Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

BACKGROUNDThe postremission therapies for adult patients generally contain consolidation chemotherapy, allogeneic hematopoietic stem cell transplantation and autologous hematopoietic stem cell transplantation (auto-HSCT). Because of the various results from different centers, the optimal therapy for adult acute lymphoblastic leukemia (ALL) patients is still uncertain. This study aimed to better understand predictive factors and role of auto-HSCT in the postremission therapy for adult ALL patients.

METHODSThe outcomes of 135 adult patients with ALL, who received the first auto-HSCT in Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 1994 to February 28, 2014, were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method and simultaneous effects of multiple covariates were estimated with the Cox model.

RESULTSOverall survival (OS) and disease-free survival (DFS) at 5 years for the whole cohort were 59.1 ± 4.5% and 59.0 ± 4.4%, respectively. The cumulative nonrelapse mortality and relapse rate at 5 years were 4.5 ± 0.03% and 36.6 ± 0.19%. For both OS and DFS, acute T-cell lymphoblastic leukemia, high lactate dehydrogenase (LDH) at diagnosis, blast cell proportion ≥5% on the 15 th day of induction therapy, and extramedullary infiltration before HSCT were the poor prognosis factors. In addition, age ≥35 years predicted poor DFS. Only T-ALL and high LDH were the independent undesirable factors associated with OS and DFS in Cox regression model. For 44 patients who had results of pretransplantation minimal residual disease (MRD), positive MRD (MRD ≥0.01%) indicated poor OS (P = 0.044) and DFS (P = 0.008). Furthermore, for the standard risk group, the patients with negative MRD (MRD <0.01%) had better results (OS at 18 months was 90.0 ± 9.5%, while for the patients with positive MRD OS was 50.0 ± 35.4%, P = 0.003; DFS at 18 months was 90.0 ± 9.5%, while for the positive MRD group DFS was 0%, P < 0.001).

CONCLUSIONSThis study confirmed that auto-HSCT combined with posttransplantation maintenance chemotherapy could be an option for adult ALL patients and pretransplantation MRD may play a significant role in the direction of therapy for adult ALL patients.

Adolescent ; Adult ; China ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm, Residual ; mortality ; therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; mortality ; therapy ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Transplantation, Homologous ; Young Adult

Objective To evaluate the possible association between RFC-1 polymorphism and cervix carcinoma.as well as the interaction between polymorphism and human papilloma virusl6(HPV16).Methods Based on a hospital-based case-control study.107 cases which were diagnosed as cervical cancer pathematologically and 107 controls with hysteromyoma,were selected by frequency,matched with age and habitation.HPV16 and RFC-1 A80G polymorphism were detected by special PCR and RFLP Results (1)HPV16 infection rate in CaseS(56.07%)Was higherthan that in controls(31.78%)with the adjusted OR with RFC-1 AA,RFC-1 GG had higher risk for cervical cancer with OR of2.42(95%CI:1.01-5.81).(4)No statistical significance was noticed regarding the interaction between RFC-l polymorphism and HPV16 in logistic regression method.Conclusion The introduction of RFC-1 80GG gene type could increase the risk of cervical cancer.

OBJECTIVETo evaluate the roles of expression and early protein E2 and E6 load of human papillomavirus type 16 (HPV16) on cervical cancer in order to explore the relation between disruption of E2 and development of cervical cancer.

METHODSA case-control study was conducted, including 141 cervical cancer patients as cases who had been diagnosed by cytological approaches and histological approaches in Shanxi province Tumor Hospital, China. Two type of controls including 137 hospital controls with hysteromyoma by cytology or histology and eligible 129 controls from 1582 healthy women in the community who took part in community-organized physical examination with neither CIN2-3 nor invasive cancer, nor other gynecologic diseases were recruited. HPV16 E2 and E6 oncogenes were detected by multiple polymerase chain reaction (multi-PCR). The levels of E2 and E6 were analyzed used Bio-1D+ + software provided by VILBER pattern formatter.

RESULTSThe positive rates of HPV16 E6 in cancer cases (46.8%) were significantly higher than that in hysteromyoma group (24.1%) or healthy control group (2.3%) and accounted for 2.77 of OR (95% CI: 1.66-4.63) and 36.96 of OR(95% CI: 11.22-121.71) respectively. The expressions and loads of HPV16 E6 and E2 in cases were significantly higher than that in two control groups. Meanwhile, the expression or level of E6 was higher than that of E2 in each group. Disruption rate of E2 was 22.73% and the ratio of E6 to E2 was 1.24 in cervical cancer group.

CONCLUSIONThe positive rates and levels of HPV16 E6 or E2 found in cervical cancer were higher than that in hysteromyoma and healthy women. High expression of E6 and disruption of E2 might play an important role in the development of HPV-induced cervical cancer.

Adult ; Aged ; Case-Control Studies ; DNA, Viral ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Gene Expression Regulation, Viral ; Human papillomavirus 16 ; genetics ; Humans ; Middle Aged ; Oncogene Proteins, Viral ; genetics ; Papillomavirus Infections ; genetics ; virology ; Polymerase Chain Reaction ; Repressor Proteins ; genetics ; Uterine Cervical Neoplasms ; genetics ; virology

OBJECTIVETo explore the relationship between the levels of estrogen (E2) and progestogen (P), expression of estrogen receptor (ER) and progesterone receptor (PR) and cervical cancer.

METHODSA case-control study with hospital and community controls was employed. The levels of serum estrogen and progesterone were detected by enzyme linked immunosorbent assay (ELISA) for 141 cervical cancer cases, 137 uterine myoma patients as controls and 129 health women as controls. ER and PR were measured by immunohistochemistry sABC in cervix tissues from patients with cervical cancer and uterus myoma as well.

RESULTSThe levels of estrogen (47.49 ng/mL) and progesterone (2.34 pg/mL) in cases were significantly higher than those in both control groups. The association between estrogen and cervical cancer was significant both before and after menopause-adjusted, with over 89% of attributable risk percentage (ARP), and showed a dose-response relation. Using the lowest value of 2 pg/ml in follicular phase as cut off point for progesterone, there were no statistically significant difference between cases and controls, and neither in progesterone nor in premenopausal. The expressions of ER and PR in cases were lower than those in controls, even after being menopause-adjusted.

CONCLUSIONThe high level of endogenous estrogen and progestogen might increase the risk of cervical cancer. Compared with progestogen, estrogen showed a higher risk that was not influenced by menopause. In some sense, ER and PR may exert certain protective effect on progressing of cervical carcinogenesis.

Adult ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Estrogens ; blood ; Female ; Humans ; Immunohistochemistry ; Leiomyoma ; blood ; metabolism ; Middle Aged ; Postmenopause ; blood ; metabolism ; Progesterone ; blood ; Receptors, Estrogen ; analysis ; Receptors, Progesterone ; analysis ; Risk Factors ; Uterine Cervical Neoplasms ; blood ; metabolism ; Uterine Neoplasms ; blood ; metabolism

OBJECTIVETo explore the effects of estrogen (E(2)) and progesterone (P) on cervical cancer and the synergistic action between estrogen, progesterone and human papillomaviruses (HPV).

METHODSHoted-start polymerase chain reaction (HS-PCR) was used to detect HPVs, HPV16 and ELISA was used to assay E(2) and P on 141 cases with cervical cancer and on 129 healthy controls.

RESULTSPositive rates of HPVs and HPV16 were 75.2% and 46.8% respectively in cervical cancer group, significantly higher than that in controls. Levels of estrogen and progesterone in case group were significantly higher than that in controls and a dose-responded relationship between the levels of estrogen and cervical cancer was revealed. Estrogen and HPV showed an additive interaction in the development of cervical cancer.

CONCLUSIONHPV16 infection played a principal role in the development of cervical cancer. The high levels of entogenous estrogen could increase the risk of cervical cancer and might serve as a cofactor in the development of HPV-induced cervical cancer.

Adult ; Aged ; China ; epidemiology ; DNA, Viral ; analysis ; Enzyme-Linked Immunosorbent Assay ; Estrogens ; blood ; Female ; Human papillomavirus 16 ; isolation & purification ; Humans ; Middle Aged ; Papillomavirus Infections ; Polymerase Chain Reaction ; Progesterone ; blood ; Risk Factors ; Uterine Cervical Neoplasms ; blood ; epidemiology ; virology