Cyclopropanation of unactivated alkenes with non-stabilized iron carbenes.

Cyclopropanes are ubiquitous in medicines, yet robust synthetic access to a wide range of sterically and electronically diverse analogs remains a challenge. To address the synthetic limitations of the most direct strategy, (2+1) cycloaddition, we sought to develop a variant that employs non-stabilized carbenes. We present herein an FeCl-catalyzed cyclopropanation that uniquely employs aliphatic (enolizable) aldehydes as carbene precursors.

Carbene reactivity from alkyl and aryl aldehydes.

Carbenes are highly enabling reactive intermediates that facilitate a diverse range of otherwise inaccessible chemistry, including small-ring formation and insertion into strong σ bonds. To access such valuable reactivity, reagents with high entropic or enthalpic driving forces are often used, including explosive (diazo) or unstable (-dihalo) compounds. Here, we report that common aldehydes are readily converted (via stable α-acyloxy halide intermediates) to electronically diverse (donor or neutral) carbenes to facilitate >10 reaction classes.

Endothelin-1 Exhibiting Pro-Nociceptive and Pro-Peristaltic Activities Is Increased in Peritoneal Carcinomatosis.

Peritoneal carcinomatosis often results in alterations in intestinal peristalsis and recurrent abdominal pain. Pain management in these patients is often unsatisfactory. This study aimed to investigate whether endothelin-1 (EDN1) was involved in pain mediation in peritoneal carcinomatosis, and thus whether the EDN1 pathway could be a new therapeutic target for peritoneal carcinomatosis-associated pain.

Theobroma cacao improves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia.

A gain-of-function mutation in the fibroblast growth factor receptor 3 gene (FGFR3) results in achondroplasia (ACH), the most frequent form of dwarfism. Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways. Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH, and natural plant compounds are prime drug candidate sources.

[Early debulking surgery after chemotherapy in advanced cancer of the ovary].

The main prognostic factor in advanced ovarian cancer is the volume of residual disease after the initial laparotomy. Early debulking surgery after several cycles of chemotherapy, before the emergence of resistant cell lines, could improve the prognosis of patients with bulky residual disease. This study concerns patients with advanced ovarian cancer entered into three prospective trials including IV cisplatin and anthracycline-based chemotherapy, early debulking surgery after three cycles of chemotherapy in case of initial residual disease superior 2 cm and intraperitoneal consolidation chemotherapy.

Dual modulation of 5-fluorouracil with folinic acid and hydroxyurea in metastatic colorectal cancer.

Leucovorin and 5-fluorouracil (5-FU) can be further modulated with hydroxyurea. Sixty-eight patients with advanced colorectal cancer received every 2 weeks hydroxyurea per os 1.5 g to 2 g days -1, 1, and 2; leucovorin 200 mg/m2 iv over 2 hours started at least 1 hour after hydroxyurea and per os 100 mg/m2 12 hours later, on days 1 and 2; 5-FU, bolus 400 mg/m2 during leucovorin infusion and 24 hours continuous infusion 600 mg/m2, repeated on days 1 and 2.

[Locoregional recurrences of breast cancer].

Aim Of The Study: To determine the characteristics of 51 cases of isolated local regional breast cancer recurrence.

Methods: Retrospective study from 1980 to 1992, survival calculated according to Kaplan-Meier and log-rank test.

Results: Twenty-five patients had had a conservative treatment of her primary tumour, 26 had been treated by modified radical mastectomy.

[Extravasation of paclitaxel (Taxol)].

Paclitaxel is a new antimitotic derived from yew-tree, used for the treatment of ovarian and breast cancers. The local toxicity of paclitaxel is still poorly known. We report one of the first observations of accidental subcutaneous extravastion of paclitaxel.

[Detection of ovarian adenocarcinoma in the occasion of cerebrovascular complication associated with consumption coagulopathy].

A 58 year-old woman was hospitalized for an hemorrhagic stroke, associated with a consumption's coagulopathy, related to a stage Ic ovarian carcinoma. After surgery and chemotherapy, hemostasic disorders disappeared. The same disorders occurred at tumoral relapse.

[Breast cancer and pregnancy].

Breast cancer is generally believed to carry a worse prognosis during pregnancy because of the potential adverse effects of anticancer treatments on the fetus and of pregnancy related hormonal and immunological modifications on the disease. Problems arise both with breast cancers diagnosed during or immediately after pregnancy and with pregnancies occurring in patients previously treated for breast cancer. The incidence of these problems is difficult to estimate, in part because pregnancy-related changes in the breasts obscure clinical and radiological manifestations.

Folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide in metastatic breast cancer.

60 patients with metastatic breast cancer were entered in a phase II study using folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide. 47 had measurable visceral metastases and 13 had exclusively bone metastases. 36 had received previous adjuvant or metastatic treatment (33/36 with anthracycline-based regimens).

[Toxicity of levamisole in adjuvant chemotherapy for colorectal cancer].

We studied the levamisole toxic effects in adjuvant therapy for colorectal cancer. The therapy toxic effects on 127 patients were statistically more important in the levamisole-treated group compared to patients treated with folinic acid and 5-fluorouracil alone. Randomized studies in progress will demonstrate the real therapeutic value of levamisole.

Bi-weekly 2-day schedule of high-dose folinic acid, 5-fluorouracil bolus and infusion in pretreated advanced epithelial ovarian cancer: a phase II study.

Twenty patients with documented progression after two or three cisplatin-based regimens for advanced epithelial ovarian carcinoma were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. One clinically complete and two partial responses were observed in 16 evaluable patients, with 5 remaining stable. Median survival was 9 months.

[Bony involvement of the calcaneum in sarcoidosis. A case report].

Bone lesions of sarcoidosis occur in 10 to 15% of the cases, most often involving the extremities. These frequently corticosteroid-dependent lesions worsen the prognosis of the disease. We report a case of sarcoidosis of 14 years duration in a 58-year old woman who presented with a bone lesion strictly localized to the calcaneum.

Survival with intraperitoneal cisplatin in advanced ovarian cancer after second-look laparotomy.

We studied survival in 36 patients with Stage III/IV ovarian cancer who received intraperitoneal high-dose cisplatin (200 mg/m2) alone or in combination with cytarabine (2 g), after intravenous (i.v.) cisplatin-based chemotherapy followed by second-look laparotomy.

Sequential cisplatin-doxorubicin, early debulking surgery and intraperitoneal chemotherapy in advanced ovarian cancer. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).

40 patients with advanced ovarian cancer were treated with immediate debulking followed by sequential cisplatin and doxorubicin every 4 weeks, followed by second-look laparotomy (SLL). Six courses were given when residual disease (RD) was under 2 cm. When RD was over 2 cm, three courses were followed by early debulking and six more courses before SLL.

High-dose folinic acid, 5-fluorouracil bolus and continuous infusion in poor-prognosis patients with advanced measurable gastric cancer.

Twenty-five patients with advanced measurable gastric cancer were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. Fourteen patients over 65 yr old and/or with a poor general status received first-line treatment, and eleven younger patients second-line. The response rate was 43.

[Results of intraperitoneal chemotherapy of ovarian cancer].

We studied a series of 42 patients with advanced ovarian cancer who received intraperitoneal chemotherapy post second-look laparotomy. High-dose cisplatin (200 mg/m2) alone or in combination with cytarabine (2 g) achieved 47% response rate. Median overall survival from second-look laparotomy was 44 months with cisplatin (36 cases), 15 months with carboplatin (600 mg/m2, 5 cases) and not reached at 3 yrs with mitoxantrone (25 mg/m2, 8 cases).