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1.
Article in Chinese | WPRIM | ID: wpr-888375

ABSTRACT

OBJECTIVE@#To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD).@*METHODS@#120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed.@*RESULTS@#The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency.@*CONCLUSION@#Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.


Subject(s)
Antigens, Neoplasm , Coronary Disease/genetics , Gene Frequency , Glycation End Products, Advanced , Heart Rate , Humans , Mitogen-Activated Protein Kinases , Polymorphism, Genetic
2.
Int. braz. j. urol ; 46(5): 691-704, Sept.-Oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134242

ABSTRACT

ABSTRACT Background: The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa. Materials and Methods: A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR−), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model. Results: With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR−, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95% CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria. Conclusions: The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.


Subject(s)
Humans , Male , Prostatic Neoplasms/diagnosis , Biomarkers, Tumor , Odds Ratio , ROC Curve , Sensitivity and Specificity , Antigens, Neoplasm
3.
Gac. méd. Méx ; 156(3): 229-236, may.-jun. 2020. graf
Article in English, Spanish | LILACS | ID: biblio-1249899

ABSTRACT

Resumen Los anticuerpos terapéuticos son proteínas recombinantes empleadas en el tratamiento del cáncer. Existe una nueva generación de anticuerpos monoclonales con actividad contra las células cancerosas, conocidos como anticuerpos conjugados a fármacos. Estas moléculas están integradas por tres elementos: un anticuerpo monoclonal, un fármaco citotóxico con alta potencia y un enlazador químico que los une. El anticuerpo reconoce antígenos tumorales, por lo que permite la entrega dirigida del agente citotóxico hacia las células cancerosas. Tras el reconocimiento de su antígeno, el anticuerpo conjugado a fármaco es endocitado por las células blanco, donde se induce la degradación lisosomal de la fracción proteica y se libera el fármaco citotóxico. En el presente artículo se revisan las características generales de los anticuerpos conjugados a fármacos y se describe la evidencia clínica de la eficacia y seguridad de los primeros cuatro aprobados por las agencias reguladoras de Estados Unidos y Europa.


Abstract Therapeutic antibodies are recombinant proteins used in the treatment of cancer. There is a new generation of monoclonal antibodies with activity against cancer cells, known as antibody-drug conjugates. These molecules are made up of three elements: a monoclonal antibody, a highly potent cytotoxic drug, and a chemical linker that binds them together. The antibody recognizes tumor antigens, thereby allowing targeted delivery of the cytotoxic agent to cancer cells. After recognizing its antigen, the antibody-drug conjugate is endocytosed by the target cells, where the protein fraction is degradated into lysosomes, releasing the cytotoxic drug. This article reviews antibody-drug conjugates general characteristics and describes the clinical evidence of efficacy and safety of the first four approved by regulatory agencies in the United States and Europe.


Subject(s)
Humans , Immunoconjugates/administration & dosage , Neoplasms/drug therapy , Antineoplastic Agents/administration & dosage , Biotechnology , Immunoconjugates/adverse effects , Immunoconjugates/pharmacology , Antigens, Neoplasm/immunology , Neoplasms/immunology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology
4.
Int. braz. j. urol ; 45(3): 541-548, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1012322

ABSTRACT

ABSTRACT Objectives: To investigate whether Glasgow Prognostic Score has prognostic significance in patients with upper urinary urothelial carcinoma. Patients and methods: We retrospectively reviewed the clinical records of 74 patients with upper urinary urothelial carcinoma. We set the cut-off value for C-reactive protein as 1.0mg/dL, and 3.5mg/dL for albumin as Glasgow Prognostic Score. Their blood data including albumin and C-reactive protein for Glasgow Prognostic Score and cytokeratin 19 fragment 21-1 as a tumor marker were measured before starting treatment. The patients were stratified into three groups with Glasgow Prognostic Score: The Group-1, albumin ≥3.5g/dL and C-reactive protein < 1.0mg/dL; Group-2, albumin < 3.5g/dL or C-reactive protein ≥1.0mg/dL; Group-3, albumin < 3.5g/dL and C-reactive protein ≥1.0mg/dL. Results: The median follow-up for all patients was 26.9 months (range: 10.9-91.1 months), during which 37 (50%) patients died. There was a significant difference in the estimated survival rate among the 3 groups stratified by Glasgow Prognostic Score. The estimated survival rate in the Group-1 was significantly higher than those in Groups 2 and 3. In the univariate analysis C-reactive protein, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were significant predictors of overall survival. On the multivariate analysis, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were independently associated with shorter overall survival. Conclusion: Our review suggests Glasgow Prognostic Score may play as a prognostic predictor for upper urinary urothelial carcinoma.


Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Prognosis , Carcinoma/blood , Urologic Neoplasms/blood , Reference Values , C-Reactive Protein/analysis , Serum Albumin/analysis , Carcinoma/pathology , Biomarkers, Tumor/blood , Proportional Hazards Models , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Urologic Neoplasms/pathology , Statistics, Nonparametric , Urothelium/pathology , Keratin-19/blood , Kaplan-Meier Estimate , Middle Aged , Antigens, Neoplasm/blood
5.
Article in Chinese | WPRIM | ID: wpr-776826

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a pedigree affected with Bartter's syndrome (BS).@*METHODS@#Panel-based next-generation sequencing (NGS) was carried out to detect mutation in BS-related genes SLC12A1, KCNJ1, BSND and CLCNKB. Sanger sequencing of MAGED2 gene and chromosomal microarray analysis (CMA) were also performed on the patient. Suspected mutation was validated in her family members.@*RESULTS@#No pathogenic mutation was detected by NGS, while a 0.152 Mb microdeletion at Xp11.21 (54 834 585-54 986 301) was found in the male fetus, which removed the entire coding region of the MAGED2 gene. His mother was a heterozygous carrier of the deletion. His father and sister did not carry the same deletion.@*CONCLUSION@#The loss of the MAGED2 gene may underlie the BS in this pedigree.


Subject(s)
Adaptor Proteins, Signal Transducing , Genetics , Antigens, Neoplasm , Genetics , Bartter Syndrome , Genetics , Female , Genetic Testing , Heterozygote , Humans , Male , Mutation , Pedigree , Sequence Deletion
6.
Journal of Experimental Hematology ; (6): 1463-1468, 2019.
Article in Chinese | WPRIM | ID: wpr-775698

ABSTRACT

OBJECTIVE@#To investigate the transcriptional regulation of transcription factor MZF-1 on acute monocytic leukemia-related gene MLAA-34.@*METHODS@#The effect of MZF-1 on the transcriptional activity of MLAA-34 gene promoter was analyzed by luciferase reporter gene detection system and site-directed mutation technique. The EMSA and ChIP assay were used to verify whether MZF-1 directly and specifically binds to the core region of MLAA-34 promoter. The over-expression vector and interference vector of MZF-1 were constructed to transfect U937 cells, and RT-PCR and Western blot were used to detect the transcription and expression changes of MLAA-34 gene.@*RESULTS@#The transcription factor MZF-1 had a regulatory effect on MLAA-34 gene expression, and the relative luciferase activity was decreased after MZF-1 binding point mutation (P<0.01). EMSA and ChIP experiments demonstrated that MZF-1 could directly bind to MLAA-34 promoter and play a regulatory role. In the over-expression test, the increase of MZF-1 could up-regulate the expression of MLAA-34 (P<0.05). In the interference test, the decrease of MZF-1 could down-regulate the expression of MLAA-34 (P<0.05).@*CONCLUSION@#Transcription factor MZF-1 can bind to the transcriptional regulatory region on the promoter of MLAA-34 gene and promote the transcription of MLAA-34 gene in acute monocytic leukemia.


Subject(s)
Antigens, Neoplasm , Genetics , Apoptosis Regulatory Proteins , Genetics , Gene Expression Regulation, Neoplastic , Genes, Reporter , Hepatocyte Nuclear Factor 1-alpha , Humans , Kruppel-Like Transcription Factors , Metabolism , Leukemia, Monocytic, Acute , Promoter Regions, Genetic , Transcription, Genetic
7.
Clinics ; 74: e701, 2019. tab, graf
Article in English | LILACS | ID: biblio-1001831

ABSTRACT

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Bone Neoplasms/therapy , Osteosarcoma/therapy , Prognosis , Austria/epidemiology , Bone Neoplasms/mortality , Bone Neoplasms/pathology , Immunohistochemistry , Biomarkers/analysis , Osteosarcoma/mortality , Osteosarcoma/pathology , Survival Rate , Retrospective Studies , Antibodies, Monoclonal/analysis , Antigens, Neoplasm/analysis
8.
Article in Chinese | WPRIM | ID: wpr-774361

ABSTRACT

OBJECTIVE@#To investigate the clinical importance of combined detection of urinary amino acid metabolite --urinary tyrosine (UT) and tumor specific growth factor (TSGF) in the disease observation and curative effect evaluation of acute leukemia(AL).@*METHODS@#In 87 cases of AL, the UT and TSGF levels were detected by using chemical chromogenic method and continuous monitoring method respectively. The 2 indicators of each treatment group were statistically analyzed and compared with that of 50 healthy control group.@*RESULTS@#In 87 AL patients, the levels of UT and TSGF after treatment were significantly lower than those before treatment (P0.05).@*CONCLUSION@#UT and TSGF levels are related with the metabolism of tumor cells in AL patients. UT level can be used to predict the recurrence of patients with CR. The combined dynamical monitoring of these 2 indicators can be used as the indexes for observation of AL status, evaluation of therapeutic efficacy, prediction of prognosis and relapse of AL.


Subject(s)
Acute Disease , Amino Acids , Antigens, Neoplasm , Humans , Leukemia, Myeloid, Acute , Neoplasm Proteins , Prognosis , Recurrence
9.
Article in Chinese | WPRIM | ID: wpr-772127

ABSTRACT

OBJECTIVE@#To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions.@*METHODS@#Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms.@*RESULTS@#Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway.@*CONCLUSIONS@#We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.


Subject(s)
Antigens, Neoplasm , Blood , Biomarkers, Tumor , Blood , Carrier Proteins , Blood , Case-Control Studies , Cervical Intraepithelial Neoplasia , Blood , Diagnosis , Chromatography, Liquid , Complement Factor I , Early Detection of Cancer , Female , Glycoproteins , Blood , Haptoglobins , Humans , Neoplasm Proteins , Blood , Orosomucoid , Precancerous Conditions , Blood , Diagnosis , Serum Albumin, Human , Tandem Mass Spectrometry , Uterine Cervical Neoplasms , Blood , Diagnosis
10.
Article in Chinese | WPRIM | ID: wpr-771905

ABSTRACT

OBJECTIVE@#To clone the promoter sequence of acute monocytic leukemia new antigen gene.MLAA-34 and identify its promoter core region.@*METHODS@#The full-length fragment of MLAA-34 gene promoter region was amplified by PCR, then was ligated into pGL3-Basic vector, and the recombinant plasmid was cloned. Constructed a series of MLAA-34 gene promoter 5' flanking region truncated plasmid. These recombinant plasmids were transfected into U937 and HEK293 cells, and the dual luciferase reporter gene was used to detect the promoter activity of each fragment to determine the minimum active region. Transcription factor binding sites were analyzed by bioinformatics methods.@*RESULTS@#The recombinant plasmid containing MLAA-34 promoter sequence and its truncated plasmid were successfully constructed, and the promoter activity was significantly increased as compared with the empty vector (P<0.001). The minimal active region of MLAA-34 located between 402 bp and 200 bp. It contained multiple transcription factor binding sites such as E2F1, MZF-1, SP1, USF2 and STAT3.@*CONCLUSION@#The promoter of luciferase reporter gene has been successfully constructed with different deletion fragments of MLAA-34, and its core promoter region may contain multiple transcription factor sequence.


Subject(s)
Adult , Antigens, Neoplasm , Genetics , Apoptosis Regulatory Proteins , Genetics , Cloning, Molecular , Genes, Reporter , HEK293 Cells , Humans , Leukemia, Monocytic, Acute , Genetics , Luciferases , Promoter Regions, Genetic
11.
Chinese Journal of Biotechnology ; (12): 1295-1306, 2019.
Article in Chinese | WPRIM | ID: wpr-771799

ABSTRACT

Tumor-specific gene mutations might generate suitable neoepitopes for cancer immunotherapy that are highly immunogenic and absent in normal tissues. The high heterogeneity of the tumor genome poses a big challenge for precision cancer immunotherapy. Mutations characteristic of each tumor can help to distinguish it from other tumors. Based on these mutations' characteristic, it is possible to develop immunotherapeutic strategies for specific tumors. In this study, a tumor neoantigen prediction scheme was proposed, in which both the intracellular antigen presentation process and the ability to bind with extracellular MHC molecule were taken into consideration. The overall design is meritorious and may help reduce the cost for validation experiments compared with conventional methods. This strategy was tested with several cancer genome datasets in the TCGA database, and a number of potential tumor neoantigens were predicted for each dataset. These predicted neoantigens showed tumor type specificity and were found in 20% to 70% of cancer patients. This scheme might prove useful clinically in future.


Subject(s)
Antigens, Neoplasm , Computational Biology , Genome, Human , Humans , Immunotherapy , Mutation , Neoplasms
12.
Chinese Journal of Traumatology ; (6): 166-171, 2019.
Article in English | WPRIM | ID: wpr-771615

ABSTRACT

PURPOSE@#To evaluate the clinico-radiological outcome of complex tibial plateau fractures treated with Ilizarov external fixation with or without minimal internal fixation.@*METHODS@#This retrospective review was conducted on all the cases of Schatzker types V and VI tibial plateau fractures treated by Ilizarov external fixation between July 2006 and December 2015 with the minimum follow-up duration of one year. There were 30 patients: 24 males and 6 females, mean age 43.33 years, and mean follow-up 3.6 years. Three of them were open fractures; 15 cases were Schatzkertype V fractures and the other 15 type VI. According to AO/OTA classification, there were 11 type C1, 12 C2 and 7 type C3 fractures. Outcome assessment was made with American Knee Society Score (AKSS) and Rasmussen's Radiological Score (RRS) at final follow-up.@*RESULTS@#Out of the 30 cases, mini-open reduction was performed in 7, bone graft in 4, minimal internal fixation in 10 and knee temporary immobilisation in 11 patients. Mean duration of external fixation was 11.8 weeks. All fractures united. Pin tract infections in 7 and common peroneal neuropathy in 2 patients were self-limiting. Two patients had axial misalignment of less than 10°. At final follow-up, the mean knee range of motion was 114.7, mean AKSS 81.5 and mean RRS 16.7. On statistical analysis, Schatzker type of fractures, use of minimal internal fixation and knee-spanning did not influence the final outcome.@*CONCLUSION@#Ilizarov external fixator with or without minimal internal fixation provides acceptable outcome for complex tibial plateau fractures. Care must be taken to look for minor loss of alignment, especially in Type VI Schatzker fractures after removal of the fixator. However small sample size precludes firm conclusions.


Subject(s)
Adult , Antigens, Neoplasm , Female , Follow-Up Studies , Fracture Fixation, Internal , Methods , Fractures, Bone , Therapeutics , Humans , Ilizarov Technique , Knee , Male , Middle Aged , Mitogen-Activated Protein Kinases , Retrospective Studies , Tibia , Wounds and Injuries , Time Factors , Treatment Outcome , Young Adult
13.
Int. braz. j. urol ; 44(3): 500-505, May-June 2018. tab
Article in English | LILACS | ID: biblio-954061

ABSTRACT

ABSTRACT Background: The association of prostate cancer antigen 3 (PCA3) polymorphism (SNP, rs544190G>A) with metastatic prostate cancer in European descent has been reported. Our aim of the current study was to re-validate the effect of PCA3 polymorphism on prostate cancer risk in an Eastern Chinese population and then estimate possible genetic discrepancies among population. Materials and Methods: Taqman assay was employed to determine genotype of SNP rs544190 in 1015 ethnic Han Chinese patients with prostate cancer and 1032 cancer-free controls. Simultaneously, odds ratios (OR) and 95% confidence intervals (95%CI) for risk relationship were calculated by logistic regression models. Results: The statistically significant relationship between PCA3 rs544190G>A and higher prostate cancer risk was not found. Stratification analysis revealed that there was no remarkable association of rs544190 variant AG/AA genotype with prostate cancer risk in every subgroup, except for patients with Gleason score ≤7(3+4). Conclusion: Although the results demonstrated that SNP rs544190 was not involved in prostate cancer risk in Eastern Chinese descent, unlike in European population, these might have clinical implications on prostate cancer heterogeneity around the World. To validate these findings, well-designed studies with different ethnic populations are warranted.


Subject(s)
Humans , Male , Aged , Prostatic Neoplasms/genetics , Risk Assessment/methods , Polymorphism, Single Nucleotide/genetics , Asian Continental Ancestry Group/genetics , Antigens, Neoplasm/genetics , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/pathology , Smoking/adverse effects , Case-Control Studies , Gene Expression , Logistic Models , China , Risk Factors , Genetic Association Studies , Neoplasm Grading , Genotype , Neoplasm Staging
15.
Clinics ; 73(supl.1): e429s, 2018. graf
Article in English | LILACS | ID: biblio-952824

ABSTRACT

The immunologic landscape of tumors has been continuously unveiled, providing a new look at the interactions between cancer cells and the immune system. Emerging tumor cells are constantly eliminated by the immune system, but some cells establish a long-term equilibrium phase leading to tumor immunoediting and, eventually, evasion. During this process, tumor cells tend to acquire more mutations. Bearing a high mutation burden leads to a greater number of neoantigens with the potential to initiate an immune response. Although many tumors evoke an immune response, tumor clearance by the immune system does not occur due to a suppressive tumor microenvironment. The mechanisms by which tumors achieve the ability to evade immunologic control vary. Understanding these differences is crucial for the improvement and application of new immune-based therapies. Much effort has been placed in developing in silico algorithms to predict tumor immunogenicity and to characterize the microenvironment via high-throughput sequencing and gene expression techniques. Each sequencing source, transcriptomics, and genomics yields a distinct level of data, helping to elucidate the tumor-based immune responses and guiding the fine-tuning of current and upcoming immune-based therapies. In this review, we explore some of the immunological concepts behind the new immunotherapies and the bioinformatic tools to study the immunological aspects of tumors, focusing on neoantigen determination and microenvironment deconvolution. We further discuss the immune-based therapies already in clinical use, those underway for future clinical application, the next steps in immunotherapy, and how the characterization of the tumor immune contexture can impact therapies aiming to promote or unleash immune-based tumor elimination.


Subject(s)
Humans , Immunotherapy/methods , Neoplasms/immunology , Neoplasms/therapy , Genetic Therapy , Cell Transformation, Neoplastic , Combined Modality Therapy , Tumor Escape/immunology , Cancer Vaccines/therapeutic use , Tumor Microenvironment/immunology , Mutation , Antigens, Neoplasm/analysis , Neoplasms/genetics
16.
Chinese Medical Journal ; (24): 1289-1295, 2018.
Article in English | WPRIM | ID: wpr-688129

ABSTRACT

<p><b>Background</b>Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma (NPC) patients. In this study, we evaluated the T cell response to melanoma-associated antigen (MAGE)-A1, MAGE-A3, or synovial sarcoma X-2 (SSX-2) in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen (HLA)-A types were analyzed to provide evidence of designing novel therapy.</p><p><b>Methods</b>Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman's rank correlation was used to analyze the relationship of T cell responses.</p><p><b>Results</b>HLA-A*02:01, A*02:07, and A*24:02 were the three most frequent alleles (18.9%, 12.3%, and 11.5%, respectively) among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/10 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A*02:01 and A*24:02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders.</p><p><b>Conclusion</b>MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Antigens, Neoplasm , Allergy and Immunology , Metabolism , Carcinoma , Allergy and Immunology , Metabolism , Female , HLA-A Antigens , Metabolism , Humans , Leukocytes, Mononuclear , Metabolism , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Allergy and Immunology , Metabolism , Neoplasm Proteins , Metabolism , Sarcoma, Synovial , Allergy and Immunology , Metabolism , Young Adult
17.
Pakistan Journal of Medical Sciences. 2018; 34 (1): 226-229
in English | IMEMR | ID: emr-192403

ABSTRACT

Objectives: Type-2 diabetes mellitus [T2DM] is an endocrine disease having a significant genetic component. Polymorphisms of many genes may affect hereditary vulnerability of the disease that is characterized by insulin resistance and islet disorder. As the genetic basis of T2DM can vary between ethnic groups, it is important to investigate the genetic link of T2DM in Pakistani populace. This study was aimed to assess the association of receptor for advanced glycation end product [RAGE] gene polymorphism [-429T>C] with Type-2 diabetes mellitus within local populace


Methods: Genomic DNA was isolated by following kit protocol. Genotyping of the RAGE gene was studied by PCR-RFLP on genomic DNA. All research work was done in molecular biochemistry laboratory [MBL], University of Agriculture Faisalabad and Postgraduate Laboratory, The University of Faisalabad, Pakistan from December 2016 to July 2017


Results: We found distribution of -429T>C genotypes between T2DM and healthy controls as 24.7% [tt], 24.7% [Tt] and 50.7% [TT]. The outcomes were highly compatible statistically


Conclusion: The techniques of PCR and RFLP when performed simultaneously can be helpful in tracing vital information regarding polymorphism of AGE receptor


Subject(s)
Humans , Polymorphism, Genetic , Genotype , Polymerase Chain Reaction , Antigens, Neoplasm , Mitogen-Activated Protein Kinases
18.
IBJ-Iranian Biomedical Journal. 2018; 22 (3): 160-170
in English | IMEMR | ID: emr-192465

ABSTRACT

Background: This study aimed to evaluate the diagnostic value of outer dense fiber 4 [ODF4], melanoma associated antigen A3 [MAGEA3], and MAGEAB4 mRNAs in transitional cell carcinoma [TCC], using a small amount of cell reverse transcriptase-polymerase chain reaction [RT-PCR] on urinary exfoliated cells


Methods: We recruited a total of 105 suspected TCC patients and 54 sex- and age-matched non-TCC controls. The candidates' genetic expression patterns were investigated with RT-PCR, while reverse transcription quantitative PCR was applied to quantify and compare each mRNA level between cases and control groups


Results: The sensitivity of ODF4, MAGEA3, and MAGEAB4 RT-PCR was 54.8%, 63%, and 53.4%, whereas the specificity was 73.7%, 86%, and 94.7%, respectively. Combining ODF4, MAGEA3, and MAGEAB4 RT-PCR offered a relatively higher sensitivity [83.6%]


Conclusion: RT-PCR with ODF4, MAGEA3, and MAGEAB4 on urinary exfoliated cells could provide clinicians with a promising method to improve TCC diagnosis, especially in the case of gross hematuria and catheterization. The method used here is non-invasive, simple and convenient, and unlike cytology, it does not rely directly on expert professional opinions. These features can be of particular importance to the management of TCC patients in whom regular and lifelong surveillance is required


Subject(s)
Humans , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/diagnosis , Urologic Neoplasms/genetics , Biomarkers, Tumor , Sperm Tail , Seminal Plasma Proteins , Antigens, Neoplasm , Neoplasm Proteins
19.
Article in English | WPRIM | ID: wpr-772983

ABSTRACT

Tumor-specific neoantigens have attracted much attention since they can be used as biomarkers to predict therapeutic effects of immune checkpoint blockade therapy and as potential targets for cancer immunotherapy. In this study, we developed a comprehensive tumor-specific neoantigen database (TSNAdb v1.0), based on pan-cancer immunogenomic analyses of somatic mutation data and human leukocyte antigen (HLA) allele information for 16 tumor types with 7748 tumor samples from The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA). We predicted binding affinities between mutant/wild-type peptides and HLA class I molecules by NetMHCpan v2.8/v4.0, and presented detailed information of 3,707,562/1,146,961 potential neoantigens generated by somatic mutations of all tumor samples. Moreover, we employed recurrent mutations in combination with highly frequent HLA alleles to predict potential shared neoantigens across tumor patients, which would facilitate the discovery of putative targets for neoantigen-based cancer immunotherapy. TSNAdb is freely available at http://biopharm.zju.edu.cn/tsnadb.


Subject(s)
Antigens, Neoplasm , Metabolism , Data Analysis , Databases, Genetic , Humans , Immunotherapy , Mutation , Genetics , Neoplasms , Genetics , Allergy and Immunology , Tumor Suppressor Protein p53 , Genetics , Urinary Bladder Neoplasms , Genetics
20.
Protein & Cell ; (12): 254-266, 2018.
Article in English | WPRIM | ID: wpr-757332

ABSTRACT

T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR-engineered T cells to target New York esophageal squamous cell carcinoma (NY-ESO-1). These successes demonstrate the potential of this approach to treat cancer. In this review, we provide a perspective on the current and future applications of TCR-engineered T cells for the treatment of cancer. Our summary focuses on TCR activation and both pre-clinical and clinical applications of TCR-engineered T cells. We also discuss how to enhance the function of TCR-engineered T cells and prolong their longevity in the tumor microenvironment.


Subject(s)
Animals , Antigens, Neoplasm , Allergy and Immunology , Metabolism , Humans , Neoplasms , Allergy and Immunology , Metabolism , Receptors, Antigen, T-Cell , Genetics , Metabolism , T-Lymphocytes , Allergy and Immunology , Metabolism
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