Infrared spectroscopy of phytochrome and model pigments

Fourier-transform infrared difference spectra between the red-absorbing and far-red-absorbing forms of oat phytochrome have been measured in H2O and 2H2O. The difference spectra are compared with infrared spectra of model compounds, i.e. the (5Z,10Z,15Z)- and (5Z,10Z,15E)-isomers of 2,3,7,8,12,13,17,18-octaethyl-bilindion (Et8-bilindion), 2,3-dihydro-2,3,7,8,12,13,17,18-octaethyl-bilindion (H2Et8-bilindion), and protonated H2Et8-bilindion in various solvents. The spectra of the model compounds show that only for the protonated forms can clear differences between the two isomers be detected. Since considerable differences are present between the spectra of Et8-bilindion and H2Et8-bilindion, it is concluded that only the latter compound can serve as a model system of phytochrome. The 2H2O effect on the difference spectrum of phytochrome supports the view that the chromophore in red-absorbing phytochrome is protonated and suggests, in addition, that it is also protonated in far-red-absorbing phytochrome. The spectra show that protonated carboxyl groups are influenced. The small amplitudes in the difference spectra exclude major changes of protein secondary structure

Phenotypic characteristics of colo-rectal cancer in I1307K APC germline mutation carriers compared with sporadic cases

The I1307K APC germline mutation is associated with an increased risk to colo-rectal cancer (CRC). Whether and to what extent the phenotype of CRC in mutation carriers differs from sporadic cases, remains unknown. To gain insight into this issue, we analysed 307 unselected Israeli patients with CRC, who were treated in a single medical centre, for harbouring the I1307K mutation. Twenty-eight mutation carriers (9.1%) were detected. Two of 28 mutation carriers (7.1%) and 93/277 (33.6%) of non-carriers, were of non-Ashkenazi origin (P< 0.01). In 74/278 (26.6%) of the sporadic cases, and only 1/28 (3.6%) of mutation carriers (3.6%) the tumour was located in the right colon (P< 0.01). Mutation carriers had a more advanced disease stage (14/28 – 50% Dukes C), as compared with 60 (19.5%) of non-carriers (P= 0.02). The mean age at diagnosis was similar: 65 (+/– 9.7) years and 66.3 (+/– 11.6) years, for mutation carriers and non-carriers, respectively. No statistical differences were noted between the two groups in sex distribution, tumour grade, and family history of cancer. We conclude that early age at diagnosis and family history of cancer cannot be used to predict who is likely to harbour the I1307K APC germline mutation carriers. However, the tumours in patients with this mutation appear different than those without, are less likely to be proximal and more likely to be advanced than tumours in non-carriers.   http://www.bjcancer.com © 2001 Cancer Research Campaig

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer : A low cost effective regimen

Recently, we reported a highly active regimen in advanced gastric cancer including a weekly administration of cisplatin, epidoxorubicin, leucovorin, 5-fluorouracil with the support of filgrastim. In order to simplify the administration and to decrease the toxicity of these drugs, mainly epidoxorubicin-induced alopecia, we designed a regimen including an infusional 5-fluorouracil schedule according to the de Gramont regimen, cisplatin and mitomycin C replacing epidoxorubicin. Forty-five patients with advanced or metastatic gastric cancer were treated with cisplatin 50 mg m−2 i.v. on day 1, every 2 weeks, 6S-stereoisomer-leucovorin 100 mg m−2 i.v. followed by 5-fluorouracil 400 mg m−2 i.v. bolus and 600 mg m−2 i.v. in a 22-h infusion, on days 1 and 2, every 2 weeks, and mitomycin C 7 mg m−2 i.v. bolus on day 2, every 6 weeks. Grades 3–4 toxicities (National Cancer Institute-Common Toxicity Criteria) consisted mainly of neutropenia and thrombocytopenia. Five patients had a complete response and 16 had a partial response for an overall response rate of 46.7% (95% confidence interval, 32.1–61.2%). The median survival was 11 months. The combination of cisplatin, 5-fluorouracil and leucovorin according to de Gramont, and mitomycin C seems to be an active and safe regimen in the treatment of advanced gastric cancer. Because of its low cost it may be suggested for patients not enrolled into clinical trials

Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer: Daegu Gyeongbuk Oncology Group

The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg m−2 plus oxaliplatin 120 mg m−2 on day 1 based on a 3-week cycle. Forty-two patients were enrolled in the current study, among whom 39 were assessable for efficacy and all assessable for toxicity. One complete response and 18 partial responses were confirmed, giving an overall response rate of 45.2% (95% confidence interval (CI); 31.7–59.7%). At a median follow-up of 7.7 months, the median time to progression and median overall survival was 5.7 (95% CI; 4.3–7.2) months and 9.9 (95% CI; 7.8–12.0) months, respectively. Grade 3/4 neutropenia occurred in 11 patients (26.1%) and febrile neutropenia was observed in four patients (9.5%). The common non-haematologic toxicity was fatigue (grade 1/2, 61.9%) and nausea (grade 1/2, 47.7%). The combination of docetaxel and oxaliplatin was found to be well tolerated and effective in patients with advanced gastric cancer

A phase II study of paclitaxel and capecitabine as a first-line combination chemotherapy for advanced gastric cancer

Paclitaxel and capecitabine, which have distinct mechanisms of action and toxicity profiles, have each shown high activity as single agents in gastric cancer. Synergistic interaction between these two drugs was suggested by taxane-induced upregulation of thymidine phosphorylase. We, therefore, evaluated the antitumour activity and toxicities of paclitaxel and capecitabine as first-line therapy in patients with advanced gastric cancer (AGC). Patients with histologically confirmed unresectable or metastatic AGC were treated with capecitabine 825 mg m−2 p.o. twice daily on days 1–14 and paclitaxel 175 mg m−2 i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities. Between June 2002 and May 2004, 45 patients, of median age 57 years (range=38–73 years), were treated with the combination of capecitabine and paclitaxel. After a median 6 cycles (range=1–9 cycles) of chemotherapy, 43 were evaluable for toxicity and response. A total of 2 patients showed complete response and 20 showed partial response making the overall response rate 48.9% (95% CI=30.3–63.5%). After a median follow-up of 42.2 months (range=31.2–54.3 months), median time to progression was 5.6 months (95% CI=3.9–7.2 months) and median overall survival was 11.3 months (95% CI=8.1–14.4 months). Grade 3 or 4 adverse events include neutropaenia (46.5% of patients), hand–foot syndrome (9.3%), arthralgia (9.3%), and asthenia (4.7%). There was no neutropaenic fever or treatment-related deaths. Paclitaxel and capecitabine combination chemotherapy was active and highly tolerable as a first-line therapy for AGC