Recently numerous studies have demonstrated that Notch signaling pathway plays a critical role in regulating cell proliferation and differentiation in hematopoietic microenvironment,which is associated with MM occurrence and the drug resistance.The latest researches show that there are close relations between hypoxia and Notch signaling pathway in tumor occurrence and progression.Exploring the interactions of microenvironment of hypoxia,HIF-1α and Notch signaling pathway will provide theoretical basis for MM targeted therapy.

Objective To compare the curative effects of CT-guided ethanol injection and lauromacrogol injection into the sac cavity in treating ovarian endometriosis cysts. Methods A total of 86 patients with ovarian endometriosis cyst were enrolled in this study. The patients were divided into ethanol group (n=44) and lauromacrogol group (n=42). Under CT guidance, injections of ethanol or lauromacrogol into the sac cavity of ovarian endometriosis cysts were respectively performed for the patients of both groups. The patients were followed up for six months, and the curative effects and the complications were analyzed. Results Six months after the treatment, the cure rates of ethanol group and lauromacrogol group were 95.50%and 92.86%respectively, and no statistically significant difference in cure rate existed between the two groups (P>0.05). The preoperative serum CA125 levels of the ethanol group and lauromacrogol group were (48.42±23.68)μg/L and(49.21±22.83) μg/L respectively, and the post operative ones were (23.56±5.89) μg/L and (25.49± 6.10) μg/L respectively; the differences between the preoperative data and the postoperative data were statistically significant in both groups (P<0.05), although the differences in serum CA125 levels between the two groups were not significant (P>0.05). The incidence of postoperative complications in the lauromacrogol group was obviously lower than that in the ethanol group (P<0.05). The cure time in the ethanol group was shorter than that in the lauromacrogol group, although the difference was not significant after six months. Conclusion For the treatment of ovarian endometriosis cysts, CT-guided lauromacrogol injection into the sac cavity has reliable curative effect. Compared to ethanol injection, injection of lauromacrogol is safer and has fewer adverse reactions. Therefore, this technique should be recommended in clinical practice. Serum CA125 can be used as an indicator for the evaluation of curative effect.

Objective To investigate the effects of Notch1 siRNA on VEGF and angiogenesis of myeloma cell line RPMI-8226 in vitro and in vivo.Methods In vitro,Notch siRNA was transfected into RPMI-8226 cells,and then cell supernatant VEGF secretion was detected using ELISA method.Expression levels of Notch1 and VEGF proteins were assayed by Western blotting.RPMI-8226 cells were subcutaneously transplanted in NOD/SCID mice,and then the tumor mice were divided into three groups randomly:NS group (Notch1 siRNA-transfected group),CS group (Control siRNA-transfected group) and UN group (Untransfected group),and the changes of tumor volume were observed.Immunohistochemical staining was used to detect the changes in expression levels of Notch1,VEGF and CD34.Results Notch1 and VEGF proteins expressions of RPMI-8226 cells were significantly decreased by Notch1 siRNA.At 48 h and 72 h,VEGF secretion level in NS group was significantly different with CS group [(120 ± 25) ng/L ∶ (175 ± 15) ng/L,t =3.27,P ＜ 0.05;(145 ± 24)ng/L ∶ (295 ± 17)ng/L,t =8.83,P＜0.01].At 13 d,17 d and 21 d,tumor volume in NS group was significantly reduced,that was significantly different with CS group [(1 548 ± 218) mm3 ∶ (1 820 ± 64) mm3,t =2.68,P ＜0.05;(1 200 ±75)mm3 ∶ (2 180 ±84)mm3,t =19.46,P＜0.01;(1 150 ±88)mm3 ∶ (2 250 ± 145)mm3,t =14.50,P ＜0.01].The expression levels of Notch1 and VEGF protein were decreased by Notch1 siRNA.The expression levels of Notchl and VEGF in NS group were different with CS group [(16.33 ±2.52)％∶ (75.33 ±2.52)％,t=28.71,P＜0.01;(5.00±1.00)％∶29.67±2.08 ％,t=18.50,P ＜ 0.01].Notch1 siRNA reduced the number of transplanted tumor neovascularization in NS group.Microvascular density in NS group was significantly less than that in CS group [(14.67 ± 2.52) ∶ (30.00 ± 5.00),t =4.74,P ＜ 0.01].Conclusion In vitro,Notch siRNA reduces human myeloma cell RPMI-8226 cell supernatant VEGF secretion.In vivo,Notch siRNA can reduce tumor volume and the number of new blood vessels in transplanted-multiple myeloma mice.Thus,Notchl is an effective molecular target for anti-angiogenesis in myeloma.

Objective To investigate risk factors for early death in acute promyelocytic leukemia patients. Methods The clinical characteristics including leucocyte counts at onset,platelet count and fibrinogen content of 42 patients with APL were evaluated. The factors of immunophenotype, genes fusion as well as gene mutations were compared. Results Among the 42 patients with APL,6 cases were observed early death with the early mortality rate of 14.3%. To be spe-cific,4 deaths were attributable to cerebral hemorrhage,whereas the other two were linked with disseminated intravas-cular coagulation complicated with multiple organ failure and myocardial infarction respectively. The leukocyte counts of dead patients were significantly more than complete remission group. At the same time, the blood platelet counts and the fibrinogen counts were all less than those of complete remission patients. 5 patients were confirmed as CD2+,5 cases were CD34 and/or HLA-DR+,and FLT3-ITD gene mutation was found in 4 subjects. Difference between the two groups was statistically significant(P<0.05). Conclusion Acute promyelocytic leukemia patients with leukocytosis,low platelet count, hypofibrinogenemia, CD2+, CD34 and/or HLA-DR+as well as FLT3-ITD gene mutation are at an increased risk of early death in the risk factor analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is one of the driver genes of non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy of pemetrexed in HER2-mutant NSCLC is controversial. The aim of this study is to investigate the efficacy of pemetrexed combined with platinum chemotherapy in patients with HER2-mutant and HER2 wild-type lung adenocarcinoma. METHODS: The clinical data of 106 cases of EGFR, ALK, ROS-1, KRAS, BRAF, RET and MET-negative patients with advanced lung adenocarcinoma patients who diagnosed by histopathology in the First Affiliated Hospital of Zhengzhou University were retrospectively reviewed. The relationships between HER2 gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed. RESULTS: All of the 106 patients' HER2 status were determined. HER2 mutations occurred in 32 cases (30.2%), no mutations in 74 cases (69.8%). HER2 mutations were common in young, non-smoking and female patients. All patients received first-line pemetrexed and platinum-based chemotherapy. The objective response rate (ORR) and disease control rate (DCR) of patients with HER2-mutant lung adenocarcinoma were significantly higher than those without HER2 mutations (40.6% vs 14.9%, χ²=8.464, P=0.004; 93.8% vs 68.9%, χ²=6.327, P=0.012), and the difference was statistically significant. According to univariate analysis, the PFS was significantly associated with the brain metastases, maintenance chemotherapy and HER2 gene status (P<0.05), but not with age, gender, smoking history, oligometastases, liver metastases and type of platinum (P>0.05). Cox multivariate analysis indicated that HER2 mutation was an independent positive prognostic factor of PFS (P=0.038). CONCLUSIONS HER2-mutant lung adenocarcinoma patients with first-line pemetrexed combined with platinum chemotherapy have greater clinical benefit than HER2 wild-type patients.
Adenocarcinoma of Lung ; drug therapy ; genetics ; pathology ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Disease-Free Survival ; Female ; Genes, erbB-2 ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Pemetrexed ; therapeutic use ; Platinum ; therapeutic use ; Retrospective Studies ; Treatment Outcome

Apoptosis ; Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma ; pathology

BACKGROUND: Adenocarcinoma is the most common type of lung cancer. It has been clinically evaluated that therapiestargeting against the epidermal growth factor receptor (EGFR) as the clinical standard first-line treatment. The response and outcome of EGFR-tyrosine kinase inhibitors (TKIs) in patients harboring common mutations in EGFR kinase domain (deletion in exon19 and L858R in exon 21) has been well demonstrated, but not in rare or complex mutations. METHODS: A total of 150 patients that harbored rare or complex mutations in EGFR diagnosed by histopathology were included in this retrospective study. The clinical-pathological characteristics of all 150 patients as well as the response and progression-free survival (PFS) in 48 patients that received EGFR-TKIs in first/second/third line treatments weredescribed and analyzed. RESULTS: Patients were divided into four groups based on the mutation types: single G719X point mutation in exon 18 (n=46, 30.7%), single L861Q point mutation in exon 21 (n=45, 30.0%), other single rare mutation (n=14, 9.3%) and complex mutations (n=45, 30.0%). The result indicated thatthere was no correlation of EGFR mutation typeswith other parameters such as gender, age, clinical stage, pathology and smoking history. For the 48 patients that received EGFR-TKIs treatment, there were no significant differencesamong 4 groups in terms of objective response rate (ORR) and disease control rate (DCR) (54.5% vs 30.0% vs 0.0% vs 35.7%, χ²=3.200, P=0.34; 90.9% vs 85.0% vs 66.7% vs 92.9%, χ²=2.162, P=0.59). The median progress-free survival (mPFS) was 11.0 months (95%CI: 4.4-17.6), and in each group of different EGFR mutation types are 15.8 months (95%CI: 9.5-22.2), 8.0 months (95%CI: 5.1-11.0), 4.9 months (95%CI: 1.4-8.4) and 23.1 months (95%CI: 15.8-30.4)(χ²=7.876, P=0.049). CONCLUSIONS The efficiency of targeting EGFR-TKIs on different types of rare or complex mutations was heterogeneous. The PFS may be better in patients that harbored complex mutations than those with single rare mutations. Further studies with larger sample size are necessary. Moreover, to discover novel therapeutic targets and develop new drugs are imminentfor those patientswith no response to the existing treatments.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Disease-Free Survival ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Exons ; genetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Retrospective Studies ; Treatment Outcome