The structure-based cancer-related single amino acid variation prediction.

Single amino acid variation (SAV) is an amino acid substitution of the protein sequence that can potentially influence the entire protein structure or function, as well as its binding affinity. Protein destabilization is related to diseases, including several cancers, although using traditional experiments to clarify the relationship between SAVs and cancer uses much time and resources. Some SAV prediction methods use computational approaches, with most predicting SAV-induced changes in protein stability. In this investigation, all SAV characteristics generated from protein sequences, structures and the microenvironment were converted into feature vectors and fed into an integrated predicting system using a support vector machine and genetic algorithm. Critical features were used to estimate the relationship between their properties and cancers caused by SAVs. We describe how we developed a prediction system based on protein sequences and structure that is capable of distinguishing if the SAV is related to cancer or not. The five-fold cross-validation performance of our system is 89.73% for the accuracy, 0.74 for the Matthews correlation coefficient, and 0.81 for the F1 score. We have built an online prediction server, CanSavPre ( http://bioinfo.cmu.edu.tw/CanSavPre/ ), which is expected to become a useful, practical tool for cancer research and precision medicine.

Comprehensive breast cancer adjuvant digital summary.

BACKGROUND: Patients with breast cancer often fail to recall the details of their original diagnosis and adjuvant therapy with the passage of time. Subsequent follow-up and treatment at a later time and a different institution wastes valuable time and effort to retrieve the original data. PATIENTS AND METHODS: Twenty-five consecutive patients with breast cancer of all stages admitted for adjuvant/neoadjuvant treatment and surgical excision were entered on study. An individualized comprehensive visual evaluation summary sheet (VESS) was created that detailed initial diagnosis, preceding relevant investigations, drug scheduling, and dosages of adjuvant therapy. Completion of a VESS required a computer, a digital camera with connection to a microscope, and radiology images over the PACS system. The completed one-page summary can be printed or stored. RESULTS: A VESS takes up an average of 4.4 MB (1.24-8 MB), each containing 11.5 images (range, 4-23 images), spanning a time period of around 216 days (range, 125-558 days). CONCLUSIONS: Patients received a complete summary of pertinent information concerning their diagnosis and adjuvant therapy.

Phase II study of docetaxel and gemcitabine combination chemotherapy in non-small-cell lung cancer patients failing previous chemotherapy.

We conducted a phase II study of docetaxel and gemcitabine chemotherapy in patients with non-small-cell lung cancer (NSCLC) who had not responded to previous chemotherapy, to assess the response to and toxicity of this combination chemotherapy. Thirty-six patients were enrolled from June 1999 to December 1999. Treatment consisted of docetaxel 30 mg/m(2) and gemcitabine 800 mg/m(2) intravenous infusion on days 1 and 8 every 3 weeks. One hundred forty-six cycles of treatment were given, with a median of four cycles (range, 1-8 cycles). All patients were evaluable for toxicity profile and response rate. The major toxicity was myelosuppression. Grade III or IV neutropenia occurred in 9 patients (25%) during treatment. Febrile neutropenia occurred in 2 patients (5.6%). Grade III or IV thrombocytopenia occurred in 6 patients (16.7%). Reversible fluid retention occurred in 9 patients (25%). Grade IV pulmonary toxicity (interstitial pneumonitis) occurred in two patients, and both died. Other toxicities were few and mild in severity. After two cycles of treatment, 13 patients (36.1%) had a partial response (95% CI 20.3-51.9%). There was no significant difference in the response rate among patients who had responded to previous chemotherapy or not. The median time to disease progression was 3.8 months, and the median survival was 6.9 months. Median survival was 7.1 and 4.9 months in patients receiving docetaxel and gemcitabine as second-line and greater than or equal to third-line chemotherapy, respectively. In conclusion, docetaxel and gemcitabine salvage chemotherapy produces a high response rate and a relatively mild toxicity profile in NSCLC. However, the issue of interstitial pneumonitis should be of concern.

Phase II and pharmacokinetic study of GL331 in previously treated Chinese gastric cancer patients.

PURPOSE: A phase II and pharmacokinetic study was designed to assess the efficacy and toxicity profile of an epidophyllotoxin analogue, GL331, in previously treated Chinese gastric cancer patients, with concurrent pharmacokinetic evaluation of the drug's metabolism. MATERIAL AND METHODS: GL331 was given at 200 mg/m(2) as a daily 3-h infusion for 5 days every 4 weeks. RESULTS: Enrolled in the study were 15 patients. One patient died from neutropenic sepsis before evaluation, one patient did not receive the full dose for reasons unrelated to GL331, nine patients had progressive disease with a median survival of 80 days, and five had stable disease with a median survival of 240 days. Grade 3 and 4 myelosuppression occurred in 10 of the 15 patients, with one death from neutropenic sepsis. This patient's peak GL331 concentration was 16.8 microg/ml, which was high compared to the mean peak drug concentration of 6+/-4.1 microg/ml. The mean systemic GL331 clearance was 12.1+/-7.2 l/h per m(2), much lower than 23.3+/-8.2 l/h per m(2) found in the phase I trial. Topoisomerase IIalpha was determined by immunohistochemistry and overexpression was detected in 3 of 11 specimens. CONCLUSIONS: GL331 was ineffective at this dose and schedule in this group of patients in spite of adequate blood levels of the drug.