Cooperative contributions of the klf1 and klf17 genes in zebrafish primitive erythropoiesis.

Krüppel-like transcription factors (Klfs), which are characterized by the three conserved C-terminal zinc fingers, are involved in various biological processes, such as haematopoiesis and angiogenesis. However, how the Klf family of transcription factors cooperate in organogenesis remains elusive. During zebrafish embryogenesis, both klf1 and klf17 are expressed in the intermediate cell mass (ICM), where primitive erythroid cells are produced. Using CRISPR-Cas9 genome editing technology, we established klf1-klf17 double mutant zebrafish to investigate the functionally interactive roles of the klf1 and klf17 genes. The klf1-klf17 mutant exhibited a diminished number of circulating primitive erythroid cells at 2 days postfertilization (dpf), while klf1 or klf17 single mutants and wild-type embryos produced comparable numbers of primitive erythroid cells. Circulating erythroid cells from the klf1-klf17 mutant possessed larger nuclei at 2 dpf than wild-type cells, suggesting the impairment of primitive erythroid cell maturation. The expression of the erythroid cell maturation markers band3 and mitoferrin, but not the haematopoietic progenitor markers c-myb and scl, was decreased in the klf1-klf17 mutant at 1 dpf. Thus, these results illustrate the cooperative function of klf1 and klf17 in the maturation processes of zebrafish primitive erythroid cells.

[Continuation of chemotherapy with bevacizumab for advanced and recurrent colorectal cancer].

We evaluated the association between the number of treatment courses with the concomitant use of bevacizumab(BV) and the reasons for discontinuation of the regimen in patients who received FOLFOX with or without BV as first-line chemotherapy and FOLFIRI with or without BV as second-line chemotherapy for advanced and recurrent colorectal cancer. In first-line treatment, 12 (2-46) and 10 (2-60) treatment courses were administered with and without BV, respectively, and this difference was not significant (p=0.60). In second-line treatment after first-line treatment with the concomitant use of BV, 11 (1-23) and 3 (1-12) treatment courses were administered with and without BV, respectively, and this difference was significant (p<0.01). Discontinuation due to adverse reactions was more frequent for first-line treatment (34.9%) than for second-line treatment (6.2%; p<0.01). The reasons for discontinuation due to adverse reactions during first-line treatment with BV were often associated with BV, and those during first-line treatment without BV were most often associated with peripheral neuropathy. Therefore, we conclude that early detection and prevention of adverse reactions are important in first-line treatment and that pharmacists as well should be involved in the monitoring and management of adverse reactions, although continued administration of BV even during second-line treatment after first-line treatment with BV is recommended.

[Assessment of chemotherapy-induced nausea and vomiting(CINV)using MASCC antiemesis tool].

Chemotherapy-induced nausea and vomiting (CINV) is one of the side effects causing significant psychological and physical suffering in patients receiving chemotherapy. Because CINV often impairs patients' quality of life and leads to cessation of treatments, antiemetic therapy has been thought important. Recently, the development of new antiemetic agents and the antiemetic guidelines provided by ASCO, NCCN, and MASCC etc. allow us to palliate CINV with appropriate antiemetic therapy. For appropriate antiemetic therapy, the patient must obtain accurate CINV information, particularly regarding whether it will be acute or delayed. MASCC first developed and posted the MASCC Antiemesis Tool (MAT) in 2004. The MAT is an eight-term scale for the assessment of acute and delayed nausea and vomiting, and is completed once per chemotherapy course. Although it is now validated in the US and UK and used worldwide, few reports have been available in Japan to use assessment tools including the MAT for acute and delayed CINV. We prospectively investigated the utility of the MAT. Fifteen ambulatory patients with breast cancer were subjected to evaluation, aged 29 to 73(median 58)years. In the results, the MAT allowed us to easily find patients treated with inappropriate antiemetic therapy. At the same time, it was easy to determine acute or delayed CINV, resulting in more appropriate treatment. The scale questions were unfamiliar to patients, but they clearly understood by means of a detailed explanation. Thus, it was suggested that the MAT is useful to assess antiemetic therapy. Consequently, it could contribute to completion of the chemotherapy.