Association between the ESR1 and ESR2 polymorphisms and osteoporosis risk: An updated meta-analysis.

BACKGROUND: Gene polymorphisms of estrogen receptor (ESR) 1 PvuII (rs2234693), XbaI (rs9340799), G2014A (rs2228480), ESR2 AluI (rs4986938), and RsaI (rs1256049) had been reported to be associated with the risk of osteoporosis. However, these conclusions were inconsistent, therefore, an updated meta-analysis was conducted to further explore these issues. OBJECTIVE: To evaluate the association between gene polymorphisms of ESR1 PvuII (rs2234693), XbaI (rs9340799), G2014A (rs2228480), ESR2 AluI (rs4986938), RsaI (rs1256049), and osteoporosis risk. MATERIALS AND METHODS: PubMed, Medline, Ovid, Embase, CNKI, and China Wanfang databases were searched. Association was assessed using odds ratio with 95% confidence interval. Moreover, the false-positive reporting probability, Bayesian false-finding probability, and Venetian criteria were used to assess the credibility of statistically significant associations. RESULTS: Overall, ESR1 PvuII (rs2234693) and XbaI (rs9340799) were associated with the risk of osteoporosis in Indians. Moreover, ESR1 G2014A (rs2228480) was associated with the decreased risk of osteoporosis in East Asians. Moreover, ESR2 Alul (rs4986938) was associated with the increased risk of osteoporosis in East Asians and Caucasians. There was a significant association between ESR2 Rsal (rs1256049) and osteoporosis risk in overall population. When only high-quality and Hardy-Weinberg equilibrium studies were included in the sensitivity analysis, all results did not change in the present study. When the credibility was evaluated applying false-positive reporting probability, Bayesian false-finding probability, and Venetian criteria, all significant associations were considered as false positive results. CONCLUSIONS: In summary, this study shows that all substantial associations between gene polymorphisms of ESR1 (PvuII, XbaI, and G2014A) and ESR 2 (AluI and RsaI) and osteoporosis risk are possibly false positive results instead of real associations or biological variables.

The prognostic value of 11th Japanese classification and 8th AJCC staging systems in Chinese patients with esophageal squamous cell carcinoma.

BACKGROUND: Two staging systems, the 8th staging system by the American Joint Committee on Cancer (AJCC) and the 11th Japanese classification by Japan Esophageal Society (JES), are currently applied in the clinic for predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The differences between the two staging systems have been widely researched. However, little studies focus on the differences in specific staging between the two systems. Therefore, we aimed to compare the performance of different staging in predicting overall survival (OS) of Chinese patients with ESCC. METHODS: This retrospective study included 268 patients who underwent radical esophagectomy and mediastinal lymph node dissection for ESCC between January 2008 and December 2013. Patients were staged by the 8th AJCC and 11th JES staging systems. OS was estimated using the Kaplan-Meier method and compared between N stages and between stage groupings using the log-rank test. Cox proportional hazards regression analysis was performed to identify factors independently related to outcome. Further, we compared the concordance indexes (C-indexes) of the two staging systems. RESULTS: The mean age was 61.25 ± 7.056 years, median follow-up was 44.82 months, and 5-year OS rate was 47%. The OS was well predicted by the 8th AJCC N staging (P < 0.001) and the 11th JES N staging (P < 0.001), with a c-index of 0.638 (95% CI: 0.592-0.683) for AJCC N staging and 0.627 (95% CI: 0.583-0.670) for JES N staging (P = 0.13). In addition, the OS was also well predicted by stage groupings of the 8th AJCC (P < 0.001) and the 11th JES systems (P < 0.001), with a c-index of 0.658 (95% CI: 0.616-0.699) for 8th AJCC stage grouping and 0.629 (95% CI: 0.589-0.668) for the11th JES stage grouping (P = 0.211). CONCLUSIONS: The prognostic effect of 11th JES staging system is comparable with that of AJCC 8th staging system for patients with ESCC. Therefore, both systems are applicable to clinical practice.

Linear correlation between patient survival and decreased percentage of tumor [(18)F]fluorodeoxyglucose uptake for late-course accelerated hyperfractionated radiotherapy for esophageal cancer.

PURPOSE: The aims of this trial were to study whether a decreased percentage of tumor fluorodeoxyglucose (FDG) uptake (%DeltaSUVmax) correlated with overall survival and local control times for patients with esophageal cancer and which patients would benefit from a late-course accelerated hyperfractionated (LCHF) radiation scheme. METHODS AND MATERIALS: A total of 50 eligible patients with squamous esophageal cancer received positron-emission tomography examinations three times and were treated with the LCHF radiation scheme, with a dose of 68.4 Gy/41 fractions in 6.5 weeks. A %DeltaSUVmax value was calculated, and patients were stratified as highly radiosensitive (HR), moderately radiosensitive (MR), and low radiosensitivity (LR) according to %DeltaSUVmax values in the conventional fraction (CF) scheme. Then, a linear correlation was calculated between patients' survival time and %DeltaSUVmax. Local control and overall survival rates were compared after stratification. RESULTS: In the MR subgroup, there was no linear correlation between %DeltaSUVmax and the CF and LCHF schemes (correlation coefficient, R < 0.4; p > 0.05). In the other subgroups (HR and LR), %DeltaSUVmax values between the CF and LCHF schemes were correlated. Also, in the HR and LR subgroups, %DeltaSUVmax after radiation correlated with overall survival or local control rates (correlation coefficient, R ＞0.5, and p < 0.05). Three-year local control rates in the HR, MR, and LR subgroups were 100%, 81.5%, and 0%, respectively (p < 0.001). Also, 3-year overall survival rates were 92.4%, 58.8%, and 0% for HR, MR, and LR subgroups, respectively (p < 0.001). CONCLUSIONS: Postradiation %DeltaSUVmax was positively correlated with survival time for patients' with esophageal cancer. Patients who benefited from LCHF schedules were those with a decrease of 30% to 60% in tumor FDG uptake after the completion of CF radiation.

Feasibility of involved-field conformal radiotherapy for cervical and upper-thoracic esophageal cancer.

BACKGROUND: The aim of this study was to investigate the feasibility of involved-field irradiation (IFI) for the treatment of cervical and upper-thoracic esophageal cancer with concurrent chemoradiation. PATIENTS AND METHODS: 102 eligible patients with cervical or upper-thoracic esophageal cancer were treated with concurrent chemoradiation and randomized to either an IFI or elective nodal irradiation (ENI) group. RESULTS: Adverse events included infection (27.4 vs. 64.7%) and nausea (25.4 vs. 54.9%), with a statistically significant difference between the IFI and the ENI group (p = 0.008 and 0.028, respectively). No difference was seen for late radiation reaction. The cumulative incidence of local/regional failure (13.7 vs. 17.6%) and regional lymph failure (7.8 vs. 9.8%) showed no statistically significant difference between the IFI versus the ENI group (p = 0.837 and 0.837, respectively). A nodal out-field relapse rate of only 2% was seen in the IFI group. 3-year survival rates for the ENI and IFI group were 41.3 and 32.0%, respectively (p = 0.58), and 3-year local control rates were 85.7 and 80.1%, respectively (p = 0.34). CONCLUSION: IFI was acceptable for cervical and upper-thoracic esophageal cancer with a decrease in acute toxicities and no increase in lymph node failure.

[Low dose-intensity docetaxel monotherapy for patients with anthracycline-resistant metastatic breast cancer in poor physical status].

OBJECTIVE: To evaluate the efficacy and safety of a weekly schedule of low dose-intensity docetaxel monochemotherapy for patients with anthracycline-resistant metastatic breast cancer (MBC) in poor physical status. METHODS: Thirty MBC patients who were previously exposed to anthracycline treatment received docetaxel alone at a dose of 30 mg/m2 on D1, D8 and D15, repeated every 4 weeks for a maximum of 6 cycles. RESULTS: Of the 30 evaluable patients, 2 (6.7%) achieved a complete response, and 9 (30.0%) a partial response, with an overall objective response rate of 36.7% (95% CI: 20.5%-53.9%). The most common adverse event was hematologic toxicity. After an average follow-up of 15.0 months, the median time to progression (TTP) was 8. 5 months and the median overall survival (OS) had not reached yet at the end of follow-up. CONCLUSION: The weekly low dose-intensity docetaxel monochemotherapy is effective and well-tolerated in patients with anthracycline-resistant metastatic breast cancer in poor physical status.

[Enhancing effect of antisense oligonucleotide targeting bFGF on apoptosis in hepatoma cells in vitro].

OBJECTIVE: To investigate the cell cycle changes of hepatoma cells and the effect of antisense oligonucleotide targeting bFGF on apoptosis in the hepatoma cells. METHODS: The oligodeoxynucleotides were transfected with Lipofectin into hepatoma HepG2 cells. Inhibition of bFGF protein expression was assessed by confocal laser scanning microscopy and Western blot under the best condition of transfection of antisense oligonucleotide targeting bFGF, and the apoptosis in those cells was determined by flow cytometry. HepG2 cells were cultured in 24-well culture dish. The cultured cells were divided into 3 groups: group 1, the normal control group without any treatment; group 2, transfected with antisense oligonucleotide targeting bFGF; group 3, transfected with scrambled sequence targeting bFGF. RESULTS: The results from confocal microscopy and Western blot showed an inhibition of expression of bFGF at different levels under the best condition of transfection with antisense oligonucleotide targeting bFGF. The treatment with antisense oligonucleotide of bFGF not only reduced the expression of bFGF revealed by confocal microscopy and Western blotting, but also increased the apoptosis in HepG 2 cells (P < 0. 01). CONCLUSION: Treatment with antisense oligonucleotide of bFGF inhibits expression of bFGF protein and increase apoptosis. bFGF may take part in apoptosis regulation of hepatoma cells and may be used as a target in the treatment of hepatocellular carcinoma.

Biweekly oxaliplatin in combination with continuous infusional 5-fluorouracil and leucovorin (modified FOLFOX-4 regimen) as first-line chemotherapy for elderly patients with advanced gastric cancer.

OBJECTIVE: The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin (OXA) in combination with continuous infusional 5-fluorouracil (5-FU) and leucovorin (LV) administered every 2 weeks (modified FOLFOX-4 regimen) in elderly patients with advanced gastric cancer (AGC). PATIENTS AND METHODS: A total of 44 previously untreated AGC patients aged 65 or older were treated with OXA 85 mg m-2 on day 1, LV 200 mg m-2 as a 2-hour infusion followed by a 22-hour infusion of 5-FU 1000 mg m using a multichannel programmable pump, repeated for 2 consecutive days every 2 weeks. RESULTS: All patients were assessable for toxicity and 40 patients for response. Median age was 69 years (65-83). The response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria was 52.5% (95% confidence interval: 44.6%-68.0%) with 3 complete responses, 18 partial responses, 11 stable diseases, and 8 progressions. Median time to progression was 6.5 months and median overall survival was 10.0 months. Toxicity was generally mild. Grade 3 hematologic toxicities of neutropenia, anemia, and thrombocytopenia were in 6.8%, 2.3%, and 4.5% of the patients, respectively. No grade 4 hematologic toxicities occurred. Grade 1 peripheral neuropathy was a common event (34.1%), whereas grade 3 peripheral neuropathy was recorded in only 1 (2.3%) patient. An acute hypersensitivity reaction was observed in 1 patient during administration. CONCLUSION: The modified FOLFOX-4 regimen is an active and well-tolerated chemotherapy for elderly patients aged > or =65 years with AGC. OXA may occasionally cause mild hypersensitivity.

[Antisense oligonucleotide targeting endostatin enhances hematopoiesis reconstitution in BMT mice].

OBJECTIVE: To explore the effect of antisense oligonucleotide targeting endostatin (endostatin-ASON) transfecting bone marrow stromal cells ( BMSC) on hematopoiesis reconstitution in BMT mice. METHODS: Inhibition of endostatin / VCAM-1 protein and mRNA expression was investigated by transfection of antisense oligonucleotide targeting endostatin with confocal microscopy, Western blot and RT-PCR. Bone marrow stromal cells were cultured and divided into 4 groups: group (1) without any treatment; group (2) BMT only; group (3) BMT + endostatin-ASON transfection; group (4) BMT + endostatin scrambled sequence transfection. RESULTS: (1) Endostatin-ASON was successfully introduced into BMSC in vitro, and the transfecting rate was 86% ;(2) After Endostatin-ASON transfected into BMSC, the expression of Endostatin mRNA and its protein on the BMSC was signficantly inhibited at different time point after BMT [the grey value of Endostatin was (0.09 +/- 0.03) - (1.44 +/- 1.19) and (0.02 + 0.02) - (0.14 +/- 0.05), respectively] (P < 0.01 and P < 0.05); (3) Transfecting with Endostatin-ASON effectively promoted the expression of VCAM-1 mRNA and its protein on the BMSC [the gray value of VCAM-1 was (1.60 +/- 0. 92) - (8.05 +/- 0.87) and (0.07 +/- 0.02) - (0.67 +/- 0.09) , respectively] (P <0.01 and P <0.05) ; (4) There was no effects of transfecting Endostatin scrambled sequence on the expression of Endostatin and VCAM-1 on the BMSC (P > 0.05). CONCLUSION: Endostatin-ASON could inhibit Endostatin expression and enhance VCAM-1 expression in BMSC after syngeneic-BMT in mice, which might be one of the mechanisms underlying the endostatin-ASON accelerating hematopoiesis reconstitution after allogeneic-BMT.

[Effect of ligustrazine on the expression of bFGF in bone marrow stromal cells of mice after BMT].

This study was purposed to investigate the effect of ligustrazine on the expression of bFGF in bone marrow stromal cells (BMSC) and to explore the mechanism of hematopoietic reconstitution after bone marrow transplantation (BMT). The mice were randomly divided into 3 groups: normal group, saline group and ligustrazine group. BMT mouse models were established. The mice of normal group were not treated, the mice of saline group were given normal saline (0.2 ml/mouse, twice a day) through gastric tube, while the mice of ligustrazine group were given ligustrazine (0.2 ml/mouse, twice a day) through gastric tube. On day 7, 14, 21 and 28 after BMT, the femora were taken and the bone marrow mononuclear cell (BMMNC) suspensions were used for the cultivation of bone marrow stromal cells according to Dexter's culture method. The mRNA and protein expressions of bFGF in BMSC were assayed by RT-PCR and Western blot respectively. The results showed that the expression of bFGF in BMSC on the level of mRNA and protein were all reduced significantly after BMT, and increased slowly with the time. On day 7, 14 and 21 after BMT, the expressions of bFGF mRNA and protein in bone marrow stromal cells of ligustrazine group and saline group were lower than that in bone marrow stromal cells of normal group, but the expressions of bFGF mRNA and protein in ligustrazine group were obviously higher than that in saline group (P < 0.01 or P < 0.05). On day 28 after BMT, the expressions of bFGF mRNA and protein in ligustrazine group returned to normal level, while the expressions of bFGF mRNA and protein in saline group not returned to normal level, there was significant difference between these two groups. It is concluded that ligustrazine can enhance bFGF expression level in bone marrow stromal cells after syngeneic bone marrow transplantation in mice, which confirms that ligustrazine can enhance the repair of bone marrow microvessels, improve bone marrow microenvironment and promote hematopoietic reconstitution.

[Relationship between endostatin and vascular cell adhesion molecule-1 expressions on bone marrow stromal cells in BMT-mice].

This study was aimed to investigate the relationship between endostatin and vascular cell adhesion molecule-1 (VCAM-1) expressions on bone marrow stromal cells (BMSC) in mice after bone marrow transplantation (BMT) and effect of ligustrazine on their expressions. The mice were randomly divided into 3 groups: normal group (without treatment), saline group (control of BMT) and ligustrazine group (BMT + ligustrazine). BMT mouse models were established. The normal group was not treated, the saline group was given normal saline (0.2 ml/mouse, twice a day) through gastric tube, while the ligustrazine group was given ligustrazine (0.2 ml/mouse, twice a day) also through gastric tube. On day 7, 14, 21 and 28 after BMT, mice were killed by euthanasia. The expression levels of endostatin and VCAM-1 in bone marrow stromal cells were detected by immunohistochemistry and RT-PCR analysis respectively. The results showed that the endostatin protein mainly expressed in nuclei of BMSCs, the VCAM-1 protein mainly expressed in plasma of BMSCs. On day 7, 14, 21 after BMT the expression levels of endostatin mRNA and protein in ligustrazine and saline groups were significantly lower than that in normal group (P < 0.01 or P < 0.05), while their expression levels in ligustrazine group were lower than that in saline group. On day 28 the expression levels in saline group returned to normal, while the expression levels in ligustrazine group not were normalized. On day 7, 14, 21 after BMT the expression levels of VCAM-1 mRNA and protein in ligustrazine and saline groups were significantly lower than that in normal group (P < 0.01 or P < 0.05), but their expression levels in ligustrazine group were significantly lighter than that in saline group (P < 0.01 or P < 0.05). On day 28 the VCAM-1 expression level in ligustrazine group returned to normal, while its expression level in saline group not were normalized. The difference between these two groups was significant (P < 0.01). Correlation analysis revealed that there was a negative correlation between endostatin and VCAM-1 expression in saline group, there was a positive correlation between endostatin and VCAM-1 expression in ligustrazine group. It is concluded that the endostatin can influence hematopoiesis in bone marrow by affecting VCAM-1 expression on BMSC and hindering connection between stromal cells and hematopoietic cells as well as extracellular stroma and hematopoietic cells, while ligustrazine can enhance the adhesion molecule expression on stromal cell surface of bone marrow in BMT-mice, accelerate the homing and proliferation of HSPC in bone marrow after BMT, meanwhile can promote the repair of bone marrow microenvironment, accelerate hematopoietic reconstitution of bone marrow after BMT through feedback regulation of endostatin expression of BMSC in BMT-mice.

[Neoadjuvant chemotherapy before radiotherapy in treatment of patients with cervical carcinoma].

OBJECTIVE: To study the value of neoadjuvant chemotherapy in treatment of cervical carcinoma. METHODS: A clinical prospective study was carried out from Jan 1991 to Dec 2003. Totally 1609 patients with cervical carcinoma were given two cycles of combined chemotherapy before radiotherapy (neoadjuvant chemotherapy group, group A). Another 375 patients who accepted radiotherapy alone in our hospital from Jan 1989 to Dec 1990 were chosen as the control group (group B). Short-term control rate, long-term survival rate and complications were observed and analyzed. RESULTS: In group A, after two cycles of neoadjuvant chemotherapy, the overall response rate was 74.5% (1199/1609), the complete response rate was 1.6% (25/1609). The survival rate of 3, 5 and 10-year was 90.3% (1017/1126), 75.3% (652/866), and 59.0% (200/339), respectively. Five-year survival rate in stage II was higher than that in stage III (P < 0.05), but 3-year and 10-year survival rate were not different between stages II and III (P > 0.05). In group B, 3, 5 and 10-year survival rate was 81.1% (304/375), 59.2% (222/375), and 40.3% (151/375), respectively. The 5-year and 10-year survival rate was significantly higher in stage II than that in stage III (P < 0.05). The 5 and 10-year survival rate was significantly higher in group A than that in group B (P < 0.05). The 3, 5 and 10-year survival rate of patients with adenocarcinoma in group A was obviously higher than that in group B (P < 0.05), and the 3 and 5-year recurrent and metastatic rate was significantly lower in group A than that in group B (P < 0.05). In group A, the short-term toxicity and side-effect of neoadjuvant chemotherapy were mainly slight and moderate, and the short-term and long-term radiation complications had no obvious difference between two groups (P > 0.05). CONCLUSIONS: Neoadjuvant chemotherapy is a safe and effective method for the treatment of cervical carcinoma. Because of satisfactory short-term control rate and high long-term survival rate, neoadjuvant chemotherapy should be popularized in clinical treatment, especially in those patients with adenocarcinoma and in patients at clinically advanced stage of cervical carcinoma.

[Assessment on the reliability and validity of the Dermatology Life Quality Index in Chinese version].

OBJECTIVE: Since the dermatology life quality index (DLQI), a self-administered general dermatology quality of life instrument, was originally developed and published in a dermatology clinic at University hospital of Wales, our goal was to popularize the disease-specific scale used in measuring the quality of life of patients with skin diseases and to assess the reliability and validity of its Chinese version. METHODS: We administered the DLQI to 236 out-patients attending our dermatology clinic and results that had been found by those who originated the DLQI, were examined. The reliability and validity of DLQI were assessed by means of reliability analysis and factor analysis. RESULTS: Overall, the DLQI seemed easy to administer and could be completed within 3 minutes. The internal consistency coefficient rates of this unidimensional measure were 0.87 (Cronbach's alpha) and 0.85 (Spearman-brown, s) with high inter-correlations found between the dimensions with a correlation coefficient ranging from 0.4024 - 0.6569. Factor analysis resulted in a unidimensional pattern, which supported the use of a total DLQI-C score. CONCLUSION: DLQI was an easy and efficient instrument for assessing the quality of life in patients with dermatological problems and with better reliability and validity. Thus, it could be used in both research and clinical settings in China.

[Prognostic factors in patients with small cell lung cancer].

OBJECTIVE: To investigate the prognostic factors of small cell lung cancer (SCLC) and establish a reliable model of clinical prognostic index. METHODS: Kaplan-Meier and Cox regression were used to analyze the relationship between survival time and prognostic factors in 60 cases of SCLC. The prognostic factors included clinical and laboratory parameters, serum cytokeratin fragment 19 (CYFRA21-1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), CA125, interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R). RESULTS: Kaplan-Meier analysis showed that poor prognosis was in patients with KPS < 80 or extensive disease and unrelated to other clinical parameters such as age, sex and smoking index, and in patients with serum NSE > 30 micro g/L, CEA > 5.0 micro g/L, CA125 > 37 KU/L and sIL-2R > 500 KU/L. Serum IL-2 and CYFRA21-1 were also elevated, but had no significant prognostic value. Multivariate analysis indicated that serum NSE, stage and treatment of disease were independent prognostic factors. The three prognostic factors enabled establishment of a prognostic index (PI) based on a simple algorithm: PI = NSE (0 if < or = 30 micro g/L, 1 if > 30 microg/L) + stage (0 = LD, 1 = ED) + CEA (0 if < or = 5.0 microg/L, 1 if > 5.0 microg/L). CONCLUSION: The stage of disease, systemic treatment and the level of serum NSE are independent prognostic factors. Without considering the influence of treatment-related factors on survival, the levels of serum CEA, NSE and stage of disease before treatment are significant independent prognostic factors. PI calculated on the basis of CEA, NSE and stage is recommended to predict the survival of SCLC.

[Prognostic factors in patients with stage III and IV non-small cell lung cancer].

OBJECTIVE: To investigate the prognostic factors in non-small cell lung cancer (NSCLC) at stage III and IV and establish a reliable model of clinical prognostic index. METHODS: Kaplan-Meier and Cox regression were used to analyze the relationship between the prognostic factors and survival time in 114 cases of NSCLC. The prognostic factors included clinical-pathological features and serum levels of cytokeratin fragment 19 (Cyfra21-1), CEA, neuron-specific enolase (NSE), CA125, interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R). RESULTS: Kaplan-Meier analysis showed that KPS, sex, disease stage, treatment, Cyfra21-1, sIL-2R and CA125 were related to prognosis. Multivariate analysis indicated that Cyfra21-1, stage and treatment were independent prognostic factors. When Cyfra21-1 > 3.5 mg/L, stage IV and chemotherapy < 3 cycles, the relative risk (RR) was 1.691, 2.229 and 3.035, respectively. In patients given 3 or more cycles of chemotherapy, serum Cyfra21-1, sIL-2R and stage at diagnosis were significantly independent prognostic factors. Three of these prognostic factors were used to establish a prognostic index (PI) model based on a simple algorithm: PI = Cyfra21-1 + sIL-2R + stage. The median survival period of patients with 3 or more cycles of chemotherapy were 18 months if PI = 0, 8 months if PI = 1 or 2, and 5 months if PI = 3. CONCLUSION: The serum Cyfra21-1, sIL-2R and disease stage in unresectable NSCLC were independent prognostic factors. PI calculated on the basis of Cyfra21-1, sIL-2R and stage is recommended to predict the survival period of NSCLC.