Three-dimensional DNA biomimetic networks (B-3D Net)-based ratiometric fluorescence platform for cancer-related gene biosensing.

Efficient detection of cancer-related nucleic acids is pivotal for early cancer diagnosis. This study introduces a target induced three-dimensional DNA biomimetic networks (B-3D Net)-based ratiometric fluorescence platform using manganese dioxide nanosheets (MnO2 NS)/o-phenylenediamine in combination with hybridization chain reaction to detect cancer-related genes (p53 gene). The incorporation of multiple signals within the B-3D networks can significantly enhance catalytic activity and amplify the output signals, enabling a high sensitivity. Compared with traditional ratio fluorescence platforms, there is no demand to synthesize fluorescent nanoprobes due to the in-situ formation of fluorescence species, which is simple and cost-effective. The corresponding assay demonstrated exceptional sensitivity (with a detection limit as low as 2 fM), selectivity, reproducibility, and accuracy, which mitigates disturbances caused by instrument errors, an inaccurate probe count, and the microenvironment. Furthermore, the ease and straightforwardness of discerning changes in fluorescent brightness and colour by the naked eye are evident. Using the relevant software, a linear relationship between fluorescent images using a smartphone and target concentration was obtained. Hence, the novel ratiometric sensing system will demonstrate new opportunities on determination of target DNA samples in complex biological environments.

P53 Gene as a Promising Biomarker and Potential Target for the Early Diagnosis of Reproductive Cancers.

One of the crucial aspects of cancer research is diagnosis with specificity and accuracy. Early cancer detection mostly helps make appropriate decisions regarding treatment and metastasis. The well-studied transcription factor tumor suppressor protein p53 is essential for maintaining genetic integrity. p53 is a key tumor suppressor that recognizes the carcinogenic biological pathways and eradicates them by apoptosis. A wide range of carcinomas, especially gynecological such as ovarian, cervical, and endometrial cancers, frequently undergo TP53 gene mutations. This study evaluates the potential of the p53 gene as a biological marker for the diagnosis of reproductive system neoplasms. Immunohistochemistry of p53 is rapid, easy to accomplish, cost-effective, and preferred by pathologists as a surrogate for the analysis of TP53 mutation. Thus, this review lays a groundwork for future efforts to develop techniques using p53 for the early diagnosis of cancer.

Low Doses of Kretek Cigarette Smoke Altered Rat Lung Histometric, and Overexpression of the p53 Gene.

Background: The components of kretek cigarettes include tobacco as the main part, clove, and sauce. Filtered kretek cigarettes are kretek cigarettes that have one end filtered. Cigarette smoke contributes to the disruption of the respiratory system, so it is necessary to know the effect of low doses of cigarette smoke on changes in the histometric of the respiratory system, and whether it affects p53 gene expression. This study aims to determine changes in the histometric of the respiratory system and p53 gene expression. Methods: In this study, we used Sprague-Dawley rats. Group I of rats breathing normal air, were not exposed to filtered kretek cigarette smoke (as a control). Group II of rats, as a treatment group, were exposed to filtered kretek cigarette smoke 1 stick/day for 3 months. The results of lung histometry measurements and p53 gene expression between groups were analyzed using the Independent Sample T-test. The difference between groups is significant if the test results show P < 0.05. Results: Bronchioles length, width, area, and perimeter in group I were 40.55±1.57 µm, 14.82±0.41 µm, 494.61±5.62 µm2, and 233.87±4.51 µm, respectively. Bronchioles length, width, area, and perimeter in group II were 30.76±0.78 µm, 9.28±0.40 µm, 297.32±2.53 µm2, and 177.84±5.15 µm, respectively. The area and perimeter of respiratory bronchioles in group I were 17.68±0.49 µm2, and 26.60±0.52 µm respectively, while those in group II were 19.28±0.35 µm2, and 29.28±0.35 µm, respectively. Mucus was found in the bronchioles and respiratory bronchioles in group II, however, there was no visible mucus observed in group I. In addition, it was also concluded that exposure to low doses of filtered kretek cigarette smoke, 1 cigarette/day for 3 months, increased the expression of the p53 gene in the lungs of rats. Conclusion: The size of bronchioles in rats decreased after being exposed to filtered kretek cigarette smoke 1 stick/day for 3 months, while the size of respiratory bronchioles increased. In addition, exposure to filtered kretek cigarette smoke increased the expression of the p53 gene in the rat lungs.

Dual amplification dynamic DNA network system for CRISPR/Cas12a based p53 gene detection.

BACKGROUND: It is estimated that over 50 % of human cancers are caused by mutations in the p53 gene. Early sensitive and accurate detection of the p53 gene is important for diagnosis of cancers in the early stage. However, conventional detection techniques often suffer from strict reaction conditions, or unsatisfied sensitivity, so we need to develop a new strategy for accurate detection of p53 gene with smart designability, multiple signal amplification in mild reaction conditions. RESULTS: In this study, CRISPR/Cas system is exploited in entropy-driven catalysis (EDC) and hybridization chain reaction (CHA) dual signal amplification sensing strategies. The products of both reactions can efficiently and separately activate CRISPR/Cas12a which greatly amplifies the fluorescent signal. The method has good linearity in p53 detection with the concentration ranged from 0.1 fM to 0.5 pM with ultra-low detection limit of 0.096 fM. It also showed good performance in serum, offering potentials for early disease detection. SIGNIFICANCE: The designed dual amplification dynamic DNA network system exhibits an ultra-sensitive fluorescence biosensing for p53 gene identification. The method is simple to operate and requires only one buffer for the experiment, and meanwhile shows smart designability which could be used for a wide range of markers. Thus, we believe the present work will provide a potential tool for the construction and development of sensitive fluorescent biosensors for diseases.

The Oncolytic Effect of Aerva lanata on Osteosarcoma Cell Lines via the Apoptotic Signaling Pathway.

Introduction Osteosarcoma, a malignant bone tumor, poses significant treatment challenges, necessitating the development of alternative therapeutic strategies. Aerva lanata (A. lanata), a medicinal plant with traditional use in various healthcare systems, has anti-cancer properties. This study looks at the oncolytic effect of A. lanata extract on osteosarcoma cell lines (sarcoma osteogenic-Saos2). Aim The aim of this study was to investigate the oncolytic effect of Aerva lanata on Saos2 cell lines through the apoptotic signaling pathway. Materials and methods A. lanata extract was prepared using Soxhlet extraction, and its cytotoxic effects on Saos2 cells were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (RT-PCR) analysis of gene activity was used to assess the extract's effect on apoptotic signaling pathways. Results The MTT assay demonstrated a dose-dependent decrease in Saos2 proliferation following treatment with A. lanata extract at concentrations ranging from 50 µg to 200 µg. The standard deviations observed ranged from 1.414 to 7.071. Gene expression analysis revealed that the extract led to a reduction in the messenger ribonucleic acid (mRNA) levels of the anti-apoptotic marker B-cell lymphoma 2 (Bcl2), with standard deviations ranging from 1 to 0.535. Conversely, it induced an increase in the mRNA levels of the tumor suppressor protein p53, with standard deviations ranging from 1 to 1.835. These findings suggest that the extract modulates the apoptotic pathways of the Bcl2 and p53 genes.  Conclusion A. lanata extract exhibits promising anti-cancer activity against Saos2 osteosarcoma cell lines, inducing apoptosis by downregulating Bcl2 and increasing p53. The study's findings suggest that A. lanata may be useful as a natural treatment for osteosarcoma.

Progress in deciphering the role of p53 in diffuse large B-cell lymphoma: mechanisms and therapeutic targets.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, accounting for 30%-40% of non-Hodgkin lymphoma in adults. The mechanisms underlying DLBCL occurrence are extremely complex, and involve the B-cell receptor (BCR) and Toll-like receptor (TLR) signaling pathways, as well as genetic abnormalities and other factors. With the development of high-throughput sequencing, an increasing number of abnormal genes have been identified in DLBCL. Among them, the tumor protein p53 (TP53/p53) gene is important in DLBCL occurrence. Patients with DLBCL carrying TP53 gene abnormalities generally have poor prognosis and studies of p53 have potential to provide a better basis for their treatment. Normally, p53 is maintained at low levels through its interaction with murine double minute 2 (MDM2), and prevents tumorigenesis by mediating cell cycle arrest, apoptosis, and repair of damaged cells, among other processes. Therefore, the prognosis of patients with DLBCL harboring TP53 gene abnormalities (mutations, deletions, etc.) is poor, and targeting p53 for tumor therapy has become a research hotspot, following developments in molecular biology technologies. Current treatments targeting p53 mainly act by restoring the function or promoting degradation of mutant p53, and enhancing wild-type p53 protein stability and activity. Based on the current status of p53 research, exploration of existing therapeutic methods to improve the prognosis of patients with DLBCL with TP53 abnormalities is warranted.

Role of cerium oxide nanoparticles in doxorubicin-induced cardiotoxicity and its effect on P53 gene expression / 中国现代医生

@#Objective To study the effect of nano-ceria on doxorubicin-induced cardiotoxic injury and its effect on P53 gene expression,and to explore the mechanism of nano-ceria on doxorubicin-induced cardiotoxic injury.Methods H9C2 myocardial cells were cultured and randomly divided into five groups:control group,model group(1μmol/L adriamycin),nano-cerium oxide group(10μg/ml nano-cerium oxide),experimental group(1μmol/L adriamycin +10μg/ml nano-cerium oxide),and positive control group(1μmol/L adriamycin+10μmol/L dexperimine).The adriamycin induced cardiotoxicity model was established,and the viability of myocardial cells was measured by CCK-8 method.The contents of lactate dehydrogenase(LDH)and malondialdehyde(MDA)in myocardial cells were detected by biochemical method.The levels of reactive oxygen(ROS)and the apoptosis rate in myocardial cells were detected by flow cytometry.The expressions of Bax,Bcl-2 and P53 proteins in myocardial cells were detected by Western blot.Results Compared with the control group,the cell viability was decreased in the model group,the cell LDH and MDA contents were increased,the intracellular ROS level and apoptosis rate were increased,the expressions of Bax and P53 proteins were increased,and the expression of Bcl-2 protein was decreased,and the ratio of Bcl-2/Bax was decreased(all P<0.001).Compared with the model group,the experimental group showed increased cell viability,decreased cell LDH and MDA contents,decreased cell ROS content and apoptosis rate,decreased Bax and P53 protein expressions,and increased Bcl-2 protein expression,and the Bcl-2/Bax ratio was increased(all P<0.001).Conclusion Ceria nanoparticles can effectively prevent adriamycin-induced cardiotoxic injury,and its effect may be related to the down-regulation of P53 gene to inhibit cardiomyocyte apoptosis.

Basic and clinical research progress in carbon ion therapy for colorectal cancer / 中华放射肿瘤学杂志

Colorectal cancer is a common clinical malignant tumor. As the main therapeutic method of colorectal cancer, radiotherapy has a good inhibitory effect on tumor progression. In recent years, because of its good physical and biological advantages, carbon ion has shown better clinical efficacy than traditional radiotherapy in the treatment of local recurrence or distant metastasis of colorectal cancer. In this article, basic and clinical studies related to the efficacy of carbon ion therapy for the recurrence of colorectal cancer in recent years were reviewed, aiming to provide theoretical basis for preventing and reducing adverse reactions after radiotherapy and prolonging the survival of colorectal cancer patients.

Enzyme-Linked Immunosorbent Assay Detection For Malignancy Using Anti-P53 Antibodies

@#Tumour protein 53 (p53) plays an important role in the instruction of the cell cycle. In a variety of transformed cell lines, tumour protein is expressed in high amounts, and it is believed to contribute to transformation and malignancy. This research aimed to detect the anti-p53 antibodies in sera of patients with various malignant tumours and to evaluate the sensitivity and specificity of an enzyme-linked immunosorbent assay (ELISA). A case-control study was conducted on samples from 49 patients with various types of malignant tumours at Sultanah Bahiyah Hospital, Alor Setar, Kedah, Malaysia, and 32 healthy control cases with non‐malignant disease collected from Universiti Sains Malaysia clinic, Penang, Malaysia. The antibodies against p53 protein in the serum samples were analysed using the commercial ELISA kit, Calbiochem® p53- ELISAPLUS. The results showed that the rate of anti-p53 antibodies in patients with various malignant tumours was 13 out of 49 (26.5 %), compared with only 2 out of 32 (6.25%) in healthy controls (p < 0.001). The sensitivity of this kit reached 28.6% and the specificity was 93.8%. In conclusion, these results suggest that the anti-p53 antibodies can be detected in different sera of malignant tumour patients and the ELISA kit is highly specific; nevertheless, its discrimination power is not perfect because of its low sensitivity to determine the anti-p53 antibodies.

The effect of p53mut,P53wt and p16 on the expression of Smad4 in lung cancer H1299 cells / 临床外科杂志

Objective To investigate the influence of exogenous p53mut, p53wt and p16 on the expression of Smad4 in lung cancer H1299 cells. Methods Target genes (p53mut, p53wtand p16) were amplified by PCR and inserted into effective eukaryotic expression vector pIRES2-EGFP, respectively. These recombinant plasmids were transfected into H1299 cells by lipofectamine. The fluorescence microscope was employed to observe the transfected cells and the expression of EGFP. RT-PCR was used to validate the transfection efficiency. Western blot assay was used to detect the change of the Smad4 expression in H1299, Results Green fluorescence was observed under fluorescence microscope in the transfected H1299 cells at 72 hour post transfection. RT-PCR indicated that p53mut, p53wt and p16 genes were highly expressed in H1299 cell. There was no significant difference in Samd4 expression between the empty plasmid group and control group(P＞0.05). But the expression of Samd4 in p53mut transfected group was decreased(P＜0.05). On the contrary, the expression of Smad4 was increased in the p53wt transfected group and P53wt and p16 co-transfected group. Moreover, the increase was more obvious in the P53wt and p16 cotransfected group(P＜ 0.05). Conclusion P53mut gene transfection reduces the expression of Smad4 and P53wt. The co-infection of p53mut and p16 increases the expression of Smad4 in the H1299 cells. The tumor promoting effect of p53mut and the antitumor effect of p53

Significance of p53 in cervical cancer and its influence on radiosensitivity / 中华放射肿瘤学杂志

Radiotherapy is a major local treatment for cervical cancer.However, local uncontrollability due to radioresistance is still common.Therefore, the prediction of radiosensitivity is quite beneficial to develop an optimal treatment strategy for individual patients.Multiple factors could influence the radiosensitivity of cells, and p53 status is one of them.The upstream or downstream molecules of p53 could also be regulated to affect the radiosensitivity of cervical cancer.The aim of the review is to analyze the difference in p53 status between different types of cervical cancer and to discuss how p53 regulates the response to radiotherapy.

A study on the cloning and sequencing of mutation of p53 gene induced by sodium pentachlorophenate in somatic cell of zebrafish / 预防医学

Objective To explore the mutagenic effect of sodium pentachlorophenate (NaPCP) on zebrafish p53 gene coding sequence(CDS) in somatic cell.Methods The experiment was carried out using tuebingen strain of zebrafish, according to the results of acute toxicity test to determine the exposure levels in zebrafish.Zebrafish were randomly divided into blank control group and exposed groups, each containing 10 zebrafish.After exposing for 45d of NaPCP, the RNA was extracted from liver of zebra fish, and the p53 gene including a complete coding sequence of was obtained by RT-PCR.Results LC50 of NaPCP was 18.4 μg/L.Sequence analysis showed that the p53 gene CDS length of 1125bp, encoding 374 amino acids.The percent identity between the published zebrafish sequence of p53 (GI:425876786)and ours was 99.2%,with the other biological sequence of p53 existing some differences.After 45d exposure, zebrafish p53 gene of NaPCP exposure group had mutated at the concentration of 1.8 μg /L.The base substitution of GAG→AAG at codon 8,CAT→CAG at codon 148 and CAG→CAA at codon 229 were detected by PCR-directed sequencing.This may result in the Glu→Lys and His→Gln of expressed p53 protein.Conclusion NaPCP is a kind of gene mutation, which can induce the mutation of p53 gene in zebrafish somatic cells, that has the potential mutagenic risk for humans.

Impact of HPV typing and p53 expression on radiosensitivity in patients with cervical cancer / 中华放射肿瘤学杂志

Objective To investigate the association of human papilloma virus (HPV) typing and p53 expression with radiosensitivity in patients with cervical cancer.Methods A total of 80 patients with cervical cancer from 2014 to 2016 were enrolled,and among these patients,40 had stage Ⅰ B+ Ⅱ A disease and 40 had stage Ⅱ B +ⅢA disease.HPV genotype was identified and p53 expression was measured.All the patients underwent external and internal pelvic irradiation alone,and the correlation between short-term therapeutic effect and HPV typing/p53 expression was analyzed.The chi-square test or the Fisher's exact test was used for statistical analysis,and Spearman rank correlation analysis was also performed.Results The radiotherapy-insensitive (stable disease+progressive disease) group had higher p53 positive rates than the radiotherapy-sensitive (complete response+partial response) group (stage Ⅰ B+ Ⅱ:100％ vs.80.0％,P=0.044;stage Ⅱ B+ⅢA:100％ vs.90.0％,P=0.013).The expression of p53 was negatively correlated with radiosensitivity (r =-0.427,P =0.000).In the radiotherapy-insensitive group of patients with stage I B + Ⅱ and Ⅱ B +Ⅲ A,the rate of HPV multiple infections was higher than that of single subtype infection (65.0％/95.0％ vs.35.0％/5.0％,P=0.004 and 0.003),while in the radiotherapy-sensitive group,the rate of single subtype infection was higher than that of multiple infections (85.0％/60.0％ vs.15.0％/40.0％,P=0.004 and 0.003).The highest detection rate of HPV16 was 66.3％ in all patients,and the highest detection rate of HPV18 was 60.0％ in the radiotherapy-insensitive group.Conclusions High expression of p53 is associated with radioresistance in patients with cervical cancer.Patients with HPV muhiple infections have poor radiosensitivity,and HPV16 is the most common subtype in dual infection.Among patients who do not achieve remission after radiotherapy,HPV multiple infections with HPV18 as the main pathogen has the highest detection rate.

p53 gene mutations of familial breast cancer and early-onset breast cancer in part population of southern China / 中南大学学报(医学版)

Objective:To investigate the site and characteristic ofp53 gene mutations in familial or early-onset breast cancer patients in part population of southern China.Methods:A total of 150 patients with familial and early-onset breast cancer in parts population of southern China were enrolled.Genomic DNA was isolated from each peripheral blood sample,and the entire coding sequence and exon and intron splicing region of p53 gene were amplificated by PCR in the 150 patients.The mutation analysis were detected by denaturing high performance liquid chromatography (DHPLC) and confirmed by DNA sequence analysis.Results:In the 150 patients with familial and early-onset breast cancer,6 mutations including one novel pathogenic mutation 869_888 ins20 (insert mutation) and 5 previously reported pathogenic mutations (deletion mutation 643_660de118 and 4 missense mutation 91G＞A,215C＞G,537T＞G,743G＞A) were identified in p53 gene encoding region in 9 patients of breast cancer.Moreover,one same sense mutation 141G＞A in exon 4,one 16 bases deletion in intron 3,and 9 single nucleotide polymorphisms in p53 gene introns were also identified.The total mutation frequency ofp53 gene in 150 patients with familial breast cancer and early-onset breast cancer from part population of southern China was 6.00％,and the mutation frequency of familial breast cancer and early-onset breast cancer was 6.81％ and 6.25％,respectively.Conclusion:The total mutation frequency ofp53 gene in 150 patients with familial breast cancer and early-onset breast cancer from partpopulation of southern China is higher than the frequency previously reported.The pathogenicity of the novel mutations (insert mutation) 869_888ins20 will be confirmed by function analysis in the future study.The deletion mutation 643_660de118 enriches the p53 gene mutation database among Chinese population,which is probably the specific mutation of breast cancer in Chinese population.

A meta analysis of p53 gene codon72 polymorphism and onset risk of prostate cancer among Asian population / 重庆医学

Objective To systematically evaluate the relationship between p53 gene codon72 polymorphism and onset risk of prostate cancer (PCa) among Asian population by meta-analysis.Methods The databases of PubMed,Medline,Ovid,Wanfang and CNKI were retrieved for screening the case control trials on the relationship between p53 gene codon72 polymorphism and onset risk of PCa among Asian population.The obtained data were statistically analyzed by using the Stata 12.0 software,moreover the data reliability and publication bias of statistical literature were evaluated.Results The meta analysis showed that the p53 gene codon72 polymorphism had no obvious correlation with PCa onset risk in Asian population.The subgroup analysis results on the control source showed the coden72 polymorphism in P vs.A,PP vs.AA,PA+PP vs.AA models based on the hospital source subgroup could significantly decrease the Pca susceptibility among Asian population[P vs.A:OR =0.680,95 ％ CI(0.546,0.847),P=0.001;PP vs.AA:OR=0.409,95％CI(0.260,0.645),P=0.000;PA+PP vs.AA:OR=0.513,95％CI(0.350,0.749),P=0.001],whereas the codon 72 polymorphism in PA vs.AA and PA+PP vs.AA genotypes in the control source subgroup based on the common population increased the PCa onset risk among Asian population [PA vs.AA:OR=1.664,95 ％CI(1.272,2.177),P=0.000;PA+ PP vs.AA:OR =1.314,95 ％ CI(1.020,1.693),P =0.003 6].The subgroup analysis was conducted according to whether conforming to the HWE equilibrium,the results showed p53 gene codon 72 polymorphosm was a protective factor for decreasing PCasusceptibility among Asian population in the subgroup unconforming to the HWE equilibrium [PP vs.AA:OR=0.251,95％CI(0.135,0.467),P=0.000;PA+PPvs.AA:OR=0.564,95％CI=(0.330,0.964),P=0.036].Conclusion p53 gene codon72 polymorphism has no relation with PCa susceptibility among Asian population.

Association between the p53 arginine/arginine homozygous genotype at codon 72 and human papillomavirus E6/E7 mRNA expression

ABSTRACT Objective: To evaluate the association between p53 polymorphisms and human papillomavirus (HPV) E6/E7 mRNA expression. Methods: We analyzed 175 cervical samples from women aged 16-69 years old who were tested for HPV E6/E7 mRNA expression (NucliSENS® EasyQ® HPV). The samples were divided into three groups: positive (n = 75) those with positive HPV E6/E7 mRNA expression and positive high-risk HPV Hybrid Capture (HR-HC) test; negative (n = 52) those with negative HPV E6/E7 mRNA expression and positive HR-HC; and control (n = 48) those with negative HPV E6/E7 mRNA expression and negative HR-HC. The p53 polymorphisms at codons 11, 72, and 248 were evaluated through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of the arginine/arginine homozygous genotype at codon 72 was significantly higher in the positive (49.3%) than in the negative (32.7%) and control groups (20.8%, p = 0.002*). The frequency of the arginine allele was also significantly higher in the positive (67.3%) than in the negative (53.8%) and control groups (38.5%, p < 0.001*). The arginine/arginine homozygous genotype was significantly associated with positive HPV E6/E7 mRNA expression (positive group) compared with negative and control groups (odds ratio: 2.633; 95% CI, 1.399-4.954, p = 0.003). The frequency of arginine/arginine homozygous genotype at codon 72 remained significantly more frequent in the positive group of women aged ≥30 years than in the other two groups. Conclusion: The presence of the p53 arginine/arginine homozygous genotype at codon 72 was significantly associated with the positive HPV E6/E7 mRNA expression.

Possible mechanism and significance of rare p53 mutation in Epstein-Barr virus-associated gastric cancer / 中国肿瘤临床

In 2014, The Cancer Genome Atlas firstly classified gastric cancer into four types according to genotype. Epstein-Barr virus (EBV) positive gastric cancer or EBV-associated gastric cancer (EBVaGC) is attracting attention because it is a possibly suitable group for immunotherapy. Among the mutations observed in tumors, such as gastric cancer, p53 mutations are the most frequent. In particular, it occurs more frequently in EBVaGC than in EBV-negative gastric cancer (EBVnGC). Meanwhile, EBV infection is considered as an early event of tumorigenesis. The interactions between wild-type p53 proteins and BZLF1 (Z) proteins are essential in maintaining the latent state of EBV infection and promoting early replication. In the latter stages of replication, wild-type p53 proteins are degraded through the ubiquitination of some viral molecules. These findings may indicate the importance of wild-type p53 genes in EBVaGC formation. Inflammatory responses induced by EBV infection, tumor with a large number of lymphocyte infiltration, genome high mutation, and PD-L1 amplification make it possible to become the appropriate group of immunotherapy, which also illustrate that the important role of immune microenvironment during tumor progression. In EBVnGC, extremely high levels of p53 mutation were observed because of several associated factors, and the p53 protein encoded by the mutant p53 gene lost its antitumor function after tumorigenesis. In this review, the possible mechanisms of rare p53 mutation in EBVaGC are summarized.

Inhibitory Effects of Typhonium Giganteum Soft Capsules on Transplantation Tumor and Expression of p53 Gene in Human Liver Cancer Hep-2 Tumor-bearing Nude Mice / 中国中医药信息杂志

Objective To observe the inhibitory effects of Typhonium Giganteum soft capsules on tumor growth in Hep-2 tumor-bearing nude mice and its effects on the expression of tumor suppressor p53 gene; To discuss its mechanism of action.Methods Human liver cancer Hep-2 cell suspension back subcutaneous vaccination was conducted to prepare tumor models. BALB/c nude mice were randomly divided into model group, cisplatinum group, and TCM high-, medium-, and low-dose groups. Each group was given relevant medicine for gavage, once a day for 21 days. Growth changes of tumor volume were monitored; HE staining was used to observe pathological changes of tumor tissues; RT-PCR was used to detect the expression of p53 gene in tumor tissue of Hep-2 nude mice.Results Compared with the model group, all medication groups could inhibit the tumor growth, and the anti-tumor rates were 55.1%, 42.8%, 30.1%, and 79.5%, respectively; the expression of p53 gene increased; pathological observation results showed that the number and the volume of tumor cells increased, with cytoplasm rarefaction and nucleus anachromasis. All medication groups had karyopyknosis, slight staining, and decreasing blood capillary and focal necrosis in varying degrees.ConclusionTyphonium Giganteum soft capsules can inhibit the growth of human liver cancer, and its mechanism may be associated with the up-regulating expression of p53 gene leading to apoptosis.

Airway epithelial cell-derived insulin-like growth factor-1 triggers skewed CD8 +T cell polarization / 中国药理学通报

Aim To investigate the effects of airway epithelial cell-derived insulin-like growth factor-1 (IGF1) on CD8 +T cell polarization. Methods Hu-man airway epithelial cell line, RPMI2650 cells, was cultured in the presence of a mice allergen, Der p1, for 72 h. IGF1 expression was checked with quantita-tive RT-PCR and Western blot. Der p1-primed RP-MI2650 cells, recombinant IGF1 and anti-IGF1 anti-body was cocultured respectively with CD8 + T cells, which were activated by anti-CD3/CD8 Ab. Apoptotic cells frequency was calculated with flow cytometry. The alteration of p53 gene hypermethylation in CD8 + T cells elicited by Der p1-primed airway epithelial cell and IGF1 was plotted. Results Both mRNA(23. 1%± 5. 2% vs 5. 2% ± 2. 3%, P < 0. 01 ) and protein (33. 4 ± 6. 4 vs 9. 2 ± 4. 6, P <0. 01 ) expression of IGF1 in RPMI2650 cells markedly increased after ex-posure to Der p1 . The increase of apoptotic CD3/CD28 Ab-activated CD8 + T cells was abolished by the pres-ence of Derp1-primed epithelial cells ( 41. 7% ± 8. 2%vs 5. 2% ± 1. 8%, P <0. 01 ) . The results were con-firmed by the addition of recombinant IGF1 . Anti-IGF1 antibody abolished the effect of the epithelial cells. Derp1-primed epithelial cells inhibited p53 gene mR-NA( 29. 1% ± 5. 9% vs 16. 2% ± 4. 3%, P <0. 01 ) and protein ( 63. 3 ± 8. 9 vs 26. 9 ± 5. 6 , P <0. 01 ) ex-pression. Anti-IGF1 antibody abolished the effect. Re-combinant IGF1 promoted CD8 + T cells′p53 gene hy-permethylation. Conclusion Der p1 induces RP-MI2650 cells to produce IGF1 , and this factor prevents CD8 + T cell apoptosis by inducing p53 gene hyperm-ethylation.

Correlation between RAR-βgene methylation and p53 gene mutation in bronchoalveolar lavage fluid in non-small-cell lung cancer / 重庆医学

Objective To investigate the clinical significance and correlation between RAR-βgene methylation and p53 gene mutation in bronchoalveolar lavage fluid(BALF)in non-small-cell lung cancer.Methods BALF samples from 85 lung cancer pa-tients(lung cancer group)and 70 cases(benign lung diseases group)with benign lung diseases were collected.RAR-βgene methyla-tion in BALF samples was detected by methylation-specific PCR (MSP),and p53 gene mutation was detected by PCR and DNA se-quencing method.Results The rate of RAR-βmethylation and p53 mutation in BALF in lung cancer were 49.4% and 36.5%,re-spectively.Both were higher than in benign lung diseases group(P <0.01).RAR-βmethylation rate(32.5%)of patients with TNM stages(Ⅰ+Ⅱ)(32.5%)was higher than the p53 mutation rate(12.5%)over the same stages (P <0.05).RAR-βmethylation rate and p53 mutation rate of patients with stages(Ⅲ+Ⅳ)were higher than those with stages(Ⅰ+Ⅱ)(P <0.01).p53 mutation rate in lung cancer patients with RAR-βmethylation was higher than those with unmethylated(P <0.01).RAR-βmethylation rate of lung cancer patients with p53 mutation was higher than those without p53 mutation(P <0.01).Conclusion Detection of RAR-βmethyl-ation and p53 mutation in BALF contribute to the diagnosis of lung cancer.