[Switching to direct intrahepatic arterial infusion of 5-FU after a progression of liver metastases from colorectal carcinoma treated with systemic infusion of FOLFOX].

Direct intrahepatic arterial infusion of 5-FU produced a significantly higher response rate than systemic infusion of FOLFOX in the treatment of hepatic metastases from colorectal carcinoma. Fourteen patients switched over from systemic FOLFOX therapy to intrahepatic protracted 5-FU infusion after a progression of liver metastases treated with systemic therapy. Of the 14 patients whose tumors had initially failed to respond to systemic FOLFOX therapy, 12 (85%) had a partial response, and 13 (93%) had a reduction in their tumor marker (CEA, CA19-9, TPA) when the treatment was switched to intrahepatic 5-FU therapy. Traditional chemotherapy toxicity, such as myelosuppression, nausea, vomiting and neurotoxicity did not occur in the intrahepatic group. Three out of 14 patients survived more than a year, and the longest was 18 months. A better survival rate can be achieved with the use of hepatic artery infusion therapy.

Basal cytokeratin expression in relation to biological factors in breast cancer.

The objective of this study was to determine the predictive impact of several established tumor biological markers and clinicopathological findings for basal-like carcinoma. Expression was determined by immunohistochemistry using antibodies to cytokeratins 5/6, 14, and 17, and the cases were divided into basal-like carcinoma and non basal-like carcinoma. These subgroups were compared in terms of biological markers (HER2, estrogen receptor, progesterone receptor, Ki-67, P-53, and P-glycoprotein) and clinicopathological behavior. Of the 49 basal-like carcinoma cases, 25(51.0%) were P-53-positive, whereas 100 (35.9%) of the 278 non basal-like carcinoma cases were P-53-positive. A high ratio of nuclear Ki-67 expression was detected in 39 (79.6%) of 49 basal-like carcinoma cases and was significantly more common than in non basal-like carcinoma cases (81/278, 29.1%). P-glycoprotein expression was identified in 29 (59.2%) of 49 basal-like carcinomas but only 85 (30.6%) of 278 non basal-like carcinomas. We observed high levels of P-53, Ki-67, and P-glycoprotein, with the reduction or loss of estrogen receptor, progesterone receptor, and HER2 being more obvious, in basal-like carcinomas than in non basal-like carcinomas. Our findings provide further evidence that basal-like carcinoma has different mechanisms of histogenesis.

MK-801 inhibits the micturition reflex in chronic bladder irritation caused by crystalluria in the rat.

Urodynamic and pharmacological studies were performed to investigate the effect of crystalluria on the micturition reflex and the involvement of glutamatergic transmission. The rats, which were given LP-805 (100 mg/kg/day) orally for 12 days, voided crystalluria. The pH of these crystalluria (LP-805 urine) was the same as normal urine. The amount of crystals was 70-100/division magnified 400 x. The end of the crystals was sharp. Intravesical administration of LP-805 urine induced hyperreflexia of the micturition reflex in normal rats. When the infusion solution was changed to LP-805 urine from saline, the latency was reduced to 57.6+/-2.1% of control in single cystometrogram (CMG) or was reduced to 51.4+/-0.9% of control in continuous CMG. The voiding volume was reduced to 52.1+/-3.6% of control in single CMG or was reduced to 62.5+/-0.8% of control in continuous CMG. These parameters were recovered after LP-805 urine was removed. Intravesical administration of acetic acid did not induce hyperreflexia of the micturition reflex in LP-805-treated rats. These data suggest that the chronic irritation by aculeate crystals might induce hyperreflexia of the micturition reflex, which increase afferent neuronal activity. Intravenous administration of MK-801 (0.001 to 1 mg/kg) inhibited the micturition reflex in a dose-dependent manner. The ID50 in LP-805-treated rats (0.03 mg/kg i.v.) was lower than that in normal rats (0.56 mg/kg i.v.). After chronic irritation of the bladder epithelium, MK-801 sensitivity was enhanced for the micturition reflex. These data suggested that crystalluria elicit hyperreflexia in the micturition reflex that mediated with NMDA glutamatergic receptors.