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Biomedical subjects

C D Runowicz

Publications and source records attributed to C D Runowicz.

At least 37 records · Page 2Linked to original sources
PubMed1996

Altered expression of transforming growth factor-beta 1 in cervical neoplasia as an early biomarker in carcinogenesis of the uterine cervix.

BACKGROUND: Transforming growth factor-beta 1 (TGF-beta 1) is a potent growth inhibitor of epithelial cell growth, but can also stimulate stromal cell growth. Loss of responsiveness to TGF-beta 1 or loss of TGF-beta 1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To examine the expression of TGF-beta in early stages of malignant transformation of the uterine cervix, paraffin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN I-III, 12 with microinvasive, and 18 with invasive squamous cell carcinoma were examined using an immunohistochemical technique. Tissues were immunostained with polyclonal antibodies that react with intracellular and extracellular forms of TGF-beta 1. RESULTS: Percent positive staining for the intracellular form of TGF-beta 1 was 100% for normal epithelium, 73.3% for CIN, and 44.1% for invasive carcinomas, (P = 0.002). Percent positive staining for the extracellular form of TGF-beta 1 was 63.6% for stroma underlying normal epithelium, 60% for stroma associated with CIN, and 94.1% for stroma surrounding invasive cancer (P = 0.007). CONCLUSIONS: Decreased expression of intracellular TGF-beta 1 in neoplastic epithelium and increased expression of extracellular TGF-beta 1 in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelia] cells may involve the loss of TGF-beta 1. Tumor progression may be indirectly promoted by TGF-beta 1 secreted into or produced by supporting stromal elements.

Biomarkers, Tumor↗
PubMed1996

Mature results of a phase II trial of concomitant cisplatin/pelvic radiotherapy for locally advanced squamous cell carcinoma of the cervix.

PURPOSE: Patients with locally advanced squamous cell carcinoma of the cervix have a poor prognosis when treated by standard radiotherapy (RT) alone. Factors such as large tumor volume or nodal disease result in pelvic and distant treatment failures. Cisplatin (CDDP), a known radiosensitizer with documented activity in squamous cell carcinomas, was used in a phase II prospective study to evaluate the efficacy of combined chemo/radiotherapy in locally advanced squamous cell carcinomas of the cervix. METHOD: CDDP was administered (20 mg/m2) daily X 5 at 21-day intervals with concomitant external beam and intracavity RT. Standard RT was delivered at 1.8-2.0 Gy/day, 5 fractions per week for 5 weeks. Intracavitary cesium insertions were planned to treat point A to approximately 80 Gy. RESULTS: Fifty-nine patients were enrolled from March 1986 to July 1990. Four patients were voluntarily withdrawn, leaving 55 patients evaluable for response. Of these, 16 were Stage IB/IIA, 11 were Stage IIB, 24 were Stage III, and 4 were Stage IV. The median age of patients enrolled was 47 years (range 27-79). Median follow-up time was 65 months (range 60-113). Histopathologic confirmation of node status was available in 33 patients, of whom 45.5% (15/33) had nodal metastases. Overall response was 96% (CR = 87%, PR = 9.0%) and 3.6% had progressive disease during treatment. Forty-six patients were evaluable at 5 years for overall and disease-free survival. Calculations were based on Kaplan-Meier product limit estimates. The 5-year survival was 73% for Stage IB/IIA, 60% for Stage IIB, 67% for Stage III, and 25% for Stage IV. The disease-free survival at 5 years was 73% for Stage for IB/IIA, 50% for Stage IIB, 67% for Stage III, and 25% for Stage IV. Hematologic toxicity was severe but tolerable. No treatment-related deaths occurred. CONCLUSION: Concomitant CDDP/RT is a safe and tolerable method of treating patients with locally advanced squamous cell carcinoma of the cervix. Our data suggest a benefit in both disease-free and 5-year survival, particularly notable among patients with Stage III disease.

Adult↗
PubMed1996

Phase I/II study of PIXY321 in combination with cyclophosphamide and carboplatin in the treatment of ovarian cancer.

OBJECTIVE: Our purpose was to evaluate the safety and biologic effects of PIXY321 after chemotherapy in patients with ovarian carcinoma. STUDY DESIGN: A multicenter, nonrandomized, phase I/II study of subcutaneously administered PIXY321 after the second cycle of chemotherapy in cohorts of three or more patients at 50, 125, 250, 500, 750, or 100 micrograms/m2 per day. RESULTS: Cyclophosphamide (600 mg/m2) and carboplatin (400 mg/m2) were administered every 28 days to 34 patients. At doses > or = 500 mg/m2 per day, the median nadir platelet and median nadir absolute neutrophil counts in cycle 2 (with PIXY321) compared with cycle 1 (control) were both higher in 13 of 26 (50%) patients. Twenty-one patients were withdrawn from the study. A total of 17 of 21 (81%) were removed for myelosuppression (n = 15) or PIXY321 toxicity (n = 2). A total of 28 of 34 (82%) patients had injection site reactions. Thirty-seven nonhematologic grade 3 events occurred. CONCLUSIONS: At these doses and schedules PIXY321 can be safely administered. Aggressive dosing of cyclophosphamide and carboplatin could not be maintained for six cycles in the majority (62%) of patients.

Adult↗
PubMed1996

Laparoscopic surgery in patients with a ventriculoperitoneal shunt. A case report.

BACKGROUND: Ventriculoperitoneal shunts have afforded many patients the opportunity to expect a normal lifespan. Since laparotomy is more likely to be associated with adhesion formation, potentially reducing the functional capacity of ventriculoperitoneal shunts, laparoscopy may be a preferable surgical alternative. CASE: A 64-year-old woman presented with a pelvic mass requiring surgical evaluation to rule out ovarian cancer. She had a ventriculoperitoneal shunt. Diagnostic laparoscopy was performed without complication. However, due to the significant adhesions from previous surgery, the mass could not be safely evaluated, and the procedure was completed by laparotomy. CONCLUSION: This is the first report of laparoscopy for a pelvic mass in an adult with a ventriculoperitoneal shunt. Laparoscopy is preferable to laparotomy for the replacement or repair of ventriculoperitoneal shunts. Also, laparoscopy should be considered for other problems requiring surgical intervention.

Female↗
PubMed1996

Squamous cell carcinoma in mature cystic teratoma in a young woman: a diagnostic and management dilemma.

Mature cystic teratomas of the ovary are one of the most common ovarian neoplasms found in reproductive age women. The most common type of malignancy associated with ovarian mature cystic teratomas is squamous cell carcinoma. The frequency of this type of malignant degeneration is age related and is most common in the fifth and sixth decade of life. A case of a squamous cell carcinoma which developed in a mature cystic teratoma in a 25-year-old female is presented and issues regarding the diagnosis and management of this rare complication are discussed.

Adult↗
PubMed1996

Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer.

Epidemiological studies continue to identify an association of dietary antioxidant micronutrients in cancer prevention. A number of case-control and cohort studies have demonstrated a relationship between high intake of foods rich in carotenoids, tocopherols, and vitamin C with a reduced risk of certain human malignancies. The purpose of this study was to investigate the comparative plasma levels of a profile of known dietary antioxidants, namely, beta-carotene, lycopene, canthaxanthin, retinol, alpha-tocopherol, and tau-tocopherol. The target population was women with a histopathological diagnosis of cervical intraepithelial neoplasia (CIN) or cervical cancer and a control group. All women resided in the same catchment area (Bronx Borough, New York City) and were of similar inner-city socioeconomic backgrounds representing a fairly homogenous population group. A cross-sectional sample of 235 women was recruited with informed consent. Plasma nutrient levels were measured by reverse-phase high pressure liquid chromatography under study codes. The mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, were significantly lower in women with CIN and cervical cancer. In contrast, the mean plasma level of tau-tocopherol was higher among patients with CIN, while the mean plasma level of retinol was comparable among the groups. There were significant linear trends for all three carotenoids and quadratic trends for alpha- and tau-tocopherol with the degree of cervical histopathology. Plasma beta-carotene concentrations in cigarette smokers were significantly lower regardless of cervical pathology, whereas plasma lycopene and canthaxanthin levels were significantly lower in smokers with CIN. The findings of a decrease in all plasma antioxidant nutrient levels except tau-tocopherol in women with CIN and cancer suggest a potential role for antioxidant deficiency in the pathogenesis of CIN and carcinoma of the cervix, which requires further investigation.

Adult↗
PubMed1996

Analysis of MDR1 expression in normal and malignant endometrium by reverse transcription-polymerase chain reaction and immunohistochemistry.

The purpose of this study was to quantitate the expression of human MDR1 mRNA levels in normal endometrium and in endometrial carcinoma and to determine the association of MDR1 levels with prognostic indicators. Endometrial samples from 43 postmenopausal patients with endometrial carcinoma and 38 patients (controls) with benign disease undergoing hysterectomy were snap-frozen. MDR1 levels were determined by quantitative reverse transcription-PCR (RT-PCR) and compared to sensitive and resistant cell lines. Immunohistochemistry was done with MM4.17, an anti-MDR1 antibody, on paraffin sections, and the results were compared to those obtained from RT-PCR. Data was analyzed using the Kruskal-Wallis and Bonferroni tests, setting the P value at 0.05. In both postmenopausal endometrial tissue and tumors, MDR1 expression was localized to the epithelial cell layer. Comparison of immunohistochemistry and RT-PCR results demonstrated a correlation of 80%. In control patients, MDR1 expression was significantly higher in postmenopausal endometrium (n = 15) than in the proliferative premenopausal endometrium (n = 15; P = 0.0024). MDR1 expression in all tumors was lower than that measured in the postmenopausal controls. Between each tumor group, there was no significant difference in the MDR1 levels observed. MDR1 expression was significantly lower in patients with high nuclear grade (n = 18) tumors when compared to patients with low nuclear grade (n = 14; P = 0.04) tumors. Comparison of MDR1 levels with multiple prognostic indicators for endometrial cancer was only significant for nuclear grade. The data indicate that MDR1 expression is not a major component of the drug resistance observed in primary endometrial tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Promising new therapies in the treatment of advanced ovarian cancer.

Advanced stage ovarian cancer is the most lethal gynecologic cancer. Despite initial response rates of 60-80% with platinum-based chemotherapy, more than 75% of women with this malignancy die of complications associated with this disease. There is a pressing need to find new chemotherapeutic agents for patients with advanced ovarian cancer. Phase II studies have identified paclitaxel as the most active drug in ovarian cancer since the introduction of cisplatin in the 1970s. Phase III studies will define the role of paclitaxel as initial therapy. Camptothecins (topotecan, CPT-11, 9-amino-camptothecin) inhibit topoisomerase I. CPT-11 and topotecan have shown activity in Phase II trials. Gemcitabine, a pyrimidine antimetabolite, has shown activity in Phase II trials. Other promising drugs (docetaxel, treosulfan) are under investigation. Modulation of drug resistance is being explored in Phase I/II studies. Clinical trials have been initiated with buthionine-sulfoximine, an inhibitor of glutathione biosynthesis, which decreases the ability of resistant cells to inactivate platinum compounds and alkylating agents. Cyclosporin has been shown to increase cisplatin cytotoxicity. Phase I trials have demonstrated the feasibility of combining cyclosporin and cisplatin. Phase II trials of cyclosporin analogs (PSC 833) and paclitaxel in refractory ovarian cancer are ongoing. Promising leads in drug development should provide new therapies for patients with ovarian cancer. Further research in the modulation of drug resistance may identify new mechanisms or strategies with which to prevent the emergence of drug resistance.

Antineoplastic Agents↗
PubMed1995

Office laparoscopy as a screening tool for early detection of ovarian cancer.

Laparoscopy is a safe and effective surgical procedures used in evaluating the peritoneal cavity. Laparoscopy, under local anesthesia, has been well documented in the literature. These studies support the concept that laparoscopy can be performed under local anesthesia. Several small studies have addressed the respiratory, cardiac, and hemodynamic changes observed using local anesthesia and suggest that, with proper monitoring, these procedures can be safely performed in an outpatient setting. Optical catheter systems now have diameters ranging from 0.25 mm to 2.5 cm. Image fibers 6 microns in diameter are combined in bundles. The catheter system produces a brighter though grainier picture than views produced by a xenon light source and a 5 mm laparoscope. An Adair Verres needle (18 gauge) is inserted through a 3 mm plastic introducer. The Adair Verres needle is removed and a gas extension tube is used to create a pneumoperitoneum with carbon dioxide. The optical catheter is placed through the extension tube. If a second site is required for biopsy or washings, a 3 mm port can be inserted under direct visualization. Miniature ultrasound transducers have now been developed as a means of imaging the internal structures of the ovary. These transducers, housed in #3.5-6.2 French catheters, can be passed through a laparoscope, adding a new dimension to laparoscopy. Although the technology of office laparoscopy as a means of detecting early ovarian cancer exists, it has limited applicability for screening the population at large. It may be more useful as secondary or tertiary testing in the work-up of patients suspected of having ovarian cancer.

Ambulatory Care↗
PubMed1995

A prospective randomized comparison of an attached silver-impregnated cuff to prevent central venous catheter-associated infection.

The VitaCuff catheter, a specialized central venous catheter (CVC) with an attached silver-impregnated cuff, is designed to permit percutaneous placement and prolonged venous access. A prospective randomized study was undertaken comparing the VitaCuff with standard triple lumen catheters to determine if the VitaCuff reduces infection during extended use. All consenting patients underwent percutaneous placement of subclavian lines. By study design, control and VitaCuff catheters could remain in site for up to 7 and 14 days, respectively. Cultures were obtained from the preinsertion skin site, and upon removal, from the skin, hubs, infusates, CVC tip, and cuff. Statistical methods included chi 2, the Student t test, and the log-rank test on Kaplan-Meier estimates. Of 133 patients completing this study, 64 patients (48.1%) underwent VitaCuff placement and 69 patients (51.8%) served as controls. In 124 patients (93.2%), the indication for catheter placement was for perioperative care. Overall, 67 patients (50.4%) required central venous access > 7 days, necessitating > or = 1 additional line in 29 patients (21.8%). The incidence of pneumothorax per patient from the initial central line insertion was 4/104 (3.85%), significantly lower than the 4/29 (13.8%) incidence during secondary catheter placement (P = 0.046). Culture results upon catheter removal demonstrated a reduction in colonization of skin sites and hubs for the VitaCuff patients, but not for catheter tips or infusates. Regardless of the type of catheter used, colonization was dependent upon duration of insertion. The incidence of catheter-related sepsis was 6.8%, and did not differ significantly between the study groups. Multiple CVC insertions increase the incidence of pneumothorax. Because VitaCuff catheters permit extended access up to 14 days without increasing the incidence of sepsis, we recommend their use in patients who require prolonged CVC access.

Catheterization, Central Venous↗
PubMed1995

Gynaecologic effects of tamoxifen.

Tamoxifen, an estrogen antagonist, is widely used as adjuvant therapy in patients with breast cancer. Its efficacy in increasing survival and reducing recurrence rates has been demonstrated in several European and American studies. However, its effects appear to be tissue specific. Tamoxifen exerts an estrogen effect (agonist) on the endometrium, myometrium and vagina. An increase in uterine cancer has been confirmed in several placebo-controlled clinical trials. Due to the widespread use of this drug, it is timely to review the gynecologic effects of tamoxifen.

Antineoplastic Agents, Hormonal↗
PubMed1995

Lack of efficacy of interferon-alpha therapy in recurrent, advanced cervical cancer.

Human papillomavirus (HPV) is associated with 65-95% of in situ or early invasive squamous cell carcinomas of the cervix. A multiinstitutional, prospective phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) to study the activity of IFN-alpha 2b in women with metastatic or locally recurrent cervix cancer. The activity of IFN-alpha 2b was correlated with the presence of HPV as measured by Southern blot hybridization or polymerase chain reaction techniques in 17 patients. All patients had failed prior definitive therapy with surgery, radiation, and chemotherapy. IFN-alpha 2b was administered at 10 MU/m2 subcutaneously three times per week. Among 31 patients enrolled, 3 achieved a clinical response to treatment. Tumor was accessible for biopsy in 17 patients. The presence of HPV was assayed by Southern blot hybridization (2 of 17) and/or polymerase chain reaction (PCR) technology (15 of 17). Of the 17 assays, 16 were informative. HPV was detected in 5 of 16 patients. Of 5 HPV-positive women, 2 responded to treatment, versus 1 of 11 HPV-negative women, thus not permitting reliable statistical analysis. It is concluded that IFN-alpha 2b has only minimal activity against advanced, recurrent cervical cancer.

Adult↗
PubMed1995

Surgical management of patients with endometrial cancer and cervical involvement.

OBJECTIVE: To evaluate the role of extrafascial hysterectomy in the management of women with endometrial carcinoma and cervical involvement. METHODS: A review of 238 medical records of patients with endometrial cancer treated at the Weiler Hospital of the Albert Einstein College of Medicine and Montefiore Medical Center from 3/86 to 3/91 was performed. Thirty-one patients were selected based on histopathologic documentation of cervical involvement in the surgical specimen. Fisher exact probability test, Kaplan-Meier and Log-Rank procedures were used for the statistical analysis of the data. RESULTS: Two patients were excluded as they received preoperative radiotherapy. Nineteen patients had Stage II disease and ten were found to have Stage III (two for positive washings, eight for positive pelvic and/or para-aortic nodes). Sixteen of 19 patients with Stage II disease received postoperative pelvic radiotherapy. Six patients with Stage III received postoperative radiotherapy, four with Stage III received chemotherapy. The probability of survival for Stage II patients was 72%, for Stage III 33% and the entire group was 60% (median follow-up 55 months). CONCLUSIONS: Extrafascial hysterectomy was performed without major complications in 86% of patients with endometrial carcinoma and microscopic cervical involvement. This procedure may be considered an adequate first line of treatment for patients without gross cervical spread of the disease.

Aged↗
PubMed1995

Cutaneous metastases from squamous cell carcinoma of the vulva. A case report and review of the literature.

Cancer of the vulva, the fourth most common malignancy of the female genital tract, accounts for approximately 4% of all gynecologic malignancies. Only one prior case of a cutaneous metastasis from a vulvar cancer has been previously reported and involved a FIGO Stage III (T2N1M0) lesion. We report a patient with Stage II (T2N0M0) vulvar carcinoma who developed cutaneous metastases. This case demonstrates the ability of vulvar carcinoma to disseminate hematogenously, despite complete surgical resection with negative skin margins, and negative lymph nodes. In addition, this case emphasizes the importance of careful and close follow-up of all patients with vulvar carcinoma.

Carcinoma, Squamous Cell↗
PubMed1995

The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma.

Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (CSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 +/- 1.8 microgram/liter) were significantly elevated compared with levels found in the 32 controls (3.5 +/- 1.1 microgram/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%), with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and <0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the expression of the protein in these tissues. Reverse transcription-PCR demonstrated the presence of mRNA for both the transmembrane and secreted forms of CSF-1 in all tumors analyzed. These results therefore support the hypotheses that CSF-1 and CSF-1R are overexpressed in endometrial adenocarcinoma, that levels of expression significantly correlate with clinicopathological risk factors for poor outcome, and that CSF-1 in association with its receptor via autocrine, juxtacrine, and/or paracrine interactions has a causal role in endometrial adenocarcinoma development and proliferation.

Adenocarcinoma↗
PubMed1994

Single-use percutaneous catheters for intraperitoneal P32 therapy.

BACKGROUND: Intraperitoneal (IP) radioactive chromic phosphate (P32) remains investigational in the treatment of patients with ovarian and/or endometrial cancer. Single-use percutaneously placed catheters offer the advantage of therapy without additional surgery. METHODS: Between August, 1986 and October, 1992, 25 patients underwent bedside percutaneous catheter placement under local anesthesia without ultrasonographic or radiologic guidance, using a specialized central venous catheter. RESULTS: Catheter insertion was successful in 22 of 25 patients (88%) with good IP distribution. Of these, 18 of 22 patients (82%) underwent successful catheter placement with one attempt and 4 of 22 (18%) after one to three additional attempts. The technical failure rate was 12%. Multiple catheter placement attempts were associated with an increased incidence of complications (r = 0.63). Bowel entry occurred in 4 of 25 patients (16%) during 5 of 43 attempts at catheter placement (12%) but was without clinical sequelae. The likelihood of bowel entry significantly increased with more than two attempts (P = 0.02). A median of 39 days (range, 7-156 days) elapsed between the preceding laparotomy and catheter insertion. CONCLUSIONS: Percutaneous catheter placement is successful and well tolerated in the majority of patients and should be considered for patients receiving IP P32.

Adult↗