disease is a controversial issue. Survival rates vary widely among published series, with some authors finding the prognosis to be much worse and others finding it to be equal. We have studied a group of 290 patients, all of whom had the diagnosis of stage IB or IIA cervical cancer, and all of whom were treated by radical hysterectomy and bilateral pelvic and paraaortic lymphadenectomy. The pathology specimens were reviewed for every case. Median follow-up for all living patients was 73 months. Forty-five patients (15.5%) had adenosquamous histology, 220 (75.9%) had squamous cell, and 25 (8.6%) had adenocarcinoma. By X2, there was no significant difference among the three groups with regard to race, economic status, number of grade 3 lesions, number with positive pelvic lymph nodes, number with positive margins, stage distribution (IB vs IIA), or number of recurrences. Using Student's t test, there was no significant difference between any combination of two groups with regard to mean patient age, mean depth of invasion, or mean tumor size. Estimated disease-free survival and overall survival were not different among the three cell types. We conclude that for early stage cervical cancer treated by radical hysterectomy, the adenosquamous cell type does not carry a worse prognosis than either of the pure cell types.

Adenocarcinoma↗

PubMed1993

Cell cycle perturbations of platinum derivatives on two ovarian cancer cell lines.

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.

Carboplatin↗

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

Chemosensitivity to the new anthracycline pirarubicin and other chemotherapeutic agents in primary and recurrent ovarian tumors in vitro.

We analysed the in vitro sensitivity of 50 fresh gynecologic cancer specimens to the new anthracycline-analogue pirarubicin (Pira). Nine endometrial and cervical tumors were excluded from the evaluation in this study. The in vitro sensitivities of 41 ovarian cancer specimens to Pira were evaluated with the adenosine triphosphate chemosensitivity assay (ATP-CSA). The results were compared to the sensitivity of drugs used in gynecologic oncology: Adriamycin, cisplatin, and the metabolite of cyclophosphamide, 4-hydroxycyclophosphamide (4-HC). Sensitivity (S) is defined as > or = 70%, partial sensitivity as 50-69% ATP decrease compared to controls at 20% of the peak plasma concentration. In vitro response is defined as S + PS. Twenty-two primary ovarian tumors were assayed, with 77% response to Pira, 12% to Adriamycin, 29% to cisplatin, and 38% to 4-HC. In 19 recurrent ovarian tumors, Pira showed 53% response; Adriamycin, 25%; cisplatin, 8%; and 4-HC, 67%. The in vitro data are partly consistent with reported data from the literature. Pira reveals a significantly higher degree of cytotoxicity compared to the three drugs listed above. The IC50 of Pira is less than 20% of the peak plasma concentration achievable in patients and is significantly lower compared with the IC50s of other drugs. We conclude from our in vitro data that Pira is more active than Adriamycin, cisplatin, and 4-HC.

Adenosine Triphosphate↗

PubMed1992

Determination of hormonal response in uterine cancer cell lines by the ATP bioluminescence assay and flow cytometry.

Although progesterone receptor status has been shown to correlate with response to hormonal therapy, not all progesterone receptor-positive patients respond to this treatment and additional biologic assays are needed to help better predict clinical response to hormonal therapy. This study explored the potential of the ATP bioluminescence assay and flow cytometry as biological assays of hormonal response. Five uterine cancer cell lines were used: AE7, ECC-1, HEC1A, AN3, and SKUT1B. Cells were exposed to Provera or tamoxifen at 0.1, 0.2, 0.5, 1, 2, and 5X (X equal to peak plasma concentrations: 1.0 micrograms/ml Provera and 0.1 micrograms/ml tamoxifen). For correlation, estrogen and progesterone receptors were determined by the standard dextran-coated charcoal method. Only AE7 and ECC-1 were positive for progesterone receptors (501 fmol/mg AE7, 194 fmol/mg ECC-1) and the rest were negative (less than 8 fmol/mg). Tamoxifen exerted no inhibition to the above cell lines. Meanwhile, Provera exerted dose-response inhibition on both AE7 and ECC-1 cell lines. The effects of accumulation of G0-G1 phase and reduction of S, G2 cells (P less than 0.05), but not on the HEC1A cell line (P = 0.4). These changes confirmed the antiproliferative property of Provera. Further studies are needed to establish the role of the ATP bioluminescence assay and flow cytometry as biological assays of hormonal response.

Adenocarcinoma↗

PubMed1992

The use of ATP bioluminescence assay and flow cytometry in predicting radiosensitivity of uterine cancer cell lines: correlation of radiotoxicity and cell cycle kinetics.

Radiotherapy remains an important part of uterine cancer treatment. This study was designed to evaluate the potential of the ATP bioluminescence assay and flow cytometry for predicting radiosensitivity. Correlation of these two modalities revealed important insights into the relationship of radiotoxicity and cell kinetic effects. Six human uterine cancer cell lines were used: AE7, ECC1, HEC1A, HEC1B, AN3, and SKUT1B. Doses of cobalt 60 were 0, 1, 2, 5, 8, and 10 Gy. The ATP bioluminescence assays were performed on Day 7. Cell samples were taken at 0, 24, 48, 72, 96, and 168 hr for flow cytometry. The linear-quadratic model was used to fit survival data and mean inactivation dose D was calculated. Among parameters such as D, alpha and beta coefficients, and surviving fraction at 2 Gy (SF2), both D and SF2 correlated best with survival data. Radiation effects on the cell cycle did not correlate with D and revealed two distinct patterns: either a G1 accumulation with mild G2 block or a G1 depletion and severe G2 block. The S cells consistently demonstrated a biphasic pattern with an initial reduction followed by an accumulation. In summary, the ATP assay was shown to have potential in the study of radiosensitivity. Radiation-induced cell kinetics appeared to vary with intrinsic cellular differences and, thus, could not be used to predict radiosensitivity.

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↗

PubMed1992

The use of ATP bioluminescence assays in selecting a drug screen panel for chemosensitivity testing of uterine cancer cell lines.

The ATP bioluminescence assay has demonstrated a strong potential to become a clinical assay for chemosensitivity testing. Currently, chemotherapy of gynecologic cancers remains controversial and empirical. To optimize the patient's chance of survival and to justify related toxicities, the chemoregimen should be individualized and based on the patient's chemosensitivity profiles. This study was performed to identify a panel of active drugs against uterine cancer cell lines for possible use in future chemosensitivity testing. We used the ATP chemosensitivity assays to screen 12 common cytotoxic agents against six uterine cancer cell lines. Drug concentrations required for a 50% surviving fraction were defined as IC50s. When using an IC50 of 0.21 PPC (peak plasma concentration) as a cutoff value for sensitivity, the following 8 drugs were considered effective for uterine cancer cell lines: actinomycin D, Adriamycin, vinblastine, etoposide, 5-fluorouracil, methotrexate, cytosine arabinoside, and mitomycin-C. Meanwhile, 4 drugs, cisplatin, 4OH-Cytoxan, bleomycin, and Alkeran with mean IC50s of 2.1 +/- 0.7, 0.8 +/- 0.1, greater than 5.0, and 0.75 +/- 0.36 PPC, respectively, were considered inactive or partially active with higher IC50s than peak plasma concentrations. In conclusion, the above panel of promising drugs can be further tested in animal models or human cancer specimens for possible use in chemosensitivity testing of uterine cancer patients.

Adenocarcinoma↗

PubMed1992

Rationale of combining radiation and interferon for the treatment of cervical cancer.

The recent surge of interest in the mechanisms of action of biomodulators, also known as biological response modifiers, offers a new avenue of approach in the treatment of cancer. The in vitro antitumor activities of these agents, such as interferons, when combined with chemo- or radiotherapy, have generated enthusiasm among clinicians for developing clinical trials. In recent years many antineoplastic agents have been investigated as neoadjuvant or adjuvant therapy for patients with cervical cancer in an attempt to improve local control and to decrease incidence of metastasis. Normal tissue tolerance limits the potential combinations of standard cytotoxic chemotherapeutic agents with radiation. Interferon used as a radiomodulator has been studied mainly for the treatment of lung cancer with promising results. In this paper we report the rationale of combining interferon and radiation for the treatment of patients with cervical cancer.

Animals↗

PubMed1991

[The localization of colorectal polyps and carcinomas in relation to their size and the histological findings].

Location, size and histological appearance of colorectal neoplasms were examined retrospectively. A total of 1,357 polyps (including small ones, diameter below 0.5 cm) were found in 1,022 of 3,057 coloscopies. The coloscopies were indicated by findings on preceding radiological or endoscopic examinations (48%), occult blood in stool (18%), during follow-up after polypectomy (21%), and after colorectal carcinoma (13%). A single polyp was found in 718 cases (70%), two to four in 221 (26%), more than five in 33 (4%), 1,106 polyps (61%) were found on high coloscopy; 380 of these (38%) were located proximal to the left flexure. Among the 1,230 polyps examined histologically 907 (74%) were adenomas (494 tubular [54%], 379 tubulovillous [42%], 34 villous [4%]). 251 (28%) of the adenomatous polyps and 49 (32%) of the 151 carcinomas were located proximal to the left flexure. The incidence of moderately severe to severe dysplasias increased with increasing diameter of the polyps: 55% of those smaller than 0.5 cm were adenomas. 70% of polyps with a diameter over 1.0 cm were tubulovillous or villous adenomas. The findings confirm that there is a high incidence of polyps proximal to the left flexure. A complete coloscopy should therefore be done as a matter of course.

Age Factors↗

PubMed1991

The effects of Provera on chemotherapy of uterine cancer cell lines.

Even though progestin is commonly added to many chemotherapy regimens in the treatment of uterine cancers, its role is still unproven. Since progestin is antiproliferative, its tendency to arrest cells in G1 phase may interfere with cytotoxic mechanisms. The ATP chemosensitivity assay and flow cytometry were used to study the effects of a progestational compound such as Provera on three single agents and four drug combinations. Uterine cancer cell lines included progesterone-receptor (PR)-positive AE7 and ECC1 and PR-negative HEC1A, HEC1B, AN3, and SKUT1B. Provera selectively affected only PR-positive cell lines. It imposed an antiproliferative effect on drug-induced cell-cycle perturbations by reducing G2 and S blocks and minimizing G1 depletion. When using IC50s (concentrations required for 50% growth inhibition) of 0.5 as a cutoff for drug sensitivity and resistance, Provera significantly improved the IC50s of the drug-resistant subgroup from 1.95 +/- 0.36 to 0.71 +/- 0.19 (P = 0.009) but not those of the drug-sensitive subgroup (P = 0.13). In summary, Provera appeared to work independently from cytotoxic mechanisms. Its improvement of cytotoxicity was most pronounced in resistant cell lines bearing progesterone receptors.

Antineoplastic Agents↗

PubMed1991

Comparative evaluation of single and combination chemotherapy in uterine cancer cell lines.

Controversy over the chemotherapy of uterine cancers still exists. This study was designed to directly compare the efficacy of various chemotherapy combinations, CAP (Cytoxan, Adriamycin, cisplatin), CAF (Cytoxan, Adriamycin, 5-fluorouracil), MF (melphalan, 5-fluorouracil), CP (Cytoxan, cisplatin), to single agents, Adriamycin (DXR), Cytoxan (CYT), cisplatin (DDP), and carboplatin (CARBO). Five human endometrial cell lines and one sarcoma cell line were used: AE7, ECC-1, HEC1A, HEC1B, AN3, and SKUT1B. The ATP chemosensitivity assay was used to determine dose-response curves of various treatments. By using mean IC50's for comparison, CAF and MF were twice as effective in cell kill as CAP (P = 0.01, 0.03, respectively). There was however no significant difference between CAF, MF, and DXR (P = 0.12, 0.46, 0.34). When dose comparison is used, combinations CAP, CAF, and MF appeared to be 3 to 15 times more potent than DDP, CYT, or CARBO. In summary, Adriamycin remained the most effective single drug for uterine cancer cell lines. Its cytotoxicity was equivalent to that of combinations CAP, CAF, and MF.

Antineoplastic Agents↗