Anti-osteosarcoma Effects and Mechanisms of 4-o-amino-phenol-4＇ - demethylepipodophyllotoxin Ether

Objective： The purpose of this study was to investigate the anti-osteosarcoma effects and mechanisms of 4-o-amino-phenol-4＇-demethylepipodophyllotoxin ether （ODE）, a new derivative of podophyllotoxin. Methods： The results showed that 2.5-200mg/L of ODE inhibited proliferation of OS-9901 cells in a time- and concentration-dependent manner as determined by microculture tetrazolium （MTT） assay. OS-9901 cells treated with ODE for 24h showed cell cycle arrest at G2/M and a parallel decrease in G0/G1 and S phase as detected by flow cytometry （FCM）. Results： Meanwhile, a fraction of cells with hypodiploid DNA content representing apoptosis can be detected by FCM. Morphology observation also revealed typical apoptotic features, including shrinkage of cellular and nuclear membranes, condensed heterochromatin around the nuclear periphery, and cytoplasmic vacuolation. Under confocal laser scanning microscope, intracellular Ca^2＋ and Mg^2＋ concentrations were greatly increased whereas pH value, mitochondrial membrane potential （MMP） and reactive oxygen species （ROS） were markedly reduced in OS-9901 cells after treatment with ODE. Conclusion： Taken together, these results suggest that the anti-osteosarcoma mechanisms of ODE are attributed to apoptosis through increasing intracellular Ca^2＋, Mg^2＋ concentrations, and reducing pH value, MMP and ROS.     

4 G/4 G polymorphism of plasminogen activator inhibitor-1 gene increases the risk of diabetic nephropathy

Diabetic nephropathy (DN) has become the most common pathogenesis of end-stage renal disease. Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathogenesis of DN. A meta-analysis was conducted to investigate the association between 4?G/5?G variants in the PAI-1 gene and DN susceptibility. Databases including Pubmed, EMBASE, ISI, etc., were searched to find relevant studies. Odds ratios (ORs) with 95% con?dence intervals (CIs) were used to evaluate the strength of associations. Ten studies involving 1366 cases and 1888 controls were included. Significant association between 4?G/4?G variant and DN risk was observed (OR 1.26, 95% CI 1.08–1.48, p?=?0.004) in overall populations by the recessive model. 4?G allele was also associated with the risk of DN than the 5?G allele (OR 1.15, 95% CI 1.04–1.27, p?=?0.008). In the subgroup analysis performed by the ethnicity, 4?G/4?G polymorphism was significantly associated with DN risk than 4?G/5?G?+?5?G/5?G in East Asians (OR 1.42, 95% CI 1.03–1.96; p?=?0.03), but not in Caucasians. In the strati?ed analysis by types of DM, the results showed significant association between 4?G/4?G variant and DN in Type-2 DM (OR 1.42, 95% CI 1.03–1.96, p?=?0.03). In conclusion, 4?G/4?G phenotype of PAI-1 gene may be associated with DN risk. Additional larger studies should be conducted in future analyses.     

Postmenopausal Breast Tuberculosis – Report of 4 Cases

Background

Breast tuberculosis is an uncommon disease even in countries where the incidence of tuberculosis is high.

Case Report

This is a case series concerning 4 postmenopausal breast tuberculosis cases encountered in Moulay Youssef Hospital between January 2007 and December 2010. Breast tuberculosis represents 0.25% of all hospitalized tuberculosis patients in our department. The mean age of our patients was 62.5 ± 5.8 years. Clinical findings were heterogeneous; 1 case was multifocal tuberculosis, and another case was coexistent tuberculosis and malignancy of the breast. Mammography and ultrasonography findings were suspicious for malignancy in all 4 cases. Fine needle aspiration was negative in 3 cases. The diagnosis was made in all patients by histological examination of biopsy specimens, which revealed typical tuberculous lesions. Anti-tuberculosis therapy formed the mainstay of treatment.

Conclusion

The clinical and radiological features of mammary tuberculosis can be very confusing and easily mistaken for breast cancer. Symptoms suggestive of tuberculosis warrant a biopsy to exclude possible cancer.     

Fourteen-year follow-up of a Tessier number 4 cleft

A 3-month-old girl of Japanese parents presented with a left oblique facial cleft (Tessier number 4 cleft). It extended from the area lateral to the Cupids bow, through the cheek on the lateral side of the ala nasi, to the medial side of the lacrimal punctum of the lower eyelid. As a result, the left lower eyelid was split, resulting in marked ectropion. There was another cleft present on the medial side of the left upper eyelid. The left ala nasi was normal morphologically but was raised upwards. The cleft extended into the secondary palate. The nasal septum was preserved, and left choanal atresia was present. CT examination revealed hypoplasia of the left maxillary bone and sinus. A total of seven operations was performed during the 14-year follow-up period; the end result was satisfactory. Artificial bone (apatite ceramics) was implanted on the anterior wall of the maxilla, when the child was aged 6 years, and to the orbital floor when she was 13. CT examination (at 13 years) revealed that the artificial bone implanted at age 6 was correctly oriented and had fused to the anterior wall of the maxilla and zygoma. Resorption had been minimal.     

Is the conservative management of ureteric calculi of > 4 mm safe?

OBJECTIVE: To determine the safety of the conservative management of ureteric calculi of > 4 mm in diameter, using mercapto-acetyltriglycine (MAG3) radioisotope renography to monitor renal parenchymal function. PATIENTS AND METHODS: Patients with symptomatic unilateral ureteric calculi were recruited prospectively. After confirming the position of the stone using contrast urography, a MAG3 radioisotope renogram was taken within 48 h of admission and again 1 month after the patients became stone-free. The indications for intervention were ipsilateral loss of function (>/= 5% loss), infection, pain or any combination of these factors. The recovery of function was determined by follow-up renography. RESULTS: In all, 54 patients were recruited; 18 were initially allocated to conservative treatment although four later required intervention for pain. The remainder required early intervention for pain (eight), diminished function only (15) or diminished function with infection (13). Of the 54 patients, 28% had 'silent' loss of renal function at presentation. No calculi of > 7 mm diameter passed without intervention. The mode of initial management was determined according to individual clinical need. The upper tracts of all patients were relieved of obstruction and all patients were rendered stone-free. Intervention for reduced function only (at 相似文献   

Evaluation of thymosin β4 in the regulation of epithelial-mesenchymal transformation in urothelial carcinoma

ObjectivesTo study the underlying alteration in the expression of epithelial markers involved in epithelial-mesenchymal transition (EMT), and elucidate the potential mechanism(s) for Tβ4-induced EMT-like phenotypic changes in bladder cancer cells.Materials and methodsAll tissue samples in this study were obtained from clinical patients of the Union Hospital of Tongji Medical College, and were confirmed by surgery and pathology. Of these, normal bladder tissues (control), primary urothelial carcinoma of different grades (Stage pTa, Stage pT3), bladder paracancerous tissues, accompanied with 2 bladder cancer cell lines (BIU-87 and T24), were divided into 6 groups. Quantitative RT-PCR, Western blotting, and immunohistochemical study of adhesion molecules Tβ4, ILK, E-cadherin, and β-catenin involved in EMT were carried out. A lentiviral gene transferring vector containing the RNA polymerase III-dependent U6 promoter to express short hairpin RNA (shRNA) directed against Tβ4 was also applied. In the present study, all agents were evaluated using commercial kits.ResultsA strong correlation between the expression levels of Tβ4, ILK, E-cadherin, and β-catenin was found in the bladder transitional cell carcinoma (TCC) patients. In the BIU-87 and T24 bladder cancer cells overexpressing Tβ4, which were accompanied by a loss of E-cadherin as well as a cytosolic accumulation of β-catenin, up-regulation of ILK was also revealed. The inhibition of the Tβ4 expression with lentiviral shRNA vector could raise EMT-like phenotypic changes, significantly depressed motility, and subsequent invasiveness of bladder cancer cells.ConclusionsOur results imply that the Tβ4 is likely to play a crucial role in EMT progression, and that inhibition of the Tβ4 expression or interactions with other genes should be novel therapeutic targets for bladder cancers with high invasive and metastatic potential.     

Calcaneus fractures, results of the sinus tarsi approach: 4 years of experience

Objective  

We present the treatment of displaced intra-articular calcaneal fractures using the sinus tarsi approach to reduce the complications described in literature obtaining good clinical and radiographical results.     

Induction of regulatory CD4⁺ cells and prolongation of survival of fully allogeneic murine cardiac grafts by danazol

Danazol, a modified testosterone, has been used to treat endometriosis and pretreatment before in vitro fertilization and embryo transfer, although its reproductive mechanisms remain unclear. We investigated the effect of danazol on alloimmune responses in murine heart transplantation. CBA male mice (H2^k) that underwent transplantation of C57BL/6 (B6, H2^b) hearts received danazol (0.4 and 4 mg/kg/d) by intraperitoneal injection from the day of transplantation to days 6. We performed an adoptive transfer study to determine regulatory cells as well as cell proliferation, cytokine, and flow cytometry assessments. Danazol-treated (4 mg/kg/d) CBA mice showed prolonged allograft survival (median survival time [MST], 63 days). Moreover, secondary CBA recipients of whole splenocytes and CD4⁺ cells from primary danazol-treated (4 mg/kg/d) CBA recipients at 30 days after transplantation displayed prolonged allograft survival (MSTs, 29 and 60 days, respectively). Cell proliferation, interleukin (IL)-2, and interferon-γ were suppressed in danazol-treated mice, whereas IL-4 and IL-10 were up-regulated. Moreover, danazol directly suppressed alloproliferation in mixed leukocyte cultures. Flow cytometry studies showed an increased CD4⁺CD25⁺Foxp3⁺ cell population among splenocytes from danazol-treated mice. In conclusion, danazol induced prolonged cardiac allograft survival and generation of regulatory CD4⁺ cells.     

Stiffness parameter β as a predictor of the 4-year all-cause mortality of chronic hemodialysis patients

Background

There is a lack of information on stiffness parameter β, an index of arterial stiffness, in hemodialysis (HD) patients. The aim of the present study was to investigate whether stiffness parameter β is predictive of the long-term mortality of chronic HD patients.

Methods

We measured biochemical parameters and the stiffness parameter β of 80 patients on maintenance HD therapy and followed their course for 4 years, and we enrolled 70 of these 80 patients in the study. We divided the 70 patients into tertiles according to their stiffness parameter β values, and conducted multivariate analyses to examine the impact of the tertiles on 4-year mortality.

Results

Older age and the presence of diabetes mellitus were found to be independently associated with higher stiffness parameter β values. Fifteen patients (21.4 %) died and 16 (22.9 %) experienced a new cardiovascular event during the follow-up period. The results of a Kaplan–Meier analysis revealed a significantly higher risk of all-cause mortality in the HD patients with highest stiffness parameter β values (p = 0.0106). According to the ROC curve, the cut-off level that yielded maximal sensitivity and specificity for predicting all-cause mortality was 10.1, and the sensitivity and specificity using the cut-off value were 69.2 and 70.2 %, respectively.

Conclusion

The results of this study suggest that stiffness parameter β is a predictor of all-cause mortality in chronic HD patients.     

Under-grading of <4 cm renal masses on renal biopsy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is well documented that biopsy of small renal masses is inaccurate and tends to under‐estimate tumour grade compared with surgical specimens. To our knowledge there has not been a study showing grading discrepancy between biopsy and surgical excision in a large population‐based cohort.

OBJECTIVE

• ? To determine whether differences exist in tumour grade between patients who undergo partial nephrectomy (PN) and those who undergo ablation for renal tumours.

PATIENTS AND METHODS

• ? Data was obtained using the Surveillance, Epidemiology and End Results database. Patients with solitary renal tumours of <4 cm treated with ablation or PN and with renal cell carcinoma (RCC) histopathology were identified.
• ? Tissue diagnosis in the ablation specimens was obtained from biopsy reports, whereas tissue from PN specimens was determined from surgical pathology.
• ? Variables analysed included: year of diagnosis, age, sex, race/ethnicity, marital status, population density, education, poverty level, and tumour size.
• ? Stacked bar graphs were created to compare the distributions of grade and histology between the groups. Multinomial logistic regression was used to determine factors independently associated with grade.

RESULTS

• ? In all, 7704 (87.4%) patients underwent PN and 1114 (12.6%) underwent either radiofrequency ablation or cryoablation.
• ? The PN patients were younger at diagnosis (59 vs 68 years, P < 0.001), more likely to be married (70% vs 64%, P < 0.001), and had smaller tumours (2.4 vs 2.6 cm, P < 0.001).
• ? There were no differences in the distribution of histology between the PN and ablation groups.
• ? Tumour grade was significantly lower in tumours treated with ablation.
• ? Compared with grade 1 disease, those undergoing ablation were 30% less likely to have grade 2 (P < 0.001), 30% less likely to have grade 3 (P < 0.001), and 92% less likely to have grade 4 disease (P < 0.01) than those having PN.

CONCLUSIONS

• ? There is a strong association between grade and treatment type in patients with small renal masses after controlling for baseline characteristics.
• ? As grade is determined by different methods, we think that this shows systematic under‐grading in biopsy of small renal masses.