Cell-derived Secretome for the Treatment of Renal Disease

Kidney disease is a major global health issue. Hemodialysis and kidney transplantation have been used in the clinic to treat renal failure. However, the dialysis is not an effective long-term option, as it is unable to replace complete renal functions. Kidney transplantation is the only permanent treatment for end-stage renal disease (ESRD), but a shortage of implantable kidney tissues limits the therapeutic availability. As such, there is a dire need to come up with a solution that provides renal functions as an alternative to the current standards. Recent advances in cell-based therapy have offered new therapeutic options for the treatment of damaged kidney tissues. Particularly, cell secretome therapy utilizing bioactive compounds released from therapeutic cells holds significant beneficial effects on the kidneys. This review will describe the reno-therapeutic effects of secretome components derived from various types of cells and discuss the development of efficient delivery methods to improve the therapeutic outcomes

コウブンシ ザイリョウ エノ サイボウ セッチャクセイ ノ フヨ ト ソノ サイセイ イリョウ エノ オウヨウ

京都大学0048新制・課程博士博士(工学)甲第10470号工博第2321号新制||工||1294(附属図書館)UT51-2003-T296京都大学大学院工学研究科高分子化学専攻(主査)教授 岩田 博夫, 教授 伊藤 紳三郎, 教授 田畑 泰彦学位規則第4条第1項該当Doctor of EngineeringKyoto UniversityDA

17p12 deletion in breast cancer predicts resistance to neoadjuvant chemotherapy

Numerous studies have attempted to identify gene expression profiles which can be utilized to predict responses to neoadjuvant chemotherapy (NAC), but their findings are not clinically applicable at present. In the present study, we sought to determine DNA copy number alterations (CNAs) in breast cancer tissues which are associated with the response to NAC. Frozen tumor tissues from 63 breast cancer patients were obtained using core needle biopsy prior to NAC (3 cycles of docetaxel plus adriamycin) and were microdissected. Array comparative genomic hybridization (array CGH) with 4,045 bacterial artificial chromosome (BAC) probes was performed to identify the CNAs. Changes in tumor size in response to NAC were measured via magnetic resonance imaging. Fluorescence in situ hybridization (FISH) was conducted to verify array CGH results and for independent validation studies. CNAs at eight chromosomal loci encompassing 24 clones were correlated with changes in tumor size after NAC (p<0.05; t-test). Two CNAs were selected, 17p12 deletion and 17q21.32-33 gain, which were significantly associated with a smaller reduction in tumor size following NAC, via prioritization of the regions containing the candidate genes. In an independent validation set of samples from 39 patients, FISH assay further showed that the 17p12 deletion was markedly associated with smaller changes in tumor size (p=0.006), while the 17q21.32-33 gain was not significant (p=0.309). In conclusion, we successfully identified a 17p12 deletion in breast cancer tissue which can be applied in predicting tumor resistance to NAC

17p12 deletion in breast cancer predicts resistance to neoadjuvant chemotherapy

Numerous studies have attempted to identify gene expression profiles which can be utilized to predict responses to neoadjuvant chemotherapy (NAC), but their findings are not clinically applicable at present. In the present study, we sought to determine DNA copy number alterations (CNAs) in breast cancer tissues which are associated with the response to NAC. Frozen tumor tissues from 63 breast cancer patients were obtained using core needle biopsy prior to NAC (3 cycles of docetaxel plus adriamycin) and were microdissected. Array comparative genomic hybridization (array CGH) with 4,045 bacterial artificial chromosome (BAC) probes was performed to identify the CNAs. Changes in tumor size in response to NAC were measured via magnetic resonance imaging. Fluorescence in situ hybridization (FISH) was conducted to verify array CGH results and for independent validation studies. CNAs at eight chromosomal loci encompassing 24 clones were correlated with changes in tumor size after NAC (p<0.05; t-test). Two CNAs were selected, 17p12 deletion and 17q21.32-33 gain, which were significantly associated with a smaller reduction in tumor size following NAC, via prioritization of the regions containing the candidate genes. In an independent validation set of samples from 39 patients, FISH assay further showed that the 17p12 deletion was markedly associated with smaller changes in tumor size (p=0.006), while the 17q21.32-33 gain was not significant (p=0.309). In conclusion, we successfully identified a 17p12 deletion in breast cancer tissue which can be applied in predicting tumor resistance to NAC