The understanding of how genetic and epigenetic factors influence tumorigenesis, progression and invasion, is vastly growing since new technologies allow the analysis of the functional genome namely the exome, the tra...The understanding of how genetic and epigenetic factors influence tumorigenesis, progression and invasion, is vastly growing since new technologies allow the analysis of the functional genome namely the exome, the transcriptome and the epigenome, besides enabling genome-wide assessment of genetic variations. With the advent of new drugs that are indicated tissue agnostic, depending on certain mutations, there is a growing demand for fast and cost-effective genetic diagnosis. The method in focus that already became an indispensable tool in viral diagnosis is next-generation sequencing (NGS). This approach allows sequencing of literally every DNA molecule in the sample and can either be used to assess numerous genetic markers of one patient at a time, or to assess fewer markers of many patients in parallel, which reduces costs. We submitted 23 samples of different tumor entities to four diagnostic companies with different analysis profiles. The results as disclosed and discussed in this report indicate that so far, the main application of NGS is rather in cancer research than in diagnosis, as none of the reports had a real impact on the therapeutic scheme. We are perfectly aware that such a small cohort cannot be generalized, but considering the costs vs. benefits, NGS should be engaged upon a very stringent evaluation only. However, in cases where obtaining a tissue biopsy is impossible or unfavorable, analysis of liquid biopsy by NGS provides a vital alternative.展开更多
While generally recognized as a potential source of contamination during the collection process, lubricants are often used at the preference of the male partner to prevent irritation. While older lubricants have been ...While generally recognized as a potential source of contamination during the collection process, lubricants are often used at the preference of the male partner to prevent irritation. While older lubricants have been studied, there is currently no conscience within programs as to what constitutes a “safe” lubricant. The object of the current study was designed to evaluate chemically unique “next generation” lubricants in comparison to lubricants currently in use in fertility treatment and/or recognized as fertility safe;the first was a silicone-based lubricant, the second is a water-based, plant-based organic compound, in comparison to two established medical lubricants and a control. Twelve deidentified semen samples from the clinical andrology laboratory were used to test the lubricants following semen analysis. In order to enter the study, the sample had to have a minimum of 30 × 10<sup>6</sup> motile cells. Samples were then processed using a simple sperm wash modified to reconstitute the pellet into a final volume of 7 mL. Half-milliliter aliquots were then transferred into 13 wells of a standard 24-well culture plate. One well was used as a control. The remaining wells received one of the four lubricants at one of three volumes (10, 50, or 100 uL), producing 12 treatment combinations (four lubricants + 3 concentration levels) and the control. The samples were then cultured at room temperature for 24 hours. At times 0, 1, 3, 12, and 24 hrs, the plate was agitated to remix the sample, and a 4 uL aliquot of each well was analyzed for standard semen parameters using a computer-assisted semen analyzer. Results indicated the expected decrease in semen parameters over time in all treatments (P < 0.001). There was also a dose-dependent drop in most of the lubricants. However, samples contaminated with the newer lubricants appeared to maintain semen parameters similar to the controls at all but the 100 ul level of contamination, while the older lubricants caused decreases in sperm function at much lower concentrations. While semen parameters alone should not be the only criteria for the selection of a lubricant, the present study suggests newer formulations of lubricant are less likely to interfere with sperm function.展开更多
This study explores the efficacy of advanced antibiotic compounds against P. aeruginosa, focusing on Antibiotic B, an enhanced derivative of Ceftriaxone. The study measured the intracellular uptake of Antibiotic B and...This study explores the efficacy of advanced antibiotic compounds against P. aeruginosa, focusing on Antibiotic B, an enhanced derivative of Ceftriaxone. The study measured the intracellular uptake of Antibiotic B and introduced a novel adjuvant, Influximax, which augmented its antibacterial activity. Results showed a diminished potential for resistance emergence with Antibiotic B, particularly when used in combination with Influximax. The study suggests that optimizing antibiotic delivery into bacterial cells and leveraging syner-gistic adjuvant combinations can enhance drug resistance combat. .展开更多
Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations...Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.展开更多
Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial ...Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.展开更多
文摘The understanding of how genetic and epigenetic factors influence tumorigenesis, progression and invasion, is vastly growing since new technologies allow the analysis of the functional genome namely the exome, the transcriptome and the epigenome, besides enabling genome-wide assessment of genetic variations. With the advent of new drugs that are indicated tissue agnostic, depending on certain mutations, there is a growing demand for fast and cost-effective genetic diagnosis. The method in focus that already became an indispensable tool in viral diagnosis is next-generation sequencing (NGS). This approach allows sequencing of literally every DNA molecule in the sample and can either be used to assess numerous genetic markers of one patient at a time, or to assess fewer markers of many patients in parallel, which reduces costs. We submitted 23 samples of different tumor entities to four diagnostic companies with different analysis profiles. The results as disclosed and discussed in this report indicate that so far, the main application of NGS is rather in cancer research than in diagnosis, as none of the reports had a real impact on the therapeutic scheme. We are perfectly aware that such a small cohort cannot be generalized, but considering the costs vs. benefits, NGS should be engaged upon a very stringent evaluation only. However, in cases where obtaining a tissue biopsy is impossible or unfavorable, analysis of liquid biopsy by NGS provides a vital alternative.
文摘While generally recognized as a potential source of contamination during the collection process, lubricants are often used at the preference of the male partner to prevent irritation. While older lubricants have been studied, there is currently no conscience within programs as to what constitutes a “safe” lubricant. The object of the current study was designed to evaluate chemically unique “next generation” lubricants in comparison to lubricants currently in use in fertility treatment and/or recognized as fertility safe;the first was a silicone-based lubricant, the second is a water-based, plant-based organic compound, in comparison to two established medical lubricants and a control. Twelve deidentified semen samples from the clinical andrology laboratory were used to test the lubricants following semen analysis. In order to enter the study, the sample had to have a minimum of 30 × 10<sup>6</sup> motile cells. Samples were then processed using a simple sperm wash modified to reconstitute the pellet into a final volume of 7 mL. Half-milliliter aliquots were then transferred into 13 wells of a standard 24-well culture plate. One well was used as a control. The remaining wells received one of the four lubricants at one of three volumes (10, 50, or 100 uL), producing 12 treatment combinations (four lubricants + 3 concentration levels) and the control. The samples were then cultured at room temperature for 24 hours. At times 0, 1, 3, 12, and 24 hrs, the plate was agitated to remix the sample, and a 4 uL aliquot of each well was analyzed for standard semen parameters using a computer-assisted semen analyzer. Results indicated the expected decrease in semen parameters over time in all treatments (P < 0.001). There was also a dose-dependent drop in most of the lubricants. However, samples contaminated with the newer lubricants appeared to maintain semen parameters similar to the controls at all but the 100 ul level of contamination, while the older lubricants caused decreases in sperm function at much lower concentrations. While semen parameters alone should not be the only criteria for the selection of a lubricant, the present study suggests newer formulations of lubricant are less likely to interfere with sperm function.
文摘This study explores the efficacy of advanced antibiotic compounds against P. aeruginosa, focusing on Antibiotic B, an enhanced derivative of Ceftriaxone. The study measured the intracellular uptake of Antibiotic B and introduced a novel adjuvant, Influximax, which augmented its antibacterial activity. Results showed a diminished potential for resistance emergence with Antibiotic B, particularly when used in combination with Influximax. The study suggests that optimizing antibiotic delivery into bacterial cells and leveraging syner-gistic adjuvant combinations can enhance drug resistance combat. .
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan
文摘Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.
基金supported by grants from Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120)General Research Project of Guangzhou Science and Technology Bureau (Grant No. 201607010391)+1 种基金National Key Research and Development Program of China (Grant No. 2016YFC1303800)Guangdong Provincial Applied S&T R&D Program (Grant No. 2016B020237006)
文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.
