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

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.

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 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.

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.

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.

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.

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.

Recombined adenovirus expressing P53 in the treatment of malignant pleural effusion with lung cancer / 局解手术学杂志

Objective To assess the therapeutic efficacy of a recombined adenovirus expressing p53 (rAd-p53) via intrapleural injec-tion in the treatment of lung cancer with malignant pleural effusion. Methods Thirty-six cases with lung cancer and malignant pleural effu-sion were randomly divided into two groups,which were given intravenous injection of Nedaplatin with (observation group,n=20) or without (control group,n=16) intrapleural injection of rAd-p53,respectively. Between the two groups,the efficacy in treatment of pleural effusion, the amelioration of maximal ventilatory volume ( MVV) ,Kamofsky scoring ( KPS) and quality of life were compared. Results The efficacy in treatment of pleural effusion in observation group are significantly higher than that in control group(17/20 vs. 50%,P<0. 05). The cases with KPS≥80 in observation group were significantly increased following treatment (5/20 vs. 11/20,P <0. 05). However,there was no difference with the cases in control group. Conclusion Intrapleural injection of recombinant adenovirus expressing p53 (rAd-p53) is effec-tive to reduce the occurrence of malignant pleural effusion and increase the quality of life remarkably.

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.

Rhesus monkey P53 gene silencing at the cellular level / 中国比较医学杂志

Objective In order to establish a rhesus monkey model of p53 gene silencing, firstly we screened and determined the effective silencing targets of p53 gene at the cellular level in rhesus monkey.Methods The expression of p53 gene was detected in COS-7 cells ( derived from the kidney of the African Green Monkey, Cercopithecus aethiops).Three small hairpin RNA ( shRNA) sequences targeting rhesus monkey p53 gene were designed, analysed by bioinformatics, and inserted into lentivirus-based gene silencing constructs FUGW-TDT.The plasmids of p53-RNAi and control vector were transfected into the COS-7 cells, respectively.The suppression of p53 mRNA was detected by real-time PCR, and the changes of p53 protein expression were detected by Western blot assay.Results p53 gene expression was detected in COS-7 cells.Bioinformatics analysis showed that three gene-silencing sequences were screened which lied in the open reading frame ( ORF) region and targeted 238 -258bp, 681 -701bp, 169 -189bp of the rhesus monkey p53 mRNA.At 48 hrs after transfection of the three silencing constructs, p53 mRNA was suppressed by(87.17 ±4.03)%, ( 72.62 ±4.11)% and(76.22 ±0.98 )%, and p53 protein was suppressed by ( 84.44 ±2.18 )%, ( 71.04 ±1.18)% and ( 74.17 ±0.95 )%, respectively. Conclusions We obtained three effective target sequences showing high efficiency in p53silencing, which can be used in further studies on gene silencing in rhesus monkey.

Combination effect of radiation and p53 gene regulated by a radiation-enhanced promoter on tumor cells / 中华放射医学与防护杂志

Objective To study the specific killing effect in human carcinoma cells aftercombination treatment of radiation and p53 gene regulated by a radiation-enhanced promoter.Methods Aplasmid pE6 (TATA)-p53 was constructed.After irradiation,the expression of P53 was detected withWestern blot assay,apoptosis was detected by Annexin V-FITC,and cell survival was detected byclonogenic assay then the sensitivity enhancement ratio (SER) was analyzed for HeLa and A549 cells.Results The expression of P53 were increased in the irradiated cells and 6 Gy irradiation triggered thestrongest activity.After p53 transfection,radiation-induced apoptosis was obviously enhanced incomparison with the control group without gene transfection (F =11.018,10.736,P ＜ 0.05).The SER ofp53-promoter was 2.36 for A549 cells and 2.56 for Hela cells.Conclusions The p53-plasmid promotercould induce apoptosis and enhance the radiosensitivity of tumor cells,which may provide a noveltherapeutic strategy for cancer treatment.

Research progress on drugs targeting p53 / 中国药理学通报

With the understanding of the development and pro-gress of the cancer,the research of targeted cancer drug devel-opment reaches into a new era.p53 is an important tumor sup-pressor gene,the protein coded by p53 plays a critical role in tumor suppression mainly by inducing cell cycle regulation, DNA repair and apoptosis.Nowadays,p53 becomes a relatively attractive target for anti-cancer drug development and there are some drugs targeting p53,moreover,APR-246 which targets mutant p53 is in Phase II clinical trial.In addition,it facilitates drugs discovery programmes in the challenging area of protein-protein interactions and mutant protein conformational change. The review discusses the research progress of drugs which target p53 and elucidates the characteristics and mechanisms of these compounds.

Clinical significance of bcl-6, p53, c-myc aberrations in diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective To investigate aberrations of bcl-6,p53,c-myc genes in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods Interphase fluorescence in situ hybridization (I-FISH) was detected in 59 DLBCL patients in vivo tissue bcl-6,p53 protein,c-myc gene status.The patients were treated with CHOP or R-CHOP chemotheralpy,and the survival rates and treatment efficiency were compared.Results The p53 deletion was detected in 18 of the 59 cases (30.5 ％),bcl-6 rearrangement in 11 cases (18.6 ％),5 cases with c-myc rearrangement (8.5 ％).In the aspects of remission rate,p53 deletion positive group contained less advantage than negative ones (33.3 ％ vs 75.6 ％,x2 =9.560,P =0.002).The prognosis of bcl-6 gene rearrangement positive group different from negative group,but the difference was not statistically significant (OS,P =0.107; PFS,P =0.094),p53 deletion positive patients was in significantly worse prognosis than the negative group (OS,P =0.031; PFS,P =0.028),c-myc rearrangement positive group difference in gene rearrangement negative group,but the difference was not statistically significant (OS,P =0.163; PFS,P =0.167).In the CHOP group,prognosis of p53 deletion,c-myc rearrangement positive group were significantly worse than the negative group,the difference was statistically significant (P ＜ 0.05).In R-CHOP group,the prognostic significance of bcl-6 gene rearrangement positive group were worse (OS,P =0.003; PFS,P =0.007).Conclusion DLBCL patients with bcl-6,p53,c-myc genes aberrations are related with poor prognosis,and they can be used as prognostic factors for predicting DLBCL and guiding therapy.

Studies on p53 in induced pluripotent stem cells / 中国组织工程研究

BACKGROUND:Induced pluripotent stem cel s can bypass the ethical issues of embryonic stem cel s, and become the hotspot of stem cel research. OBJECTIVE:To explore the research progress and problems of induced pluripotent stem cel s. METHODS:A retrospective analysis on the findings, research progress and problems of induced pluripotent stem cel s in recent years was performed. The Thomson Reuters Web of Science was searched for the articles related to the induced pluripotent stem cel s and p53 gene. RESULTS AND CONCLUSION:In recent years, domestic and foreign scholars have conducted a lot of researches on induced pluripotent stem cel s. For example, a Japanese group is establishing the stem cel bank to provide a basis for the treatment of retinal diseases. However, the safety issues of induced pluripotent stem cel s need to be solved before routine cel treatment application, in which the functional research of related p53 gene is one of the essential concerns. The other member of p53 gene, p73 gene, also participates in the generation and differentiation of induced pluripotent stem cel s, and the in-depth studies are needed. The finding of p53 gene function wil promote the in-depth development of regenerative medicine and translational medicine.

Cancer cells with p53 deletion detected by fluorescent in situ hybridization in peritoneal drainage fluid is correlated with early peritoneal seeding in resectable pancreatic cancer / 대한외과학회지

PURPOSE: Free tumor cells in peritoneal fluid in patients with pancreatic cancer may have prognostic significance but there are few reports on methods for the effective detection of free tumor cells. The aims of this study were to identify free cancer cells in peritoneal fluid with fluorescent in situ hybridization (FISH) technique and to investigate its prognostic significance. METHODS: Twenty-eight patients with resectable pancreatic cancer who underwent surgical resection were included. Peritoneal washing and peritoneal drainage fluid were examined by FISH for p53 deletion. RESULTS: Among the study subjects, the R0 resection rate was 75%. None of the patients had positive cytology with Papanicolaou's method. p53 deletion was detected in 9 peritoneal washings (32.1%) and in 5 peritoneal drainage fluids (17.9%). After a median of 18 months of follow-up, 25 patients (89.3%) experienced recurrence and 14 patients (50.0%) had peritoneal seeding. Patients with p53 deletion detected in the peritoneal drainage fluid had positive radial margin (60.0% vs. 17.4%, P = 0.046) more frequently and a lower peritoneal metastasis free survival (median, 11.1 months vs. 30.3 months; P = 0.030). Curative resection (P < 0.001) and p53 deletion in peritoneal drainage fluid (P = 0.030) were independent risk factors of peritoneal metastasis free survival after multivariate analysis. CONCLUSION: FISH technique detects free cancer cells with higher sensitivity compared to Papanicolaou's method. p53 deletion detected in peritoneal drainage fluid is correlated with positive radial resection margin and results in early peritoneal seeding. Patients with p53 deletion in peritoneal drainage fluid need more aggressive adjuvant treatment.

Characterization and Prognostic Value of Mutations in Exons 5 and 6 of the p53 Gene in Patients with Colorectal Cancers in Central Iran

BACKGROUND/AIMS: We aimed to investigate the relation-ships among various mutations of the p53 gene and their protein products, histological characteristics, and disease prognosis of primary colorectal cancer in Isfahan, central Iran. METHODS: Sixty-one patients with colorectal adenocarcinoma were enrolled in the study. Mutations of the p53 gene were detected by single-stranded conformation polymorphism and DNA sequencing. The protein stability was evaluated by immunohistochemistry. Patients were followed up to 48 months. RESULTS: Twenty-one point mutations in exons 5 and 6 were detected in the tumor specimens of 14 patients (23%). Of those, 81% and 9.5% were missense and nonsense mutations, respectively. There were also two novel mutations in the intronic region between exons 5 and 6. In 11 mutated specimens, protein stability and protein accumulation were identified. There was a relationship between the type of mutation and protein accumulation in exons 5 and 6 of the p53 gene. The presence of the mutation was associated with an advanced stage of cancer (trend, p<0.009). Patients with mutated p53 genes had significantly lower survival rates than those with wild type p53 genes (p<0.01). CONCLUSIONS: Mutations in exons 5 and 6 of the p53 gene are common genetic alterations in colorectal adenocarcinoma in central Iran and are associated with a poor prognosis of the disease.