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Biomedical subjects

A Manetta

Publications and source records attributed to A Manetta.

At least 55 records · Page 3Linked to original sources
PubMed1995

Inhibition of growth of human ovarian cancer in nude mice by luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75).

OBJECTIVE: To report on the in vitro and in vivo inhibitory effects of LH-releasing hormone (LH-RH) antagonist Cetrorelix (SB-75; Asta Medica, Frankfurt-Main, Germany) against a panel of human ovarian carcinomas. INTERVENTIONS IN VITRO STUDIES: the effect of SB-75 was measured using a standardized chemosensitivity assay in the following ovarian cancer cell lines: UCI 101; UCI 107; PA-1; NIH: OVCAR 3; UCLA: 222; A2780, parental; A2780-CR, cisplatin resistant; A2780-DR, doxorubicin resistant; and the human breast cancer cell line, MCF-7. Results were expressed as percent growth inhibition determined by crystal violet photometric analysis. In vivo studies: the antiproliferative effect of this agent was examined using UCI-107, a primary epithelial ovarian carcinoma cell line, in a nude mouse model. On day 0, 10 x 10(6) UCI 107 cells were implanted subcutaneously into 20 intact female athymic nude mice (5 to 6 weeks old). On day 8, the mice were randomly divided into two groups of 10; control mice were implanted with miniosmotic pumps filled with a vehicle solution consisting of 5.2% mannitol in saline; and treated animals received pumps filled to deliver continuous administration of SB-75 at 60 micrograms per mouse per day. RESULTS IN VITRO STUDIES: direct inhibition of cell proliferation by SB-75 was not observed at concentrations ranging from 1 nM to 100 microM (exposure lasting three to four cell doublings) with the exception of MCF-7, which demonstrated a 33% inhibition at the latter concentration. In vivo studies: on day 16, caliper measurements were taken from subcutaneous tumor nodules in SB-75-treated and untreated mice and a significant difference of 270% in mean tumor volume was observed. End point was determined, on day 30, when control tumor volume approached 10,000 mm3. At that time the difference in mean tumor volumes increased to 600%, indicating a substantial antiproliferative effect had been achieved in the SB-75-treated group. CONCLUSION: Our in vitro findings show direct inhibition by SB-75 on proliferation of human breast cancer cells. This direct inhibition in vitro was not observed in our ovarian cancer cell lines. However, in vivo SB-75 caused a significant inhibition of growth of human epithelial ovarian cancer. This may be a result of inhibition of the pituitary gonadal axis and gonadotropin secretion. Our results warrant further investigation.

Animals↗
PubMed1994

Cyclosporin enhancement of cisplatin chemotherapy in patients with refractory gynecologic cancer. A Gynecologic Oncology Group Study.

BACKGROUND: Cyclosporin has been demonstrated to reverse resistance to several antineoplastic agents including cisplatin in vitro. The purpose of this Phase I trial was to study the potential clinical application of cyclosporin modulation of cisplatin and to establish a tolerable dose of cyclosporin when combined with a standard dose of cisplatin of 75 mg/m2. METHODS: A course of therapy consisted of two cyclosporin infusions over 2 hours each, 24 hours apart, with cisplatin given 6 hours after the first dose. Treatment was repeated every 21 days. Cyclosporin was studied in a Phase I fashion at five different levels, from 1-5 mg/kg per dose. Twenty patients with refractory gynecologic cancer received 81 courses of therapy. All patients had received extensive prior chemotherapy containing cisplatin. RESULTS: Grade 4 nephrotoxicity was seen in 4 of 20 patients: 1 treated at 1 mg/kg, 1 at 2 mg/kg, and 2 at 5 mg/kg of cyclosporin. The patient treated at the 1 mg/kg level was a partial clinical responder and tolerated six courses. The patient at the 2 mg/kg level had received 14 prior courses of cisplatin and tolerated only two additional courses before a Grade 4 renal toxicity developed. Grade 4 nephrotoxicity developed in the two patients receiving 5 mg after two courses of chemotherapy. Two of the 20 patients achieved a complete response (CR) and 3 patients achieved a partial response (PR), for a total response rate of 25% (5 of 20). The two women who achieved CR started treatment with symptomatic ascites; one of whom also had multiple pulmonary lesions that were no longer evident after three courses of therapy. CONCLUSIONS: Cyclosporin at a dose of 4 mg/kg per day given for 2 consecutive days in association with 75 mg/m2 of cisplatin can be given with reasonable assurance of safety.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

What is a normal CA125 level?

CA125 is a coelomic epithelial antigen which is widely used to monitor residual disease in patients undergoing chemotherapy for ovarian cancer. Interpretation of serum CA125 levels has been based on a normal value of 35 U/ml which was derived by screening a young, general population of blood donors which included women with intact reproductive systems. This study addresses the issue of what constitutes a normal serum CA125 level following successful surgical therapy for gynecologic malignancy. Three hundred ninety-three CA125 values were measured in 145 patients after an elapsed time of at least 1 year following completion of surgical therapy for early-stage endometrial or cervical adenocarcinoma. All patients were without evidence of recurrent disease. The mean duration of followup was 4.3 years with a median of 3.7 years. Sixty-seven percent of the CA125 values were less than 10 U/ml; 95% were less than or equal to 20 U/ml. The median value for this patient population was 7.5 U/ml with a mode of 7.1 U/ml. There was no correlation between patient age and CA125 levels. These data suggest that the normal value for CA125 used for patient follow-up after treatment for gynecologic adenocarcinoma needs to be redefined. Our data support an upper limit of normal of 20 U/ml and encourage further study on the clinical impact of this new definition.

Adenocarcinoma↗
PubMed1994

Extent of disease as an indication for pelvic radiation following radical hysterectomy and bilateral pelvic lymph node dissection in the treatment of stage IB and IIA cervical carcinoma.

The role of adjuvant pelvic radiation following radical hysterectomy and pelvic lymph node dissection in the treatment of stage IB and IIA cervical cancer is controversial. Patients most likely to benefit from postoperative radiation include those with lesions that invade deeply into the cervical stroma, extend into the parametria, or have metastasized to regional lymph nodes. Between 1977 and 1987, 95 patients were treated with this combined regimen at the University of California Irvine Medical Center and Long Beach Memorial Medical Center, including 30 patients with deep cervical stromal invasion alone, 9 patients with parametrial extension alone, 37 patients with lymph node metastasis alone, and 19 patients with both positive nodes and parametrial extension. The estimated 5-year survival for this high-risk population was 67%. Pelvic recurrences alone occurred in 12 (13%) patients, and 14 additional patients (15%) recurred outside of the radiation field. In the node-positive group, the 5-year survival was 78% when the parametrium was not involved but decreased to 39% when parametrial extension was documented (P < 0.05). Patients with grossly involved nodes or multiple nodal metastases were also more likely to recur. Finally, the estimated 5-year survival for patients with deep cervical stromal invasion as the sole indication for radiotherapy was 73%. A retrospective analysis identified tumor grade and cell type also to be of prognostic importance. Severe complications attributable to radiation combined with radical surgery included two small bowel obstructions and one urinary tract fistula. These data suggest that radical hysterectomy, pelvic lymphadenectomy, and adjuvant radiotherapy produce favorable survival results with limited morbidity in patients with high-risk cervical cancer independent of node status except in that subset of patients with both occult parametrial spread and nodal metastasis.

Adult↗
PubMed1994

Primary vaginal melanoma: improved survival with radical pelvic surgery.

Primary vaginal melanoma is an aggressive and rare gynecological malignancy with < 150 reported cases to date. Historically, patients with this disease have a poor prognosis for all types of treatment. In several studies containing small numbers of patients conservative therapy often has been recommended. Eight patients from our institute with this disease were divided into two groups according to therapy: Group A, radical (4); and Group B, conservative (4). The groups were compared for stage, age, surface area of the lesion, and quality of life. The 2-year survival in Group A (75%) was significantly better than that of group B (0%). There was also found to be an improved survival in patients who had lesions with a surface area < 10 cm2. Age and stage of disease did not affect prognosis. Quality of life was not reduced in the radical group. A review of all reported cases since 1949 (119) was then performed. These were divided into the same Group A, radical (50); and Group B, conservative (69). Again, a statistically significant improved outcome was found with the radically treated patients (48%) when compared to the conservatively treated patients (20%). Our findings suggest that radical surgery for patients with primary vaginal melanoma is recommended in patients with lesions < 10 cm2.

Adult↗
PubMed1994

A new respiratory valve system for measuring oxygen uptake during swimming.

We describe a new respiratory valve system with minimal dead space, which allows measurement of ventilation and oxygen uptake during swimming. The device offers considerable advantages in efficiency and accuracy over current equipment, and can be used in conjunction either with a miniaturized telemetry system for oxygen uptake measurement or with a conventional system. The valve has a low airflow resistance, a small dead space (15 ml), and an electrically operating, closed-circuit pump to remove excess water from the expiratory tube. The external form and the buoyancy of the valve have been hydrostatically and hydrodynamically designed to reduce drag and to ensure a correct mass in the water. To obtain this result a very sophisticated material, carbon fibre, has been utilized. Our studies showed that this respiratory system is ideal for obtaining valid and reliable values of oxygen uptake during swimming, even at high speed and in endurance swimming tests.

Air Pressure↗
PubMed1994

Cost analysis of Hickman catheter insertion at bedside in gynecologic oncology patients.

BACKGROUND: Cost-containment issues are becoming increasingly important in medicine. The current study compares bedside versus operating room insertion of Hickman catheters from a cost and safety standpoint. STUDY DESIGN: A prospective chart review of all patients undergoing Hickman catheter insertion during the study period was performed to determine location of the procedure, rate of successful catheter placement, complications, and cost. RESULTS: Ninety-six patients underwent placement of 108 Hickman catheters during a seven year period. Fifty-three catheters were inserted at bedside while 55 catheters were placed in the operating room. The complication rate was 8 percent for the bedside and 9 percent for the operating room group. Due to anesthesia standby, operating room time, and fluoroscopy, cost analysis revealed a substantial savings of $1,545 per patient if bedside insertion was utilized. CONCLUSIONS: The data indicate that, in select patients, percutaneous insertion of Hickman catheters at bedside is a safe, cost-effective procedure.

Catheterization, Central Venous↗
PubMed1994

Identification of the MN antigen as a diagnostic biomarker of cervical intraepithelial squamous and glandular neoplasia and cervical carcinomas.

A new tumor-associated antigen, MN, has been identified whose expression correlates with the tumorigenic phenotype of HeLa x fibroblast somatic cell hybrids. Because HeLa is a cell line derived from a cervical carcinoma, we investigated the diagnostic utility of MN expression in cervical neoplasia. It was found that normal cervical tissue does not express the antigen, or does so in occasional focal areas of weakly staining reserve cells. In contrast, significant immunoreactivity (immunoperoxidase staining of paraffin-embedded sections) was observed in cervical intraepithelial neoplasias, adenocarcinoma in situ, and frank carcinomas, both squamous cell and adenocarcinoma. Varying patterns of immunoreactivity were observed and were characterized as diffuse, diffuse/focal, or focal. Greater than 90% of dysplastic or malignant tissues showed immunoreactivity. An interesting observation was that normal cervical tissue associated with cervical intraepithelial neoplasias, or adenocarcinoma in situ showed a staining pattern in the reserve cells and/or normal columnar cells that approximated the level of intensity exhibited by the dysplastic tissue. These results indicate that MN antigen expression has potential utility as a biomarker of cervical neoplasms.

Adenocarcinoma↗
PubMed1993

Toxicity of the mitochondrial poison dequalinium chloride in a murine model system.

Dequalinium chloride (DECA), a cationic, lipophilic mitochondrial poison, selectively targets the mitochondrial membrane of certain epithelial carcinoma cells, in which it inhibits cellular energy production. It has demonstrated potency as a cytotoxic agent specific for carcinomas and may provide a novel approach for cancer therapy, either as a single agent or as an adjunct to conventional chemotherapy. The purpose of this study was to determine the toxicity of DECA in the murine model. One hundred female BALB/c mice were divided into three schedule groups. Group one received a single intraperitoneal (ip) dose of DECA at 10, 15, 20, or 25 mg/kg of body weight. Group two received DECA at 6, 7, 8, 9, or 10 mg/kg ip every other day (QOD), and group three received DECA at 10, 11, 12, 13, or 14 mg/kg ip every 7 days. Over a 30- to 60-day period, acute and subchronic toxicities were evaluated on the basis of the following clinical parameters: respiratory distress, weight loss, and mortality. After a single ip administration, we found a maximum tolerated dose of 15 mg/kg and a lethal dose (LD50) of 18.3 mg/kg. Single ip doses of 20 and 25 mg/kg produced > 50% mortality. Histologic examination of the tissues revealed significant damage to the liver and kidneys, with pulmonary congestion occurring secondary to renal-hepatic failure. A cumulative assessment revealed that 60% of the animals tolerated 15 doses of 6 and 7 mg/kg QOD and that 100% tolerated 5 doses of 11 and 12 mg/kg (every 7 days). Higher DECA doses under either regimen induced severe toxic effects and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Characterization of a human ovarian carcinoma cell line: UCI 101.

A new epithelial ovarian carcinoma cell line (UCI 101) has been established from the ascitic fluids and solid tumor of a patient with progressive papillary adenocarcinoma of the ovary shown previously to be refractory to combination chemotherapy consisting of cyclophosphamide, Adriamycin, and cisplatin as well as single-agent chemotherapy of taxol and high-dose cisplatin. The UCI 101 cell line grows well with an in vitro doubling time of 24 hr. The cell line expresses the B 72.3 (Tag 72), CA125, MH99 (ESA), and E29 (EMA) cell surface antigens and AE1/AE3 cytokeratins. This cell line overexpresses (as determined by immunocytochemistry) both p-glycoprotein and the epidermal growth factor receptor. The in vitro drug response to single agents including Adriamycin, cisplatin, dequalinium chloride, etoposide, 5-fluorouracil, taxol, and tumor necrosis factor was examined. Intraperitoneal transplantation of the cells into athymic mice resulted in foci of tumor on all peritoneal surfaces including the viscera and diaphragm ultimately leading to solid bulky disease with massive production of ascites. High levels of CA125 (> 500 units/ml) were detected in the serum of tumor-bearing mice. Cytogenetic analysis of cultured cells shows several marker chromosomes containing deletions, duplications, and translocations. Cytologic and histologic evaluation of the xenograft revealed morphological characteristics identical to those of the original tumor.

Animals↗
PubMed1993

Failure to enhance the in vivo killing of human ovarian carcinoma by sequential treatment with dequalinium chloride and tumor necrosis factor.

Dequalinium chloride (DECA) is a cationic, lipophilic compound with structure similar to the dye rhodamine 123. DECA is selectively accumulated and retained within the mitochondria of carcinoma cells where it acts as a mitochondrial poison by blocking mitochondrial enzymes which can then disrupt cellular energy production, eventually resulting in cell death. In this manner it is similar to the antimitochondrial effects observed with tumor necrosis factor (TNF). We have previously shown that DECA can synergize the in vitro antitumor effects of TNF against a panel of human ovarian cancer cell lines. Those drug studies have been extended to a xenogenic tumor system with a resultant increase in animal survival. Athymic mice were injected intraperitoneally with 2.0 x 10(7) PA-1 human ovarian cancer cells and DECA +/- TNF treatments begun either on Days 3 or 7 postinjection. Peritoneal tumor implantation was not histologically confirmed by Day 3 postinjection but confirmed by Day 7 following tumor cell injection. Single-agent DECA (5 mg/kg; qod) increased animal survival by 37% (P = 0.002) whereas recombinant human TNF (0.5 micrograms/mouse; qod) only increased survival by 13% (P = 0.27) relative to control animals for those animals treated 3 days post-tumor-injection. Sequential DECA/TNF enhanced animal survival by 45% (P = 0.0002) in similarly treated animals. When drug treatment was initiated 7 days following tumor injection, DECA increased survival by 23% (P = 0.04) while TNF had no effect on prolonging animal survival (3% increase; P = 0.79). Combination DECA/TNF increased survival by 23% (P = 0.04). In the UCI-101 ovarian tumor model, single-agent DECA increased survival by 28% (P = 0.04) while TNF treatment stimulated tumor growth (11% decrease in survival; P = 0.006). Combination DECA + TNF resulted in a 41% increase in survival (P = 0.003). No statistical differences were detected between survival rates for single-agent DECA vs DECA + TNF except for the UCI-101 tumor which showed potentiation due to the in vivo stimulatory effects of TNF.

Animals↗
PubMed1993

Measurement of the soluble membrane receptors for tumor necrosis factor and lymphotoxin in the sera of patients with gynecologic malignancy.

The shed portion of the 55 and 75 kDa membrane receptors for tumor necrosis factor (TNF) and lymphotoxin (LT) have been described in the serum of patients with cancer. This study was designed to determine whether serum levels of the 55 and 75 kDa soluble TNF/LT receptors (sTNFr) had clinical significance in patients with gynecologic malignancies. Serum samples from 79 patients with ovarian, endometrial, or cervical cancer were assayed for CA 125 levels by RIA and the 55 and 75 kDa sTNFr levels by ELISA. Receptor and CA 125 levels were also analyzed with respect to disease status and response to treatment in banked serum samples from 14 patients with epithelial ovarian cancer who had been followed clinically for 1-3 years. Patients resulted were compared to serum samples tested from normal donors. We found that serum levels of both sTNFr's were elevated in the 79 patients with various gynecologic malignancies [55 kDa of 3.07 +/- 3.79 ng/ml (P < 0.02) and 75 kDa of 2.93 +/- 1.27 ng/ml (P < 0.001)] compared to 16 normal controls (55 kDa of 0.65 +/- 0.22 ng/ml and 75 kDa of 1.62 +/- 0.37 ng/ml). Serum levels of 55 and 75 kDa TNF/LT receptors were a more sensitive indicator of active cancer and had greater predictive value for detecting tumor in patients with ovarian cancer than CA 125. The sTNFr's were also more sensitive than CA 125 in detecting persistent or recurrent tumor and measuring response to therapy. These preliminary results suggest that measurement of serum levels of 55 and 75 kDa sTNFr's, even though not tumor specific, may be a uniquely new method for identifying and monitoring patients with gynecologic malignancy.

Adult↗
PubMed1993

Salvage intraperitoneal therapy of ovarian cancer employing cisplatin and etoposide: a Gynecologic Oncology Group study.

BACKGROUND: To further explore the potential of salvage intraperitoneal cisplatin-based therapy in patients with small-volume residual ovarian cancer a Phase II trial was conducted by the Gynecologic Oncology Group. METHODS: Ninety-two patients entered into this trial were treated with a regimen of cisplatin (100 mg/m2) and etoposide (200 mg/m2) delivered intraperitoneally every 4 weeks for a maximum of six cycles. RESULTS: Of the 84 patients evaluable for toxicity, grades 3-4 neutropenia, thrombocytopenia, neurotoxicity, and nephrotoxicity were observed in 25, 12, 6, and 9% of patients, respectively. A total of 41 patients were evaluable for response to the treatment program. Of the 25 evaluable patients with favorable pretreatment characteristics (prior response to systemic cisplatin or relapse > 6 months after completing initial chemotherapy), 10 (40%) achieved a surgically documented response (S-R), including 6 (24%) who achieved a surgically documented complete response (S-CR). Of the 16 patients with unfavorable pretreatment characteristics (less than a partial response to systemic cisplatin or a response of < 6 months duration) the S-R rate was only 12% (S-CR: 6%). CONCLUSIONS: In this large multi-institutional cooperative group study, we have confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer who have favorable pretreatment characteristics. The overall impact of these responses on disease-free and overall survival remains to be defined.

Adenocarcinoma↗
PubMed1993

Extraovarian peritoneal serous papillary carcinoma: a case-control retrospective comparison to papillary adenocarcinoma of the ovary.

Since the establishment of extraovarian peritoneal serous papillary carcinoma (EPSPC) as a clinical entity in 1959, less than 250 cases have been described and its clinicopathologic features remain obscure. The present series is a retrospective, case-controlled study comparing the response and survival to cytoreductive surgery followed by cisplatin-based multiagent chemotherapy of 33 women with confirmed EPSPC versus 33 cases with papillary serous ovarian cancer (PSOC). Each EPSPC case was matched to a PSOC control for extent and distribution of disease prior to and following cytoreductive surgery, tumor grade, patient age, and treatment. Additionally, the new Gynecologic Oncology Group criteria for the diagnosis for EPSPC are discussed. There were no significant differences in tumor response to therapy, disease-free interval, and actuarial survival between cases and controls. These data suggest that EPSPC is clinically similar to PSOC and support the need for a prospective clinical trial to compare these two entities further.

Adenocarcinoma, Papillary↗
PubMed1993

To drain or not to drain: a retrospective study of closed-suction drainage following radical hysterectomy with pelvic lymphadenectomy.

The records of 115 patients were reviewed following radical hysterectomy with pelvic lymphadenectomy for early stage (IA2 to IIB) cervical cancer to determine the effectiveness of closed-suction drainage in decreasing postoperative morbidity. In Group 1 (n = 67), closed-suction (Jackson-Pratt) drains were placed bilaterally in the pelvic lymphadenectomy sites, whereas in Group 2 (n = 48), no drains were utilized. The groups were similar for mean age, tumor histology, disease stage, and preoperative serum albumin and total protein. There was no difference in the mean operative time, mean estimated blood loss, or transfusion rate. Likewise, febrile morbidity rates, incidence of pelvic cellulitis, length of postoperative ileus, and total hospital stay were similar. Group 1 had an increased rate of rehospitalization and morbidity directly related to the presence of the drains. The data suggest that prophylactic surgical drainage may not be necessary to prevent postoperative morbidity following radical hysterectomy with pelvic lymphadenectomy and on occasion contributes to postoperative complications.

Adult↗
PubMed1993

Effects of rotation discipline on medical student grades in obstetrics and gynecology throughout the academic year.

OBJECTIVES: Our purpose was to determine whether the sequence of rotation disciplines taken can effect medical student examination scores on the National Board of Medical Examiners Subject Exam score for obstetrics and gynecology. STUDY DESIGN: A retrospective study was conducted of 439 student files for the academic years 1987 through 1991. The final clerkship grades and subject examination scores for internal medicine, pediatrics, psychiatry, surgery, and obstetrics and gynecology were reviewed. RESULTS: It was determined that completion of internal medicine or surgery before obstetrics and gynecology yielded higher scores in obstetrics and gynecology (p < 0.00001), with the largest improvement (from 533 to 586) observed when obstetrics and gynecology followed the internal medicine rotation. CONCLUSION: The sequence of rotation can affect scores on the National Board of Medical Examiners subject examination in obstetrics and gynecology. The largest improvement in student scores was observed when obstetrics and gynecology followed the internal medicine or surgery clerkships.

Curriculum↗
PubMed1993

Effect of administration route and estrogen manipulation on endometrial uptake of Photofrin porfimer sodium.

OBJECTIVE: Our purpose was to evaluate the influence of the route of drug administration and target tissue vascularity on the distribution of a photosensitizer, Photofrin porfimer sodium, in the uterus. STUDY DESIGN: The study was divided in two phases. In phase I 80 mature female rats were hormonally suppressed and then stimulated with estrogen. They were randomized to receive intravenous, intraperitoneal, or intrauterine Photofrin and killed 3, 6, 24, or 48 hours later. Drug distribution and levels were then determined. In phase II 40 female rats were randomized to receive hormonal stimulation, suppression, both, or neither. All received intrauterine Photofrin and were killed 24 hours later. Statistical analysis was performed with the unpaired t test and the two-way analysis of variance. RESULTS: Intrauterine administration was determined to be the simplest and most effective method of delivery because it provided for optimal uptake and distribution (p = 0.05) within the uterus, at lower doses. CONCLUSIONS: Selective localization of photosensitizer within the target tissue suggests that highly selective photodynamic destruction of endometrial tissue can be achieved. Furthermore, the combination of intrauterine administration of photosensitizer with estrogen adjuvant may minimize the most debilitating side effect of Photofrin, cutaneous phototoxicity.

Animals↗