Search PubMed⌕ Search

Biomedical subjects

A Gabriele

Publications and source records attributed to A Gabriele.

At least 19 recordsLinked to original sources

Activity and toxicity of oxaliplatin and bolus fluorouracil plus leucovorin in pretreated colorectal cancer patients: a phase II study.

The aim of the current study was to evaluate the activity and toxicity of a combination of oxaliplatin with bolus fluorouracil and leucovorin in colorectal cancer (CRC) patients pretreated for advanced disease with various schedules including continuous fluorouracil infusion. Thirty consecutive patients with pretreated advanced CRC received oxaliplatin 130 mg/m2 by 2-h infusion dl, leucovorin 100 mg/m2 by 1-h infusion followed by fluorouracil 425 mg/m2 i.v. bolus from day 1 to 3 every 3 weeks for a maximum of 6 cycles. The best overall response rate in an intent-to-treat analysis was 13% (2 complete responses and 2 partial responses) (95% CI, 1.2-25.5%) and 37% of patients obtained stable disease with a tumor growth control rate of 50% (95% CI, 32.1-67.9%). The median progression-free survival was 4.0 months (95% CI, 1.4-6.5 months) and median overall survival was 12.0 months (95% CI, 9.9-14.1 months). The independent prognostic factors for improved overall survival were a good performance status and a response/stabilization of disease to chemotherapy. Severe neutropenia was quite common (43.3% of patients and 14.4% of cycles), although complicated by fever only in one case (3.3% of patients). There was one toxic death. In conclusion, the study combination showed an interesting rate of tumor growth control in a cohort of patients previously treated for advanced disease with various schedules including continuous fluorouracil infusion.

Adult↗

Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients.

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET(+)/CT(-) relapsed, as compared with zero out of 29 patients in the PET(-)/CT(-) subset. Among the 41 CT(+) patients, 10 out of 11 (91%) who were PET(+) relapsed, as compared with 0 out of 30 who were PET(-). The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET(+) and PET(-) subsets, respectively (P=0.00001). All five patients who were PET(+)/CT(-) underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET(-)/CT(+) (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

Adolescent↗

Ophthalmological manifestations in segmental neurofibromatosis type 1.

AIMS: To study the ophthalmological manifestations in individuals with the typical features of neurofibromatosis type 1 (NF1) circumscribed to one or more body segments, usually referred to as segmental NF1. METHODS: Visual acuity and colour tests, visual field examination, slit lamp biomicroscopy of the anterior segment, and a detailed examination of the retina by indirect ophthalmoscopy were performed at diagnosis and follow up in 72 consecutive subjects (29 males, 43 females; aged 1-64 years; mean age 14.6 years) seen at the university departments of paediatrics in Catania and Rome, Italy, during years 1990-2003, who had in restricted body areas: (1) typical pigmentary manifestations of NF1 (cafe au lait spots and freckling) only (n = 48); (2) NF1 pigmentary manifestations and neurofibromas alone (n = 2); (3) neurofibromas only (n = 15); and (4) plexiform neurofibromas only (n = 7). RESULTS: None of the 72 patients had Lisch nodules in the iris irrespective of age at eye examination or hypertelorism (a "minor" NF1 feature) and none developed typical associated ophthalmological NF1 complications. An additional child had an isolated optic pathways glioma (OPG), which behaved both biologically and radiographically as an NF1 associated OPG. CONCLUSIONS: This represents the first systematic study reporting on eye involvement in the largest series of individuals at different ages having segmental NF1. As one of the postulated mechanisms to explain segmental NF1 is somatic mosaicism for the NF1 gene (so far demonstrated only in two patients) the present findings could be explained either by the fact that the eye is too far from the mutated area with NF1 lesions in most cases or by the NF1 (or other "predisposing" or "cooperating") gene mutation restricted to too few cellular clones or to tissues embryologically different from the eye.

Adolescent↗

The combination of carboplatin and weekly paclitaxel: a safe and active regimen in advanced non small-cell lung cancer patients. A phase I-II study.

The combination of carboplatin and paclitaxel given every three weeks is a tolerated and reasonably active regimen in advanced non-small cell lung cancer (NSCLC). This study was designed to evaluate the maximum tolerated dose (MTD) of a fixed dose of carboplatin with an area under the curve (AUC) of 6 and escalating doses of weekly paclitaxel with an initial dose of 50 mg/m2 with 10 mg/m2 increments at each level in untreated NSCLC patients (phase I study). The study continued with a phase II study. Thirty patients entered the phase I study. The MTD was: carboplatin AUC = 6 on days 1 and 28 plus paclitaxel 100 mg/m2 (1 hour) on days 1, 8,15, 28. The dose-limiting toxicity (DLT) was severe neutropenia and cardiological toxicity. Subsequently, 42 patients entered the phase II study with the same treatment schedule. The 2-drug combination was globally well tolerated. The overall response rate (RR) was 42% [CI 95%: 26.3-57.7], stable disease (SD) 29% and progression (PD) 29%. The median duration of response was 8.0 mos (range: 1.0-19.0). The median time to progression was 8.0 mos (range: 7.0-19.0) and the median survival was 14.0 months (range: 9.0-19.0). The association of carboplatin AUC = 6 and weekly paclitaxel 100 mg/m2 proved to be manageable, active and extremely safe even in elderly patients (one third of all patients in our cohort). The survival results were interesting: the median survival time was 14 months (9-19 months) and the 1- and 2-year survival was 59% and 16%, respectively.

Adult↗

The impairment of renal function is not associated to altered circulating vascular endothelial growth factor in patients with Type 2 diabetes and hypertension.

BACKGROUND: Metabolic and haemodynamic factors concur in the development of diabetic nephropathy. Moreover, in diabetes, the presence of hypertension may accelerate the development of renal damage. Vascular endothelial growth factor (VEGF) stimulates microvascular permeability, endothelium-dependent vasodilation and angiogenesis and its synthesis is enhanced by hyperglycaemia, advanced glycation end-products (AGEs), tissue hypoxia and hypertension. VEGF appears to play a central role in mediating diabetic vasculopathy, and although VEGF and its receptors are expressed at renal level, its action in renal pathophysiology is unknown. The aim of this study was to elucidate whether presence and/or severity of renal dysfunction is related to circulating VEGF in patients with Type 2 diabetes and hypertension. DESIGN AND METHODS: Fifty hypertensive Type 2 diabetic patients and 20 non-diabetic patients were included in the study. Renal function parameters such as albumin excretion rate (AER), and glomerular filtration rate (GFR), and VEGF plasma levels were analysed in all subjects, whereas %HbA1c and AGEs levels were evaluated in diabetic patients. RESULTS: GFR was significantly decreased in diabetic patients compared with the control subjects (74.36 +/- 15.95 vs 111.5 +/- 17.0 ml/min, p<0.0001). Three diabetic patients showed AER abnormalities (53.8 +/- 2.3 mg/24h). VEGF in diabetic patients was higher than in the control group (77.95 +/- 65.98 vs 49.30 +/- 40.8 pg/ml), but not significantly. %HbA1c and AGE levels were 6.6 +/- 1.5% and 11.59 +/- 8.09 UAGE/ml, respectively. No correlation was found between renal function, circulating VEGF levels and metabolic control. CONCLUSION: Diabetes, in association with hypertension, significantly decreases renal function, but circulating VEGF may not reflect its concentration and action at renal level.

Aged↗

Phase II study of capecitabine and oxaliplatin as first-line treatment in advanced colorectal cancer.

BACKGROUND: Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer. The aim of this phase II study is to determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced non-pretreated colorectal cancer. PATIENTS AND METHODS: Forty-three chemotherapy-naïve patients were enrolled. Capecitabine 2500 mg/m(2)/day was administered orally twice a day continuously for 14 days and oxaliplatin 120 mg/m(2) was administered as a 2-h infusion on day 1, repeated every 3 weeks. RESULTS: Forty-three patients were assessable for toxicity and 39 for clinical activity: the main toxicity was grade 3 or 4 diarrhea, which occurred in 28% of the patients. The response rates were 44% [95% confidence interval (CI), 29.3% to 59.0%] and 48.7% (95% CI 33.0% to 64.4%) (intention-to-treat and per protocol analysis, respectively). The median overall survival was 20 months (95% CI 12-28). CONCLUSIONS: Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer; therefore, the capecitabine dose we utilized is probably too high. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. This combination may be preferable compared to a standard combination with infusional fluorouracil/leucovorin as it is more convenient and practical with similar efficacy. Thus, phase III trials are needed to clarify its role in the treatment of chemotherapy-naïve advanced colorectal cancer patients.

Adult↗

Synchronous fallopian tube and breast cancers: case report and literature review.

A case of fallopian tube cancer was intraoperatively diagnosed in a patient submitted to laparoscopic hysterectomy and bilateral salpingo-oophorectomy because of an ultrasound diagnosis of a probable endometriotic cyst of the right ovary. Postoperatively a complete staging was performed and a synchronous carcinoma of the breast was diagnosed. Consequently the patient completed laparotomic debulking and a left mastectomy. A case of a premenopausal woman with fallopian tube cancer and synchronous breast cancer is reported together with a review of the most recent literature.

Adenocarcinoma, Papillary↗

Analysis of treatment failures and survival of patients with fallopian tube carcinoma: a cooperation task force (CTF) study.

OBJECTIVE: The objective of this retrospective multicenter study was to assess the pattern of failures and survival of patients with primary carcinoma of the fallopian tube. METHODS: The hospital records of 88 patients with primary carcinoma of the fallopian tube were reviewed. Surgery was the initial therapy for all patients. Tumor stage was I in 21 (23.9%), II in 21 (23.9%), III in 43 (48.8%), and IV in 3 (3.4%) patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 55 months (range, 7-182). RESULTS: Of the 21 patients with stage I disease, 10 had no postoperative treatment and 11 had platinum-based chemotherapy. Five (23.8%) patients recurred after a median of 29 months (range, 8-93) from initial surgery. Of the 21 patients with stage II disease, 2 had no postoperative treatment, 2 underwent external pelvic irradiation, 16 received platinum-based chemotherapy, and 1 patient had oral melphalan. Eight (38.1%) patients recurred after a median of 25.5 months (range, 7-57). Of the 46 patients with stage III-IV disease, 1 patient refused chemotherapy and died after 19 months and 45 patients received platinum-based chemotherapy. A clinical complete response was obtained in 29 (64.4%) patients and a partial response in 8 (17.8%). A second-look laparotomy was performed in 14 of the 29 clinically complete responders: 12 patients were found to be in pathological complete response and 2 had persistent disease. Six (50.0%) of the former recurred after a median of 22 months (range, 13-101) from initial surgery. The two patients with persistent disease developed tumor progression after 15 and 11 months, respectively. Fifteen clinically complete responders did not undergo second-look, and 7 (46.7%) of them had a recurrence after a median of 18 months (range, 9-41). For the whole series, 5-year survival was 57%. By log-rank test, survival was related to FIGO stage (III-IV vs I-II, P = 0.0001), tumor grade (G3 vs G1 + G2, P = 0.0038), and patient age (>58.5 years vs <58.5 years, P = 0.0069), but not to histological type. The Cox model showed that FIGO stage (P = 0.0018) and patient age (P = 0.0290) were independent prognostic variables for survival. Among the patients with stage III-IV disease, 5-year survival was 55% for the patients who had residual tumor <1 cm compared with 21% for those who had larger residuum (P = 0.0169). CONCLUSIONS: Primary carcinoma of the fallopian tube shares several biological and clinical features with ovarian carcinoma. However, when compared with the latter, fallopian tube carcinoma more often tends to recur in retroperitoneal nodes and distant sites. Stage, patient age, and, among patients with advanced disease, residual tumor after initial surgery represent important prognostic variables for survival.

Adult↗

Effect of hyaluronic acid on human chondrocyte cell lines from articular cartilage.

The effects of hyaluronic acid (HA) derivative on the proliferation and metabolism of human chondrocytes were examined. Cells were obtained from cartilage from metatarsal phalangeal joints of 20 adult humans (aged 22-63) and from femoral knee condyles of 10 subjects (aged 22-77). Chondrocytes isolated by collagenase/Dnase digestion were cultured with addition of different doses of HA for 4 weeks. Morphological studies demonstrated that HA enhanced the adhesion of cells to substrate; HA-treated chondrocytes proliferated better than chondrocytes cultured in HA-free medium. This study shows that HA improves in vitro substrate adhesion ability and proliferative activity of human cartilage cells and that the response to the treatment varies on an individual basis.

Adjuvants, Immunologic↗

[Embolization of the uterine artery in the treatment of uterine myoma].

PURPOSE: To propose uterine myoma embolization as an alternative to myomectomy or hysterectomy in the treatment of symptomatic myomas; to evaluate the efficacy of the procedure in terms of clinical outcome, adopting all procedural and technical precautions to ensure minimal X-ray exposure and preserve reproductive potential. MATERIAL AND METHODS: Between April 1998 and February 2000, 26 patients, age range 32-54 years (mean 41 years), underwent uterine arterial embolization for menorrhagia, pelvic pain, and sensation of mass and pressure. Inclusion criteria were: single myomas, intramural localization and rich vascolarization of the lesion. Dose to patient was obtained by placing a thermoluminescent dosimeter (Harshaw, Solon, Ohio) both placed in posterior fornix of the vagina and on the skin at the beam entrance site. The procedure was performed under peridural anesthesia; polyvinil alcohol particles 355-500 mu (Contour) (Target Therapeutics, Boston Scientific Corporation, Fremont CA, USA) were employed as embolic agent. The uterine arteries were incannulated with a 5F (Glidecath, Terumo, Europe NV, Belgium) and successively 3F coaxial microcatheter (Target, Boston Scientific Corporation, Fremont CA, USA); the embolic material was injected as distally as possible. Color Power Doppler Ultrasound follow-up before and after i.v. contrast media administration (Levovist SHU 508 A, Shering, Berlin, Germany) was carried out at 15 days, at 1, at 3, at 6 months, and at 1 year from embolization. Pre-procedural evaluation and follow-up at 1 year was performed by MRI using T1 and T2 weighted images before and after Gadolinium (GdDTPA Shering, Berlin, Germany) administration. RESULTS: The technical success of the interventional procedure was 100% (26/26 cases). The mean fluoroscopy time was 20 minutes, and the mean number of angiographic exposures was 10. The mean estimated ovarian dose was 18.75 cGy and the mean adsorbed skin dose was 126.71 cGy. The imaging follow-up showed a 55% reduction of myoma volume at 6 months and a 75% reduction at 1 year. All patients reported a marked decrease in symptoms. No major complications were observed. The appearance of pelvic pain in the 24-48 hours after the procedure required sedation by analgesic pump; transitorial amenorrhea was observed in 3 patients. As for term complications, 2 patients have eliminated necrotic material through the vagina four weeks after procedure. The patients reported great satisfaction with the procedure. DISCUSSION: Many treatment options are currently available for symptomatic uterine myomas. One is surgical myomectomy which is associated with increased blood loss, pain and post operative morbidity and requires an additional surgical procedure for fibroma recurrence in 20-25% of patients. Another alternative treatment is hormonal therapy, which drammatically improves symptoms and reduces fibroid size although leiomyomas regrow to their original size within a few months of discontinuing treatment. Uterine embolization is a relatively new treatment for uterine fibroids that can be considered as an alternative to surgical and medical procedures. The radiation exposure adsorbed by the patient is reduced by using pulsed fluoroscopy and taking all the precautionary measures required to minimize the dose. CONCLUSIONS: The technical success, the patient' satisfation, the short hospitalization time and preservation of fertility confer to uterine artery embolization the role of a new alternative therapy for the treatment of symptomatic uterine myomas.

Adult↗

Unusual recurrence of cervical adenosquamous carcinoma after conservative surgery.

The use of less radical procedures for the treatment of early cervical cancers is gaining interest among physicians and young patients. Some authors have described surgical procedures aimed at reducing the surgical aggressiveness but the safety of such procedures remains debated. After a polypectomy, a young patient had a diagnosis of stage Ia(2) cervical adenosquamous carcinoma in 1995. As she wished to preserve her fertility, she underwent a cone biopsy and pelvic lymphadenectomy, without evidence of tumor spread. In 1998, at the 13th week of gestation, she had a diagnosis of a pelvic mass. The mass was a recurrence of carcinoma involving the myometrium, just underneath the peritoneum. She underwent a radical hysterectomy with bilateral oophorectomy. An ovarian metastasis was also detected at pathological exam. She received chemotherapy postoperatively and remains alive without evidence of disease. The recurrence of cervical cancer is traditionally regarded as an issue concerning the cervix, the parametria, or the lymph nodes. When the uterus is preserved we must also consider the possibility of a recurrence involving the corpus. With wider acceptance of limited therapeutic approaches we must be prepared for the detection of previously unknown patterns of recurrence and the follow-up modalities must be consequently adapted.

Adult↗

Induction of endothelin-1 expression by glucose: an effect of protein kinase C activation.

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.

Animals↗

Paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy for recurrent or persistent squamous-cell cervical cancer.

PURPOSE: The results of salvage chemotherapy for recurrent or persistent squamous-cell cervical cancer are unsatisfactory. Cisplatin and Ifosfamide are effective compounds in cervical cancer. Paclitaxel has recently been tested with promising results. The aim of this study was to assess the efficacy of a combination of paclitaxel, ifosfamide and cisplatin (TIP) for persistent/recurrent squamous-cell cervical carcinoma in a phase II trial. PATIENTS AND METHODS: Forty-five women were treated with the TIP regimen. Thirty-one had received prior irradiation. Paclitaxel was given at a dose of 175 mg/m2, ifosfamide at a dose of 5 g/m2, and cisplatin at a dose of 75 mg/m2 (50 mg/m2 in irradiated patients) at three-week intervals. RESULTS: We observed 15 clinical complete responses, 15 partial responses, 9 stable diseases and 6 progressions. The objective response rate was 67% (95% confidence interval: 51%-81%). Ten complete responders underwent subsequent surgery and seven had pathology-defined complete responses (two in irradiated areas). The response rate was 52% in irradiated and 75% in non-irradiated areas. The median survival for non-responders is 6 months, 9+ month for partial responders and 13+ for complete responders. The most relevant side effect was myelotoxicity, with 91% of patients experiencing grade 3-4. One woman had life-threatening toxic effects. CONCLUSIONS: This combination is highly effective for salvage treatment in non-irradiated patients. For irradiated women the response rate is higher than that observed with other regimens but further investigation is warranted. The toxicity is relevant but adequate hydration and prolonged infusion of ifosfamide make it acceptable.

Adult↗

Human chondrocyte cell lines from articular cartilage of metatarsal phalangeal joints.

Chondrocytes can be isolated from human adult cartilage from metatarsal phalangeal joints. After enzymatic digestion to isolate viable cells, confluent monolayers were obtained 2-4 weeks after the start of cell division. Chondrocytes cultures, initiated and maintained in HAM's F12 with bovine fetal serum without the addition of other growth factors, produced in vitro a matrix rich in collagen and proteoglycans. Although several studies reported phenotypic instability, our results showed that the cell retain for more than 5 months in culture their differentiated characteristics, including the ability to produce cartilage-specific molecules. Chondrocyte cell lines should be useful in studying the functions of these cells from normal and abnormal tissue and for pharmacological studies in vitro.

Adult↗

Uterine rupture after hysteroscopic metroplasty and labor induction. A case report.

BACKGROUND: Hysteroscopic metroplasty has become the method of choice for the treatment of uterine septa. Uterine perforation has been reported in about 1% of surgical hysteroscopic procedures. Ultrasound allows the detection of uterine lesions. CASE: A woman who conceived after complicated hysteroscopic metroplasty underwent emergency cesarean section because of uterine rupture during labor induced with prostaglandins (PGE2). An ultrasound scan performed two years later revealed a uterine lesion that corresponded to the myometrial tear reported at cesarean section. CONCLUSION: Complicated hysteroscopic metroplasty may promote acute uterine rupture during pregnancy and labor. Ultrasound is a useful tool for the detection of uterine lesions. If adequately considered, it might have allowed more rational management of labor in this case. PGE2 should never be used for induction of labor after complicated metroplasty.

Adult↗

Fertility-sparing surgery in uterine leiomyosarcoma.

BACKGROUND: Leiomyosarcoma of the uterus is a rare malignancy with a poor prognosis. Total abdominal hysterectomy is considered the treatment of choice. Occasionally, the diagnosis is made on myomectomy specimen, and in young patients the role of conservative management is not well defined. PATIENTS AND METHODS: Between 1982 and 1996, eight patients with a diagnosis of uterine leiomyosarcoma following myomectomy were conservatively managed at our institution. Median age of the patients was 29 years (range 19-32 years), and all were nulliparous. The tumor was confined to a myoma in all patients. Patients were adequately informed about the risk and were submitted to strict follow-up including pelvic examination, hysteroscopy, ultrasonography, chest X-ray, and abdominopelvic MRI or CT scan. RESULTS: Mean mitotic count of leiomyosarcomas was 6 per 10 HPF, ranging between 5 to 33. At a median follow-up of 42 months three pregnancies were recorded. Two patients had a spontaneous delivery at term. The third patient had diagnosis of recurrent disease at the time of cesarian section. Despite further surgery and chemotherapy, she died of disseminated disease 26 months after diagnosis. The remaining seven patients are alive and well. Two patients received a second surgical procedure after diagnosis of leiomyosarcoma, 24 and 16 months after primary operation. Both were found to have leiomyomas. CONCLUSIONS: Selected cases of uterine leiomyosarcoma might be managed conservatively in young nulliparous women desiring pregnancy. A strict follow-up is mandatory, and at the completion of the reproductive life, a demolitive procedure could be considered.

Adult↗

Complete remission of brain metastases from ovarian carcinoma with carboplatin.

Central nervous system involvement by epithelial ovarian carcinoma is rare. We report the case of a 49 year old woman with stage IV serous carcinoma of the ovary who developed multiple cerebral and cerebellar metastases 7 months after achieving complete response to platin-based chemotherapy. Eight courses of carboplatin (400 mg/m2) were administered and after the second cycle complete remission of the brain deposits occured. The treatment afforded rapid subjective and objective relief and was associated with a good quality of life. Abdominal recurrent disease was diagnosed 22 months after treatment for brain involvement. Paltin-based chemotherapy was reinstated, but the patient died from progressive adbominal disease without any sign of cerebral involvement and any neurological symptomatology. Carboplatin should be considered for the treatment of ovarian carcinoma metastatic to the brain.

Antineoplastic Agents↗

Carbohydrate binding activity in human spermatozoa: localization, specificity, and involvement in sperm-egg fusion.

Sperm carbohydrate binding activity is involved in gamete recognition. We identified a human sperm protein extracted under reducing conditions, and with a molecular mass of 65 kDa on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and which binds D-mannose coupled to albumin (DMA) in presence of cations and a neutral pH. Epifluorescence microscopy showed that fluorescein-DMA binds to dead or permeabilized sperm heads. The DMA-binding activity of human sperm heads was highly specific for a polysaccharide structure containing charged sugar residues. After capacitation, or induction of the acrosome reaction using solubilized zonae pellucidae, fluorescein-DMA was bound respectively to 10.3% (+/- 3.5%) and to 37.6% (+/- 2.1%) of viable sperm heads. The sequential analysis of viable spermatozoa for fluorescein-DMA binding and for rhodamine-Pisum sativum agglutinin binding, showed that DMA-binding sites are present in viable acrosome-reacted spermatozoa. Three dimensional analysis of fluorescence and ultrastructural studies showed that DMA-binding sites are mostly restricted to the sub-acrosomal space of the equatorial segment. Incubation of spermatozoa and zona-free hamster eggs in the presence of DMA was associated with a dose-dependent significant reduction in the number of spermatozoa bound to the oolemma, compared with a control, and to a dose-dependent inhibition of oocyte penetration. This effect was highly specific for DMA, suggesting that DMA-binding sites in human spermatozoa are involved in sperm-egg fusion.

Adult↗