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Biomedical subjects

G Deppe

Publications and source records attributed to G Deppe.

At least 19 recordsLinked to original sources
PubMed1992

Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms.

To determine if gynecologic malignancies are candidates for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) therapy we measured vitamin D receptor (VDR) levels in 11 tumor specimens using a radiolabeled ligand-binding assay. VDR was demonstrated in 3 of 6 ovarian tumors and 1 of 1 uterine sarcomas, but not in endometrial tumors (2), cervical tumors (1), or Krukenberg tumors (1). Scatchard plots revealed that [3H]1,25(OH)2D3 was bound to a single class of high-affinity (Kd = 0.3 to 0.6 nM), saturable sites characteristic of authentic 1,25(OH)2D3 receptors. Specificity of binding activity for 1,25(OH)2D3, the active vitamin D3 metabolite, was demonstrated by failure of 25-hydroxy- and 24,25-dihydroxyvitamin D3 to compete effectively against 1,25(OH)2D3 binding in total cellular tumor extracts. The ovarian carcinoma cell line NIH:OVCAR3 was shown to possess VDR (binding capacity = 137 fmol/mg protein, Kd = 0.48 nM). A 3-day incubation of NIH:OVCAR3 cells with 100 nM 1,25(OH)2D3 resulted in 49% inhibition of cell growth. The growth inhibition of an ovarian carcinoma line and the observation that 36% of gynecologic tumors assayed were shown to be VDR-positive suggest that further study is warranted to delineate the mechanism and possible therapeutic aspects of 1,25(OH)2D3 action in gynecologic tumors.

Calcitriol↗
PubMed1991

Combination chemotherapy for advanced adenocarcinoma of the cervix.

A patient with advanced adenocarcinoma of the cervix was treated only with cisplatin and mitomycin C (MMC). The regimen achieved a complete response, confirmed by chest radiograph and computed axial tomography scan, lasting 50 months. The patient is alive with recurrent disease 59 months after diagnosis. No severe drug-related toxicity occurred.

Adenocarcinoma, Mucinous↗
PubMed1991

Combined effects of 1,25-dihydroxyvitamin D3 and platinum drugs on the growth of MCF-7 cells.

The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and platinum treatments (both singly and combined) on the growth inhibition of MCF-7 cells, an epithelial cell line shown to possess specific receptors for 1,25(OH)2D3, were evaluated. The inhibitory effects of 1,25(OH)2D3 and platinum on MCF-7 cell proliferation in vitro were time and dose related. The data showed that 10 nM and 100 nM 1,25(OH)2D3 inhibited MCF-7 cell growth by 10.8 +/- 2.4% and 34.9 +/- 0.5% (mean +/- SE), respectively. The degrees of growth inhibition induced by 0.2 to 200 micrograms/ml of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin) were slightly less than those induced by 0.02 to 20 micrograms/ml of cis-diamminedichloroplatinum(II) (cisplatin). The combined administration of 10 nM and 100 nM 1,25(OH)2D3 with either carboplatin (200 to 0.2 micrograms/ml) or cisplatin (20 to 0.02 micrograms/ml) was evaluated. Addition of 1,25(OH)2D3 to the platinum resulted in marginal to marked enhancement of growth inhibition over that observed with either platinum alone. The strength of these interactions varied inversely with the dose of the platinum drugs. Evaluation of drug interactions with isobolograms showed that at near-serum levels, carboplatin or cisplatin interacted synergistically with 1,25(OH)2D3 to inhibit MCF-7 cell growth. Our findings suggest potential usefulness in combining 1,25(OH)2D3, a biological modifier, with cytotoxic agents for the treatment of malignant disease.

Ascites↗
PubMed1991

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult↗
PubMed1991

High-dose-rate afterloading brachytherapy, external radiation therapy, and combination chemotherapy in poor-prognosis cancer of the cervix.

Fourteen patients with poor-prognosis cervical cancer were treated with concurrent chemotherapy (cisplatin and mitomycin-C), external radiation therapy (RT), and high-dose-rate (HDR) brachytherapy. Pelvic RT was delivered as (a) external-beam radiation (four-field box technique, 40.0 Gy), (b) brachytherapy using HDR 60Co or 192Ir (3.80 Gy/fraction, thrice weekly; total dose, 46.83 Gy) with intrauterine stent, and (c) parametrial boost using an AP field with custom-fabricated step wedges. Post-radical-hysterectomy patients received 50.40 Gy external RT and 3.23 Gy/day vaginal cylinder HDR at 1/2-cm depth (total dose, 16.15 Gy). Complete clinical and radiographic response was noted in all evaluable patients who are alive with no evidence of disease, 3 to 27 months after completion of therapy (median, 9 months). Toxicity consisted of grade 2 to 3 hematologic toxicity (4 patients) and nausea and vomiting in all, but grade 3 in only 2 patients. One patient had grade 2 diarrhea. The only major complication (small bowel obstruction) occurred in a patient with lupus vasculitis. This pilot study demonstrates the feasibility of this regimen in an outpatient setting with acceptable toxicity. More prolonged follow-up of our patients is required to determine its impact on long-term survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Ovarian cancer. Advances in management.

Substantial progress has been made in understanding the biologic behavior of ovarian cancer and in assessing disease states and response to therapy with transvaginal sonography, CT scan, and tumor markers such as CA-125. There is no longer controversy regarding the importance and feasibility of adequate surgical staging, the need for cytoreduction, and the utility of cisplatin- or carboplatin-based combination chemotherapy in the management of patients with ovarian cancer. Increasing chemotherapy dose through escalated systemic doses or intraperitoneal administration, revising multidrug resistance, the use of biologic response modifiers, and the development of new methods of chemosensitivity testing may help improve the current 5-year survival rate of less than 30% for patients with stage III ovarian cancer. Significant improvement in screening tests and diagnostic capabilities will be necessary for a dramatic increase in survival.

Adult↗
PubMed1991

Intraperitoneal doxorubicin in combination with systemic cisplatinum and cyclophosphamide in the treatment of stage III ovarian cancer.

Recent concepts and technical development have led to the successful application of the principles of intraperitoneal chemotherapy in the management of advanced epithelial ovarian cancer. In a pilot study we treated five patients with Stage III ovarian cancer after maximal cytoreductive effort (residual tumor less than or equal to 2 cm) with combination chemotherapy consisting of intraperitoneal doxorubicin and intravenous cisplatinum and cyclophosphamide. Although intraperitoneal doxorubicin demonstrates a pharmacologic advantage over the intravenous administration of this drug, its use is limited by severe abdominal pain requiring narcotic analgesics. Chemical peritonitis and extensive peritoneal adhesions are frequent complications. The role of combination intraperitoneal and systemic chemotherapy in ovarian cancer warrants further study.

Aged↗
PubMed1990

Detoxifying enzymes in human ovarian tissues: comparison of normal and tumor tissues and effects of chemotherapy.

Many anticancer drugs exert their cytotoxic effects via formation of oxygen free radicals. Cellular thiols, glutathione (GSH)-dependent enzymes and other redox enzymes are involved in the metabolism of these anticancer drugs and of the oxygen free radicals that may be generated during their metabolism. We quantified these biochemical parameters in cytosol from human ovarian tissues. We compared non-protein thiol levels, GSH transferase, GSH peroxidase, superoxide dismutase, catalase, DT diaphorase and aldehyde dehydrogenase activity in serous ovarian tumors (n = 15), other malignant ovarian tumors (n = 12), benign ovarian tissue (n = 10) and histologically normal ovarian tissue (n = 12). Mean GSH transferase and DT diaphorase activities were similar in serous and other malignant ovarian tumors. GSH transferase activity was decreased in malignant tissues relative to normal and benign tissues. Mean DT diaphorase and superoxide dismutase activities were increased in the malignant tissues, although this was not statistically significant. The mean levels of all enzymes except superoxide dismutase and aldehyde dehydrogenase in benign tissues were fairly similar to the mean levels found in normal tissue samples. Tissues from patients with serous ovarian tumors, who had received cyclophosphamide and cisplatin prior to surgery, also were analyzed (n = 7). Except for aldehyde dehydrogenase, all the parameters measured were decreased in these samples relative to serous tissue from untreated patients. These biochemical analyses may be useful in understanding the mechanisms involved in the response to chemotherapy.

Adult↗
PubMed1990

Pharmacokinetics of intraperitoneal doxorubicin in combination with systemic cyclophosphamide and cis-platinum in the treatment of stage III ovarian cancer.

The pharmacokinetics of intraperitoneal doxorubicin in three previously untreated patients with ovarian cancer are described. All patients were maximally cytoreduced (largest residual tumor less than or equal to 2 cm). The average total body clearance (TBC) was 16.3 ml/kg/min (range 10.6-20.4 ml/kg/min) and the mean volume of distribution (VD) was 42.4 liter/kg (range 27.6-46.9 liter/kg). Half-life of elimination (t 1/2 beta) was 2.6 hr. In spite of a therapeutic advantage of 60 when administered intraperitoneally, prohibitive local toxicity limited the use of doxorubicin via the intraperitoneal route in patients with ovarian cancer.

Aged↗
PubMed1990

Benign teratoma of the omentum and ovary coexistent with an ovarian neoplasm.

Benign cystic teratoma of the omentum is a rare abdominal tumor. Review of the literature describes seven reported cases of omental teratomas in association with ovarian teratomas. Our patient is a 68-year-old woman who presented with an asymptomatic abdominal mass and uterine prolapse. Ultrasound revealed a right-sided, cystic and solid pelvic mass. CT scan revealed a second mass with calcifications situated along the right iliac crest. This is the first description of an omental teratoma in association with a benign ovarian cystic teratoma coexistent with a malignant neoplasm. Possible etiologies of the present case are discussed and additional literature investigated.

Aged↗
PubMed1990

Results of treatment in locally advanced carcinoma of the endometrium.

The impact of treatment on survival was analyzed in 106 patients with carcinoma of the endometrium stage II (n = 61) and stage III (n = 45). There was no significant difference in survival in patients with stage II who were treated with radiation therapy alone or with combination of surgery and radiation therapy. Their five-year actuarial survival was 74.5% and 71.3% respectively (p = greater than 0.05). However, combined treatment was associated with significantly superior survival in patients with stage III disease where the survival was 57.3% versus 17.5% in patients who received irradiation alone (p = 0.01). Diagnosis of stage III disease based upon clinical (CS III) or pathological (PS III) findings was responsible for this difference in survival. Patients with CS III whose tumor could not be resected because of its extent carried poorer prognosis. Patients with stage II had excellent tumor control in pelvis as compared to patients with stage III. Treatment-related complications were minimal. Overall survival of patients with stage III was poor (33.8%) due to a high rate of pelvic and/or extrapelvic recurrences.

Adenocarcinoma↗
PubMed1990

Debulking of pelvic and para-aortic lymph node metastases in ovarian cancer with the cavitron ultrasonic surgical aspirator.

Six patients with metastatic ovarian cancer with extensive involvement of the pelvic and/or para-aortic lymph nodes underwent surgical debulking with the Cavitron Ultrasonic Surgical Aspirator. Intraoperative and postoperative morbidity was minimal. It is suggested that this technique may be used for cytoreductive surgery in combination with standard surgical techniques.

Adult↗
PubMed1990

Prochlorperazine and transdermal scopolamine added to a metoclopramide antiemetic regimen. A controlled comparison.

Cisplatin-induced nausea and vomiting occurs both acutely and over a prolonged period of time. These symptoms may be incapacitating and are frequently given as a reason to discontinue therapy. We compared prochlorperazine and transdermal scopolamine when added to a standardized metoclopramide antiemetic regimen. Twenty-seven patients receiving cisplatin at 100 mg/m2 were randomly assigned to one of the two treatment arms. Patients were observed during chemotherapy and answered a standard questionnaire 24-26 hours later. Among similar treatment groups no differences were seen regarding the number of emetic events, level of nausea, degree of sedation or overall acceptability of one treatment arm or another. While not superior to prochlorperazine, transdermal scopolamine is a useful antiemetic agent and can be combined with metoclopramide in an attempt to reduce cisplatin-induced nausea and vomiting. Further evaluation of this approach is needed.

Administration, Cutaneous↗
PubMed1989

Radiation therapy in stage II carcinoma of the endometrium.

A retrospective analysis of 61 patients with Stage II carcinoma of the endometrium was carried out. Our results suggest that when given carefully and adequately, radiation therapy alone is as effective as a combination of surgery and irradiation and is well tolerated. Five-year actuarial survival was 74.5% in patients treated with radiation therapy alone (16 patients) as compared to those patients who received either preoperative radiation (35 patients) or postoperation radiation (ten patients) where the survival was 70.8% and 78.3%, respectively (P greater than or equal to 0.05). Tumor was controlled in the pelvis in 93.4% of patients. Complications of treatment were seen in 8.2%. With the exception of one patient with bowel obstruction requiring surgery, the rest of the complications were minor. From these results, it appears that a planned radiotherapy is a good alternative to combination of surgery and irradiation.

Combined Modality Therapy↗
PubMed1989

Actinomycosis mimicking pelvic malignancy.

Pelvic actinomyces, usually a complication of an intrauterine device (IUD), is uncommon and may present a diagnostic dilemma because of an atypical clinical presentation. We present a patient with a cervical tumor, extensive parametrial induration with involvement of the posterior bladder wall, and regional lymph nodes which mimicked advanced cervical cancer and presented a significant diagnostic problem.

Actinomycosis↗
PubMed1989

Retroorbital metastases in ovarian cancer.

We report a patient with unilateral metastasis to the posterior orbit from poorly differentiated ovarian carcinoma with neuroendocrine features. Ocular metastases from pelvic neoplasms have been reported infrequently; however, we report the first case of an ovarian cancer with orbital metastasis as the initial presenting symptom.

Aged↗