Cancer gene discovery continues to drive current cancer research with the promise of identifying new diagnostic markers and therapeutic targets by elucidating novel genetic interactions that promote or sustain tumor f...Cancer gene discovery continues to drive current cancer research with the promise of identifying new diagnostic markers and therapeutic targets by elucidating novel genetic interactions that promote or sustain tumor formation. Sleeping Beauty(SB) transposoniated insertional mutagenesis has emerged as an exciting approach to identify novel cancer-causing genes in the mouse. The SB transposon faithfully "hops" throughout the genome by a cut-and-paste mechanism mediated by the ubiquitous expression of the SB transposase. Initial tumor data generated using an SB transposon harboring the MSCV promoter demonstrated a bias towards hematopoietic tumors. More recently, experiments using a modified SB transposon containing the CAG promoter have generated cohorts of mice with solid tumors, primarily carcinomas, which in some cases metastasize. Many animals also develop multiple, inde- pendent primary tumors. These data demonstrate the utility of the SB transposition system for cancer gene discovery across organ systems.展开更多
Polymorphisms in promoter regions of inflammatory cytokines have been widely studied,and potentially functional polymorphisms have been discovered.Conflicting results from meta-analyses of interleukin(IL)-1B and IL-10...Polymorphisms in promoter regions of inflammatory cytokines have been widely studied,and potentially functional polymorphisms have been discovered.Conflicting results from meta-analyses of interleukin(IL)-1B and IL-10 polymorphisms show differences in gastric cancer susceptibilities between Caucasian and Asian populations.In particular,we note the suggestion of an allele flip in IL-1B and IL-10 gene polymorphisms.In Asian populations,the IL-1B-1464G/-511C/-31T haplotype indicates risk for gastric cancer,while the opposite haplotype,IL-1B-1464C/-511T/-31C is the risk-related allele in Caucasians.Furthermore,while IL-10-1082G/-819C/-592C is associated with gastric cancer in Asians,IL-10-1082A/-819T/-592T is linked to gastric cancer risk in Caucasians.These seemingly contradictory results may be attributed to distinct carcinogenic mechanisms underlying the different gastric cancer subtypes.The allele flip observed in IL-10 and gastric cancer appears to reflect allelic heterogeneity,similar to that observed in IL-1B.In this review,we focus on the allele flip phenomenon observed between different ethnic groups in an effort to resolve certain controversial results from recent studies on interleukin polymorphism.In addition,we re-emphasize the importance of stratifying gastric cancer subtypes based on anatomical site and Lauren classification to prevent false associations arising through dilution of true ones.展开更多
This study was performed to demonstrate the transportation of an engineered MSC-produced intracellular anticancer gene product between mesenchymal stem cell (MSC) and cancer cells.? MSC-mediated anticancer strategy ha...This study was performed to demonstrate the transportation of an engineered MSC-produced intracellular anticancer gene product between mesenchymal stem cell (MSC) and cancer cells.? MSC-mediated anticancer strategy has held great promise owing to MSCs’ capacity of tumor-directed migration and the availability of specific anticancer genes.? All anticancer genes that have been used in previous MSC-mediated anticancer studies were limited in functioning via extracellular mechanisms, mainly because of the restriction by cell membrane to macromolecules including proteins.? In order to apply the majority of potent anticancer genes to the MSC-mediated anticancer system, a specifically designed expression vector which bears an intracellular anticancer gene, PTEN, is utilized to demonstrate the feasibility of the system in cancer therapies.? A transacting activator of transcription (TAT) was introduced into an expression vector followed by a segment for PTEN-RFP fusion protein.? A direct demonstration of PTEN-RFP transportation between MSC and cancer cells was obtained from direct co-cultures.? A marked cancer cell death was observed in indirect co-cultures with conditioned media from PTEN-transfected MSCs.? The demonstration of PTEN-engineered MSC-produced PTEN transportation indicates the feasibility of applying intracellular anticancer gene expression system in MSC-mediated strategies for cancer therapy.展开更多
The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. T...The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. They will also review presymptomatic testing of hereditary cancers, and the application of expression profiling to identify patients likely to benefit from particular therapeutic approaches.展开更多
Objective: The mortality and morbidity rates associated with pancreatic cancer (PaCa) are extremely high. Various studies have demonstrated that pancreatic cancer will be the fourth cancer-related death by 2030, raisi...Objective: The mortality and morbidity rates associated with pancreatic cancer (PaCa) are extremely high. Various studies have demonstrated that pancreatic cancer will be the fourth cancer-related death by 2030, raising more concern for scholars to find effective methods to prevent and treat in order to improve the pancreatic cancer outcome. Using bioinformatic analysis, this study aims to pinpoint key genes that could impact PaCa patients’ prognosis and could be used as therapeutic targets. Methods: The TCGA and GEO datasets were integratively analyzed to identify prognosis-related differentially expressed genes. Next, the STRING database was used to develop PPI networks, and the MCODE and CytoNCA Cytoscape in Cytoscape were used to screen for critical genes. Through CytoNCA, three kinds of topology analysis were considered (degree, betweenness, and eigenvector). Essential genes were confirmed as potential target treatment through Go function and pathways enrichment analysis, a developed predictive risk model based on multivariate analysis, and the establishment of nomograms using the clinical information. Results: Overall, the GSE183795 and TCGA datasets associated 1311 and 2244 genes with pancreatic cancer prognosis, respectively. We identified 132 genes that were present in both datasets. The PPI network analysis using, the centrality analysis approach with the CytoNCA plug-in, showed that CDK2, PLK1, CCNB1, and TOP2A ranked in the top 5% across all three metrics. The independent analysis of a risk model revealed that the four key genes had a Hazard Ratio (HR) > 1. The monogram showed the predictive risk model and individual patient survival predictions were accurate. The results indicate that the effect of the selected vital genes was significant and that they could be used as biomarkers to predict a patient’s outcome and as possible target therapy in patients with pancreatic cancer. GO function and pathway analysis demonstrated that crucial genes might affect the P53 signaling pathway and FoxO signaling pathway, through which Meiotic nuclear division and cell cycle may have a significant function in essential genes affecting the outcome of patients who have pancreatic cancer. Conclusions: This study suggests that CDK2, CCNB1, PLK1 and TOP2A are four key genes that have a significant influence on PaCa migration and proliferation. CDK2, CCNB1, PLK1, and TOP2A can be used as potential PaCa prognostic biomarkers and therapeutic targets. However, experimental validation is necessary to confirm these predictions. Our study comes into contributions to the development of personalized target therapy for pancreatic cancer patients.展开更多
Lung cancer is a highly heterogeneous malignancy with a complex pathogenesis, involving a series of endogenous alterations such as genetic mutations, epigenetic modifications, and oxidative stress. Recent advancements...Lung cancer is a highly heterogeneous malignancy with a complex pathogenesis, involving a series of endogenous alterations such as genetic mutations, epigenetic modifications, and oxidative stress. Recent advancements in lung cancer research, especially at the genomic and molecular biology levels, have continuously provided new potential targets and perspectives for the diagnosis and treatment of lung cancer. Therefore, this article summarizes the recent progress in the study of endogenous factors related to the pathogenesis of lung cancer, aiming to enhance the understanding of intrinsic factors in lung cancer and to organize ideas for subsequent related research.展开更多
Background: Protein kinase B (AKT/PKB) family is frequently amplified in ovarian cancer (OC). To the greatest of our knowledge, there is a lack of published reports about the amplification of the genes belonging to th...Background: Protein kinase B (AKT/PKB) family is frequently amplified in ovarian cancer (OC). To the greatest of our knowledge, there is a lack of published reports about the amplification of the genes belonging to the AKT family among Sudanese women with OC. The present study was conducted to detect the AKT1 gene amplification and its association with tumour types, grades, and ages among Sudanese women with OC, bearing in mind the ethnic variation. Methods: This institution-based study included 79 cases of women diagnosed with ovarian cancer (OC) at Omdurman Maternity Hospital in the period 2013-2018. Formalin-fixed, paraffin-embedded (FFPE) tissue sections were used to extract RNA. AKT1 gene amplification was assessed using quantitative real-time PCR. Results: The mean age (±SD) of included women was 49.29 (±13.612). The amplification of AKT1 gene was observed in 18/79 (22.8%) of OC women, with a high frequency in women with undifferentiated 1/2 (50%), clear cell 2/6 (33.3%), mucinous 3/11 (27.3%), endometrioid 3/17 (17.6%), and serous carcinomas 5/30 OC (16.7%). High frequency was seen in women with low (26.3%;n = 10/28) rather than in higher (19.5%;n = 8/33) grade carcinoma, and in older (25.8%;n = 8/23) rather than younger (18.2%;n = 2/9) women. No significant association between AKT1 gene amplification and tumour types, grades, and ages of women was observed (Fisher’s Exact test: p = 0.405, 0.593 and 0.851, respectively). Conclusion: AKT1 gene amplification arises in around one-fifth of Sudanese women with ovarian cancer (OC). It is seen more in undifferentiated, clear cell, and mucinous tumours types, and more frequently in low tumour grade and older women, but not to a statistically significant level. These outcomes sustenance previous studies suggesting that activated AKT genes have a vital role in OC progression and may offer a plan for targeted therapy and prognostic evaluation.展开更多
There have been many skewed cancer gene expression datasets in the post-genomic era. Extraction of differential expression genes or construction of decision rules using these skewed datasets by traditional algorithms ...There have been many skewed cancer gene expression datasets in the post-genomic era. Extraction of differential expression genes or construction of decision rules using these skewed datasets by traditional algorithms will seriously underestimate the performance of the minority class, leading to inaccurate diagnosis in clinical trails. This paper presents a skewed gene selection algorithm that introduces a weighted metric into the gene selection procedure. The extracted genes are paired as decision rules to distinguish both classes, with these decision rules then integrated into an ensemble learning framework by majority voting to recognize test examples; thus avoiding tedious data normalization and classifier construction. The mining and integrating of a few reliable decision rules gave higher or at least comparable classification performance than many traditional class imbalance learning algorithms on four benchmark imbalanced cancer gene expression datasets.展开更多
The development of colorectal cancer(CRC)can be influenced by genetic factors in both familial cases and sporadic cases.Familial CRC has been associated with genetic changes in high-,moderate-and low-penetrance suscep...The development of colorectal cancer(CRC)can be influenced by genetic factors in both familial cases and sporadic cases.Familial CRC has been associated with genetic changes in high-,moderate-and low-penetrance susceptibility genes.However,despite the availability of current gene-identification techniques,the genetic causes of a considerable proportion of hereditary cases remain unknown.Genome-wide association studies of CRC have identified a number of common lowpenetrance alleles associated with a slightly increased or decreased risk of CRC.The accumulation of low-risk variants may partly explain the familial risk of CRC,and some of these variants may modify the risk of cancer in patients with mutations in high-penetrance genes.Understanding the predisposition to develop CRC will require investigators to address the following challenges:the identification of genes that cause uncharacterized hereditary cases of CRC such as familial CRC type X and serrated polyposis;the classification of variants of unknown significance in known CRC-predisposing genes;and the identification of additional cancer risk modifiers that can be used to perform risk assessments for individual mutation carriers.We performed a comprehensive review of the genetically characterized and uncharacterized hereditary CRC syndromes and of lowand moderate-penetrance loci and variants identified through genome-wide association studies and candidate-gene approaches.Current challenges and future perspectives in the field of CRC predisposition are also discussed.展开更多
Pancreatic cancer (PC) occurs when malignant cells develop in the part of the pancreas, a glandular organ behind the stomach. For 2015, there are about 40,560 people dead of pancreatic cancer (20,710 men and 19,850...Pancreatic cancer (PC) occurs when malignant cells develop in the part of the pancreas, a glandular organ behind the stomach. For 2015, there are about 40,560 people dead of pancreatic cancer (20,710 men and 19,850 women) in the US (Siegel et al., 2015). Though PC accounts for about 3% of all cancers in the US, it can cause about 7% of cancer deaths. This is mainly because that the early stages of this cancer do not usually produce symptoms, and thus the cancer is almost always fatal when it is diagnosed.展开更多
Herein we report an electrochemical DNA biosensor for the rapid detection of sequence (5’ AAT GGA TTT ATC TGC TCT TCG 3’) specific for the breast cancer 1 (BRCA1) gene. The proposed electrochemical genosensor is bas...Herein we report an electrochemical DNA biosensor for the rapid detection of sequence (5’ AAT GGA TTT ATC TGC TCT TCG 3’) specific for the breast cancer 1 (BRCA1) gene. The proposed electrochemical genosensor is based on short oligonucleotide DNA probe immobilized onto zinc oxide nanowires (ZnONWs) chemically synthesized onto gold electrode via hydrothermal technique. The morphology studies of the ZnONWs, performed by field emission scanning electron microscopy (FESEM), showed that the ZnO nanowires are uniform, highly dense and oriented perpendicularly to the substrate. Recognition event between the DNA probe and the target was investigated by differential pulse voltammetry (DPV) in 0.1 M acetate buffer solution (ABS), pH 7.00;as a result of the hybridization, an oxidation signal was observed at +0.8 V. The influences of pH, target concentration, and non-complimentary DNA on biosensor performance were examined. The proposed DNA biosensor has the ability to detect the target sequence in the range of concentration between 10.0 and 100.0 μM with a detection limit of 3.32 μM. The experimental results demonstrated that the prepared ZnONWs/Au electrodes are suitable platform for the immobilization of DNA.展开更多
Background:Recently,researchers have been attracted in identifying the crucial genes related to cancer,which plays important role in cancer diagnosis and treatment.However,in performing the cancer molecular subtype cl...Background:Recently,researchers have been attracted in identifying the crucial genes related to cancer,which plays important role in cancer diagnosis and treatment.However,in performing the cancer molecular subtype classification task from cancer gene expression data,it is challenging to obtain those significant genes due to the high dimensionality and high noise of data.Moreover,the existing methods always suffer from some issues such as premature convergence.Methods:To address those problems,we propose a new ant colony optimization(ACO)algorithm called DACO to classify the cancer gene expression datasets,identifying the essential genes of different diseases.In DACO,first,we propose the initial pheromone concentration based on the weight ranking vector to accelerate the convergence speed;then,a dynamic pheromone volatility factor is designed to prevent the algorithm from getting stuck in the local optimal solution;finally,the pheromone update rule in the Ant Colony System is employed to update the pheromone globally and locally.To demonstrate the performance of the proposed algorithm in classification,different existing approaches are compared with the proposed algorithm on eight high-dimensional cancer gene expression datasets.Results:The experiment results show that the proposed algorithm performs better than other effective methods in terms of classification accuracy and the number of feature sets.It can be used to address the classification problem effectively.Moreover,a renal cell carcinoma dataset is employed to reveal the biological significance of the proposed algorithm from a number of biological analyses.Conclusion:The results demonstrate that CAPS may play a crucial role in the occurrence and development of renal clear cell carcinoma.展开更多
Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are ...Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.展开更多
AIM:To conduct a systematic review of the published epidemiological studies investigating the association of the interactions between gene variants and dietary intake with gastric cancer risk.METHODS:A literature sear...AIM:To conduct a systematic review of the published epidemiological studies investigating the association of the interactions between gene variants and dietary intake with gastric cancer risk.METHODS:A literature search was conducted in PubMed,EMBASE,and MEDLINE for articles published between January 2000 and July 2013,and 38 studies were identified.Previous studies included various dietary factors(e.g.,fruits and vegetables,soybean products,salt,meat,and alcohol)and genetic variants that are involved in various metabolic pathways.RESULTS:Studies suggest that individuals who carry high-risk genetic variants and demonstrate particular dietary habits may have an increased risk of gastric cancer compared with those who do not carry high-risk genetic variants.Distinctive dietary patterns and variations in the frequency of genetic variants may explain the higher incidence of gastric cancer in a particular region.However,most previous studies have limitations,such as a small sample size and a retrospective casecontrol design.In addition,past studies have been unable to elucidate the specific mechanism in gene-diet interaction associated with gastric carcinogenesis.CONCLUSION:Additional large prospective epidemiological and experimental studies are required to identify the gene-diet metabolic pathways related to gastric cancer susceptibility.展开更多
AIM:Optimal molecular markers for detecting colorectal cancer(CRC)in a blood-based assay were evaluated.METHODS:A matched(by variables of age and sex)case-control design(111 CRC and 227 non-cancer samples)was applied....AIM:Optimal molecular markers for detecting colorectal cancer(CRC)in a blood-based assay were evaluated.METHODS:A matched(by variables of age and sex)case-control design(111 CRC and 227 non-cancer samples)was applied.Total RNAs isolated from the338 blood samples were reverse-transcribed,and the relative transcript levels of candidate genes were analyzed.The training set was made of 162 random samples of the total 338 samples.A logistic regression analysis was performed,and odds ratios for each gene were determined between CRC and non-cancer.The samples(n=176)in the testing set were used to validate the logistic model,and an inferred performance(generality)was verified.By pooling 12 public microarray datasets(GSE 4107,4183,8671,9348,10961,13067,13294,13471,14333,15960,17538,and 18105),which included 519 cases of adenocarcinoma and 88 controls of normal mucosa,we were able to verify the selected genes from logistic models and estimate their external generality.RESULTS:The logistic regression analysis resulted in the selection of five significant genes(P<0.05;MDM2,DUSP6,CPEB4,MMD,and EIF2S3),with odds ratios of 2.978,6.029,3.776,0.538 and 0.138,respectively.The five-gene model performed stably for the discrimination of CRC cases from controls in the training set,with accuracies ranging from 73.9%to 87.0%,a sensitivity of 95%and a specificity of 95%.In addition,a good performance in the test set was obtained using the discrimination model,providing 83.5%ac-curacy,66.0%sensitivity,92.0%specificity,a positive predictive value of 89.2%and a negative predictive value of 73.0%.Multivariate logistic regressions analyzed 12 pooled public microarray data sets as an external validation.Models that provided similar expected and observed event rates in subgroups were termed well calibrated.A model in which MDM2,DUSP6,CPEB4,MMD,and EIF2S3 were selected showed the result in logistic regression analysis(H-L P=0.460,R2=0.853,AUC=0.978,accuracy=0.949,specificity=0.818 and sensitivity=0.971).CONCLUSION:A novel gene expression profile was associated with CRC and can potentially be applied to blood-based detection assays.展开更多
AIM: To discuss the possible effect of PTEN gene mutations on occurrence and development of gastric cancer. METHODS: Fifty-three gastric cancer specimens were selected to probe PTEN gene mutations in genome of gastric...AIM: To discuss the possible effect of PTEN gene mutations on occurrence and development of gastric cancer. METHODS: Fifty-three gastric cancer specimens were selected to probe PTEN gene mutations in genome of gastric cancer and paracancerous tissues using PCR-SSCP-DNA sequencing method based on microdissection and to observe the protein expression by immunohistochemistry technique. RESULTS: PCR-SSCP-DNA sequencing indicated that 4 kinds of mutation sites were found in 5 of 53 gastric cancer specimens. One kind of mutation was found in exons. AA-TCC mutation was located at 40bp upstream of 3’ lateral exon 7 (115946 AA-TCC). Such mutations led to terminator formation in the 297th codon of the PTEN gene. The other 3 kinds of mutation were found in introns,including a G-C point mutation at 91 bp upstream of 5’ lateral exon 5(90896 G-C),a T-G point mutation at 24 bp upstream of 5’ lateral exon 5 (90963 T-G),and a single base A mutation at 7 bp upstream of 5’ lateral exon 5 (90980 A del). The PTEN protein expression in gastric cancer and paracancerous tissues detected using immunohistochemistry technique indicated that the total positive rate of PTEN protein expression was 66% in gastric cancer tissue,which was significantly lower than that (100%) in paracancerous tissues (P < 0.005). CONCLUSION: PTEN gene mutation and expression may play an important role in the occurrence and development of gastric cancer.展开更多
Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most common cause of death i...Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most common cause of death in cancer related deaths. Gastric cancer like almost all other cancers has a molecular genetic basis which relies on disruption in normal cellular regulatory mechanisms regarding cell growth, apoptosis and cell division. Thus novel therapeutic approaches such as gene therapy promise to become the alternative choice of treatment in gastric cancer. In gene therapy, suicide genes, tumor suppressor genes and anti-angiogenesis genes among many others are introduced to cancer cells via vectors. Some of the vectors widely used in gene therapy are Adenoviral vectors. This review provides an update of the new developments in adenoviral cancer gene therapy including strategies for inducing apoptosis, inhibiting metastasis and targeting the cancer cells.展开更多
文摘Cancer gene discovery continues to drive current cancer research with the promise of identifying new diagnostic markers and therapeutic targets by elucidating novel genetic interactions that promote or sustain tumor formation. Sleeping Beauty(SB) transposoniated insertional mutagenesis has emerged as an exciting approach to identify novel cancer-causing genes in the mouse. The SB transposon faithfully "hops" throughout the genome by a cut-and-paste mechanism mediated by the ubiquitous expression of the SB transposase. Initial tumor data generated using an SB transposon harboring the MSCV promoter demonstrated a bias towards hematopoietic tumors. More recently, experiments using a modified SB transposon containing the CAG promoter have generated cohorts of mice with solid tumors, primarily carcinomas, which in some cases metastasize. Many animals also develop multiple, inde- pendent primary tumors. These data demonstrate the utility of the SB transposition system for cancer gene discovery across organ systems.
文摘Polymorphisms in promoter regions of inflammatory cytokines have been widely studied,and potentially functional polymorphisms have been discovered.Conflicting results from meta-analyses of interleukin(IL)-1B and IL-10 polymorphisms show differences in gastric cancer susceptibilities between Caucasian and Asian populations.In particular,we note the suggestion of an allele flip in IL-1B and IL-10 gene polymorphisms.In Asian populations,the IL-1B-1464G/-511C/-31T haplotype indicates risk for gastric cancer,while the opposite haplotype,IL-1B-1464C/-511T/-31C is the risk-related allele in Caucasians.Furthermore,while IL-10-1082G/-819C/-592C is associated with gastric cancer in Asians,IL-10-1082A/-819T/-592T is linked to gastric cancer risk in Caucasians.These seemingly contradictory results may be attributed to distinct carcinogenic mechanisms underlying the different gastric cancer subtypes.The allele flip observed in IL-10 and gastric cancer appears to reflect allelic heterogeneity,similar to that observed in IL-1B.In this review,we focus on the allele flip phenomenon observed between different ethnic groups in an effort to resolve certain controversial results from recent studies on interleukin polymorphism.In addition,we re-emphasize the importance of stratifying gastric cancer subtypes based on anatomical site and Lauren classification to prevent false associations arising through dilution of true ones.
文摘This study was performed to demonstrate the transportation of an engineered MSC-produced intracellular anticancer gene product between mesenchymal stem cell (MSC) and cancer cells.? MSC-mediated anticancer strategy has held great promise owing to MSCs’ capacity of tumor-directed migration and the availability of specific anticancer genes.? All anticancer genes that have been used in previous MSC-mediated anticancer studies were limited in functioning via extracellular mechanisms, mainly because of the restriction by cell membrane to macromolecules including proteins.? In order to apply the majority of potent anticancer genes to the MSC-mediated anticancer system, a specifically designed expression vector which bears an intracellular anticancer gene, PTEN, is utilized to demonstrate the feasibility of the system in cancer therapies.? A transacting activator of transcription (TAT) was introduced into an expression vector followed by a segment for PTEN-RFP fusion protein.? A direct demonstration of PTEN-RFP transportation between MSC and cancer cells was obtained from direct co-cultures.? A marked cancer cell death was observed in indirect co-cultures with conditioned media from PTEN-transfected MSCs.? The demonstration of PTEN-engineered MSC-produced PTEN transportation indicates the feasibility of applying intracellular anticancer gene expression system in MSC-mediated strategies for cancer therapy.
文摘The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. They will also review presymptomatic testing of hereditary cancers, and the application of expression profiling to identify patients likely to benefit from particular therapeutic approaches.
文摘Objective: The mortality and morbidity rates associated with pancreatic cancer (PaCa) are extremely high. Various studies have demonstrated that pancreatic cancer will be the fourth cancer-related death by 2030, raising more concern for scholars to find effective methods to prevent and treat in order to improve the pancreatic cancer outcome. Using bioinformatic analysis, this study aims to pinpoint key genes that could impact PaCa patients’ prognosis and could be used as therapeutic targets. Methods: The TCGA and GEO datasets were integratively analyzed to identify prognosis-related differentially expressed genes. Next, the STRING database was used to develop PPI networks, and the MCODE and CytoNCA Cytoscape in Cytoscape were used to screen for critical genes. Through CytoNCA, three kinds of topology analysis were considered (degree, betweenness, and eigenvector). Essential genes were confirmed as potential target treatment through Go function and pathways enrichment analysis, a developed predictive risk model based on multivariate analysis, and the establishment of nomograms using the clinical information. Results: Overall, the GSE183795 and TCGA datasets associated 1311 and 2244 genes with pancreatic cancer prognosis, respectively. We identified 132 genes that were present in both datasets. The PPI network analysis using, the centrality analysis approach with the CytoNCA plug-in, showed that CDK2, PLK1, CCNB1, and TOP2A ranked in the top 5% across all three metrics. The independent analysis of a risk model revealed that the four key genes had a Hazard Ratio (HR) > 1. The monogram showed the predictive risk model and individual patient survival predictions were accurate. The results indicate that the effect of the selected vital genes was significant and that they could be used as biomarkers to predict a patient’s outcome and as possible target therapy in patients with pancreatic cancer. GO function and pathway analysis demonstrated that crucial genes might affect the P53 signaling pathway and FoxO signaling pathway, through which Meiotic nuclear division and cell cycle may have a significant function in essential genes affecting the outcome of patients who have pancreatic cancer. Conclusions: This study suggests that CDK2, CCNB1, PLK1 and TOP2A are four key genes that have a significant influence on PaCa migration and proliferation. CDK2, CCNB1, PLK1, and TOP2A can be used as potential PaCa prognostic biomarkers and therapeutic targets. However, experimental validation is necessary to confirm these predictions. Our study comes into contributions to the development of personalized target therapy for pancreatic cancer patients.
文摘Lung cancer is a highly heterogeneous malignancy with a complex pathogenesis, involving a series of endogenous alterations such as genetic mutations, epigenetic modifications, and oxidative stress. Recent advancements in lung cancer research, especially at the genomic and molecular biology levels, have continuously provided new potential targets and perspectives for the diagnosis and treatment of lung cancer. Therefore, this article summarizes the recent progress in the study of endogenous factors related to the pathogenesis of lung cancer, aiming to enhance the understanding of intrinsic factors in lung cancer and to organize ideas for subsequent related research.
文摘Background: Protein kinase B (AKT/PKB) family is frequently amplified in ovarian cancer (OC). To the greatest of our knowledge, there is a lack of published reports about the amplification of the genes belonging to the AKT family among Sudanese women with OC. The present study was conducted to detect the AKT1 gene amplification and its association with tumour types, grades, and ages among Sudanese women with OC, bearing in mind the ethnic variation. Methods: This institution-based study included 79 cases of women diagnosed with ovarian cancer (OC) at Omdurman Maternity Hospital in the period 2013-2018. Formalin-fixed, paraffin-embedded (FFPE) tissue sections were used to extract RNA. AKT1 gene amplification was assessed using quantitative real-time PCR. Results: The mean age (±SD) of included women was 49.29 (±13.612). The amplification of AKT1 gene was observed in 18/79 (22.8%) of OC women, with a high frequency in women with undifferentiated 1/2 (50%), clear cell 2/6 (33.3%), mucinous 3/11 (27.3%), endometrioid 3/17 (17.6%), and serous carcinomas 5/30 OC (16.7%). High frequency was seen in women with low (26.3%;n = 10/28) rather than in higher (19.5%;n = 8/33) grade carcinoma, and in older (25.8%;n = 8/23) rather than younger (18.2%;n = 2/9) women. No significant association between AKT1 gene amplification and tumour types, grades, and ages of women was observed (Fisher’s Exact test: p = 0.405, 0.593 and 0.851, respectively). Conclusion: AKT1 gene amplification arises in around one-fifth of Sudanese women with ovarian cancer (OC). It is seen more in undifferentiated, clear cell, and mucinous tumours types, and more frequently in low tumour grade and older women, but not to a statistically significant level. These outcomes sustenance previous studies suggesting that activated AKT genes have a vital role in OC progression and may offer a plan for targeted therapy and prognostic evaluation.
基金Supported by the National Natural Science Foundation of China (No.61105057)the Ph.D Foundation of Jiangsu University of Science and Technology (Nos.35301002 and 35211104)
文摘There have been many skewed cancer gene expression datasets in the post-genomic era. Extraction of differential expression genes or construction of decision rules using these skewed datasets by traditional algorithms will seriously underestimate the performance of the minority class, leading to inaccurate diagnosis in clinical trails. This paper presents a skewed gene selection algorithm that introduces a weighted metric into the gene selection procedure. The extracted genes are paired as decision rules to distinguish both classes, with these decision rules then integrated into an ensemble learning framework by majority voting to recognize test examples; thus avoiding tedious data normalization and classifier construction. The mining and integrating of a few reliable decision rules gave higher or at least comparable classification performance than many traditional class imbalance learning algorithms on four benchmark imbalanced cancer gene expression datasets.
基金The Spanish Ministry of the Economy(State Secretariat for Research,Development and Innovation),grant SAF2012-38885Ramon y Cajal contract+1 种基金L’Oreal-UNESCO"For Women in Science"and the Scientific Foundation Asociacion Espanola Contra el Cancer
文摘The development of colorectal cancer(CRC)can be influenced by genetic factors in both familial cases and sporadic cases.Familial CRC has been associated with genetic changes in high-,moderate-and low-penetrance susceptibility genes.However,despite the availability of current gene-identification techniques,the genetic causes of a considerable proportion of hereditary cases remain unknown.Genome-wide association studies of CRC have identified a number of common lowpenetrance alleles associated with a slightly increased or decreased risk of CRC.The accumulation of low-risk variants may partly explain the familial risk of CRC,and some of these variants may modify the risk of cancer in patients with mutations in high-penetrance genes.Understanding the predisposition to develop CRC will require investigators to address the following challenges:the identification of genes that cause uncharacterized hereditary cases of CRC such as familial CRC type X and serrated polyposis;the classification of variants of unknown significance in known CRC-predisposing genes;and the identification of additional cancer risk modifiers that can be used to perform risk assessments for individual mutation carriers.We performed a comprehensive review of the genetically characterized and uncharacterized hereditary CRC syndromes and of lowand moderate-penetrance loci and variants identified through genome-wide association studies and candidate-gene approaches.Current challenges and future perspectives in the field of CRC predisposition are also discussed.
文摘Pancreatic cancer (PC) occurs when malignant cells develop in the part of the pancreas, a glandular organ behind the stomach. For 2015, there are about 40,560 people dead of pancreatic cancer (20,710 men and 19,850 women) in the US (Siegel et al., 2015). Though PC accounts for about 3% of all cancers in the US, it can cause about 7% of cancer deaths. This is mainly because that the early stages of this cancer do not usually produce symptoms, and thus the cancer is almost always fatal when it is diagnosed.
基金the Ministry of Higher Education Malaysia for the ERGS grant(600/RMI/st/ERGS/5/3/fst12/2011)Universiti Teknologi MARA for financial support via postgraduate teaching assistant scheme(UPTA)to Nur Azimah Mansor for conducting this research.
文摘Herein we report an electrochemical DNA biosensor for the rapid detection of sequence (5’ AAT GGA TTT ATC TGC TCT TCG 3’) specific for the breast cancer 1 (BRCA1) gene. The proposed electrochemical genosensor is based on short oligonucleotide DNA probe immobilized onto zinc oxide nanowires (ZnONWs) chemically synthesized onto gold electrode via hydrothermal technique. The morphology studies of the ZnONWs, performed by field emission scanning electron microscopy (FESEM), showed that the ZnO nanowires are uniform, highly dense and oriented perpendicularly to the substrate. Recognition event between the DNA probe and the target was investigated by differential pulse voltammetry (DPV) in 0.1 M acetate buffer solution (ABS), pH 7.00;as a result of the hybridization, an oxidation signal was observed at +0.8 V. The influences of pH, target concentration, and non-complimentary DNA on biosensor performance were examined. The proposed DNA biosensor has the ability to detect the target sequence in the range of concentration between 10.0 and 100.0 μM with a detection limit of 3.32 μM. The experimental results demonstrated that the prepared ZnONWs/Au electrodes are suitable platform for the immobilization of DNA.
基金supported by the Langfang Science and Technology Plan Project(No.2018013151)from Hebei Petro China Central Hospital.
文摘Background:Recently,researchers have been attracted in identifying the crucial genes related to cancer,which plays important role in cancer diagnosis and treatment.However,in performing the cancer molecular subtype classification task from cancer gene expression data,it is challenging to obtain those significant genes due to the high dimensionality and high noise of data.Moreover,the existing methods always suffer from some issues such as premature convergence.Methods:To address those problems,we propose a new ant colony optimization(ACO)algorithm called DACO to classify the cancer gene expression datasets,identifying the essential genes of different diseases.In DACO,first,we propose the initial pheromone concentration based on the weight ranking vector to accelerate the convergence speed;then,a dynamic pheromone volatility factor is designed to prevent the algorithm from getting stuck in the local optimal solution;finally,the pheromone update rule in the Ant Colony System is employed to update the pheromone globally and locally.To demonstrate the performance of the proposed algorithm in classification,different existing approaches are compared with the proposed algorithm on eight high-dimensional cancer gene expression datasets.Results:The experiment results show that the proposed algorithm performs better than other effective methods in terms of classification accuracy and the number of feature sets.It can be used to address the classification problem effectively.Moreover,a renal cell carcinoma dataset is employed to reveal the biological significance of the proposed algorithm from a number of biological analyses.Conclusion:The results demonstrate that CAPS may play a crucial role in the occurrence and development of renal clear cell carcinoma.
文摘Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.
基金Supported by A grant from the National Cancer Center,South Korea,No.1110300 and No.1410260
文摘AIM:To conduct a systematic review of the published epidemiological studies investigating the association of the interactions between gene variants and dietary intake with gastric cancer risk.METHODS:A literature search was conducted in PubMed,EMBASE,and MEDLINE for articles published between January 2000 and July 2013,and 38 studies were identified.Previous studies included various dietary factors(e.g.,fruits and vegetables,soybean products,salt,meat,and alcohol)and genetic variants that are involved in various metabolic pathways.RESULTS:Studies suggest that individuals who carry high-risk genetic variants and demonstrate particular dietary habits may have an increased risk of gastric cancer compared with those who do not carry high-risk genetic variants.Distinctive dietary patterns and variations in the frequency of genetic variants may explain the higher incidence of gastric cancer in a particular region.However,most previous studies have limitations,such as a small sample size and a retrospective casecontrol design.In addition,past studies have been unable to elucidate the specific mechanism in gene-diet interaction associated with gastric carcinogenesis.CONCLUSION:Additional large prospective epidemiological and experimental studies are required to identify the gene-diet metabolic pathways related to gastric cancer susceptibility.
基金Supported by Taiwan’s SBIR promoting program from the De-partment of Industrial Technology of the Ministry of Economic Affairs,Advpharma,Incthe National Defense Medical Cen-ter(NDMC),Bureau of Military Medicine,Ministry of Defense,Taiwan
文摘AIM:Optimal molecular markers for detecting colorectal cancer(CRC)in a blood-based assay were evaluated.METHODS:A matched(by variables of age and sex)case-control design(111 CRC and 227 non-cancer samples)was applied.Total RNAs isolated from the338 blood samples were reverse-transcribed,and the relative transcript levels of candidate genes were analyzed.The training set was made of 162 random samples of the total 338 samples.A logistic regression analysis was performed,and odds ratios for each gene were determined between CRC and non-cancer.The samples(n=176)in the testing set were used to validate the logistic model,and an inferred performance(generality)was verified.By pooling 12 public microarray datasets(GSE 4107,4183,8671,9348,10961,13067,13294,13471,14333,15960,17538,and 18105),which included 519 cases of adenocarcinoma and 88 controls of normal mucosa,we were able to verify the selected genes from logistic models and estimate their external generality.RESULTS:The logistic regression analysis resulted in the selection of five significant genes(P<0.05;MDM2,DUSP6,CPEB4,MMD,and EIF2S3),with odds ratios of 2.978,6.029,3.776,0.538 and 0.138,respectively.The five-gene model performed stably for the discrimination of CRC cases from controls in the training set,with accuracies ranging from 73.9%to 87.0%,a sensitivity of 95%and a specificity of 95%.In addition,a good performance in the test set was obtained using the discrimination model,providing 83.5%ac-curacy,66.0%sensitivity,92.0%specificity,a positive predictive value of 89.2%and a negative predictive value of 73.0%.Multivariate logistic regressions analyzed 12 pooled public microarray data sets as an external validation.Models that provided similar expected and observed event rates in subgroups were termed well calibrated.A model in which MDM2,DUSP6,CPEB4,MMD,and EIF2S3 were selected showed the result in logistic regression analysis(H-L P=0.460,R2=0.853,AUC=0.978,accuracy=0.949,specificity=0.818 and sensitivity=0.971).CONCLUSION:A novel gene expression profile was associated with CRC and can potentially be applied to blood-based detection assays.
基金Zabei Medical Science and Technology Foundation of Shanghai,No.grant 200701
文摘AIM: To discuss the possible effect of PTEN gene mutations on occurrence and development of gastric cancer. METHODS: Fifty-three gastric cancer specimens were selected to probe PTEN gene mutations in genome of gastric cancer and paracancerous tissues using PCR-SSCP-DNA sequencing method based on microdissection and to observe the protein expression by immunohistochemistry technique. RESULTS: PCR-SSCP-DNA sequencing indicated that 4 kinds of mutation sites were found in 5 of 53 gastric cancer specimens. One kind of mutation was found in exons. AA-TCC mutation was located at 40bp upstream of 3’ lateral exon 7 (115946 AA-TCC). Such mutations led to terminator formation in the 297th codon of the PTEN gene. The other 3 kinds of mutation were found in introns,including a G-C point mutation at 91 bp upstream of 5’ lateral exon 5(90896 G-C),a T-G point mutation at 24 bp upstream of 5’ lateral exon 5 (90963 T-G),and a single base A mutation at 7 bp upstream of 5’ lateral exon 5 (90980 A del). The PTEN protein expression in gastric cancer and paracancerous tissues detected using immunohistochemistry technique indicated that the total positive rate of PTEN protein expression was 66% in gastric cancer tissue,which was significantly lower than that (100%) in paracancerous tissues (P < 0.005). CONCLUSION: PTEN gene mutation and expression may play an important role in the occurrence and development of gastric cancer.
文摘Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most common cause of death in cancer related deaths. Gastric cancer like almost all other cancers has a molecular genetic basis which relies on disruption in normal cellular regulatory mechanisms regarding cell growth, apoptosis and cell division. Thus novel therapeutic approaches such as gene therapy promise to become the alternative choice of treatment in gastric cancer. In gene therapy, suicide genes, tumor suppressor genes and anti-angiogenesis genes among many others are introduced to cancer cells via vectors. Some of the vectors widely used in gene therapy are Adenoviral vectors. This review provides an update of the new developments in adenoviral cancer gene therapy including strategies for inducing apoptosis, inhibiting metastasis and targeting the cancer cells.