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Biomedical subjects

E Fenig

Publications and source records attributed to E Fenig.

At least 19 recordsLinked to original sources
PubMed2006

Radiation treatment for ductal carcinoma in situ (DCIS): is a boost to the tumor bed necessary?

The aim of the presented study was to evaluate the long-term outcome of breast-conserving surgery and radiation for the treatment of ductal carcinoma in situ (DCIS) and the role of the radiation boost to the tumor bed. The files of 75 women with DCIS treated by breast-conserving surgery followed by definitive radiation from 1988 to 1997 were reviewed for demographic data, prognostic variables, radiation dose, radiation boost, recurrence, and outcome. Total radiation dose was 5000 cGy delivered in 25 fractions. Twenty patients (26.7%) received an additional boost to the tumor bed of 1000 cGy in 5 fractions. Median follow-up time was 81.5 months (range, 22-145). Pearson correlation coefficient and its significance was calculated between the variables. Log rank test was used to analyze differences in local recurrence rates between patients who did or did not receive a boost, and a Cox regression model was fitted to the data to predict recurrence. Ten patients (13%) had local recurrence; one patient showed lymphatic spread. Histopathologic examination revealed DCIS in 6 cases (60%) and invasive duct carcinoma in 4 (40%)(one minimally invasive). The recurrence group included 3 of the 20 patients who received a radiation boost (15%) and 7 of the 55 who did not (12.7%) (p=0.7). Correlation analysis of patient characteristics, prognostic factors, and treatment was significant only between mastitis as the presenting symptom (n=4) and longer time to recurrence (p=0.02). The recurrence rate in the present study was similar to other series of conservative treatment for DCIS of the breast. No additional value was found for the radiation boost. Larger controlled randomized studies are needed to confirm these findings.

Adult↗
PubMed2005

Imatinib mesylate (Gleevec) downregulates telomerase activity and inhibits proliferation in telomerase-expressing cell lines.

Imatinib mesylate (IM) is a tyrosine kinase inhibitor, which inhibits phosphorylation of downstream proteins involved in BCR-ABL signal transduction. It has proved beneficial in treating patients with chronic myeloid leukaemia (CML). In addition, IM demonstrates activity against malignant cells expressing c-kit and platelet-derived growth factor receptor (PDGF-R). The activity of IM in the blastic crisis of CML and against various myeloma cell lines suggests that this drug may also target other cellular components. In the light of the important role of telomerase in malignant transformation, we evaluated the effect of IM on telomerase activity (TA) and regulation in various malignant cell lines. Imatinib mesylate caused a dose-dependent inhibition of TA (up to 90% at a concentration of 15 microM IM) in c-kit-expressing SK-N-MC (Ewing sarcoma), SK-MEL-28 (melanoma), RPMI 8226 (myeloma), MCF-7 (breast cancer) and HSC 536/N (Fanconi anaemia) cells as well as in ba/F3 (murine pro-B cells), which do not express c-kit, BCR-ABL or PDGF-R. Imatinib mesylate did not affect the activity of other DNA polymerases. Inhibition of TA was associated with 50% inhibition of proliferation. The inhibition of proliferation was associated with a decrease in the S-phase of the cell cycle and an accumulation of cells in the G2/M phase. No apoptosis was observed. Inhibition of TA was caused mainly by post-translational modifications: dephosphorylation of AKT and, to a smaller extent, by early downregulation of hTERT (the catalytic subunit of the enzyme) transcription. Other steps of telomerase regulation were not affected by IM. This study demonstrates an additional cellular target of IM, not necessarily mediated via known tyrosine kinases, that causes inhibition of TA and cell proliferation.

Animals↗
PubMed2002

Prediction of outcome in locally advanced breast cancer by post-chemotherapy nodal status and baseline serum tumour markers.

In spite of the apparent improvement in outcome in locally advanced breast cancer, the prognosis remains dismal in many patients. The aim of this study was to define prognostic subgroups within this heterogeneous entity. Between 1990 and 1999, 104 consecutive patients with locally advanced breast cancer were treated by a multimodality programme consisting of 4-6 courses of CAF induction chemotherapy followed by surgery, breast-conserving when feasible. In most cases, chemotherapy was then resumed, up to a total of eight courses, followed by locoregional radiation therapy. Patients with hormone receptor-positive tumours received tamoxifen (20 mg day(-1)) for 5 years. At a median follow-up of 57 months, the 5-year overall survival for the entire group and the disease-free survival for the 94 operated patients were 65% and 53%, respectively. Univariate analysis identified 10 prognostic factors of overall and disease-free survival, of which four retained significance on multivariate analysis: inflammatory breast cancer (P=0.0000, P=0.0004, respectively), baseline tumour markers (P=0.003 for both), post-chemotherapy number of involved nodes (P=0.003; P=0.017) and extracapsular spread (P=0.052; P=0.014). In conclusion, besides inflammatory features, baseline tumour markers and post-chemotherapy nodal status are strong predictors of outcome in locally advanced breast cancer.

Adult↗
PubMed2001

Second neoplasms in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) has been associated with a high incidence of other skin tumors and hematological malignancies. The purpose of this study was to analyze data from the Israel Cancer Registry regarding the incidence of second neoplasms in patients with MCC and their impact on survival. METHODS: Sixty-seven patients in whom MCC was diagnosed between 1983 and 1999 were included. Data were collected on age, gender and ethnic origin, dates of diagnosis of MCC and any other neoplasm, and date and cause of death, if applicable. Comparison of MCC-specific survival, estimated by the Kaplan-Meier product limit method, between patients with no other neoplasm and those with second primary tumors was performed by log rank test. Age-specific standardized incidence ratio (SIR) was calculated using 5751 age- and ethnic-matched malignant melanoma patients as a control group. RESULTS: Seventeen patients (25%) had a second neoplasm before, concomitant with, or after the diagnosis of MCC; 2 of them also had a third primary tumor. The SIR was 2.8 (95% CI; range, 1.38-4.22), significantly higher than the control group. Almost half the tumors were squamous cell carcinomas, either skin or head and neck, and most of the remainder were hematological malignancies or breast and ovarian adenocarcinomas. On univariate analysis, the presence of another neoplasm, regardless of its chronology, was associated with higher MCC-specific mortality (65% vs. 40% for patients with MCC only; P = 0.022). Analysis of only those patients in whom a second neoplasm developed during follow-up after treatment for MCC yielded an estimated actuarial risk of developing a second primary of 2.1% for each year of observation. CONCLUSIONS: There is a high incidence of second neoplasms, including noncutaneous solid tumors, in patients with MCC. The presence of these neoplasms, whether they appear before, after, or simultaneously with MCC, is associated with a higher MCC-specific mortality.

Adult↗
PubMed2001

Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor.

Recent studies from our laboratory have revealed that basic fibroblast growth factor (bFGF) selectively inhibits the proliferation of human MCF-7 breast cancer cells. It has also been shown to enhance cis-platinum-induced apoptosis, decrease levels of the anti-apoptotic gene product bcl-2, and increase levels of the cyclin-dependent protein kinase inhibitor p21/WAF1/Cip1. Transforming growth factor beta-1 (TGFbeta1), a cell growth regulator has been found to have an inhibitory effect on breast cancer cells. The aim of the present study was to evaluate the possible role of TGFbeta1 in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGFbeta1 mRNA expression in the cells and enhanced the secretion of TGFbeta1 into culture medium. However, exogenous addition of TGFbeta1 neither led to a decrease in bcl-2 nor induced an increase in the levels of p21/WAF1/Cip1 and neutralizing antibodies to TGFbeta1, did not reverse bFGF-induced G1 arrest northe increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGFbeta1 abrogated the antiproliferative effects and inhibited the induction of p21/WAF1/Cip1 by bFGF in MCF-7 cells. These data suggest that the anti-proliferative effects of bFGF in human MCF-7 breast cancer cells are mediated by endogenous TGFbeta1, while exogenous TGFbeta1 does not mimic all the effects of bFGF on these breast cancer cells. These findings provide an important basis for further investigations into the autocrine and paracrine processes that control the growth of breast cancer cells.

Angiogenesis Inhibitors↗
PubMed2001

Pregnancy and radiation.

The risk of foetal irradiation during pregnancy is discussed. It seems that, due to the low level of X-ray exposure to the foetus, neither diagnostic radiography nor nuclear diagnostic examination justifies termination of pregnancy. Radiotherapy for breast cancer, Hodgkin's disease and cervical cancer in pregnant women is reviewed. Radiation therapy for breast cancer is not an absolute contraindication for pregnancy and the risk-benefit assessment should be discussed with the mother. The risk to the foetus during radiotherapy for supradiaphragmatic Hodgkin's disease appears to be minimal, provided special attention is paid to the treatment techniques and the foetus is adequately shielded. Radiotherapy for the treatment of cervical cancer may be necessary during pregnancy, but the timing should be adjusted taking into consideration gestational age. Offspring of cancer patients who were treated by radiotherapy appear to be at little risk of childhood cancer or birth defects. Cancer patients should not be discouraged from having children and can expect a good outcome of pregnancy. However, in the non-pregnant woman, to further reduce any risk it is advisable to delay pregnancy for 12 months following completion of radiation therapy.

Breast Neoplasms↗
PubMed2001

Successful use of high dose rate brachytherapy for non-malignant bronchial obstruction.

High dose rate (HDR) endobronchial brachytherapy is a palliative treatment for symptomatic airway obstruction by malignant tumours. We report a novel use of HDR brachytherapy for treating non-malignant bronchial obstruction. The patient had a metal stent placed in a reconstructed airway after a bronchial tear to ensure patency. Granulation tissue formation in and around the stent caused symptomatic occlusion of the airway, necessitating multiple laser applications. A single treatment of HDR brachytherapy (1000 cGy) was delivered following laser therapy. The patient remains well 15 months after treatment with no evidence of recurrent granulation tissue formation on bronchoscopy. HDR brachytherapy is an effective treatment for non-malignant airway obstruction.

Adult↗
PubMed2000

[Breast cancer after mantle field irradiation for Hodgkin's disease].

Effective use of modern therapeutic modalities results in the cure of 75%-80% of Hodgkin's disease patients, regardless of stage. The major threat to continued survival is, therefore, not recurrent disease but development of second malignancies. Recent reports have firmly established the increased risk of breast cancer developing in women treated with mantle field irradiation. We describe 3 women who developed breast carcinoma following mantle field irradiation for Hodgkin's disease. Their clinical course was consistent with that reported in larger series. They were relatively young when irradiated and there was a long interval between radiation therapy and the diagnosis of breast cancer. Review of the literature shows that there may be a role for prophylactic mastectomy after irradiation for Hodgkin's disease.

Adult↗
PubMed2000

[High dose endobronchial brachytherapy for malignant airway obstruction: first study of 30 patients].

Brachytherapy is especially suitable for palliative treatment of endobronchial tumors adjacent to internal organs that might be damaged by intensive external beam radiation, but are easily accessed with a flexible bronchoscope. This treatment is mostly palliative. 30 patients underwent such palliative high-dose endobronchial brachytherapy to alleviate malignant airway obstruction. With the aid of a flexible fiberoptic bronchoscope an endobronchial catheter was inserted adjacent to the tumor and treatment delivered using a 192Ir remote afterloader for 5-10 min, in 2 or 3 sessions. There was symptomatic improvement in 26 (86%) and objective improvement in 27 (90%). 1 patient died of hemoptysis.

Aged↗
PubMed2000

Standard and nonstandard applications of sentinel node-guided melanoma surgery.

Identification and histologic study of the sentinel node (SN) is an acceptable, yet not firmly established, guide for treating intermediate-thickness melanoma. This study widens the range of applications of this technique. We included 97 patients with intermediate-thickness melanoma lesions or lesions for which there is no standard treatment. Fifty-six underwent preoperative lymphoscintigraphy, and all underwent intraoperative lymphatic mapping (IOLM) using blue dye, followed by frozen section study and total node processing by serial sections. Elective lymph node dissection was performed in cases of metastasis to the sentinel node or technical failures with high risk. Four categories were defined: (A) intermediate-thickness lesions (mean 2.27 mm) (n = 45); (B) thin lesions (mean 1.14 mm) with risk factors of regional failure (n = 27); (C) lesion thickness close to but more than 4 mm (n = 10); and (D) lesions of undetermined thickness (n = 15). Median follow-up was 30 months (range 13-51 months). Intraoperative lymphatic mapping successfully identified the sentinel node (SN) in 93% of basins explored. Metastases were detected in 11 SNs. There were three lymph basin recurrences in patients with previously negative SNs, all salvaged by therapeutic lymph basin dissection and are NED (no evidence of disease). Two SN(+) patients had systemic recurrences; one died of his disease, and the other is alive with disease. One SN(-) patient died NED owing to other cause. This technique spared 83% of category A patients from lymph node dissection. It allowed better staging and better decision making for treatment in categories B and D; and it prevented early regional recurrences in category C patients. Intraoperative lymphatic mapping with SN guidance is a novel, lo

Adult↗
PubMed2000

Gemcitabine in soft tissue or bone sarcoma resistant to standard chemotherapy: a phase II study.

PURPOSE: To assess the efficacy of gemcitabine in patients with a variety of sarcomas that have failed to respond or escaped Adriamycin- and ifosfamide-based chemotherapy. PATIENTS AND METHODS: A group of 18 symptomatic heavily pretreated patients with sarcomas of bone or soft tissue received one induction course of gemcitabine at a dose of 1000 mg/m(2) per week for 7 consecutive weeks, followed by 1 week rest. Response to the induction course was assessed by interview and by repeated ancillary tests. If no progression was observed, maintenance by gemcitabine 1000 mg/m(2) per week for 3 weeks every 28 days was given until failure was clinically or radiologically evident. RESULTS: A total of 51 cycles of gemcitabine were given including 18 cycles of induction. A mean of 3.6 postinduction cycles were given to nine patients. The treatment was well tolerated by the patients. One partial response (leiomyosarcoma) and one minimal response (angiosarcoma) were observed, yielding a true objective response rate of 5.5%. An additional six patients achieved stabilization of disease (chondrosarcoma and osteosarcoma), yielding an overall progression-free rate of 44%. The median time to progression was more than 27 weeks. Clinical benefit response was observed only in those who also achieved a progression-free state. CONCLUSION: Gemcitabine was found to be effective in achieving stabilization and even a minimal response of soft tissue or bone sarcoma refractory to standard chemotherapy.

Adolescent↗
PubMed2000

Applicability of the sentinel node technique to Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) resembles malignant melanoma in several ways. Both are cutaneous lesions of the same embryonic origin. Both have an unpredictable biologic behavior, early regional lymph node involvement, early distant metastases, and high recurrence rate. OBJECTIVE: To apply the sentinel node technique described for melanoma to MCC in light of the common biologic features of these two tumors. METHODS: Preoperative lymphoscintigraphy, intraoperative lymphatic mapping, and sentinel node biopsy and frozen section histology were performed to guide the surgical treatment of three patients with MCC. RESULTS: Application of this approach in patients with MCC is feasible, reproducible, and seems reliable. CONCLUSION: The use of the sentinel node technique for MCC will reduce the number of unnecessary lymphadenectomies, will enable identification of microscopic metastases to lymph nodes, and will improve the stratification and accrual of patients into adjuvant treatment protocols. It may even lead to a survival benefit.

Aged↗
PubMed2000

Oral etoposide for Merkel cell carcinoma in patients previously treated with intravenous etoposide.

We describe three patients with advanced Merkel cell carcinoma who were treated with etoposide given orally for recurrent regional lymph node involvement 18 to 30 months after exposure to etoposide given intravenously. Etoposide given orally (100 mg/day) was given for 10 to 14 consecutive days and repeated every 21 to 28 days for a median of three courses (range: two to four). Toxicity was minimal and mainly hematologic. Two patients showed a complete response and one a partial response, all of very rapid onset. All three patients are alive 6, 9, and 42 months from the start of oral treatment. Two remain progression free, and one had a recurrence 1 month after completion of chemotherapy. We suggest that orally administered etoposide, a topoisomerase II inhibitor, has a strong antitumor effect in advanced Merkel cell carcinoma, even in patients previously treated parenterally with the same drug. This action may be explained by the greater dependence of the drug's efficacy on the duration of administration rather than the dose intensity.

Administration, Oral↗
PubMed1999

Decreased phagocytic capacity of rat peritoneal macrophages following photon abdominal irradiation.

Photon irradiation of the abdomen may be accompanied by complications due to a decrease in the immune defense of the recipient. Since peritoneal macrophages are an important component of the immune system, we examined the phagocytic activity and oxygen superoxide anion generation by peritoneal macrophages from rats 2 and 4 weeks after abdominal irradiation with 6 MV photons applying a single dose of 2 Gy. Two and 4 weeks after irradiation, peritoneal macrophages were harvested and their capacity to engulf latex particles and to produce oxygen superoxide anions was determined. Non-irradiated rats, treated identically otherwise, served as controls. Two weeks after irradiation the phagocytic capacity and oxygen superoxide anion generation decreased by 61 and 70%, respectively, compared with controls. This tendency persisted after 4 weeks post irradiation, the decrease in both functions being 50 and 74%, respectively. It is suggested that the altered function of peritoneal macrophages following irradiation may further compromise the immune defense in patients receiving abdominal radiotherapy.

Abdomen↗
PubMed1999

Effects of psychotropic drugs on cell proliferation and differentiation.

Some of the psychotropic agents widely used for the amelioration of anxiety, depression, and psychosis also show an effect at the cellular proliferation level. Surprisingly little research, however, has been directed to the antitumoral potential of these drugs, alone or in combination with established cancer treatments. Our review of the literature to date has yielded some promising early findings. Ligands active at the benzodiazepine (BZ) receptors have been studied the most extensively and were found to have differential, concentration-dependent effects on the growth and proliferation of both normal and cancer cells. Of the phenothiazines tested, chlorpromazine (CPZ) and perphenazine (PPZ) had the most potent cytotoxic action on fibroblasts and glioma cells. Antiproliferative effects also were noted by these and other agents in leukemic and breast cancer cell lines. Additional psychotropic drugs studied include the atypical antipsychotics, antidepressants, and mood stabilizers, especially lithium. Most of the reported activities were observed in in vitro studies and were achieved at high pharmacological concentrations. Further in vivo studies in well-designed animal models are warranted to determine whether these well-tolerated, relatively inexpensive, and widely available drugs or their derivatives may be added in the future to the armamentarium of cancer pharmacotherapy.

Anticonvulsants↗
PubMed1999

Basic fibroblast growth factor potentiates cisplatinum-induced cytotoxicity in MCF-7 human breast cancer cells.

Basic fibroblast growth factor (bFGF) is a classical mitogen in fibroblasts and endothelial cells. Our previous studies have demonstrated that bFGF inhibits the growth of MCF-7 human breast cancer cells. The aim of the present study was to examine the effect of bFGF on cis-diamminedichloroplatinum(cisplatin)-induced cytotoxicity in MCF-7 breast cancer cells as compared to normal endothelial cells. MCF-7/NCF cells transduced with a vector expressing the bFGF gene and overexpressing its product, and MCF-7/N2 cells transduced with the backbone vector were incubated with a combination of bFGF and cisplatin for 5 days; results were compared with those obtained with bovine aortic endothelial cells. Cell proliferation was assessed with the sulforhodamine B colorimetric cytotoxicity assay. Apoptosis was quantitatively determined by flow-cytometric analysis for DNA damage and the apoptotic death assay for DNA fragmentation, and qualitatively by electron microscopy. Reverse transcriptase/polymerase chain reaction analysis and an enzyme immunoassay were used to determine the mRNA and protein level, respectively, of the anti-apoptotic bcl-2 gene product. We found that bFGF enhanced cisplatin-induced cytotoxicity in MCF-7 breast cancer sublines. bFGF enhanced proliferation of normal endothelial cells and did not increase cisplatin-induced cytotoxicity. This effect was accompanied by down-regulation of the anti-apoptotic protooncogene bcl-2 and the enhancement of cisplatin-induced apoptosis. We suggest that the improved understanding of the role of bFGF in the differential modulation of the response of breast cancer and normal endothelial cells to chemotherapy may enable active intervention to alter the therapeutic ratio favorably in breast cancer patients.

Antineoplastic Agents↗