Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-‍1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Humans ; Carcinoma, Hepatocellular/pathology* ; Cell Hypoxia ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Liver Neoplasms/pathology* ; Signal Transduction/genetics* ; tRNA Methyltransferases/metabolism*

Objective:To propose a method of cervical cytology screening based on deep convolutional neural network and compare it with the diagnosis of cytologists.Method:The deep segmentation network was used to extract 618 333 regions of interest (ROI) from 5, 516 cytological pathological images. Combined with the experience of physicians, the deep classification network with the ability to analyze ROI was trained. The classification results were used to construct features, and the decision model was used to complete the classification of cytopathological images.Results:The sensitivity and specificity were 89.72%, 58.48%, 33.95% and 95.94% respectively. Among the smears derived from four different preparation methods, this algorithm had the best effect on natural fallout with a sensitivity of 91.10%, specificity of 69.32%, positive predictive rate of 41.41%, and negative predictive rate of 97.03%.Conclusion:Deep convolutional neural network image recognition technology can be applied to cervical cytology screening.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

OBJECTIVETo evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).

METHODSPatients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.

RESULTSA total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).

CONCLUSIONAnagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.

Humans ; Hydroxyurea ; administration & dosage ; therapeutic use ; Platelet Aggregation Inhibitors ; administration & dosage ; therapeutic use ; Platelet Count ; Quinazolines ; administration & dosage ; therapeutic use ; Thrombocythemia, Essential ; drug therapy ; Treatment Outcome

OBJECTIVETo explore the influence of BCL6, MYC, P53 genes abnormalities can on the prognosis of diffuse large B-cell lymphoma (DLBCL), and to identify independent prognostic factors for DLBCL in order to facilitate clinical prognosis and selection of stratification treatment for the patients.

METHODSSixty five newly diagnosed DLBCL pathological specimens were collected from 2009 to 2012. Interphase fluorescence in situ hybridization technique (I-FISH) was used to detect the status of BCL6, MYC and P53 genes. Clinical factors were combined with immunohistochemical results for multiple-factor survival analysis.

RESULTSThe rates of BCL6 gene rearrangement, P53 gene deletion and MYC rearrangement were 21.5% (14/65), 35.4% (23/65) and 7.7% (5/65), respectively. BCL6 rearrangement group has obviously poorer overall survival (OS)(P< 0.05). COX proportional hazards model analysis showed that gender, BCL6 protein, BCL6 rearrangement, Ki67 index were prognosis factors independent of international prognostic index (IPI).

CONCLUSIONBCL6 can influence the prognosis of patients with DLBCL at gene and protein levels and both are independent prognostic factors for DLBCL.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; DNA-Binding Proteins ; genetics ; Female ; Gene Deletion ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; genetics ; mortality ; Male ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; Proto-Oncogene Proteins c-myc ; genetics ; Survival Analysis ; Survival Rate ; Tumor Suppressor Protein p53 ; genetics ; Young Adult

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; therapeutic use ; Female ; Follow-Up Studies ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; therapy ; Male ; Middle Aged ; Transplantation Conditioning ; Transplantation, Autologous ; Treatment Outcome ; Vidarabine ; analogs & derivatives ; therapeutic use ; fms-Like Tyrosine Kinase 3 ; genetics

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.

ObjectiveTo evaluate the clinical efficacy and toxicity of reduced dose idarubicin and cytarabine,semustine(IAS) regimen as induction therapy in patients with acute myeloid leukemia.MethodsA total of fifty-eight newly acute myeloid leukemia(AML) patients were randomly divided into 2 groups,including 30 cases with IAS regimen,28 cases with DA regimen The IAS regimen was treated with reduced dose idarubicin (8 ～ 10 mg/m2,days 1 to 3) and cytarabine( 100 ～ 150 mg/m2,days 1 to 7),semustine(200mg,d0).The DA regimen was treated with daunorubicin(40 ～60 mg/m2,days 1 to 3) and cytarabine ( 100 ～ 150 mg/m2,days 1 to 7).The responses ( CR and overall response rate ) were compared between the 2 groups.Results Complete remission(CR) rate in IAS and DA groups were 24 of 30( 80.0％ ) and 16 of 28 (57.1％ ) respectively,while the overall response rate were 26 of 30 ( 86.7％ ) and 18 of 28 ( 64.3％ ) respectively.There was significant difference in CR rate and overall response rate between IAS group and DA group( P ＜ 0.05 ).Myelosuppression and infections due to neutropenia were the most frequent adverse effects,severe nonhematologic toxicity was not observed.The incidence rates of toxicities in the 2 groups were not significantly different ( P ＞ 0.05 ).Conclusion The effect of reduced dose idarubicin and cytarabine,semustine regimen in the treatment for acute myeloid leukemia is superior to that of DA regimen,and the toxicities are tolerable.IAS regimen can be as the optional induction therapy in newly patients with acute myeloid leukemia.

Objective To explore the clinical significance of the coagulation and fibrolysis parameters changes for the knowledge of complicated thrombosis after chemotherapy in malignant lymphomas. Methods Morning fasting anti-coagulation blood samples were taken to detect plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and thrombin time (TT) with automatic coagulation analyzer in 71 hospitalized malignant lymphomas and 20 normal controls. The plasma D-dimer levels of the two groups were detected with immunoturbidimetry. Results The levels of plasma APTT, Fib and D-dimer in 71 malignant lynphomas were (30.44±1.43) s, (3.28±0.20) g/L, (297.05±56.59) μg/L respectively, which were significantly higher than those in normal controls at the levels of (23.72±0.76) s, (2.57±0.22) g/L, (94.50±26.07) μg/L respectively (P ＜0.05). The coagulation and fibrolysis parameters were of no statistic differences between the normal controls and lymphomas of stage Ⅰ and Ⅱ (P ＞0.05). The APTT and Fib levels in lymphomas of stage Ⅲ and Ⅳ were higher than those in normal controls and lymphomas of stage Ⅰ and Ⅱ (P ＜0.05). There are 7 malignant lymphomas complicated venous thrombosis . Of the 7 cases, the FIB and D-dimer levels were higher than those of stage Ⅰ and Ⅱ, furthermore the D-dimer levels were higher than those of stage Ⅲ and Ⅳ. Conclusion The abnormalities of coagulation and fibrolysis parameters occurred in malignant lymphomas with requirement of periodic monitoring. After chemotherapy, the lymphoma patients had a high incidence of venous thrombosis, which need early prevention for prolongation of the survival.

Objective To investigate the common chromosome abnormalities in the patients with multiple myeloma and the relationships of cytogenetic abnormalities and clinical features. Methods The interphase fluorescence in situ hybridization (I-FISH) analysis method was designed to detect RB1-/13q14-and 14q32 rearrangements in 49 MM patients. The statistic value of its effect on clinical features were determined. Results FISH disclosed 14q32 translocations in 26 of the 40 (53.1%) patients. 25 out of the 49 (51.02 %) cases were found with deletion of chromosome 13q14 included del(RB1) in 9 (18.4 %) and del(13q14.3) in 18 (36.7 %). 13q14 deletion and 14q32 translocation were simultaneously observed in 18 (36.7 %) cases. Spearman correlation analysis were found associated of 14q32 rearrangement with the percentage of plasma cells in bone marrow (r=0.316, P=0.27). Conclusion The frequency of 13q14 deletion and 14q32 gene translocation in multiple myeloma are high. There is a significant correlation between the presence of 14q32 translocations and chromosome 13 abnormalities in MM patients. The percentage of 14q32 translocation in plasma cells was increased significantly. The 14q32 translocation is an independent prognostic factor.