Fluorouracil-alone versus high-dose folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research (GOIRC).

One hundred eighty-one patients with measurable recurrent or metastatic colorectal cancer, who had not received prior chemotherapy, were randomized in a prospective controlled trial to receive 5-fluorouracil (5FU), 13.5 mg/kg, for five days (arm A) or high-dose folinic acid [Cyanamid-Lederle, Italy] (FA), 200 mg/m2, for five days and 5FU, 400 mg/m2 for five days (arm B). The treatments were repeated every four weeks. One hundred fifty-five patients were evaluable for response. The two arms were balanced for all potential prognostic factors studied. The response rate (CR+PR) was 18% in the 5FU arm and 16% in the 5FU plus FA arm. Median duration of response was 56 weeks for 5FU alone and 42 weeks for the combination (p = 0.48). Median time to failure (TTF) was 20 weeks for arm A and 21 for arm B (p = 0.62). Median survival was 62 weeks on the 5FU arm and 53 weeks on the FA plus 5FU arm (p = 0.14). Dose intensity (DI) delivered was the same in both arms. Diarrhea and mucositis were the most frequent adverse reactions in arm B; 20% of the patients in arm A and 38% of those in arm B experienced diarrhea (p = 0.008). Mucositis occurred in 34% of patients in arm A and 42% in arm B (p = 0.04). In general nausea and vomiting were moderate. Hematological toxicity was more severe in patients treated with 5FU alone: 31% in arm A and 14% in arm B developed leukopenia (p = 0.015). In the combination arm one patient died due to gastrointestinal and hematological toxicity after the seventh cycle. This study indicates that, in advanced colorectal cancer, the combination of high-dose FA and 5FU is not superior to 5FU alone when utilized at standard high-dose intensity.     

Problems in the design of anticancer agents

Theoretically, two predominant paths for obtaining more selective anticancer agents may be envisaged. These are: (a) to make compounds which distribute only or preferentially in cancer cells; (b) to make compounds that are able selectively to kill or to differentiate cancer cells. Although in the last two decades research into new anticancer drugs has not produced satisfactory results, there is solid ground on which novel strategies can be developed, mainly based on a much greater biological knowledge of human tumours. This article does not review all the possible approaches that may be followed, but simply discusses some ideas and problems mainly taken from the current research of our laboratory.     

Salvage therapy with ilosfamide and mitoxantrone in advanced ovarian cancer

OBJECTIVE:: To evaluate the anti-tumour activity and toxicity of ifosfamide(5 g/m² continuous infusion) and mitoxantrone (10 mg/ m² givenin combination every 3 weeks in patients with ovarian cancerresistant to at least two previous regimens which included platinum. PATIENTS AND METHODS:: Additional eligibility criteria were an ECOG performance status2 and measurable disease. Of 47 patients entered in the study,8 were defined as platinum-resistant and 39 as potentially sensitiveaccording to Markman's criteria. Thirty-five patients had alsoreceived pacitaxel as last treatment before entering this study.Tumour response was evaluated every three cycles. RESULTS:: One complete and 11 partial responses were reported, for anoverall response rate of 25% (95% CI: 14%–40%). Threeof the partial responders were resistant to num. None of the7 partial responders pretreated with had responded to it. Theoverall median urvival was months. Neutropema G4 was reportedin 18 patients(42%) with hospitalisation because of febrileneutropenia in 3 of them. CONCLUSIONS:: In patients with ovarian cancer failing least 2 previous therapiesincluding platinum, the nation of ifosfamide and mitoxantronehas shown antitumour activity comparable to that of paclitaxel,with accept able toxicity. Objective responses were reportedalso patients failing pacitaxel, suggesting a lack of crossresistance. ifosfamide, mitoxantrone, ovarian cancer     

In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model.

PURPOSE: The purpose of this research was to assess in vivo by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) the antiangiogenic effect of SU6668, an oral, small molecule inhibitor of the angiogenic receptor tyrosine kinases vascular endothelial growth factor receptor 2 (Flk-1/KDR), platelet-derived growth factor receptor, and fibroblast growth factor receptor 1. EXPERIMENTAL DESIGN: A s.c. tumor model of HT29 human colon carcinoma in athymic mice was used. DCE-MRI with a macromolecular contrast agent was used to measure transendothelial permeability and fractional plasma volume, accepted surrogate markers of tumor angiogenesis. CD31 immunohistochemical staining was used for assessing microvessels density and vessels area. Experiments were performed after 24 h, and 3, 7, and 14 days of treatment. RESULTS: DCE-MRI clearly detected the early effect (after 24 h of treatment) of SU6668 on tumor vasculature as a 51% and 26% decrease in the average vessel permeability measured in the tumor rim and core (respectively). A substantial decrease was also observed in average fractional plasma volume in the rim (59%) and core (35%) of the tumor. Histological results confirmed magnetic resonance imaging findings. After 3, 7, and 14 days of treatment, postcontrast magnetic resonant images presented a thin strip of strongly enhanced tissue at the tumor periphery; histology examination showed that this hyperenhanced ring corresponded to strongly vascularized tissue adjacent but external to the tumor. Histology also revealed a strong decrease in the thickness of peripheral viable tissue, with a greatly reduced vessel count. SU6668 greatly inhibited tumor growth, with 60% inhibition at 14 days of treatment. CONCLUSIONS: DCE-MRI detected in vivo the antiangiogenic efficacy of SU6668.     

Eyebrow reconstruction

This is a systematic review of eyebrow reconstruction options, using the PubMed database, as well as dermatology and plastic surgery texts. Eyebrow reconstruction options in various clinical scenarios (small, large, medial, lateral, and total defects) are presented. The goals of eyebrow reconstruction are to provide structural, functional, and aesthetic restoration. A good understanding of various eyebrow reconstruction techniques is essential for plastic, dermatologic, and oculoplastic surgeons.     

Sexually dimorphic behavioral effects of maternal separation in anorexic rats

Exposure to negative events during the neonatal period is one of the leading factors contributing to the development of psychiatric disorders, including anorexia nervosa. In this study, we investigated the effects of maternal separation (MS) on the development of anorexia in rodents using the mild-stress form of the activity-based anorexia (ABA) model (2 hr of free access to a running wheel and a 1-hr feeding test) in both male and female rats. We assessed anxiety-like and locomotor behavior and hyperactivity with the open field and elevated plus maze tests. Our results showed that ABA rats of both sexes displayed hyperactive behavior associated with reduced anxiety-like behavior when compared to controls. However, a sexually dimorphic effect of MS emerged in anorexic rats: while the females exposed to MS + ABA were hyperactive with diminished anxiety-related behaviors compared to females of the ABA group, MS in males attenuated or did not alter the effects of the ABA protocol. In conclusion, our data reveal that the synergistic effects of MS and ABA on physical activity and anxiety-like behavior act in opposite directions in the two sexes.     

Soluble HLA-G molecules in follicular fluid: a tool for oocyte selection in IVF?

Currently, different approaches are used to select oocytes for in vitro fertilization (IVF) procedures, but they do not assure a significant association with the pregnancy outcome. Since several studies have proposed the expression of HLA-G antigens in early embryos to be a possible marker of elevated implantation rate, we have investigated the presence of soluble HLA-G molecules in 50 follicular fluids (FFs). The results have shown soluble HLA-G antigens (sHLA-G) in 19/50 (38%) FFs. Furthermore, we have related the presence of sHLA-G molecules in FFs to detection of the soluble antigens in culture supernatants of the corresponding fertilized oocyte, evidencing a significant relationship (p=1.3 x 10(-6); Fisher exact p-test). Specific ELISA and Western blot approaches identified both HLA-G5 and soluble HLA-G1 molecules in FFs while immunocytochemical analysis indicated polymorphonuclear-like and granulosa cells as responsible for production of sHLA-G1 and HLA-G5 molecules. In contrast, only sHLA-G1 antigens were detected in culture supernatants of fertilized oocytes. Overall, these results suggest a role for sHLA-G molecules in the ovulatory process and propose the FFs analysis for sHLA-G molecule presence as a useful tool for oocyte selection in IVF.