RASSF1A and ERCC1 expression levels might be predictive of prognosis in advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck treated with docetaxel and cisplatin.

BACKGROUND: The purpose of this study was to test the hypothesis that the immunohistochemical expression of ERCC1 and RASSF1A would predict both response to and survival after docetaxel and cisplatin combination chemotherapy in inoperable or recurrent head and neck squamous cell carcinoma. PATIENTS AND METHODS: A total of 54 patients were treated with frontline systemic chemotherapy composed of docetaxel (60 mg/m(2)) and cisplatin (65 mg/m(2)), every 3 weeks for up to 6 cycles. The expression levels of ERCC1 and RASSF1A were evaluated in the available 36 prechemotherapy samples. RESULTS: The overall objective response rate was 35% (complete remission 12% and partial remission 23%). The median progression-free survival and overall survival (OS) times were 5.0 months (95% confidence interval (CI), 3.7-6.4 months) and 24.2 months (95% CI, 3.5-45.0 months), respectively. The status of low ERCC1 and high RASSF1A expression was an independent favorable prognostic factor for OS in multivariate analysis (p = 0.043; hazard ratio, 7.224; 95% CI, 1.060-49.217). Toxicities were comparable with those of previously reported trials. CONCLUSIONS: Less intensive doses of cisplatin and docetaxel are active but not effective in reducing toxicity. Also, both ERCC1 and RASSF1A might be useful prognostic markers in this regimen.

Five-year changes in ovarian function restoration in premenopausal patients with breast cancer taking tamoxifen after chemotherapy: An ASTRRA study report.

BACKGROUND: Adding ovarian function suppression (OFS) after chemotherapy improves survival in young women with moderate- and high-risk breast cancer. Assessment of ovarian function restoration after chemotherapy becomes critical for subsequent endocrine treatment and addressing fertility issues. PATIENTS AND METHODS: In the adding OFS after chemotherapy trial, patients who resumed ovarian function up to 2 years after chemotherapy were randomised to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. Ovarian function was evaluated from enrolment to randomisation, and patients who did not randomise because of amenorrhoea for 2 years received tamoxifen and were followed up for 5 years. Prospectively collected consecutive hormone levels (proportion of patients with premenopausal follicle-stimulating hormone [FSH] levels <30 mIU/mL and oestradiol [E2] levels ≥40 pg/mL) and history of menstruation were available for 1067 patients with breast cancer. RESULTS: Over 5 years of tamoxifen treatment, 69% of patients resumed menstruation and 98% and 74% of patients satisfied predefined ovarian function restoration as per serum FSH and E2 levels, respectively. Menstruation was restored in 91% of patients younger than 35 years at baseline, but in only 33% of 45-year-old patients over 5 years. Among these patients, 41% experienced menstruation restoration within 2 years after chemotherapy and 28% slowly restored menstruation after 2-5 years. Younger age (<35 years) at baseline, anthracycline without taxanes and ≤90 days of chemotherapy were predictors of menstruation restoration. CONCLUSIONS: During 5 years of tamoxifen treatment after chemotherapy, two-thirds of the patients experienced menstruation restoration, especially patients younger than 35 years. Young age, Adriamycin without taxanes and short duration of chemotherapy appeared to have a positive effect on ovarian reserves in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00912548.

Capecitabine monotherapy as salvage treatment after failure of chemotherapy containing oxaliplatin and irinotecan in patients with metastatic colorectal cancer.

AIM: There has been limited data on capecitabine monotherapy in metastatic colorectal cancer (CRC) patients who were previously treated with both oxaliplatin/5-fluorouracil(FU)/leucovorin (FOLFOX) and irinotecan/5-FU/leucovorin (FOLFIRI). METHODS: We analyzed 20 patients between August 2002 and March 2008 with metastatic CRC who had been treated with capecitabine monotherapy after the failure of FOLFOX and FOLFIRI. RESULTS: Overall, one partial response was observed (overall response rate, 5%) and stable disease was observed in 11 patients (55.0%). The disease control rate was 60.0%. The median progression-free survival (PFS) was 2.3 months (95% CI 1.9-2.7) and the median overall survival (OS) was 5.3 months (95% CI 4.6-6.0). Patients without ascites had longer PFS than those with ascites (P=0.02). Patients with more than three metastatic sites had poorer OS than those with less than two (P=0.01). Grade 3 or 4 non-hematological toxicities included hand-foot syndrome in one patient. There were no grade 3 or 4 hematological toxicities or treatment-related deaths. CONCLUSION: The capecitabine monotherapy had a moderate disease control rate and a tolerable toxicity profile as third-line or fourth-line treatment for metastatic CRC patients who were refractory to standard chemotherapy with no further treatment options.

Genomic signatures of strain selection and enhancement in Bacillus atrophaeus var. globigii, a historical biowarfare simulant.

BACKGROUND: Despite the decades-long use of Bacillus atrophaeus var. globigii (BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS). RESULTS: Archival strains and two "present day" type strains were compared to simulant strains on different laboratory media. Several of the samples produced multiple colony morphotypes that differed from that of an archival isolate. To trace the microevolutionary history of these isolates, we obtained WGS data for several archival and present-day strains and morphotypes. Bacillus-wide phylogenetic analysis identified B. subtilis as the nearest neighbor to B. atrophaeus. The genome of B. atrophaeus is, on average, 86% identical to B. subtilis on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the "military" isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of "military" isolates on lactate-containing media, and showed that the "military" strains exhibited a hypersporulating phenotype. CONCLUSIONS: Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation.