Cisplatin-5-fluorouracil chemotherapy for advanced inoperable squamous carcinoma of the head and neck

Patients with locally advanced, inoperable squamous cell carcinoma of the head and neck were offered three courses of cisplatin and 96-h 5-fluorouracil (5-FU) infusion. Subsequent therapy included surgery when feasible, irradiation therapy, and a maintenance program of methotrexate (MTX)-5-FU. Thirty-three patients were evaluated prospectively. Seven patients underwent a single course of chemotherapy. Five patients underwent two courses of chemotherapy. Twenty-one patients underwent three courses of adjuvant chemotherapy. The overall response rate was 48% (16 of 33). Fifteen of 21 patients (76%) receiving three courses of chemotherapy evidenced a response; this included three complete responses (CRs) (9%). No responses were seen in patients receiving only one or two courses of chemotherapy. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. Patients who failed to demonstrate any response after two courses of chemotherapy did not respond after a third course. A significant group of patients fail to respond and should be offered participation in other investigational protocols as they become available.     

Effects of the AMPA receptor antagonist NBQX on the development and expression of behavioral sensitization to cocaine and amphetamine

 We examined the effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), an antagonist of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptor, on the development and expression of behavioral sensitization to amphetamine and cocaine in rats. A single injection of NBQX (12.5 mg/kg) administered 30 min prior to cocaine during the induction phase (days 1–5) prevented the development of cocaine sensitization, assessed by responsiveness to cocaine challenge on day 8. This NBQX regimen did not affect development of amphetamine sensitization. Two pretreatment injections of NBQX, one 20 min before and one 70 min after amphetamine on each day of the induction phase (days 1–6), did not affect sensitization of stereotypy but prevented sensitization of post-stereotypy ambulatory hyperactivity (both assessed by responsiveness to amphetamine challenge on day 8). The effect of NBQX on ambulatory sensitization was dose-dependent (attenuation with 12.5 mg/kg, complete prevention with 25 mg/kg). In contrast to its effects on development, NBQX (25 mg/kg) did not prevent expression of sensitization to cocaine or amphetamine. NBQX itself exerted no significant effects on locomotor activity in either drug-naive rats or rats that had received either NBQX or amphetamine repeatedly. These findings support a requirement for AMPA receptor stimulation in the development of locomotor sensitization to cocaine and amphetamine, but suggest a different mechanism for sensitization of amphetamine stereotypy. Received: 14 January 1997 / Final version: 24 June 1997     

Histological and scanning electron microscopic alterations in ileal conduit depending on the time factor

Five ileal conduit biopsies, taken after 1-7 years, were examined by light microscopy and scanning electron microscopy. The total height of the lamina mucosa decreased from 700 to 275 microns. The height of the villi diminished from 550 to 50 microns; the depth of the crypts increased from 130 to 244 microns and the villus-crypt index changed from 4.2 to 0.2. Signs of chronic inflammation could be observed. Scanning electron microscopy shows that the number of microvilli per cell was markedly reduced. There was a varied picture of different stages of atrophy. After 3 years microvilli could no longer be observed. In view of the prolonged urinary contamination time, it appears to be imperative to check neobladders with regard to possible carcinoma induction.     

Origins of heterogeneous ovarian carcinomas. A molecular cytogenetic analysis of histologically benign, low malignant potential, and fully malignant components.

It is unclear whether ovarian carcinomas develop from malignant transformation of benign precursors or whether they arise de novo. Thus, histologically benign or low malignant potential components found in heterogeneous ovarian carcinomas may be remnants of pre-existing lesions that progressed to malignancy or, alternatively, elements that arose independently (de novo). In a third possible interpretation, they represent areas of malignant epithelium that matured. We evaluated clonal relationships of histological components in 10 heterogeneous ovarian carcinomas using fluorescence in situ hybridization and confocal microscopy. Detailed analysis of aneuploidy for chromosomes 8, 12, and 17 on intact paraffin sections revealed that two tumors were aneuploid in all components, two lacked abnormalities in benign-appearing components, and one lacked aneuploidy in both histologically benign and low malignant potential components. Histological appearance was significantly related to aneuploidy (P < 0.05). The distribution of aneuploidy among tumor components strongly supports the tumor progression theory and demonstrates that the de novo hypothesis is highly unlikely (P < 0.001). Results also indicate that benign-appearing components in heterogeneous ovarian carcinomas do not represent maturation of malignant tissue and suggest that some benign tumors that become cancerous may have genetic aberrations that predispose them to malignant transformation.