Pub Date : 2022-01-01DOI: 10.1515/pteridines-2022-0045
Lenka Sasková, P. Tvrdý, B. Melichar, R. Pink, David Kral, P. Michl, Z. Dvořák
Abstract Because of an increasing incidence of malignant tumours of the head and neck there is an unmet medical need for early diagnosis of the primary disease or precancerous lesions, and timely detection of recurrence by simple non-invasive tests. The analysis of biomarkers in body fluids may be appropriate for this goal. In this review, we compare the data on utilization of neopterin and interleukin-6 (IL-6) measurements in saliva and plasma/serum of patients with oral and oropharyngeal squamous cell carcinoma, indicating the suitability of using saliva as a diagnostic matrix in head and neck cancers on behalf of close anatomical proximity and a potential to study the tumour microenvironment. Salivary neopterin and IL-6 are potential biomarkers of head and neck cancer suitable not only for early diagnosis, but also for monitoring of treatment results and detection of the disease recurrence.
{"title":"Salivary and serum neopterin and interleukin 6 as biomarkers in patients with oral and oropharyngeal squamous cell carcinoma","authors":"Lenka Sasková, P. Tvrdý, B. Melichar, R. Pink, David Kral, P. Michl, Z. Dvořák","doi":"10.1515/pteridines-2022-0045","DOIUrl":"https://doi.org/10.1515/pteridines-2022-0045","url":null,"abstract":"Abstract Because of an increasing incidence of malignant tumours of the head and neck there is an unmet medical need for early diagnosis of the primary disease or precancerous lesions, and timely detection of recurrence by simple non-invasive tests. The analysis of biomarkers in body fluids may be appropriate for this goal. In this review, we compare the data on utilization of neopterin and interleukin-6 (IL-6) measurements in saliva and plasma/serum of patients with oral and oropharyngeal squamous cell carcinoma, indicating the suitability of using saliva as a diagnostic matrix in head and neck cancers on behalf of close anatomical proximity and a potential to study the tumour microenvironment. Salivary neopterin and IL-6 are potential biomarkers of head and neck cancer suitable not only for early diagnosis, but also for monitoring of treatment results and detection of the disease recurrence.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"33 1","pages":"78 - 86"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49314250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1515/pteridines-2022-0036
Zachary Bennett, Kassidy Grumbles, J. Pruet
Abstract Pterins, such as folate and biopterin, and their derivatives hold significant importance given their biological relevance, as well as the numerous pterin-based inhibitors developed for targeting various biological targets. For this reason, pterins can be viewed as a privileged scaffold, as the discovery of new pterin analogs gives rise to a vast array of potential drug candidates. 7-carboxymethyl-pterin (7-CMP) represents a useful scaffold for the rapid generation of structurally diverse pterin amides and has been a key building block in medicinal chemistry. In an effort to facilitate rapid generation of this pterin scaffold, we have explored multiple routes towards 7-CMP to assess the most efficient method of generation. Methods were evaluated based on yield, regioselectivity, reaction time, and hazardous reaction conditions. This work can aide in the synthesis and discovery of new pterin-based drug candidates.
{"title":"Comparative routes to 7-carboxymethyl-pterin: A useful medicinal chemistry building block","authors":"Zachary Bennett, Kassidy Grumbles, J. Pruet","doi":"10.1515/pteridines-2022-0036","DOIUrl":"https://doi.org/10.1515/pteridines-2022-0036","url":null,"abstract":"Abstract Pterins, such as folate and biopterin, and their derivatives hold significant importance given their biological relevance, as well as the numerous pterin-based inhibitors developed for targeting various biological targets. For this reason, pterins can be viewed as a privileged scaffold, as the discovery of new pterin analogs gives rise to a vast array of potential drug candidates. 7-carboxymethyl-pterin (7-CMP) represents a useful scaffold for the rapid generation of structurally diverse pterin amides and has been a key building block in medicinal chemistry. In an effort to facilitate rapid generation of this pterin scaffold, we have explored multiple routes towards 7-CMP to assess the most efficient method of generation. Methods were evaluated based on yield, regioselectivity, reaction time, and hazardous reaction conditions. This work can aide in the synthesis and discovery of new pterin-based drug candidates.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"33 1","pages":"1 - 8"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44631525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.1515/pteridines-2020-0013
Jinyun Chen, He Chen, P. Chen
Abstract Objective To explore the expression and genotypes of thymidylate synthase (TS) in patients of non-small cell lung cancer (NSCLC) with different clinicopathological characteristics. Methods The expression profiles of TS were examined by immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in 160 patients with NSCLC. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect TS-5′UTR tandem repeats, G/C nucleotide polymorphisms, and 3′UTR 6 bp deletion/insertion polymorphisms. The relationships between clinicopathological characteristics and TS expression or genotypes were investigated through χ 2 test. Kaplan–Meier survival analysis was used to analyze the association between TS expression and overall survival (OS) and disease-free survival (DFS) of NSCLC patients. Results The expression levels of TS protein and TS gene in NSCLC tissues were significantly higher than that in paracancerous tissues (P < 0.05). Furthermore, high expression of TS protein and 5′UTR polymorphism of TS gene showed significant correlation with differentiation, TNM stage, and lymph node metastases. The frequency of −6 bp/−6 bp genotypes in patients with NSCLC was 43.13% (69/160), which was higher than others. In addition, the rate of TS protein overexpression in NSCLC patients with 3R/3R was 79.79%, which was higher than others. Interestingly, high expression of TS protein predicted shorter DFS and OS and lower 3-year DFS rate and 3-year OS rate. Conclusions The expression levels of TS in NSCLC were significantly increased and may help to predict the prognosis of NSCLC, and high expression of TS protein and 5′UTR polymorphism of TS gene were significantly related to differentiation, TNM stage, and lymph node metastases.
{"title":"Association of expression and genotypes of thymidylate synthase in non-small cell lung cancer patients with different clinicopathological characteristics","authors":"Jinyun Chen, He Chen, P. Chen","doi":"10.1515/pteridines-2020-0013","DOIUrl":"https://doi.org/10.1515/pteridines-2020-0013","url":null,"abstract":"Abstract Objective To explore the expression and genotypes of thymidylate synthase (TS) in patients of non-small cell lung cancer (NSCLC) with different clinicopathological characteristics. Methods The expression profiles of TS were examined by immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in 160 patients with NSCLC. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect TS-5′UTR tandem repeats, G/C nucleotide polymorphisms, and 3′UTR 6 bp deletion/insertion polymorphisms. The relationships between clinicopathological characteristics and TS expression or genotypes were investigated through χ 2 test. Kaplan–Meier survival analysis was used to analyze the association between TS expression and overall survival (OS) and disease-free survival (DFS) of NSCLC patients. Results The expression levels of TS protein and TS gene in NSCLC tissues were significantly higher than that in paracancerous tissues (P < 0.05). Furthermore, high expression of TS protein and 5′UTR polymorphism of TS gene showed significant correlation with differentiation, TNM stage, and lymph node metastases. The frequency of −6 bp/−6 bp genotypes in patients with NSCLC was 43.13% (69/160), which was higher than others. In addition, the rate of TS protein overexpression in NSCLC patients with 3R/3R was 79.79%, which was higher than others. Interestingly, high expression of TS protein predicted shorter DFS and OS and lower 3-year DFS rate and 3-year OS rate. Conclusions The expression levels of TS in NSCLC were significantly increased and may help to predict the prognosis of NSCLC, and high expression of TS protein and 5′UTR polymorphism of TS gene were significantly related to differentiation, TNM stage, and lymph node metastases.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"32 1","pages":"39 - 47"},"PeriodicalIF":0.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pteridines-2020-0013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41676119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.1515/pteridines-2020-0034
He Huang,Juan Liu,Haiyan Wu,Fang Liu,Xiaoxi Zhou
Abstract Objective Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides, which was involved in the progression of malignant tumors including non-small cell lung cancer (NSCLC). Material/methods Ferroptosis inhibiting gene solute carrier family 7 member 11 (SLC7A11) mRNA expression was investigated in the database of TCGA and Oncomine and compared between the cancer tissue and the normal corresponding tissue of NSCLC patients. SLC7A11 gene mutation of NSCLC was investigated in the TCGA database by the online data analysis tool of Catalog of Somatic Mutations in Cancer (COSMIC) and cBioPortal. The protein–protein interaction (PPI) network of SLC7A11 and associated genes were constructed with the STRING database. Gene ontology (GO) and the KEGG pathway of genes involved in the PPI network were explored and demonstrated by a bubble plot. Progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) between SLC7A11high and SLC7A11low expression groups were compared and demonstrated by the survival curve. Results SLC7A11 mRNA was upregulated in cancer tissues compared to paired normal tissues in colorectal adenocarcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma rectum adenocarcinoma and uterine corpus endometrial carcinoma. Missense and synonymous substitutions were 66.67% and 16.67% for lung squamous cell carcinoma. For lung adenocarcinoma, the missense and synonymous substitutions were 66.67% and 33.33% respectively. In the case of single nucleotide mutation, A>T, C>G, G>A, G>T for lung squamous cell carcinoma and G>T, C>A, G>A, T> for lung adenocarcinoma were the most common mutations in the SLC7A11 coding strand. Fifty-one genes were included in the PPI network with an edge number of 287, average node degree of 11.3 and local clustering coefficient of 0.694, which demonstrated that the PPI network was enriched significantly (p = 1.0 × 10−16). In terms of the KEGG pathway, the SLC7A11 and PPI-involved genes were mainly enriched in ferroptosis, NSCLC, pathways in cancer, tp53 signaling pathway, etc. The overall survival (OS) in the SLC7A11high group was significantly lower than those of SLC7A11low groups in NSCLC (HR = 1.15, 95% CI: 1.02–1.31, p = 0.027). However, the progression-free survival (PFS) (HR = 1.17, 95% CI: 0.97–1.42, p = 0.098) and postprogression survival (PPS) (HR = 1.00, 95% CI: 0.78–1.29, p = 0.97) between SLC7A11high and SLC7A11low expression groups were not statistically different. Conclusion SLC7A11 was upregulated in NSCLC and correlated with the patient’s poor overall survival. SLC7A11 may be a potential target for NSCLC treatment through the ferrop
{"title":"Ferroptosis-associated gene SLC7A11 is upregulated in NSCLC and correlated with patient’s poor prognosis: An integrated bioinformatics analysis","authors":"He Huang,Juan Liu,Haiyan Wu,Fang Liu,Xiaoxi Zhou","doi":"10.1515/pteridines-2020-0034","DOIUrl":"https://doi.org/10.1515/pteridines-2020-0034","url":null,"abstract":"Abstract Objective Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides, which was involved in the progression of malignant tumors including non-small cell lung cancer (NSCLC). Material/methods Ferroptosis inhibiting gene solute carrier family 7 member 11 (SLC7A11) mRNA expression was investigated in the database of TCGA and Oncomine and compared between the cancer tissue and the normal corresponding tissue of NSCLC patients. SLC7A11 gene mutation of NSCLC was investigated in the TCGA database by the online data analysis tool of Catalog of Somatic Mutations in Cancer (COSMIC) and cBioPortal. The protein–protein interaction (PPI) network of SLC7A11 and associated genes were constructed with the STRING database. Gene ontology (GO) and the KEGG pathway of genes involved in the PPI network were explored and demonstrated by a bubble plot. Progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) between SLC7A11high and SLC7A11low expression groups were compared and demonstrated by the survival curve. Results SLC7A11 mRNA was upregulated in cancer tissues compared to paired normal tissues in colorectal adenocarcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma rectum adenocarcinoma and uterine corpus endometrial carcinoma. Missense and synonymous substitutions were 66.67% and 16.67% for lung squamous cell carcinoma. For lung adenocarcinoma, the missense and synonymous substitutions were 66.67% and 33.33% respectively. In the case of single nucleotide mutation, A>T, C>G, G>A, G>T for lung squamous cell carcinoma and G>T, C>A, G>A, T> for lung adenocarcinoma were the most common mutations in the SLC7A11 coding strand. Fifty-one genes were included in the PPI network with an edge number of 287, average node degree of 11.3 and local clustering coefficient of 0.694, which demonstrated that the PPI network was enriched significantly (p = 1.0 × 10−16). In terms of the KEGG pathway, the SLC7A11 and PPI-involved genes were mainly enriched in ferroptosis, NSCLC, pathways in cancer, tp53 signaling pathway, etc. The overall survival (OS) in the SLC7A11high group was significantly lower than those of SLC7A11low groups in NSCLC (HR = 1.15, 95% CI: 1.02–1.31, p = 0.027). However, the progression-free survival (PFS) (HR = 1.17, 95% CI: 0.97–1.42, p = 0.098) and postprogression survival (PPS) (HR = 1.00, 95% CI: 0.78–1.29, p = 0.97) between SLC7A11high and SLC7A11low expression groups were not statistically different. Conclusion SLC7A11 was upregulated in NSCLC and correlated with the patient’s poor overall survival. SLC7A11 may be a potential target for NSCLC treatment through the ferrop","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"44 1","pages":"106-116"},"PeriodicalIF":0.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138517911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.1515/pteridines-2020-0032
M. Pospíšková, Ondřej Strouhal, E. Hlídková, Z. Vlachová, B. Melichar, M. Doležel
Abstract The aim of this study was to investigate the changes in circulating concentrations of citrulline, neopterin, kynurenine, and tryptophan during the course of chemoradiation in patients with cervical cancer. Sixteen patients with histologically confirmed carcinoma of the uterine cervix, aged 53 ± 15 years (range 29–76 years), were included in this study. Plasma neopterin, kynurenine, and tryptophan were determined with an enzyme-linked immunosorbent assay. Plasma citrulline was measured with high-performance liquid chromatography. Compared to baseline, citrulline concentration was markedly and statistically significantly decreased at visits 2, 3, and 4, while returning to pretreatment concentrations at visit 5. A significant increase in serum neopterin concentrations was observed at visits 4 and 5. With the exception of decreased kynurenine/tryptophan ratio at visit 3, no significant changes were observed in the concentrations of kynurenine, tryptophan, and kynurenine/tryptophan ratio throughout the course of the treatment. In conclusion, present data demonstrate that citrulline concentrations decrease early and neopterin concentrations increase late during the course of chemoradiation in patients with cervical carcinoma. Citrulline represents a biomarker of intestinal toxicity in this population.
{"title":"Circulating concentrations of citrulline, neopterin, kynurenine, and tryptophan during chemoradiation in patients with cervical carcinoma","authors":"M. Pospíšková, Ondřej Strouhal, E. Hlídková, Z. Vlachová, B. Melichar, M. Doležel","doi":"10.1515/pteridines-2020-0032","DOIUrl":"https://doi.org/10.1515/pteridines-2020-0032","url":null,"abstract":"Abstract The aim of this study was to investigate the changes in circulating concentrations of citrulline, neopterin, kynurenine, and tryptophan during the course of chemoradiation in patients with cervical cancer. Sixteen patients with histologically confirmed carcinoma of the uterine cervix, aged 53 ± 15 years (range 29–76 years), were included in this study. Plasma neopterin, kynurenine, and tryptophan were determined with an enzyme-linked immunosorbent assay. Plasma citrulline was measured with high-performance liquid chromatography. Compared to baseline, citrulline concentration was markedly and statistically significantly decreased at visits 2, 3, and 4, while returning to pretreatment concentrations at visit 5. A significant increase in serum neopterin concentrations was observed at visits 4 and 5. With the exception of decreased kynurenine/tryptophan ratio at visit 3, no significant changes were observed in the concentrations of kynurenine, tryptophan, and kynurenine/tryptophan ratio throughout the course of the treatment. In conclusion, present data demonstrate that citrulline concentrations decrease early and neopterin concentrations increase late during the course of chemoradiation in patients with cervical carcinoma. Citrulline represents a biomarker of intestinal toxicity in this population.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"32 1","pages":"93 - 97"},"PeriodicalIF":0.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42022646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.1515/pteridines-2020-0033
Biqiang Sun, Zhi-qing He, Gan Liu, Xiao-juan Fu, Zhi-yang Chen, Guoli Li
Abstract Objective To investigate methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) expression, biological function, and correlation with head and neck squamous cell carcinoma (HNSCC) patient’s prognosis. Methods The relative expression levels of MTHFD2 gene mRNA in tumor tissues of HNSCC and adjacent normal tissues were analyzed in the Cancer Genome Atlas and oncomine database. MTHFD2 protein relative expression in tumor tissue of HNSCC patients was analyzed in human proteome database. Protein–protein interaction (PPI) network of MTHFD2 and correlated genes were constructed in STRING database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway of MTHFD2 and relevant proteins involved in the PPI network was enriched. The Tumor Immune Estimation Resource database was used to analyze the relationship between MTHFD2 expression and immune infiltration. Overall survival (OS) and progression-free survival (PFS) for MTHFD2 high and low expression groups were investigated in the Kaplan–Meier Plotter database. Results In HNSCC, MTHFD2 mRNA relative expression level in tumor tissue was significantly higher than the corresponding normal tissue with statistical difference (p < 0.05). In the PPI network, 21 protein coding genes were involved in the network with 124 edges, which indicated that the enrichment was significant (p < 0.05). MTHFD2 and PPI network involved genes were mainly enriched in tetrahydrofolate metabolic process, one-carbon metabolic process biological process. In KEGG pathway, MTHFD2 and PPI network involved genes were mainly enriched in one-carbon pool by folate, metabolic pathways, glyoxylate, and dicarboxylate metabolism, and carbon metabolism. The relative expression level of MTHFD2 gene was correlated with immune infiltration of macrophage (r = 0.712, p < 0.05), neutrophil (r = 0.158, p < 0.05), dendritic cell (r = 0.1825, p < 0.05), and CD4+ T lymph cell (r = 0.1825, p < 0.05). HNSCC patients with high expression MTHFD2 had low OS compared to low expression cases (hazard ratio = 1.53, 95% CI: 1.16–2.02, p < 0.05). Conclusion MTHFD2 is overexpressed in HNSCC and correlated with patient’s prognosis. MTHFD2 maybe a potential target for HNSCC target treatment and provides a possible direction for the research and development of related targeted drugs.
{"title":"Methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) is overexpressed in head and neck squamous cell carcinoma (HNSCC) and correlated with patient’s poor prognosis","authors":"Biqiang Sun, Zhi-qing He, Gan Liu, Xiao-juan Fu, Zhi-yang Chen, Guoli Li","doi":"10.1515/pteridines-2020-0033","DOIUrl":"https://doi.org/10.1515/pteridines-2020-0033","url":null,"abstract":"Abstract Objective To investigate methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) expression, biological function, and correlation with head and neck squamous cell carcinoma (HNSCC) patient’s prognosis. Methods The relative expression levels of MTHFD2 gene mRNA in tumor tissues of HNSCC and adjacent normal tissues were analyzed in the Cancer Genome Atlas and oncomine database. MTHFD2 protein relative expression in tumor tissue of HNSCC patients was analyzed in human proteome database. Protein–protein interaction (PPI) network of MTHFD2 and correlated genes were constructed in STRING database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway of MTHFD2 and relevant proteins involved in the PPI network was enriched. The Tumor Immune Estimation Resource database was used to analyze the relationship between MTHFD2 expression and immune infiltration. Overall survival (OS) and progression-free survival (PFS) for MTHFD2 high and low expression groups were investigated in the Kaplan–Meier Plotter database. Results In HNSCC, MTHFD2 mRNA relative expression level in tumor tissue was significantly higher than the corresponding normal tissue with statistical difference (p < 0.05). In the PPI network, 21 protein coding genes were involved in the network with 124 edges, which indicated that the enrichment was significant (p < 0.05). MTHFD2 and PPI network involved genes were mainly enriched in tetrahydrofolate metabolic process, one-carbon metabolic process biological process. In KEGG pathway, MTHFD2 and PPI network involved genes were mainly enriched in one-carbon pool by folate, metabolic pathways, glyoxylate, and dicarboxylate metabolism, and carbon metabolism. The relative expression level of MTHFD2 gene was correlated with immune infiltration of macrophage (r = 0.712, p < 0.05), neutrophil (r = 0.158, p < 0.05), dendritic cell (r = 0.1825, p < 0.05), and CD4+ T lymph cell (r = 0.1825, p < 0.05). HNSCC patients with high expression MTHFD2 had low OS compared to low expression cases (hazard ratio = 1.53, 95% CI: 1.16–2.02, p < 0.05). Conclusion MTHFD2 is overexpressed in HNSCC and correlated with patient’s prognosis. MTHFD2 maybe a potential target for HNSCC target treatment and provides a possible direction for the research and development of related targeted drugs.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"32 1","pages":"98 - 105"},"PeriodicalIF":0.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48234791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.1515/pteridines-2020-0026
Feng Han, Wengui Xu
Abstract Objective The aim of this study was to investigate the correlation between MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in advanced non-small-cell lung cancer (NSCLC) by pooling the open published relevant studies. Methods Clinical studies associated with MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC were systematically searched in databases of Pubmed, Embase, Cochrance Library, China national knowledge infrastructure (CNKI) and Wanfang. The correlation was expressed by odds ratio (OR) and corresponding 95% confidence interval (95% CI). The publication bias of the included studies was evaluated through Begg’s funnel plot and Egger’s line regression test. Results Ten prospective clinical studies relevant to MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in NSCLC were included in the present meta-analysis. The pooled results indicated that the partial response in NSCLC patients with TT or CT genotype was inferior to CC genotype in a dominant gene model (TT + CT vs CC) (OR = 0.16, 95% CI: 0.06–0.41, P = 0.001). NSCLC cases with T genotype were inferior to C genotype in the objective response rate treated with pemetrexed-based chemotherapy for dominant (OR = 0.28, 95% CI: 0.18–0.45, P = 0.001), recessive (OR = 0.43, 95% CI: 0.19–0.94, P = 0.03) and homozygous models (OR = 0.30, 95% CI: 0.13–0.67, P = 0.003). However, there was no statistical difference in disease control rate, progressive disease between different genotypes of different gene models (P all > 0.05). Conclusion The pemetrexed-based chemotherapy response was decreased in NSCLC cases with T genotype, which can be applied as a potential pemetrexed-based chemotherapy response marker.
摘要目的通过汇集已公开发表的相关研究，探讨MTHFR 677C>T多态性与培美曲塞化疗对晚期非小细胞肺癌癌症（NSCLC）疗效的相关性。方法系统检索Pubmed、Embase、Cochrance Library、CNKI和Wanfang等数据库中MTHFR677C>T多态性及培美曲塞化疗对晚期NSCLC疗效的临床研究。相关性用比值比（OR）和相应的95%置信区间（95%CI）表示。纳入研究的发表偏倚通过Begg漏斗图和Egger线性回归检验进行评估。结果本荟萃分析纳入了10项与MTHFR 677C>T多态性和培美曲塞化疗在NSCLC中的疗效相关的前瞻性临床研究。汇总结果表明，在显性基因模型中，TT或CT基因型的NSCLC患者的部分反应低于CC基因型（TT+CT vs CC）（or=0.16，95%CI:0.06–0.41，P=0.001）。以培美曲塞为基础的显性化疗的客观反应率低于C基因型（or=0.28，95%CI:0.18–0.45，P=0.001，隐性（OR=0.43，95%CI:0.19-0.94，P=0.03）和纯合模型（OR=0.30，95%CI:0.13-0.67，P=0.003）。但不同基因型和不同基因型模型的疾病控制率和疾病进展率无统计学差异（P>0.05），其可作为潜在的基于培美曲塞的化疗反应标志物应用。
{"title":"Correlation between MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC: A meta-analysis","authors":"Feng Han, Wengui Xu","doi":"10.1515/pteridines-2020-0026","DOIUrl":"https://doi.org/10.1515/pteridines-2020-0026","url":null,"abstract":"Abstract Objective The aim of this study was to investigate the correlation between MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in advanced non-small-cell lung cancer (NSCLC) by pooling the open published relevant studies. Methods Clinical studies associated with MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC were systematically searched in databases of Pubmed, Embase, Cochrance Library, China national knowledge infrastructure (CNKI) and Wanfang. The correlation was expressed by odds ratio (OR) and corresponding 95% confidence interval (95% CI). The publication bias of the included studies was evaluated through Begg’s funnel plot and Egger’s line regression test. Results Ten prospective clinical studies relevant to MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in NSCLC were included in the present meta-analysis. The pooled results indicated that the partial response in NSCLC patients with TT or CT genotype was inferior to CC genotype in a dominant gene model (TT + CT vs CC) (OR = 0.16, 95% CI: 0.06–0.41, P = 0.001). NSCLC cases with T genotype were inferior to C genotype in the objective response rate treated with pemetrexed-based chemotherapy for dominant (OR = 0.28, 95% CI: 0.18–0.45, P = 0.001), recessive (OR = 0.43, 95% CI: 0.19–0.94, P = 0.03) and homozygous models (OR = 0.30, 95% CI: 0.13–0.67, P = 0.003). However, there was no statistical difference in disease control rate, progressive disease between different genotypes of different gene models (P all > 0.05). Conclusion The pemetrexed-based chemotherapy response was decreased in NSCLC cases with T genotype, which can be applied as a potential pemetrexed-based chemotherapy response marker.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"32 1","pages":"23 - 32"},"PeriodicalIF":0.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pteridines-2020-0026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43830181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.1515/pteridines-2021-0001
D. Fuchs, M. Gisslén
Abstract The new coronavirus SARS-CoV-2 was identified to be responsible for the COVID-19 pandemic. There are striking differences in the response to infection, some people develop no or mild symptoms, while other outcomes are severe of even fatal. For those COVID-19 patients who require hospitalization, prognostic markers could help clinicians to identify patients with a poor outcome early. The serum levels of the immune activation marker neopterin have already been shown to be of prognostic value in patients with SARS-CoV-1 and a similar pattern can be observed for SARS-CoV-2. This comment discusses the biochemical circuits that support the clinical value of neopterin measurements in COVID-19 patients.
{"title":"Laboratory diagnostic value of neopterin measurements in patients with COVID-19 infection","authors":"D. Fuchs, M. Gisslén","doi":"10.1515/pteridines-2021-0001","DOIUrl":"https://doi.org/10.1515/pteridines-2021-0001","url":null,"abstract":"Abstract The new coronavirus SARS-CoV-2 was identified to be responsible for the COVID-19 pandemic. There are striking differences in the response to infection, some people develop no or mild symptoms, while other outcomes are severe of even fatal. For those COVID-19 patients who require hospitalization, prognostic markers could help clinicians to identify patients with a poor outcome early. The serum levels of the immune activation marker neopterin have already been shown to be of prognostic value in patients with SARS-CoV-1 and a similar pattern can be observed for SARS-CoV-2. This comment discusses the biochemical circuits that support the clinical value of neopterin measurements in COVID-19 patients.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"32 1","pages":"1 - 4"},"PeriodicalIF":0.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pteridines-2021-0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43478980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.1515/pteridines-2020-0027
Xiao Chen, Weiran Zhang, Jingmin Huang
Abstract Objective The aim of the study is to investigate the correlations among serum homocysteine (Hcy), D-dimer, and the risk of developing deep venous thrombosis (DVT) of the lower extremities in patients who underwent operation for lower limb fracture. Methods Seventy-five cases who underwent operation for lower limb fracture were included and further divided into DVT group (n = 26) and control group (n = 49) based on post-DVT diagnostic criteria. The serum Hcy and D-dimer were examined 48 h after operation. The serum Hcy and D-dimer levels were compared between the two groups. The correlation between serum Hcy and D-dimer was investigated by the Pearson correlation test. The receiver-operating characteristic (ROC) curve was applied to evaluate the diagnostic performance of serum Hcy and D-dimer as serological markers for DVT. Results The serum Hcy concentrations were 11.96 ± 3.98 μmol/L and 7.92 ± 3.27 μmol/L for DVT and control groups, respectively, with statistical difference (t = 4.72, P < 0.01). The serum D-dimer in the DVT group was significantly higher than that of the control group (8.99 ± 4.50 vs 1.70 ± 2.11) μg/mL with statistical difference (t = 9.56, P < 0.01). Line regression analysis indicated that serum Hcy was positively correlated with serum D-dimer concentration and can be demonstrated by the equation of Y = 0.6651*X + 1.036 for the DVT group. Using serum Hcy as the biomarker for predicting DVT, the prediction sensitivity and specificity were 76.92 and 71.44%, respectively, with the AUC of 0.7804 under the cut-point of 9.54 μmol/L. For serum D-dimer, the prediction sensitivity and specificity were 96.15 and 73.47%, respectively, with the area under the ROC (AUC) of 0.9455 under the cut-point of 1.66 μg/mL. Conclusion Serum Hcy was significantly elevated in DTV patients, and hence, it can be applied as a serological marker for DVT prediction in patients who underwent operation for lower limb fracture. However, the DVT prediction performance of serum Hcy was inferior to D-dimer especially for diagnostic sensitivity.
摘要目的探讨下肢骨折手术患者血清同型半胱氨酸（Hcy）、D-二聚体与下肢深静脉血栓形成（DVT）风险的相关性。方法将75例下肢骨折手术患者按DVT后诊断标准分为DVT组（n=26）和对照组（n=49）。检测血清Hcy和D-二聚体48 h。比较两组患者血清Hcy和D-二聚体水平。用Pearson相关检验法研究血清Hcy与D-二聚体的相关性。应用受试者操作特征（ROC）曲线评价血清Hcy和D-二聚体作为DVT血清学标志物的诊断性能。结果血清Hcy浓度为11.96±3.98 μmol/L和7.92±3.27 μmol/L，DVT组血清D-二聚体浓度显著高于对照组（8.99±4.50 vs 1.70±2.11）μg/mL，差异有统计学意义（t=9.56，P<0.01）DVT组为1.036。使用血清Hcy作为预测DVT的生物标志物，预测灵敏度和特异性分别为76.92%和71.44%，在9.54的分界点下AUC为0.7804 μmol/L。对于血清D-二聚体，预测灵敏度和特异性分别为96.15%和73.47%，ROC下面积（AUC）为0.9455，切点为1.66 μg/mL。结论DTV患者血清Hcy明显升高，可作为下肢骨折术后DVT预测的血清学标志物。然而，血清Hcy的DVT预测性能不如D-二聚体，尤其是在诊断灵敏度方面。
{"title":"Homocysteine is potential serological marker for predicting the risk of deep venous thrombosis of the lower extremities in patients received operation of lower limb fracture","authors":"Xiao Chen, Weiran Zhang, Jingmin Huang","doi":"10.1515/pteridines-2020-0027","DOIUrl":"https://doi.org/10.1515/pteridines-2020-0027","url":null,"abstract":"Abstract Objective The aim of the study is to investigate the correlations among serum homocysteine (Hcy), D-dimer, and the risk of developing deep venous thrombosis (DVT) of the lower extremities in patients who underwent operation for lower limb fracture. Methods Seventy-five cases who underwent operation for lower limb fracture were included and further divided into DVT group (n = 26) and control group (n = 49) based on post-DVT diagnostic criteria. The serum Hcy and D-dimer were examined 48 h after operation. The serum Hcy and D-dimer levels were compared between the two groups. The correlation between serum Hcy and D-dimer was investigated by the Pearson correlation test. The receiver-operating characteristic (ROC) curve was applied to evaluate the diagnostic performance of serum Hcy and D-dimer as serological markers for DVT. Results The serum Hcy concentrations were 11.96 ± 3.98 μmol/L and 7.92 ± 3.27 μmol/L for DVT and control groups, respectively, with statistical difference (t = 4.72, P < 0.01). The serum D-dimer in the DVT group was significantly higher than that of the control group (8.99 ± 4.50 vs 1.70 ± 2.11) μg/mL with statistical difference (t = 9.56, P < 0.01). Line regression analysis indicated that serum Hcy was positively correlated with serum D-dimer concentration and can be demonstrated by the equation of Y = 0.6651*X + 1.036 for the DVT group. Using serum Hcy as the biomarker for predicting DVT, the prediction sensitivity and specificity were 76.92 and 71.44%, respectively, with the AUC of 0.7804 under the cut-point of 9.54 μmol/L. For serum D-dimer, the prediction sensitivity and specificity were 96.15 and 73.47%, respectively, with the area under the ROC (AUC) of 0.9455 under the cut-point of 1.66 μg/mL. Conclusion Serum Hcy was significantly elevated in DTV patients, and hence, it can be applied as a serological marker for DVT prediction in patients who underwent operation for lower limb fracture. However, the DVT prediction performance of serum Hcy was inferior to D-dimer especially for diagnostic sensitivity.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"32 1","pages":"33 - 38"},"PeriodicalIF":0.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pteridines-2020-0027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49108818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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