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ABSTRACT: Doxorubicin is one of the most effective drugs available for cancer chemotherapy. However, the clinical use of doxorubicin has been greatly limited because of severe side effects on cardiomyocytes. Since Nd1-L, a novel actin-binding protein, is expressed most abundantly in the heart of adult mice, we examined a role of Nd1-L in doxorubicin-induced cardiomyopathy. When doxorubicin (5 mg/kg x 4 times) was injected into adult mice at a 3-day-interval, approximately 50% of injected mice died within 4 weeks of the first injection. Nd1-L mRNA expression in the heart decreased within 3 weeks after the first injection and many cardiomyocytes of injected mice died by apoptosis. Overexpression of Nd1-L in the heart of transgenic mice protected the cardiomyocytes from apoptosis and improved survival rate after doxorubicin injection. Furthermore, activation of Erk1/2 was observed in cultured cells overexpressing Nd1-L. Thus, Nd1-L plays a critical role in protecting the heart from doxorubicin-induced cardiomyopathy.
Transgenic Research 11/2006; 15(5):573-81. · 2.75 Impact Factor
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ABSTRACT: We report herein a case with stage IV gastric cancer previously treated with TS-1 completely responding to second-line chemotherapy with weekly paclitaxel therapy. A 65-year-old female was diagnosed as having type 3 gastric cancer with para-aortic lymph node metastases. She underwent total gastrectomy with extended lymph node dissection on March 2003. Histopathological examination revealed that the tumor was poorly-differentiated adenocarcinoma with para-aortic lymph nodes metastases and completely resected. After the operation,she was treated by adjuvant chemotherapy with TS-1. In March of 2004, she suffered from hematuria, and a CT scan revealed para-aortic lymph nodes metastases and left kidney metastasis. Then, she was treated by a weekly infusion of paclitaxel as second-line chemotherapy. After 3 courses, the tumor disappeared and efficacy was judged as CR. Moreover, CR was maintained after 7 courses. At this writing in January of 2005, she is well and has been treated with paclitaxel without any severe adverse events. Therefore, weekly paclitaxel therapy was considered to be one of the promising second-line chemotherapies for advanced or recurrent gastric cancer previously treated by TS-1.
Gan to kagaku ryoho. Cancer & chemotherapy 01/2006; 32(13):2117-20.
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ABSTRACT: The murine Nd1 gene encodes two forms of protein, Nd1-L and Nd1-S, both of which share the BTB/POZ domain, but Nd1-S lacks the kelch repeats. Although Nd1-L ubiquitously expresses, localizes in the cytoplasm and functions as a stabilizer of actin filaments, expression and function of Nd1-S were unknown. Here we show that Nd1-S were expressed in all tissues examined and localized in the nucleus as a speckled-like pattern. Furthermore, overexpression of Nd1-S perturbed cell growth of NIH3T3 cells at the G1/S phase of the cell cycle. These results suggest that Nd1-S may play a role in cell cycle progression in the nucleus.
DNA and Cell Biology 02/2005; 24(1):30-4. · 2.07 Impact Factor
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ABSTRACT: We isolated Nd1, a novel kelch family gene that encodes two forms of proteins, Nd1-L and Nd1-S. Nd1-L contains a BTB/POZ domain in its N terminus and six kelch repeats in the C terminus. Nd1-S has the BTB/POZ domain but lacks the six kelch repeats. Nd1-L but not Nd1-S mRNA is detected ubiquitously in normal mouse tissues. Nd1-L and Nd1-S proteins can form a dimer through the BTB/POZ domain. Nd1-L colocalizes with actin filaments detected using a confocal microscope, and its kelch repeats bind to them in vitro. Overexpression of Nd1-L in NIH3T3 cells delayed cell growth by affecting the transition of cytokinesis. Furthermore, the overexpression prevented NIH3T3 cells from cell death induced by actin destabilization but not by microtubule dysfunction. These data suggest that Nd1-L functions as a stabilizer of actin filaments as an actin-binding protein and may play a role in the dynamic organization of the actin cytoskeleton.
Journal of Biological Chemistry 12/2002; 277(46):44140-6. · 4.77 Impact Factor
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ABSTRACT: The murine Nd1 gene encodes a novel Kelch family protein and expresses two forms of mRNA, long (Nd1-L) and short (Nd1-S), in various tissues. We characterized the genomic organization of the Nd1 gene, and found that Nd1-L and Nd1-S consist of 16 and nine exons respectively, and that exons I–VIII are shared between them. Three transcription initiation sites were identified in the 5′-flanking region and the most 3′ side (+1) is likely to be a major one. Promoter analysis revealed that the region between positions −247 and −86 was sufficient for expression, and that two Sp1-binding sites and one NF-κB-binding site in the region were critical for promoter activity. Furthermore, the promoter region lacks a TATA and a CAAT box and has a highly GC-rich region with two important Sp1-binding sites. These characteristics of the Nd1 gene promoter are similar to the properties of housekeeping genes.
Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression.
