Introduction Loss of the cell-cycle inhibitory protein p27 Kip1 is associated with a poor prognosis in breast cancer. The decrease in the levels of this protein is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1). Skp2 was recently found to be overexpressed in breast cancers, but the role of Cks1 in these cancers is unknown. The present study was undertaken to examine the role of Cks1 expression in breast cancer and its relation to p27 Kip1 and Skp2 expression and to tumor aggressiveness.
PET/CT improves the accuracy of FDG imaging in oesophageal cancer and provides data of diagnostic and therapeutic significance for further patient management.
Myelotoxicity induced by chemotherapy may become life-threatening. Neutropenia may be prevented by granulocyte colony-stimulating factors (GCSF), and epoetin may prevent anemia, but both cause substantial side effects and increased costs. According to non-established data, wheat grass juice (WGJ) may prevent myelotoxicity when applied with chemotherapy. In this prospective matched control study, 60 patients with breast carcinoma on chemotherapy were enrolled and assigned to an intervention or control arm. Those in the intervention arm (A) were given 60 cc of WGJ orally daily during the first three cycles of chemotherapy, while those in the control arm (B) received only regular supportive therapy. Premature termination of treatment, dose reduction, and starting GCSF or epoetin were considered as "censoring events." Response rate to chemotherapy was calculated in patients with evaluable disease. Analysis of the results showed that five censoring events occurred in Arm A and 15 in Arm B (P = 0.01). Of the 15 events in Arm B, 11 were related to hematological events. No reduction in response rate was observed in patients who could be assessed for response. Side effects related to WGJ were minimal, including worsening of nausea in six patients, causing cessation of WGJ intake. In conclusion, it was found that WGJ taken during FAC chemotherapy may reduce myelotoxicity, dose reductions, and need for GCSF support, without diminishing efficacy of chemotherapy. These preliminary results need confirmation in a phase III study.
The Mayo Clinic regimen of leucovorin 20 mg/m followed immediately by 5-fluorouracil 425 mg/m administered for 5 consecutive days every 4 weeks is commonly used in the treatment of colorectal cancer. This study was aimed at prospectively determining the incidence and pattern of severe toxicity associated with this regimen. We evaluated prospectively 243 patients with colorectal cancer treated in our department with the Mayo Clinic regimen for the incidence of severe toxicity (defined as toxicity requiring hospitalization). Of the 243 patients, 32 (13%) were hospitalized for chemotherapy-related toxicity. Major toxicities included neutropenic fever in 21 (9%), grade III/IV mucositis in 25 (10%) and grade III/IV diarrhea in 20 (8%). There were five (2%) treatment-related deaths. Female patients exhibited a higher incidence of severe toxicity (18%) and toxic death (4/105) than did male patients (9% and 1/138, respectively). Elderly patients (> or =70 years) had a higher incidence of severe toxicity than younger patients did (24% versus 7%, < 0.001). Toxic death occurred in 4 of 89 patients aged 70 years or more compared to 1 of 154 in younger patients. Most episodes of severe toxicity (56%) and toxic deaths (4/5) were observed after the first cycle. We conclude that the Mayo Clinic regimen can be associated with severe toxicity, usually occurring after the first cycle. Female gender and advanced age predict severe toxicity; therefore, dose reduction in high-risk patients should be considered, especially during the first cycle.
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