Autopsy findings of acute erythroid leukemia

ABSTRACT Acute erythroid leukemia (AEL) is an exceedingly uncommon but distinct hematological malignancy that shows neoplastic proliferation of erythroid precursors with maturation arrest and no significant myeloblasts. We describe an autopsy case of this rare entity in a 62-year-old man with co-morbidities. He underwent a bone marrow (BM) examination for pancytopenia during the first outpatient department visit, which revealed an increased number of erythroid precursors with dysmegakaryopoiesis suggesting the possibility of Myelodysplastic syndromes (MDS). Thereafter, his cytopenia got worsened, warranting blood and platelet transfusions. Four weeks later on the second BM examination, AEL was diagnosed based on morphology and immunophenotyping. Targeted resequencing for myeloid mutations revealed TP53 and DNMT3A mutations. He was initially managed along febrile neutropenia with the stepwise escalation of antibiotics. He developed hypoxia attributed to anemic heart failure. Subsequently, he had hypotension and respiratory fatigue pre-terminally and succumbed to his Illness. A complete autopsy showed infiltration of various organs by AEL and leukostasis. Besides, there was extramedullary hematopoiesis, arterionephrosclerosis, diabetic nephropathy (ISN-RPS class II), mixed dust pneumoconiosis, and pulmonary arteriopathy. The histomorphology of AEL was challenging, and the differential diagnoses were many. Thus, this case highlights the autopsy pathology of AEL, an uncommon entity with a strict definition, and its relevant differentials.

Expressions of survivin, p53 and human epidermal growth factor receptor 2 in breast cancer tissues and their prognostic value / 肿瘤研究与临床

Objective:To investigate the expressions of apoptosis-related factors survivin, p53 and human epidermal growth factor receptor 2 (HER2) in breast cancer tissues and their prognostic value.Methods:A total of 131 patients undergoing radical mastectomy for breast cancer who were admitted to Tangshan Maternal and Child Health Care Hospital from February 2015 to January 2019 were selected as the research subjects. During the operation, the cancer tissues and adjacent tissues (normal tissues >3 cm from the tumor margin) were collected from the patients. Expressions of survivin, p53 and HER2 in cancer tissues and adjacent tissues of patients were detected by using immunohistochemistry. The prognoses of patients were recorded after the follow-up for 3 years; the recurrence, metastasis and death treated as the poor prognosis, the rest prognoses of patients were treated as the good prognosis group. The difference of clinicopathological characteristics between the poor prognosis group and the good prognosis group was compared. Multivariate logistic regression was used to analyze risk factors for prognosis of breast cancer patients. The result of prognosis of breast cancer was taken as the golden standard. The receiver operating characteristic (ROC) curve was used to analyze the value of survivin pasitive, p53 pasitive, HER2 pasitive alone, the combination of both and the combination of the there in the judgement of poor prognosis of breast cancer.Results:The positive expression rates of survivin [49.6% (65/131) vs. 7.6% (10/131)], p53 [60.3% (79/131) vs. 13.0% (17/131)] and HER2 [79.4% (104/131) vs. 16.8% (22/131)] in cancer tissues were higher than those in adjacent tissues (all P<0.001). A total of 131 breast cancer patients were followed up for 3 years without any loss of follow-up, and the follow-up rate was 100%. Within the follow-up for 3 years, there were 15 (11.5%) cases of recurrence, 8 (6.1%) cases of metastasis, and 10 (7.6%) cases of death, the incidence of poor prognosis was 25.2% (33/131); and the remaining 98 cases had good prognosis. The proportions of patients with TNM stage Ⅲ, lymph node metastasis, poorly differentiated histology, tumor diameter ≥3 cm, survivin, p53, and HER2 positive expressions in the poor prognosis group were higher than those in the good prognosis group (all P<0.05). Multivariate logistic regression analysis showed that TNM stage Ⅲ [ OR = 5.323 (95% CI 2.190-12.936)], lymph node metastasis [ OR = 4.773 (95% CI 1.964-11.600)], tumor diameter ≥3 cm [ OR = 3.582(95% CI 1.474-8.706)], positive survivin [ OR = 2.740 (95% CI 1.127-6.659)], positive p53 [ OR = 3.271 (95% CI 1.346-7.949)], and positive HER2 [ OR = 3.873 (95% CI 1.594-9.412)] were independent risk factors for prognosis of breast cancer (all P<0.001). The ROC curve results showed that the area under the curve (AUC) values of survivin positive, p53 positive,HER2 positive, and the combination of any two were more than 0.80 (all P<0.001); the AUC of the combination of the three was 0.944 (95% CI 0.890-0.977) ( P<0.001). Conclusions:The expressions of survivin, p53, and HER2 are highly expressed in breast cancer tissues. The expressions of the three can be used to judge the prognosis of breast cancer patients, and the combination of the three has a higher judgement value.

Research progress of p53 protein in the development mechanism of triple negative breast cancer / 中国医师杂志

Tumor suppressor gene p53 plays an important role in regulating cell cycle, controlling apoptosis and repairing damaged DNA. Mutation of this gene is closely related to the occurrence, development and drug resistance of various tumors. The mutant p53 protein is closely related to the growth and metastasis of triple negative breast cancer (TNBC) with higher malignancy and higher risk of metastasis. This paper expounds the mechanism of p53 protein participating in the occurrence, development and metastasis of TNBC, introduces the effect of interfering with mouse dual-microbody gene 2 (MDM2), activated T cell nuclear factor 1 (NFAT1) and other proteins on p53, as well as small molecular targeted drugs closely related to p53 protein, and provides a new direction and theoretical basis for targeted treatment of TNBC.

The mechanism of p53 signaling pathway regulating ferroptosis in hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is the most common type of liver cancer in China, and the development and progression of HCC is a complex pathological process. As a new way of cell death, ferroptosis has huge potential in the treatment of HCC. This article introduces the mechanism of action of the tumor suppressor p53 in regulating ferroptosis and briefly describes its role in the development and progression of HCC. The tumor suppressor p53 can promote or inhibit ferroptosis by affecting solute carrier family 7 member 11, spermidine/spermine N1-acety-ltransferase 1, glutaminase 2, dipeptidyl peptidase 4, and cyclin-dependent kinase inhibitor 1A, which in turn affects the progression of HCC. The treatment of HCC by regulating the ferroptosis pathway has great application prospects.

USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.

DNA damage-related proteins in smokers and non-smokers with oral cancer

Abstract: Tobacco smoking involves a high risk of human malignancies, including oral cancer, because it contains multiple carcinogens that cause genetic instability. Thus, a worse prognosis would be expected for cancer patients who are smokers. The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), H2A histone family member X (H2AX), and P53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). Associations between immunoexpression of proteins and clinicopathological data and histopathological grading were also analyzed. A total of 35 individuals (18 non-smokers and 17 smokers) with OSCC of the tongue and/or floor of the mouth were included. Immunohistochemistry for H2AX was conducted for the identification of double-strand breaks, CHK2, and P53 to evaluate the expression of this protein in cell cycle regulation. The sample consisted of 22 males and 13 females, with a mean age of 63.9±11.8 years. OSCC of non-smokers were well-differentiated tumors in 50% of the cases, and those of smokers were equally distributed into moderately differentiated and poorly differentiated tumors (35.3% each). Overall, 31 (88.6%) cases were CHK2-positive, 27 (77.1%) were H2AX-positive, and 23 (65.7%) were P53-positive, with no difference between smokers and non-smokers (p > 0.05). No association was found between proteins and clinicopathologic data (p > 0.05). Similarities in CHK2, H2AX, and P53 immunohistochemical staining patterns were observed between smokers and non-smokers, and immunoexpression was not associated with clinicopathological parameters. However, the findings indicated consistent expression of these proteins in OSCC.

Evaluation of a new detection method for microsatellite instability and its relationship with the expression of human epidermal growth factor receptor 2 and P53 in gastric cancer tissues / 中华老年医学杂志

Objective:To investigate the expression of human epidermal growth factor receptor 2(HER2)and P53 and their relationship with microsatellite instability(MSI)in gastric cancer tissues.Methods:A total of 103 patients diagnosed with gastric cancer between January 2018 and October 2020 at Yueyang Hospital were enrolled in this study.HER2, P53 and mismatch repair proteins in gastric cancer tissues were detected with immunohistochemical(IHC)methods, and MSI screening was conducted at 7 sites with a new Idylla MSI(multiple fluorescent PCR)method.Results:Of 103 gastric cancer patients in this study, 77(74.8%)showed microsatellite stability(MSS)and 26(25.2%)showed MIS via IHC, and PCR also detected 77 MSS cases and 26 MSI cases.In MSI, there was more low HER2 expression than high HER2 expression, and the rate of low HER2 expression in MSI was higher than the rate of high HER2 expression in MSI( P<0.05).Also in MSI, there was more low P53 expression than high P53 expression, and the rate of low P53 expression in MSI was higher than the rate of high expression in MSI( P<0.05). Conclusions:MSS may exist in the process of gastric carcinogenesis and in gastric cancer it may be accompanied by low expression of HER2 and p53 in cancer tissues.There may be a mutually exclusive relationship between MSI and expressions of HER2 and p53, suggesting that carcinogenic mechanisms involving MSI may be very different from those involving HER2 and p53.MSI detection is very valuable in guiding treatment drug selection and prognosis assessment.

p53 & Cyclin D1 expression in surgically resected clear margins of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most well-known malignancies that affect the human population worldwide. The early diagnosis and early intervention of OSCC help improve the survival rate of the patients. The tumour free surgical margins are a positive prognostic factor for recurrence-free survival. The molecular markers can be used to detect the tumour free surgical margins. Aim: The aim of the study is to evaluate the expression of p53 & Cyclin D1 marker in resected surgical apparently clear margins and to correlate the p53 & Cyclin D1 expression with clinicopathological characteristics and patient outcome. Methods: The study population included retrospective cases of OSCC with apparently clear margins (2017-18) n=10 and Clinicopathological variables relevant to survival analysis were recorded. Finally, two margins were selected from each case, a total of 20 margins were included in this study. Paraffin-embedded wax blocks retrieved and tissue sections were made. Expression of cyclin D1 and p 53 was assessed by the immunohistochemical staining procedure Results: Positive expressions Cyclin D1 in 40% of mild dysplasia margins and 60% in clearance adequate margins were present. p53 expression was seen in 16% of mild dysplasia margins and 84% in clearance adequate margins. The expression of p53 and Cyclin D1 molecular markers are noted in the basal & parabasal layer of epithelium. Conclusion: Molecular markers could play a more reliable method for the assessment of dysplasia at the margins

Research progress on HPV-positive oropharyngeal carcinoma sensitive to radiation therapy / 口腔疾病防治

@#Oropharyngeal carcinoma is a highly heterogeneous disease that is mainly caused by tobacco and alcohol abuse or high-risk human papillomavirus (HPV) infection. HPV-positive oropharyngeal carcinoma and HPV-negative oropharyngeal carcinoma have obvious differences in etiology, epidemiology and prognosis; therefore, different methods should be adopted for treatment. It is known that the TP53 gene is not mutated in HPV-positive oropharyngeal carcinoma, and radiation therapy can activate it and induce cell apoptosis via DNA damage. There are common repair pathways to DNA damage, such as nonhomologous end joining, and this pathway is more sensitive to radiotherapy under the inhibition of HPV oncoprotein. In addition, the further activation of the immune response under the effect of radiation also participates in the elimination of tumors. In this paper, we reviewed the research on the sensitivity of HPV-positive oropharyngeal cancer to radiotherapy to provide a scientific basis for targeted treatment for various pathogenic factors and clinical stages of oropharyngeal cancer in the future.

Could the intestinal epithelial alterations promoted by roux-en-y gastric bypass explain higher tendency for colonic diseases in bariatric patients? / As alterações epiteliais intestinais promovidas pelo bypass em y-de-roux podem explicar maior tendência a doenças colônicas em pacientes bariátricos?

ABSTRACT Background: Intestinal diversions have revolutionized the treatment of morbid obesity due to its viability and sustained response. However, experimental studies suggest, after these derivations, a higher risk of colon cancer. Aim: To analyze the histological and immunohistological changes that the jejunojejunal shunt can produce in the jejunum, ileum and ascending colon. Method: Twenty-four male Wistar rats were randomly divided into two groups, control (n=12) and experiment (n=12) and subdivided into groups of four. Nine weeks after the jejunojejunal shunt, segmental resection of the excluded jejunum, terminal ileum and ascending colon was performed. Histological analysis focused on the thickness of the mucosa, height of the villi, depth of the crypts and immunohistochemistry in the expression of Ki-67 and p53. Results: Significant differences were found between the experiment and control groups in relation to the thickness of the mucosa in the jejunum (p=0.011), in the ileum (p<0.001) and in the colon (p=0.027). There was also a significant difference in relation to the height of the villus in the ileum (p<0.001) and the depth of the crypts in the jejunum (p0.001). The results indicated that there is a significant difference between the groups regarding the expression of Ki-67 in the colon (p<0.001). No significant differences were found between the groups regarding the expression of Ki-67 in the jejunum and ileum. In the P53 evaluation, negative nuclear staining was found in all cases. Conclusion: The jejunojejunal deviation performed in the Roux-in-Y gastrojejunal bypass, predispose epithelial proliferative effects, causing an increase in the thickness of the mucosa, height of the villi and depth of the crypts of the jejunum, ileum and ascending colon.

RESUMO Racional: As derivações intestinais revolucionaram o tratamento da obesidade mórbida pela sua viabilidade e resposta sustentada. Porém, estudos experimentais sugerem, após estas derivações, risco maior de câncer de cólon. Objetivo: Analisar as alterações histológicas e imunoistológicas que a derivação jejunojejunal possa produzir no jejuno, íleo e cólon ascendente. Método: Foram utilizados 24 ratos Wistar machos randomicamente divididos em dois grupos, controle (n=12) e experimento (n=12) e subdivididos em grupos de quatro. Nove semanas após a derivação jejunojejunal procedeu-se a ressecção segmentar do jejuno excluso, íleo terminal e cólon ascendente. Análise histológica focou na espessura da mucosa, altura dos vilos, profundidade das criptas e a imunoistoquímica na expressão do Ki-67 e p53. Resultados: Foram encontradas diferenças significativas entre os grupos experimento e controle em relação à espessura da mucosa no jejuno (p=0,011), no íleo (p<0,001) e no cólon (p=0,027). Também houve diferença significativa em relação à altura dos vilos no íleo (p<0,001) e profundidade das criptas no jejuno (p<0,001). Os resultados indicaram que existe diferença significativa entre os grupos em relação à expressão do Ki-67 no cólon (p<0,001). Não foram encontradas diferenças significativas entre os grupos em relação à expressão do Ki-67 no jejuno e no íleo. Na avaliação do P53, foi encontrada coloração nuclear negativa em todos os casos. Conclusão: O desvio realizado na derivação gastrojejunal em Y-de-Roux, predispõem efeitos proliferativos epiteliais, causando aumento da espessura da mucosa, altura dos vilos e profundidade das criptas do jejuno, íleo e cólon ascendente.

Value of combined determination of hepatitis C virus genotype, AFP-L3, and P53 antibody in the diagnosis of hepatitis C virus-related hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate the value of combined determination of hepatitis C virus (HCV) genotype, the alpha-fetoprotein variant AFP-L3, and P53 antibody in HCV-related hepatocellular carcinoma (HCV-HCC). MethodsA total of 84 patients with HCV-HCC who were diagnosed in our hospital from January 2016 to December 2019 were enrolled as HCV-HCC group, and 84 patients with benign liver diseases (hepatitis C and HCV liver cirrhosis) were enrolled as control group. The PCR-reverse dot blot hybridization technique was used to determine HCV genotype, ELISA was used to measure P53 antibody, and electrochemical luminescence was used to measure AFP-L3. The t-test and the Kruskal-Wallis H test were used for comparison between two groups; the chi-square test was used for comparison of categorical data between two groups. The logistic regression analysis and the receiver operating characteristic (ROC) curve were used to compare the value of each index in the diagnosis of HCV-HCC. ResultsCompared with the control group, the HCV-HCC group had a significantly higher proportion of patients with HCV 1b genotype or AFP-L3 and a significantly higher level of P53 antibody (χ2=5714, Z=-9.27, Z=-9.92, all P＜0.05). The logistic regression analysis showed that HCV genotype, AFP-L3, and P53 antibody had significant effects on HCV-HCC (all P＜0.05). The above indices were fitted to establish a model of Logit(Y)=-3.881+0031XAFP-L3(%)+0.043XP53+1218XHCV genotype, in which Y was the positive probability value of combined determination. In the screening of HCV-HCC, Y had a significantly larger area under the ROC curve than HCV genotype (0.945 vs 0.758, Z=6.17, P＜0001), AFP-L3 (0.945 vs 0.863, Z=3.97, P＜0.001), and P53 antibody (0.945 vs 0.887, Z=3.07, P=0.002). Y had higher AUC (0.945), sensitivity (90.90%), specificity (94.00%), positive predictive value (93.80%), negative predictive value (9116%), and diagnostic accuracy (92.44%) than each index alone. ConclusionHCV 1b genotype, AFP-L3, and P53 antibody level are associated with the risk of HCV-HCC, and the combined determination of the three indices has important clinical significance in the early diagnosis of HCV-HCC.

Effect of moxibustion on cardiac function and expression of autophagy-related proteins of cardiomyocytes in chronic heart failure rats / 针刺研究

OBJECTIVE: To observe the effect of moxibustion on cardiac function and expression of myocardial tumor suppressor protein p53, mammalian target of rapamycin (mTOR) and phosphorylated(p)-mTOR (excessive autophagy-associated proteins of cardiomyocytes) in rats with chronic heart failure (CHF), so as to explore its mechanisms underlying improvement of CHF. METHODS: SD rats were divided into blank control (n＝11), model(n＝8), autophagy activator (n＝8), autophagy inhibitor (n＝9) and moxibustion(n＝9) groups. The CHF model was established by i．p. injection of Doxorubicin Hydrochloride (DOX, 1 mg/mL, 1-4 mg/kg) every other day. Moxibustion was applied to bilateral "Feishu" (BL13) and "Xinshu" (BL15) for 20 min, 5 times a week for 3 weeks. Rats of the autophagy activator group received gavage of Rapamycin (RAPA, 2 mg/kg) and those of the autophagy inhibitor group received i．p. injection of Methyladenine (3-MA, 15 mg/kg) 5 times a week for 3 weeks after successful modeling. The heart weight and body weight were measured to calculate heart mass index (HW/BW＝heart weight ÷ body weight). Cardiac output (CO) and heart rate (HR) were measured by using a cardiac function meter. Serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) content was assayed by using ELISA, and the expression of myocardial p53, p-mTOR and mTOR proteins was examined by Western blot. RESULTS: (1) Compared with the blank control group, the HR, HW/BW, NT-pro BNP content and p53 expression levels were significantly increased (P<0.01), and the CO and ratio of p-mTOR/mTOR were significantly decreased in the model group (P<0.01). (2) Compared with the model group, the HR, HW/BW and NT-pro BNP content of the autophagy inhibitor and moxibustion groups were significantly decreased (P<0.01, P<0.05), and CO and p-mTOR/mTOR ratio were significantly increased in both autophagy inhibitor and moxibustion groups (P<0.01). (3) Compared with the autophagy activator group, the levels of HR, HW/BW, NT-pro BNP and p53 in the autophagy inhibitor and moxibustion groups were significantly lower (P<0.01), and those of CO and p-mTOR/mTOR levels were significantly higher (P<0.01). CONCLUSION: Moxibustion, similar to the autophagy inhibitor, has a protective action on myocardium in CHF rats, which is possible by preventing over expression of myocardial autophagy-associated proteins during CHF.

Fibroblast Growth Factor 21 Attenuates Diabetes-Induced Renal Fibrosis by Negatively Regulating TGF-β-p53-Smad2/3-Mediated Epithelial-to-Mesenchymal Transition via Activation of AKT

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.METHODS: Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.RESULTS: DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).CONCLUSION: FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.

Expressions of p53, p63 and PIM1 proteins in nodal or extranodal diffuse large B-cell lymphoma and their prognostic significance / 肿瘤

Objective: To investigate the correlation between the expression of p53, p63 or PIM1 protein and the survival of patients with nodal or extranodal diffuse large B-cell lymphoma (DLBCL). Methods: Immunohistochemical staining was applied to examine the expressions of p53, p63 and PIM1 proteins in nodal or extranodal DLBCL. The differences in the expressions of p53, p63 and PIM1 proteins between nodal and extranodal DLBCL were analyzed by χ2 test. Kaplan-Meier survival curve and COX proportional hazard model were used to analyze the relationship between the clinicopathological factors (including p53, p63 and PIM1 expressions) and the prognosis of patients with nodal or extranodal DLBCL. Results: Among 212 DLBCL cases, there were 101 nodal cases and 111 extranodal cases (including 55 cases of gastrointestinal DLBCL and 56 cases of non-gastrointestinal DLBCL). The expression rates of p53, p63 and PIM1 proteins in all cases were 19.0%, 25.2% and 54.7%, respectively. Among them, p53 was expressed more frequently in extranodal gastrointestinal cases (P 0.05). Much more p53-positive cases were observed with international prognostic index (IPI) ≥ 3 (P 0.05). Survival analysis showed that the expression of p53 or p63 protein was a significant inferior prognostic factor for overall survival (OS) and progression-free survival (PFS) in nodal patients or extranodal non-gastrointestinal DLBCL patients, respectively (both P < 0.05), while PIM1 expression was an inferior prognostic factor for PFS in extranodal gastrointestinal cases (P < 0.05). Conclusion: The molecular mechanisms of DLBCL pathogenesis may be different between different locations of DLBCL, which is worth further exploration.

Progress of the relationship between aberrant p53 protein and tumorigenesis / 肿瘤研究与临床

TP53 gene has been found to have the highest correlation with human tumors, and its mutations occurr in about 50% malignant tumors. Its encoded p53 protein is a well-known tumor-suppressor factor in vivo, which is closely related to tumorigenesis. It is found that tumorigenesis has a close relationship with various abnormal biological processes, including cell cycle regulation, apoptosis, DNA damage repair, cell senescence, autophagy, metabolic regulation. This paper reviews the complex network relationship between p53 protein and tumorigenesis from biological processes affecting the tumorigenesis.

Relationship between the precursors of high grade serous ovarian cancer and patient characteristics: decreased incidence of the p53 signature in pregnant women / 부인종양

OBJECTIVE: To investigate the relationship between the precursors of high grade serous ovarian cancer (HGSOC) and the characteristics of patients with a low HGSOC risk in terms of the effects of pregnancy. METHODS: We prospectively examined consecutive cases in which the bilateral fallopian tubes were removed during benign gynecological or obstetric surgery and assessed the relationship between the patient characteristics, including parity and pregnancy, and the incidence of HGSOC precursors. All the fallopian tubes were examined by applying the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) Protocol. RESULTS: Of the 113 patients enrolled, 67 were gynecological and 46 were obstetric. The p53 signature was identified in 21 patients. No other precursors were identified. In a comparison of the p53 signature-positive and negative groups, parous women and pregnant women were significantly fewer in the p53 signature-positive group (53% vs. 86%, p=0.002, 10% vs. 47%, p=0.001, respectively). Current pregnancy was also associated with a significantly lower incidence of the p53 signature after multivariate adjustment (odds ratio [OR]=0.112; 95% confidence interval [95% CI]=0.017–0.731; p=0.022). Among gynecological patients, parous women were fewer in the p53 signature-positive group on univariate (47% vs. 73%, p=0.047) and multivariate analysis (OR=0.252; 95% CI=0.069–0.911; p=0.036). No other characteristics were associated with p53 signature positivity. CONCLUSIONS: The incidence of the p53 signature was significantly lower in parous women and pregnant women. This decreased incidence of early phase serous carcinogenesis may be one of the possible mechanisms underlying HGSOC risk reduction among parous women.

Progress of the relationship between aberrant p53 protein and tumorigenesis / 肿瘤研究与临床

TP53 gene has been found to have the highest correlation with human tumors, and its mutations occurr in about 50％ malignant tumors. Its encoded p53 protein is a well-known tumor-suppressor factor in vivo, which is closely related to tumorigenesis. It is found that tumorigenesis has a close relationship with various abnormal biological processes, including cell cycle regulation, apoptosis, DNA damage repair, cell senescence, autophagy, metabolic regulation. This paper reviews the complex network relationship between p53 protein and tumorigenesis from biological processes affecting the tumorigenesis.

Effects of ascorbic acid on the expression of p53 and Bcl-2 protein in NIH/3T3 cells exposed to nickel / 中华劳动卫生职业病杂志

Objective@#To study the protective effect of Ascorbic acid (AA) on the injury of nickel-exposed mouse embryonic fibroblasts (NIH/3T3) .@*Methods@#A model of damage induced by 50 μg/mL nickel refining dust was established to determine the relative survival rate of cells, superoxide dismutase (SOD) , lactate dehydrogenase (LDH) and glutathione peroxidase. (GSH-Px) activity, hydrogen peroxide (H2O2) and malondialdehyde (MDA) content, and p53 (wild-type) , Bcl-2 protein expression. To investigate the protective effect of different doses of ascorbic acid (25, 50, 100 mmol/L) on nickel-refined dust-induced NIH/3T3 cell injury.@*Results@#The study showed that ascorbic acid Ⅲ group can make the NIH/3T3 cell survival rate increased significantly; Apoptosis rate was reduced; The vitality of SOD and GSH-Px increased significantly, and the difference was statistically significant (P<0.05) . At the same time, the level of MDA and H2O2 and the activity of extracellular LDH enzyme were significantly reduced, and the difference was statistically significant (P<0.05) . The results showed that nickel refining dust induced cell damage through up-regulation of p53 protein and down-regulation of Bcl-2 protein expression; ascorbic acid interventions, the expression level of Bcl-2 protein in ascorbic acid II and III groups was higher than that of nickel refining dust group, and the difference was statistically significant (P<0.05); The expression level of p53 protein in each dose group of ascorbic acid was lower than that of nickel refined dust group, and the difference was statistically significant (P<0.05).@*Conclusion@#With the increase of concentration of ascorbic acid, oxidative damage levels, antioxidant enzyme levels, reduce cell apoptosis, reduce expression of p53, increased expression of Bcl-2. It showed that ascorbic acid had protective effect on NIH/3T3 cell injury induced by nickel refining dust.

Retention Esophagitis as a Significant Clinical Predictor of Progression to Esophageal Cancer in Achalasia

BACKGROUND/AIMS: Chronic liquid and/or food stasis caused by retention esophagitis (RE) in achalasia is a notable endoscopic finding because of the presence of a thickened or whitish esophageal mucosa and histologically altered squamous hyperplasia. We aimed to identify the clinical features of RE associated with achalasia and to clarify the clinical definition of RE in achalasia as a precancerous lesion identified by analyzing biomarker expressions. METHODS: From 2006 to 2015, we retrospectively reviewed 37 patients with achalasia without previous treatment. Among them, 21 patients had diagnostic findings of RE (RE+) and 16 patients had no diagnostic findings of RE (RE−). Immunohistochemical staining of p53, p16, and Ki-67 was performed on the endoscopic biopsy tissues from the patients with achalasia and 10 control patients with non-obstructive dysphagia. RESULTS: The symptom duration and transit delay were significantly longer in the RE+ group than in the RE− group. We found particularly high p53 positivity rates in the RE+ group (p<0.001). The rate of p16 expression was also significantly higher in the RE+ group than in the other two groups (p=0.003). CONCLUSIONS: A high p53 expression rate was more frequently found in the RE+ group than in the other two groups. RE could be a meaningful clinical feature of achalasia for predicting esophageal carcinogenesis.

Modulating Effects and Mechanisms of p53-miR-34a-SIRT1 Feedback Loop on Reproductive Senescence of Vascular Endothelial Progenitor Cells / 中国循环杂志

Objectives: To explore the modulating effects and related mechanisms of p53-miR-34a-SIRT1 feedback loop in the process of replication senescence of vascular endothelial progenitor cells (EPC). Methods: EPC derived from umbilical cord blood were cultured and identified. Differences on senescence, cell apoptosis, cell cycle and blood tube formation were observed in EPC of 3rdand 6thgeneration. Protein expression of p53, Acetyl-p53, and SIRT1 was also detected by Western blotting in EPC of 3rdand 6thgeneration. The miR-34a inhibitor lentiviral vector was constructed and used to identify whether miR-34a inhibitor can protect 6thgeneration EPC from apoptosis. Results: EPC derived from umbilical cord blood were successfully cultured. The cells senescence rate and apoptosis rate of the 6thgeneration EPC were significantly higher than those of the 3rdgeneration EPC. The cell cycle of 6thgeneration EPC was mainly arrested at G0/G1 phase. The protein expression level of p53 was significantly higher, while the protein expression of acetyl-p53 and SIRT1 was significantly lower in the 6thgeneration EPC than in the 3rdgeneration EPC, all P<0.05. The senescence was significantly attenuated, and late apoptotic cells were significantly reduced, while angiogenesis ability was significantly enhanced in the 6thgeneration EPC transfected with lentiviral vector carrying miR-34a inhibitor. Conclusions: p53-miR-34a-SIRT1 is an important feedback mechanism in the process of EPC replication senescence. The miR-34a inhibitor may be the potential target of delaying EPC senescence.