Liquid biopsy with circulating tumor DNA (ctDNA) has become widely applied in clinical settings in step with progress in innovative technologies. Since circulating free DNA (cfDNA) was found in human plasma from patients with various cancers as well as auto-immune diseases, clinical application to oncology has spread, especially involving molecular analysis. cfDNA contains ctDNA derived from cancer cells, and it is not possible to isolate ctDNA from cfDNA derived from normal cells. Therefore, we need to recognize ctDNA by detection of somatic mutations corresponding to those observed in cancer tissue. Early on, these mutations were detected by polymerase chain reaction-based methods such as digital PCR. Recently, comprehensive genomic analysis with next generation sequencing (NGS) has been developed for liquid biopsy. Clinical applications include monitoring of tumor progression, analysis of mechanisms of resistance to molecular targeted therapy, and the possibility of detecting minimum residual disease after surgery. However, the sensitivity of ctDNA detection is unsatisfactory, and application is still limited to advanced cancers. To solve these problems, it is necessary to perform basic analysis of ctDNA and establish an efficient system for ctDNA isolation. Recent investigations showed that the cfDNA size distribution differs between ctDNA and cfDNA derived from normal cells, leading to efficient detection of ctDNA. Such new concepts could lead to greater development of liquid biopsy.
{"title":"Current achievements and future perspectives with liquid biopsy","authors":"N. Sueoka-Aragane","doi":"10.46459/pmu.2020010","DOIUrl":"https://doi.org/10.46459/pmu.2020010","url":null,"abstract":"Liquid biopsy with circulating tumor DNA (ctDNA) has become widely applied in clinical settings in step with progress in innovative technologies. Since circulating free DNA (cfDNA) was found in human plasma from patients with various cancers as well as auto-immune diseases, clinical application to oncology has spread, especially involving molecular analysis. cfDNA contains ctDNA derived from cancer cells, and it is not possible to isolate ctDNA from cfDNA derived from normal cells. Therefore, we need to recognize ctDNA by detection of somatic mutations corresponding to those observed in cancer tissue. Early on, these mutations were detected by polymerase chain reaction-based methods such as digital PCR. Recently, comprehensive genomic analysis with next generation sequencing (NGS) has been developed for liquid biopsy. Clinical applications include monitoring of tumor progression, analysis of mechanisms of resistance to molecular targeted therapy, and the possibility of detecting minimum residual disease after surgery. However, the sensitivity of ctDNA detection is unsatisfactory, and application is still limited to advanced cancers. To solve these problems, it is necessary to perform basic analysis of ctDNA and establish an efficient system for ctDNA isolation. Recent investigations showed that the cfDNA size distribution differs between ctDNA and cfDNA derived from normal cells, leading to efficient detection of ctDNA. Such new concepts could lead to greater development of liquid biopsy.","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76539865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wataru Matsunaga, Misa Ichikawa, T. Ishikawa, A. Gotoh
: Background: Viral vector-mediated gene therapy has been eagerly studied as a new strategy for cancer treatment in recent years. We hypothesized that lentiviral vector-mediated gene therapy could be a promising strategy for the treatment of cancers that are highly refractory to chemotherapy or radiotherapy, such as malignant mesothelioma. In this study, we exam-ined the effects of lentiviral vector-mediated transfection of tumor suppressor genes on the growth of malignant mesothelioma and other cancer cell lines. Methods: We transfected the tumor suppressor genes p53, p16, and PTEN into various human cancer cell lines with lentiviral vectors. Results and conclusion: After transfection of the tumor suppressor genes, we observed marked growth inhibition of the cancer cells. Thus, lentivirus-mediated transfection of tumor suppressor genes exerts promising anti-tumor effects on cancer cell lines.
{"title":"Lentiviral vector-mediated transfection of human cancer cell lines with tumor suppressor genes inhibits proliferation in vitro","authors":"Wataru Matsunaga, Misa Ichikawa, T. Ishikawa, A. Gotoh","doi":"10.46459/pmu.2020001","DOIUrl":"https://doi.org/10.46459/pmu.2020001","url":null,"abstract":": Background: Viral vector-mediated gene therapy has been eagerly studied as a new strategy for cancer treatment in recent years. We hypothesized that lentiviral vector-mediated gene therapy could be a promising strategy for the treatment of cancers that are highly refractory to chemotherapy or radiotherapy, such as malignant mesothelioma. In this study, we exam-ined the effects of lentiviral vector-mediated transfection of tumor suppressor genes on the growth of malignant mesothelioma and other cancer cell lines. Methods: We transfected the tumor suppressor genes p53, p16, and PTEN into various human cancer cell lines with lentiviral vectors. Results and conclusion: After transfection of the tumor suppressor genes, we observed marked growth inhibition of the cancer cells. Thus, lentivirus-mediated transfection of tumor suppressor genes exerts promising anti-tumor effects on cancer cell lines.","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"109 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79189144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katsuhiko Takahashi, T. Uchida, Nobuaki Higashi, J. Kamei
Purpose: Pin1 is a peptidyl prolyl cis/trans-isomerase (PPIase) that regulates phosphorylated protein function by cistrans-isomerization. Pin1 catalytic activity has been associated with the pathogenesis of cancer, asthma, neurodegenerative diseases, nonalcoholic steatohepatitis, and viral infections. Recently, imidazole dipeptide molecules from natural products have attracted interest as functional food components. Here, we evaluated the effects of natural imidazole dipeptides on the PPIase activity of Pin1 to identify novel Pin1 inhibitors. Methods: PPIase catalytic activity of Pin1 was measured using chymotrypsin-coupled isomer specific protein degradation. The test substance was preincubated with recombinant Pin1 to form their complex. Results: Our results showed that among the imidazole dipeptide molecules, L-balenine, and not L-anserine and Lcarnosine, reduced the PPIase activity of Pin1. Both β-alanine and 1-methyl-L-histidine obtained by hydrolysis of Lbalenine did not affect Pin1 PPIase activity. These results suggested that the structure of L-balenine allows it to occupy the active site of the Pin1 enzyme. Conclusion: Among imidazole dipeptides from natural products, L-balenine inhibited the PPIase catalytic activity of Pin 1.
{"title":"L-balenine inhibits the catalytic activity of Pin1, a peptidyl prolyl cis/trans-isomerase","authors":"Katsuhiko Takahashi, T. Uchida, Nobuaki Higashi, J. Kamei","doi":"10.46459/pmu.2020003","DOIUrl":"https://doi.org/10.46459/pmu.2020003","url":null,"abstract":"Purpose: Pin1 is a peptidyl prolyl cis/trans-isomerase (PPIase) that regulates phosphorylated protein function by cistrans-isomerization. Pin1 catalytic activity has been associated with the pathogenesis of cancer, asthma, neurodegenerative diseases, nonalcoholic steatohepatitis, and viral infections. Recently, imidazole dipeptide molecules from natural products have attracted interest as functional food components. Here, we evaluated the effects of natural imidazole dipeptides on the PPIase activity of Pin1 to identify novel Pin1 inhibitors. Methods: PPIase catalytic activity of Pin1 was measured using chymotrypsin-coupled isomer specific protein degradation. The test substance was preincubated with recombinant Pin1 to form their complex. Results: Our results showed that among the imidazole dipeptide molecules, L-balenine, and not L-anserine and Lcarnosine, reduced the PPIase activity of Pin1. Both β-alanine and 1-methyl-L-histidine obtained by hydrolysis of Lbalenine did not affect Pin1 PPIase activity. These results suggested that the structure of L-balenine allows it to occupy the active site of the Pin1 enzyme. Conclusion: Among imidazole dipeptides from natural products, L-balenine inhibited the PPIase catalytic activity of Pin 1.","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"195 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90216694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuko Nakano-Narusawa, K. Yamakawa, Juanjuan Ye, M. Yokohira, Y. Matsuda
Purpose: Autofluorescence (AF) is the fluorescence of naturally occurring substances, such as nicotinamide adenine dinucleotide (NADH) and collagen. Two-photon microscopy (2PM) allows for the evaluation of living organs or tissues by excitation of tissue AF. Methods: In the present study, we compared AF intensities of pancreatic tissues in different culture mediums [Roswell Park Memorial Institute (RPMI) 1640, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), and phosphate buffered saline (PBS) ] to determine the optimal conditions for observing unfixed and unstained tissues with 2PM. Results: Tissues incubated in RPMI 1640 showed the highest overall fluorescence intensity, followed by those in HEPES and PBS. Comparing the fluorescence intensities of the respective wavelengths, two broad peaks (approximately 760 nm and 860 nm) were recognized. At approximately 760 nm, acinar cells and ductal cells were observed below the surface. This wavelength primarily detects NADH. At approximately 860 nm, dense fibrous tissue was observed on the pancreatic surface, suggesting the presence of a connective tissue surrounding the pancreas. Conclusion: 2PM imaging using AF of the murine pancreas is a promising technique to provide new insights on structure and morphology.
目的:自体荧光(Autofluorescence, AF)是天然存在物质的荧光，如烟酰胺腺嘌呤二核苷酸(NADH)和胶原蛋白。双光子显微镜(2PM)可以通过激发组织AF来评估活体器官或组织。方法:在本研究中，我们比较了不同培养基(Roswell Park Memorial Institute (RPMI) 1640, 4-(2-羟乙基)-1-哌酸乙磺酸(HEPES)和磷酸盐缓冲盐水(PBS))中胰腺组织的AF强度，以确定用2PM观察未固定和未染色组织的最佳条件。结果:RPMI 1640中培养的组织整体荧光强度最高，HEPES和PBS中次之。比较各自波长的荧光强度，识别出两个宽峰(约760 nm和860 nm)。在约760 nm处，表面下可见腺泡细胞和导管细胞。这个波长主要检测NADH。在约860nm处，胰腺表面可见致密纤维组织，提示胰腺周围存在结缔组织。结论:利用AF对小鼠胰腺进行2PM成像是一种很有前途的技术，可以对胰腺的结构和形态提供新的认识。
{"title":"Comparison of the effect of culture medium on unfixed rat pancreatic tissue in two-photon excitation microscopy","authors":"Yuko Nakano-Narusawa, K. Yamakawa, Juanjuan Ye, M. Yokohira, Y. Matsuda","doi":"10.46459/pmu.2020004","DOIUrl":"https://doi.org/10.46459/pmu.2020004","url":null,"abstract":"Purpose: Autofluorescence (AF) is the fluorescence of naturally occurring substances, such as nicotinamide adenine dinucleotide (NADH) and collagen. Two-photon microscopy (2PM) allows for the evaluation of living organs or tissues by excitation of tissue AF. Methods: In the present study, we compared AF intensities of pancreatic tissues in different culture mediums [Roswell Park Memorial Institute (RPMI) 1640, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), and phosphate buffered saline (PBS) ] to determine the optimal conditions for observing unfixed and unstained tissues with 2PM. Results: Tissues incubated in RPMI 1640 showed the highest overall fluorescence intensity, followed by those in HEPES and PBS. Comparing the fluorescence intensities of the respective wavelengths, two broad peaks (approximately 760 nm and 860 nm) were recognized. At approximately 760 nm, acinar cells and ductal cells were observed below the surface. This wavelength primarily detects NADH. At approximately 860 nm, dense fibrous tissue was observed on the pancreatic surface, suggesting the presence of a connective tissue surrounding the pancreas. Conclusion: 2PM imaging using AF of the murine pancreas is a promising technique to provide new insights on structure and morphology.","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77792909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Neural tube defects (NTDs) are major congenital anomalies. To establish new and effective strategies to prevent these defects, public-private partnerships (PPPs) were formed between a healthcare company in Japan and numerous local governments to create educational activities regarding the importance of folic acid supplementation. Methods: Projects for promoting maternal and child health using healthcare products and services created by a healthcare company were proposed to local governments as PPPs. Results: Nine municipalities distributed folic acid supplements together with a Mother and Child Handbook while seven municipalities conducted surveys to identify people’s knowledge and behavior toward folic acid use. Conclusions: Recent studies have shown that periconceptional folic acid use improves many pregnancy outcomes; therefore, establishing educational activities regarding the importance of folic acid supplementation through PPPs is a rational and effective measure to promote maternal and child health.
{"title":"Educational activities for the prevention of neural tube defects using folic acid supplementation through public-private partnerships in Japan","authors":"S. Kamohara","doi":"10.46459/pmu.2020007","DOIUrl":"https://doi.org/10.46459/pmu.2020007","url":null,"abstract":"Objectives: Neural tube defects (NTDs) are major congenital anomalies. To establish new and effective strategies to prevent these defects, public-private partnerships (PPPs) were formed between a healthcare company in Japan and numerous local governments to create educational activities regarding the importance of folic acid supplementation. Methods: Projects for promoting maternal and child health using healthcare products and services created by a healthcare company were proposed to local governments as PPPs. Results: Nine municipalities distributed folic acid supplements together with a Mother and Child Handbook while seven municipalities conducted surveys to identify people’s knowledge and behavior toward folic acid use. Conclusions: Recent studies have shown that periconceptional folic acid use improves many pregnancy outcomes; therefore, establishing educational activities regarding the importance of folic acid supplementation through PPPs is a rational and effective measure to promote maternal and child health.","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"22 1","pages":"42-45"},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72936405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Purpose: Helical tomotherapy (HT) is one of the radiotherapy methods that has become widespread in recent years. The aim of this study is to investigate the safety of high-dose HT for medically inoperable esophageal cancer that is unable to tolerate chemoradiotherapy. Methods: Eight patients with medically inoperable esophageal squamous cell carcinoma who cannot tolerate chemoradiotherapy were irradiated to 60 Gy at 2 Gy/fraction with HT. Results: The 1-, and 2-year overall survival rate were 75.0%, and 46.9%, respectively. The 1-, and 2-year locoregional recurrence-free survival rate ware 72.9%, and 72.9%, respectively. Three patients developed grade 2 or 3 hematological acute toxicity, and one patient developed grade 2 late pericardial effusion. Conclusions: Medically inoperable patients with esophageal cancer who cannot tolerate chemoradiotherapy might be treated safely by high-dose HT with minimal adverse events.
{"title":"Initial experience of high-dose helical tomotherapy for medically inoperable esophageal cancer patients","authors":"E. Tate, Y. Hama, M. Hashimoto","doi":"10.46459/pmu.2020005","DOIUrl":"https://doi.org/10.46459/pmu.2020005","url":null,"abstract":": Purpose: Helical tomotherapy (HT) is one of the radiotherapy methods that has become widespread in recent years. The aim of this study is to investigate the safety of high-dose HT for medically inoperable esophageal cancer that is unable to tolerate chemoradiotherapy. Methods: Eight patients with medically inoperable esophageal squamous cell carcinoma who cannot tolerate chemoradiotherapy were irradiated to 60 Gy at 2 Gy/fraction with HT. Results: The 1-, and 2-year overall survival rate were 75.0%, and 46.9%, respectively. The 1-, and 2-year locoregional recurrence-free survival rate ware 72.9%, and 72.9%, respectively. Three patients developed grade 2 or 3 hematological acute toxicity, and one patient developed grade 2 late pericardial effusion. Conclusions: Medically inoperable patients with esophageal cancer who cannot tolerate chemoradiotherapy might be treated safely by high-dose HT with minimal adverse events.","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89897963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Objectives: Measures by Public-Private Partnerships (PPPs) have been considered as possible modalities for local governments to conduct health promotion policies. The low energy meal replacement regimens are used for weight loss in obese patients. The aim of this project is to evaluate the feasibility and efficacy of a weight loss intervention program by a local government through PPPs in Japan. Methods: Overweight or obese subjects in Sakai-town, Ibaraki pref., participated in the weight loss program, using telephone and/or personalized website to receive individual dietary counseling from medical professionals. Meal replacements were consumed once daily instead of regular meals. A standardized product contains 20.1 g of protein, one-third of the RDA of vitamins/minerals, and other food ingredients in 1 bag gross weight 50 g or 167 kcal. Anthropometric parameters and body composition were assessed before and after the 12-week weight-loss program. Results: Ninety-two participants (male 47, female 45) completed the program between 1st, August 2018 and 13th, No-vember 2018. Compared with the baseline, the significant decreases in BMI, body weight and waist circumference were ob-served. Conclusion: The result demonstrated that a technology-based intervention, combined with meal replacements was feasible and effective for reducing body weight in obese subjects. The issues in implementing health promotion projects as PPPs will be examined, and further efforts to achieve the extension of the healthy lifespan will be taken to realize a healthy lon-gevity society. The scheme of PPPs will play pivotal roles in the implementation of integrative health measure through public health services.
{"title":"Feasibility and efficacy of a technology-based weight loss intervention program through public-private partnerships in Japan","authors":"S. Kamohara, Yoshiko Terasaki, Sachiyo Tomita, Rika Kishino, Sayaka Kanmuri, Hiroe Ajioka, Hiromichi Seki","doi":"10.46459/pmu.2020006","DOIUrl":"https://doi.org/10.46459/pmu.2020006","url":null,"abstract":": Objectives: Measures by Public-Private Partnerships (PPPs) have been considered as possible modalities for local governments to conduct health promotion policies. The low energy meal replacement regimens are used for weight loss in obese patients. The aim of this project is to evaluate the feasibility and efficacy of a weight loss intervention program by a local government through PPPs in Japan. Methods: Overweight or obese subjects in Sakai-town, Ibaraki pref., participated in the weight loss program, using telephone and/or personalized website to receive individual dietary counseling from medical professionals. Meal replacements were consumed once daily instead of regular meals. A standardized product contains 20.1 g of protein, one-third of the RDA of vitamins/minerals, and other food ingredients in 1 bag gross weight 50 g or 167 kcal. Anthropometric parameters and body composition were assessed before and after the 12-week weight-loss program. Results: Ninety-two participants (male 47, female 45) completed the program between 1st, August 2018 and 13th, No-vember 2018. Compared with the baseline, the significant decreases in BMI, body weight and waist circumference were ob-served. Conclusion: The result demonstrated that a technology-based intervention, combined with meal replacements was feasible and effective for reducing body weight in obese subjects. The issues in implementing health promotion projects as PPPs will be examined, and further efforts to achieve the extension of the healthy lifespan will be taken to realize a healthy lon-gevity society. The scheme of PPPs will play pivotal roles in the implementation of integrative health measure through public health services.","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"63 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91462459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayaka Nakamura, Minako Abe, Y. Saeki, Fumika Kono, Yasuha Ono, H. Abe
Cancer has been the leading cause of death in Japan since 1981, and deaths due to cancer continue to rise. The early detection of cancer and determining therapeutic effect using noninvasive techniques are critical in the treatment of cancer. We conducted a study assaying both circulating tumor cells (CTCs) and cell-free DNA (cfDNA) using a small quantity of blood (5 mL) in order to explore the utility of using liquid biopsies to detect and monitor various types of cancers. Our results confirm that not only are CTCs detected in multiple types of cancers, but also that there is a clinical correlation between the number of CTCs and cancer progression and the presence or absence of tumor metastasis. Furthermore, a significant increase in cfDNA concentration levels between healthy volunteers and cancer patients was confirmed. The measurements of CTCs and cfDNA levels have clinical significance, and can be expected to play a larger role in the diagnosis and treatment of cancer in the near future.
{"title":"Circulating tumor cells (CTC) and Cell-free DNA (cfDNA): Liquid biopsy for cancer diagnostics","authors":"Ayaka Nakamura, Minako Abe, Y. Saeki, Fumika Kono, Yasuha Ono, H. Abe","doi":"10.46459/pmu.2020011","DOIUrl":"https://doi.org/10.46459/pmu.2020011","url":null,"abstract":"Cancer has been the leading cause of death in Japan since 1981, and deaths due to cancer continue to rise. The early detection of cancer and determining therapeutic effect using noninvasive techniques are critical in the treatment of cancer. We conducted a study assaying both circulating tumor cells (CTCs) and cell-free DNA (cfDNA) using a small quantity of blood (5 mL) in order to explore the utility of using liquid biopsies to detect and monitor various types of cancers. Our results confirm that not only are CTCs detected in multiple types of cancers, but also that there is a clinical correlation between the number of CTCs and cancer progression and the presence or absence of tumor metastasis. Furthermore, a significant increase in cfDNA concentration levels between healthy volunteers and cancer patients was confirmed. The measurements of CTCs and cfDNA levels have clinical significance, and can be expected to play a larger role in the diagnosis and treatment of cancer in the near future.","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"421 1","pages":"59-63"},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84922261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Yamashita, T. So, Takeaki Miyata, T. Yoshimatsu, Ryuji Nakano, T. Oyama, Wataru Matsunaga, A. Gotoh
In solid tumors, cancer stem cells (CSCs) are defined as cells that have the ability to perpetuate themselves through self-renewal and to generate mature cells of a particular tissue through differentiation [1]. The CSCs hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. This suggests that CSCs resistant to these treatments are involved in cancer recurrence and metastasis. Therefore, there is an urgent need to identify new therapeutic drug targets for successful treatment. Lung cancer is the most common cancer worldwide with a 5-year survival rate of < 15%, the reason seems to be a lack of useful therapeutic targets [2]. As previously reported by Miyata et al. in our group, we reviewed ALDH1 and CD133 [3]. In addition, we investigated CD44standard (CD44st) and CD44variant6 (CD44v6) as CSC markers. ALDH1 proteins (mainly ALDH1A1, ALDH1A2 and ALDH1A3), which are primarily localized in the cytosol of cells from various tissues, include enzymes able to oxidize retinol and aliphatic aldehydes [4]. ALDH enzyme activity has also emerged as a promising marker of CSCs, and indeed as normal stem cells. In addition to being a putative stem-cell marker, ALDH activity is also known to be involved in drug resistance. In order to assess CSC markers in lung cancer specimens, a paraffin-embedded section is prepared, and histological diagnosis is performed by HE staining. The IHC staining is also performed by the LSAB method using the ALDH1A1 monoclonal antibody. The results were semi-quantitatively graded based on the percentage of cells stained and the intensity of staining. Briefly, the staining intensity was rated as weak (1+), moderate (2+), or strong (3+) and multiplied by the percentage of positive cells. ALDH1A1 score = (% of cells of intensity 1×1) + (% of cells of intensity 2×2) + (% of cells of intensity 3×3). The total scores were categorized as follows: 0-100 = Grade 1, 101-200 = Grade 2, 201-300 = Grade 3. Grade 2 or 3 tumors were considered positive for ALDH1A1 [4]. CD133 antigen, also called prominin 1 (PROM1), is a 120 kDa five-transmembrane glycoprotein. The function is currently unknown but it is expressed on the cell surface in many malignancies [4]. There is also considerable evidence here suggesting that CD133 expression in a subpopulation of lung cancer cells also identifies CSCs. The IHC staining of CD133 was performed on 5 micrometer (μm) paraffin sections using monoclonal antibodies. The CD133 expression score was defined as the percentage of cells showing strong expression levels in membrane sections of tumor
{"title":"Cancer stem cell markers in lung adenocarcinoma","authors":"N. Yamashita, T. So, Takeaki Miyata, T. Yoshimatsu, Ryuji Nakano, T. Oyama, Wataru Matsunaga, A. Gotoh","doi":"10.46459/pmu.2020002","DOIUrl":"https://doi.org/10.46459/pmu.2020002","url":null,"abstract":"In solid tumors, cancer stem cells (CSCs) are defined as cells that have the ability to perpetuate themselves through self-renewal and to generate mature cells of a particular tissue through differentiation [1]. The CSCs hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. This suggests that CSCs resistant to these treatments are involved in cancer recurrence and metastasis. Therefore, there is an urgent need to identify new therapeutic drug targets for successful treatment. Lung cancer is the most common cancer worldwide with a 5-year survival rate of < 15%, the reason seems to be a lack of useful therapeutic targets [2]. As previously reported by Miyata et al. in our group, we reviewed ALDH1 and CD133 [3]. In addition, we investigated CD44standard (CD44st) and CD44variant6 (CD44v6) as CSC markers. ALDH1 proteins (mainly ALDH1A1, ALDH1A2 and ALDH1A3), which are primarily localized in the cytosol of cells from various tissues, include enzymes able to oxidize retinol and aliphatic aldehydes [4]. ALDH enzyme activity has also emerged as a promising marker of CSCs, and indeed as normal stem cells. In addition to being a putative stem-cell marker, ALDH activity is also known to be involved in drug resistance. In order to assess CSC markers in lung cancer specimens, a paraffin-embedded section is prepared, and histological diagnosis is performed by HE staining. The IHC staining is also performed by the LSAB method using the ALDH1A1 monoclonal antibody. The results were semi-quantitatively graded based on the percentage of cells stained and the intensity of staining. Briefly, the staining intensity was rated as weak (1+), moderate (2+), or strong (3+) and multiplied by the percentage of positive cells. ALDH1A1 score = (% of cells of intensity 1×1) + (% of cells of intensity 2×2) + (% of cells of intensity 3×3). The total scores were categorized as follows: 0-100 = Grade 1, 101-200 = Grade 2, 201-300 = Grade 3. Grade 2 or 3 tumors were considered positive for ALDH1A1 [4]. CD133 antigen, also called prominin 1 (PROM1), is a 120 kDa five-transmembrane glycoprotein. The function is currently unknown but it is expressed on the cell surface in many malignancies [4]. There is also considerable evidence here suggesting that CD133 expression in a subpopulation of lung cancer cells also identifies CSCs. The IHC staining of CD133 was performed on 5 micrometer (μm) paraffin sections using monoclonal antibodies. The CD133 expression score was defined as the percentage of cells showing strong expression levels in membrane sections of tumor","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78246335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The launch of personalized medicine based on human genome information has become widespread across Japan over the last few years. Against the expectation of patients, remarkable success occurs in less than 20% of patients in the most advanced hospitals in Japan [1,2], which is consistent with the rate in other countries. Nevertheless, the ability of cancer patients to access these state-of-the-art treatments is not equal, even in our government-supported universal health coverage system. Health professionals and clinicians in rural practice feel frustrated or incompetent for not being able to provide the best care based on the information they have learned. Most practicing doctors in the local community, like those in many other countries, have spent years sharpening their professional skills and continue to be very enthusiastic in following advances in medical science while they are involved with traditional daily patient care. This nature of the profession will be more prominent in the most diligent and sincere tier of medical professionals. In current medical education, the curriculum sometimes addresses “social justice rather than treating illness” [3]. The situation is not exactly the same in Japan, but still I share the same feeling during my 30 years of teaching in a medical school without a long history and tradition. It may be rarer in research universities, but almost every semester our curriculum committee has added a course on the social aspects of medical practice, ranging from appropriate bedside manner to holistic medicine in terminal patients. Teaching social justice alongside the medical curriculum are essential, although naïve students may not think of this as an “improvement“ as they prioritize keeping up with the cutting edge in medicine. The subsequent arguments that have arisen in the American literature are also instructive for us. The frequently debated issues differ from country to country and culture to culture; however, the competing priorities between patients’ merits, doctors’ enthusiasm for new therapies, and researchers’ curiosity are ubiquitous [4]. Correspondence between them is also available in the same journal [5]. No one would argue against that both biology and social justice are important. In the context of personalized medicine, we explored evaluating the delivery and availability of the latest genomic medicine and targeted therapy for germline diagnosis of familial cancer in Japan by inviting practitioners from local clinics, clinical oncologists from small local universities, and one of the national leaders of Japanese oncological medicine in performing systematic and basic cancer research. There may be a significant difference in the realization of genomic medicine between a central institute in Tokyo and other local and rural community hospitals. Again, both are important. We must realize and communicate with each other that differences exist everywhere. Practicing doctors in rural communities in Japan
{"title":"Personalized cancer medicine: A reality across Japan","authors":"H. Sugimura","doi":"10.46459/pmu.2020008","DOIUrl":"https://doi.org/10.46459/pmu.2020008","url":null,"abstract":"The launch of personalized medicine based on human genome information has become widespread across Japan over the last few years. Against the expectation of patients, remarkable success occurs in less than 20% of patients in the most advanced hospitals in Japan [1,2], which is consistent with the rate in other countries. Nevertheless, the ability of cancer patients to access these state-of-the-art treatments is not equal, even in our government-supported universal health coverage system. Health professionals and clinicians in rural practice feel frustrated or incompetent for not being able to provide the best care based on the information they have learned. Most practicing doctors in the local community, like those in many other countries, have spent years sharpening their professional skills and continue to be very enthusiastic in following advances in medical science while they are involved with traditional daily patient care. This nature of the profession will be more prominent in the most diligent and sincere tier of medical professionals. In current medical education, the curriculum sometimes addresses “social justice rather than treating illness” [3]. The situation is not exactly the same in Japan, but still I share the same feeling during my 30 years of teaching in a medical school without a long history and tradition. It may be rarer in research universities, but almost every semester our curriculum committee has added a course on the social aspects of medical practice, ranging from appropriate bedside manner to holistic medicine in terminal patients. Teaching social justice alongside the medical curriculum are essential, although naïve students may not think of this as an “improvement“ as they prioritize keeping up with the cutting edge in medicine. The subsequent arguments that have arisen in the American literature are also instructive for us. The frequently debated issues differ from country to country and culture to culture; however, the competing priorities between patients’ merits, doctors’ enthusiasm for new therapies, and researchers’ curiosity are ubiquitous [4]. Correspondence between them is also available in the same journal [5]. No one would argue against that both biology and social justice are important. In the context of personalized medicine, we explored evaluating the delivery and availability of the latest genomic medicine and targeted therapy for germline diagnosis of familial cancer in Japan by inviting practitioners from local clinics, clinical oncologists from small local universities, and one of the national leaders of Japanese oncological medicine in performing systematic and basic cancer research. There may be a significant difference in the realization of genomic medicine between a central institute in Tokyo and other local and rural community hospitals. Again, both are important. We must realize and communicate with each other that differences exist everywhere. Practicing doctors in rural communities in Japan ","PeriodicalId":101009,"journal":{"name":"Personalized Medicine Universe","volume":"140 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86660902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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