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H Levavi

Publications and source records attributed to H Levavi.

At least 19 recordsLinked to original sources
PubMed2002

Effect of BRCA mutations on the length of survival in epithelial ovarian tumors.

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

Case-Control Studies↗
PubMed2001

The polymorphic CAG repeat in the androgen receptor gene in Jewish Israeli women with endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is considered a hormonal-dependent tumor; estrogen induces endometrial cellular proliferation, whereas progestins display an antiproliferative effect on endometrial tissue. The role that androgen and its receptor (androgen receptor [AR]) play in the pathogenesis of endometrial carcinoma is less clear. Although androgen has an in vitro inhibitory effect on endometrial cell proliferation, up to 75% of endometrial carcinoma express AR somatically. A polymorphic CAG repeat within exon 1 of the AR encodes for a polyglutamine tract, with length range of 8 to 33 repeats, which is inversely correlated with the transcriptional activity of the AR. METHODS: To gain insight into the role of AR in endometrial carcinoma, the authors analyzed the polymorphic CAG repeat in 79 Jewish Israeli patients with endometrial carcinoma as compared with 44 healthy Jewish women serving as controls. Analysis was conducted using germline DNA as template and using polymerase chain reaction primers flanking the CAG repeat with subsequent fluorescent determination of allele sizes. RESULTS: Allele size range of the longer of the two alleles in the patients was 11-33 (mean, 19.8 +/- 2.7) and in the controls 10-22 (mean, 17.9 +/- 1.9), a statistically significant difference (P < 0.01). Allele size variation within the patient group did not correlate with disease stage, grade, reproductive history, or age at diagnosis. CONCLUSIONS: The authors conclude that AR-CAG repeat length differs in Jewish patients with endometrial carcinoma as compared with healthy individuals in Israel, and this finding increases the possibility that the AR is involved in the predisposition to this neoplasm.

Aged↗
PubMed2001

A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers.

RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a "c" allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 "c" allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the "c" allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown.

Adult↗
PubMed2000

Connective tissue activating peptide III expression disappears progressively with increased dysplasia in human cervical epithelium.

OBJECTIVE: The aim of this study was to explore the possible involvement of CTAP-III in the development of cervical cancer as it progresses through several cervical intraepithelial neoplasia (CIN) stages. MATERIAL AND METHODS: Twenty-four cervical specimens were obtained by direct punch biopsy, conization, or hysterectomy. Diagnosis of CIN I to CIN III was based on standard morphological criteria in 12 specimens. Tissue specimens were also obtained from 4 normal uteri and 8 cases of invasive squamous cell cervical carcinoma. RT-PCR, using CTAP-III-specific primers, was used to identify CTAP-III mRNA and polyclonal antibodies, directed against the N-terminus of CTAP-III, for immunostaining of the CTAP-III protein. RESULTS: RT-PCR yielded amplified fragments in RNA derived from normal cervical tissue, while no PCR product was detected in the invasive cervical carcinoma tissue. The PCR product corresponded to a CTAP-III plasmid PCR product. Both tissues expressed the same amounts of GAPDH mRNA as the control for the integrity and equal amounts of the isolated RNA. In each of the 16 specimens of normal cervices and of CIN tissues, epithelial cells were stained with the anti-CTAP-III antibodies. In normal epithelium, CTAP-III staining was homogeneously distributed in all epithelial layers, except in the highly active and proliferating basal cells. CTAP-III was localized at the epithelial cell membrane or between adjacent epithelial cells in a granular, chain-like pattern of staining. In the CIN specimens, CTAP-III staining was no longer seen in the deep epithelial layers, consistent with the dysplastic appearance of the cells, and remained in the seemingly normal superficial epithelial layers. Cells of invasive cervical carcinoma did not stain for CTAP-III and were detected in endothelial cells of capillary blood vessels. CONCLUSION: The specific localization of CTAP-III between adjacent epithelial cells suggests a possible role of this chemokine in maintaining the normal architecture of epithelial tissues. Its progressive disappearance in increasingly severe CIN may be applied to distinguish between specific stages in the progression of cervical carcinoma.

Amino Acid Sequence↗
PubMed1996

Conservative management of postmenopausal pelvic echo-free findings--preliminary results.

OBJECTIVES: To develop a conservative protocol for the treatment of echo-free findings in the pelvis, diagnosed by sonography in post-menopausal women, in order to avoid unnecessary surgical intervention. METHODS: A prospective study where each post-menopausal-patient underwent sonographic evaluation of the pelvic mass, serum Ca-125 levels, ambulatory aspiration of the cyst, and operative laparoscopy if necessary. RESULTS: One hundred and eighty-two women were included in the 3 years of the study. Only two cases of malignancy were diagnosed. There were no false-negative results. CONCLUSION: Although the results of our protocol of conservative management look promising, we cannot draw final conclusions because of the small sample size. Perhaps as our knowledge increases, physicians will feel more confident in handling adnexal findings conservatively.

Adnexa Uteri↗
PubMed1996

The biology of ovarian cancer of epithelial origin.

Ovarian cancer of epithelial origin is associated with the highest mortality rate of all gynecologic malignancies. Since no symptoms or signs are manifested at the early stages of the disease, it is no surprise that in 75% of patients peritoneal metastases are found during primary surgery. Despite advances in conservative treatment methods (invasive and noninvasive), screening for early detection of the disease is not yet available, and the overall survival rate is as low as 5-15%. Recent studies in molecular biology have drawn attention to different research directions in ovarian cancer and have contributed much to our understanding of this disease and its underlying pathologic mechanisms. This review is intended to highlight some of the new aspects of this research, specifically: hereditary ovarian cancer, genetic background in terms of chromosomal changes, DNA anomalies, oncogenes, tumor-suppressor genes, peptide growth factors and cytokines, invasiveness and metastasis, and finally, drug resistance. No breakthrough has as yet occurred in any of the subjects screened in this review, but results are promising. The clinical application of the steadily increasing knowledge in the biology of ovarian cancer may assist in the development of new treatment modalities that will improve survival.

Cell Transformation, Neoplastic↗
PubMed1995

Laser versus loop electrosurgical excision in vulvar condyloma for eradication of subclinical reservoir demonstrated by assay for 2'5' oligosynthetase human papillomavirus.

We studied, in an open clinical trial, 28 women with giant solitary human papillomavirus (HPV) lesions of the vulva that were treated by both laser and the loop electrosurgical excision procedure (LEEP), and analyzed the biopsy specimens of normal skin adjacent to the lesions for papillomavirus sequences by Southern blot hybridization and 2'-5' oligo-A synthetase (interferon) activity. The patients were reexamined after 3 weeks when a second treatment to the still infected areas was reapplied. They were reexamined for recurrence after 3 months: 4 patients harbored HPV-DNA genomes on the laser-treated side, adjacent to the original lesion, compared to 1 patient who developed recurrence on the LEEP side in a more distant, previously untreated, area. The optimal extent of laser or LEEP treatment necessary to reduce recurrence of vulvar condyloma remains to be established. Good in situ hybridization tests combined with the polymerase chain reaction and measurements of oligosynthetase activity to determine the types of cells involved at different sites of infection and to assess harboring of latent HPV genomes in histologically normal tissue are necessary in order to plan proper HPV treatment modality strategies.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Three-dimensional modelling of tumor-induced ovarian angiogenesis.

It is now well established that unrestricted growth of tumors is dependent upon angiogenesis. However, previous studies on tumor growth have not yet revealed how the transition to an angiogenetic state in ovarian malignancy is reflected in the vascular architecture of the ovary. We report here our preliminary observations based upon three-dimensional imaging of normal and tumor-induced ovarian angiogenesis created with a computer-assisted three-dimensional interactive application. The findings suggest that tumor-induced angiogenesis creates a bizarre vascular architecture, with a possible link to chaotic behavior.

Cystadenocarcinoma, Serous↗
PubMed1994

An evaluation of lateral and medial transposition of the ovaries out of radiation fields.

BACKGROUND: Transposition of the ovaries is practiced in young women before possible radiation to the pelvic fields. In patients with carcinoma of the uterine cervix (Ca cervix), the ovaries are transposed laterally (LOT), whereas in patients with Hodgkin's disease (HD), they are usually transposed medially (MOT). Nevertheless, not all transposed ovaries are successfully protected. METHODS: Computed tomography was performed in 16 patients (7 Ca cervix and 9 HD) after ovarian transposition. The location of all identified ovaries was depicted on diagrams of the respective radiation fields for evaluation of the efficacy of LOT or MOT in relocating the ovaries out of these fields. RESULTS: All 13 ovaries transposed laterally were easily identified by CT, as compared with only 13 of 18 ovaries transposed medially (P = 0.2). Eleven of the 13 ovaries that underwent lateral transposition (6 of 7 patients) were located outside the radiation field. In contrast, only 3 of 13 identified ovaries in the medially transposed group were completely outside the radiation field (P = 0.005). Of the remainder, six were completely within the radiation field, and four were at least partially within the radiation field. CONCLUSIONS: Although LOT achieves its purpose in patients with Ca cervix, the use of MOT in patients with HD should be revised to achieve better protection of the ovaries from the effects of radiation. The authors suggest that LOT is preferred over MOT also in patients with HD if radiation of the pelvic lymph nodes is planned.

Adult↗
PubMed1994

Translocation of bacteria due to direct mucosal damage caused by Gastrografin. An experimental study in newborn rats.

A study was carried out on 40 newborn rats to determine the effect of Gastrografin (a hyperosmolar solution, 1700 mosm/liter) on the gastrointestinal tract. All the newborns received an inoculum of Klebsiella bacteria to the gastrointestinal tract. Thirty received, in addition to maternal milk, a feeding of Gastrografin twice daily. The Gastrografin was found to cause severe and irreversible damage to the mucosa of the small intestine, causing the death of 24 rats less than a week after start of the experiment. The 10 rats who received no Gastrografin and served as controls showed no signs of disease or damage to the intestinal tract. Cultures taken from the peritoneal cavity after sacrifice were all positive for Klebsiella in the Gastrografin group (30 rats) and negative in the controls (10 rats). This study has therefore demonstrated that severe damage to the small intestine mucosa will lower the intestinal barrier and lead to transmural translocation of bacteria into the peritoneal cavity.

Animals↗
PubMed1994

Ovarian tumors in women over 70.

OBJECTIVES: To discuss and evaluate the management of ovarian masses in women over 70. METHODS: The nature of adnexal masses and the outcome of surgical intervention in 38 women over 70 was reviewed. RESULTS: There were seven cases of malignant ovarian tumors in our series of 38 patients reviewed. The most frequent presenting sign was abdominal pain (11 cases). The presence of an adnexal mass was suspected on the basis of routine gynecologic examination in 8 cases, whereas by routine ultrasound scan in 30 patients. Postoperative complications were rare. CONCLUSIONS: It is suggested that in all postmenopausal women routine yearly pelvic examination and ultrasound scan is advisable. Furthermore, in view of our favorable results in recent years, we feel that surgical intervention is justified in all cases of adnexal tumors in the woman over 70.

Age Factors↗
PubMed1994

[Large loop transformation zone excision in premalignant cervical lesions].

Colposcopic expertise is necessary in cases of cervical intraepithelial neoplasia (CIN) to avoid conservative treatment of microinvasive and invasive lesions. Large loop excision of the transformation zone (LLETZ) enables the pathologist to examine the entire tumor, and especially its margins. We describe this method and its indications, and review the results of our first 100 cases (mean age 28 years, range 19-46). Indications for LLETZ were biopsy findings of CIN III or of a large CIN II, a lesion entering the endocervical canal, and recurrent CIN after CO2-laser treatment. The procedure was performed under local anesthesia in 93 patients; complications were minimal (8 cases of bleeding requiring local tamponade). In 14% marginal involvement was found, but in only 4 was re-treatment necessary during follow-up of 12-33 months. Only 3 developed recurrent CIN, which was again treated by LLETZ. The cure rate of the initial treatment was 97%. This ablative, nondestructive method is easy to perform, requires only local anesthesia, has few, mild complications and gives an accurate histopathological result, including information on margins. The procedure is becoming the method of choice for treating high-grade and recurrent CIN.

Adult↗
PubMed1993

"Hook effect" in complete hydatidiform molar pregnancy: a falsely low level of beta-HCG.

BACKGROUND: In some cases of gestational trophoblastic disease, a large amount of serum beta-hCG may lead to the high-dose "hook effect" with falsely low serum levels, creating misdiagnosis or delay in diagnosis and therapeutic hazards to the patient. CASES: In two cases of the hook effect in complete hydatidiform mole, ultrasonographic scan showed intrauterine echogenic material, whereas diluted serum specimens gave very high levels of beta-hCG (1,600,000 and 2,225,000 mIU/mL). CONCLUSION: The possibility of a method-dependent hook effect must be considered. Early recognition of falsely low values of beta-hCG can allow correction to the true values by various methods, such as serum dilution before the radioimmunometric method.

Adult↗