Effect of maternal smoking during pregnancy on fetus: a cytogenetic perspective.

OBJECTIVE: The examination of the genotoxic, cytostatic and cytotoxic effects of smoking during pregnancy. METHOD: Lymphocyte cultures of peripheral blood were received from 20 women who smoked during pregnancy as well as umbilical cord blood of their newborns. Fluorescence Plus Giemsa staining technique was used in order to perform cytogenetic analyses for three indices, Sister Chromatid Exchanges (SCEs), Proliferation Rate Index (PRI) and Mitotic Index (MI). To reveal any underlying chromosome instability, CPT-11 was used as a positive control. RESULTS: Newborns whose mothers smoke during pregnancy had increased SCEs levels on their lymphocytes when they were exposed to the mutagenic agent CPT-11 (p < 0.01) compared with newborns lymphocytes exposed to the same agent with non-smoking mothers. Also, mothers smoking during pregnancy had increased SCE levels when their lymphocytes were exposed to CPT-11 (p < 0.01) compared with non smoking mothers whose lymphocytes were exposed to the same agent. In both groups newborns appeared as having decreased (p < 0.01) spontaneous SCEs levels compared with the corresponding SCE rates of their mothers. Decreases of PRIs and MIs are observed in mothers compared to their newborns. CONCLUSION: Smoking during pregnancy can promote cytogenetic damage in newborn's DNA, causing chromosome instability. The clinical importance of this indirect damage lies in the fact that this type of damage can act synergistically with other environmental and/or chemical mutagenic substances possibly leading to carcinogenicity.

Cytogenetic evaluation of pre-pregnancy smoking in maternal and newborn lymphocytes.

OBJECTIVE: To study cytogenetic damage in order to estimate the effect of pre-pregnancy smoking on pregnant women and their foetuses. STUDY DESIGN: Lymphocyte cultures were obtained from peripheral blood of 20 women who quit smoking during pregnancy, and umbilical cord blood of their newborns at delivery. Cytogenetic analyses were performed for sister chromatid exchanges (SCEs), proliferation rate index (PRI) and mitotic index (MI) using the Fluorescence Plus Giemsa staining technique. Twenty non-smoking women and their newborns were evaluated as controls. CPT-11, a known antineoplastic, was used as a positive genotoxic agent in order to correlate non-smoking women with smoking women and reveal any underlying chromosome instability. Statistical evaluation of SCE frequencies, PRI and MI was based on independent samples t-test in order to estimate the effect of pre-pregnancy smoking on mothers and their newborns. RESULTS: SCEs were induced in the cord blood lymphocytes of newborns whose mothers smoked before pregnancy when they were exposed to the mutagenic agent CPT-11 (p<0.01). A similar increase in SCEs was observed in both non-smoking and smoking mothers exposed to CPT-11. Newborns in both groups had significantly lower SCE levels than their mothers (p<0.01). CONCLUSION: Pre-pregnancy smoking results in cytogenetic damage for both mothers and newborns, and is an important risk factor for cancer and/or other genetic-related diseases. Smoking cessation needs to occur well before conception in order to avoid the strong cytogenetic association between pre-pregnancy smoking by mothers and their newborns.

Co-expression of survivin, c-erbB2, and cyclooxygenase-2 (COX-2): prognostic value and survival of endometrial cancer patients.

AIM: The purpose of this study was to investigate the co-expression of survivin, c-erbB2, and COX-2 in endometrial cancer tissues and evaluate its prognostic significance in endometrial cancer METHODS: Tumor tissue biopsies from 110 patients with primary untreated endometrial carcinomas were studied by immunohistochemistry. Statistical analysis evaluated correlation of antigen expression with tumor stage, grade, myometrial invasion, and histologic type. Association with disease outcome was also investigated RESULTS: The results showed that expression of the three antigens was independently associated with histological grade, disease stage, and myometrial invasion. Clinicopathological parameters were also associated with the number of antigens expressed by each tumor, the expression of more antigens correlating with advanced stage disease and deep myometrial invasion. In a 10-year follow-up, patients with tumors expressing more of these three antigens had significantly lower survival rate that those with smaller expression score CONCLUSIONS: Our results indicate that the co-expression score has independent prognostic value for endometrial cancer.

Postoperative accelerated radiotherapy with cytoprotection followed by three-dimensional conformal boost in patients with early endometrial/cervical cancer.

AIMS AND BACKGROUND: Adjuvant external beam radiotherapy is highly recommended for uterine carcinomas invading beyond the inner half of the myometrium or cervical stage IIa carcinomas. The addition of a booster intracavitary dose is widely used. METHODS: We assessed the feasibility and toxicity of a hypofractionated accelerated conformal radiotherapy scheme (2.7 Gy per fraction, for 14 consecutive fractions to the pelvis) supported with the cytoprotective agent amifostine (HypoARC). The amifostine dose was individualized (500-1000 mg daily subcutaneously). A booster dose of radiation was given to the vagina and stump using a 6-field 3D-conformal technique (3 x 4 Gy or 4 x 3 Gy) instead of intracavitary radiotherapy. RESULTS: Grade 2 diarrhea appeared in 9/25 (36%) and grade 1 cystitis in 7/25 (28%) cases. Analysis according to the amifostine dose level clearly showed reduced toxicity in patients receiving a daily dose of 750-1000 mg (P < 0.009). Within a median follow-up of 31 months (range, 11-52), there was only one case with grade 2 colitis (the patient had received no amifostine). None of the patients treated has relapsed locally or to distant organs within a median of 31 months of follow-up. CONCLUSIONS: It is concluded that HypoARC followed by 3D-conformal booster dose to the vagina is feasible and convenient for patients and for busy radiotherapy departments, as it reduces the overall time by 50%. When supported by high-dose daily amifostine, it has an impressively low rate of early and late radiation toxicity.

Acute abdomen as initial presentation of gestational choriocarcinoma.

Choriocarcinoma is the most malignant tumor of gestational trophoblastic neoplasia. Choriocarcinoma presenting as postpartum hemorrhage and spontaneous uterine perforation with intra-abdominal hemorrhage is very rare. We present a 29-year-old woman with spontaneous uterine rupture due to choriocarcinoma following a live birth pregnancy. The long time interval (2 years) between the previous live birth pregnancy and the diagnosis of the disease, the acute onset of the disease by uterine rupture as the first symptom and the negative urine hCG test are presented and discussed in this case report.

Serum and tissue LDH levels in patients with breast/gynaecological cancer and benign diseases.

BACKGROUND: Lactate dehydrogenase A (LDHA) is involved in anaerobic glycolysis. In cancer patients, serum total lactate dehydrogenase (LDH) levels are often increased, and the gene for one of its isoenzymes, LDHA, is up-regulated. These features have been linked to poor prognosis in several studies. METHODS: We investigated comparatively the total serum LDH activity and tissue isoenzyme LDH5 and hypoxia-inducible factor 1alpha (HIF1alpha) levels in patients with breast (n = 18) and gynaecological (n = 23) malignancies and benign diseases (n =54). RESULTS: The serum LDH levels were significantly higher in patients with endometrial adenocarcinoma (349 +/- 100 IU/l) and ovarian cystadenocarcinomas (383 +/- 116 IU/l) compared to healthy controls (256 +/- 68 IU/l) (p values 0.01 and 0.006, respectively). This difference did not reach significance in patients with breast cancer (328 +/- 169 IU/l; p = 0.17)). Uterine leiomyoma patients showed intermediate LDH levels (310 +/- 81 IU/l), while patients with breast fibroadenomas and ovarian cystadenomas had LDH serum levels close to carcinomas (308 +/- 60 and 348 +/- 135 IU/l, respectively). LDH5 isoenzyme was strongly expressed in cancer cells, exhibiting a mixed cytoplasmic/nuclear subcellular pattern. Interestingly, a high LDH5 content in tissue sections was not invariably accompanied by high LDH serum levels. High HIF1alpha tissue expression was linked to high tissue LDH5 expression. CONCLUSION: Serum and tissue LDH is up-regulated in gynaecologic and breast malignancies and in a subset of benign conditions such as fibro- and cystadenomas. The release of LDH, however, in the bloodstream is partly related to the LDHA gene up-regulation.