Cyclooxygenase-2 dependent and independent antitumor effects induced by celecoxib in urinary bladder cancer cells

Transitional cell carcinoma of the urinary bladder is the second most common genitourinary malignancy in people in the United States. Cyclooxygenase-2 (COX-2) is overexpressed in bladder cancer. COX-2 inhibitors have had antitumor activity against bladder cancer, but the mechanisms of action are unclear. Clinically relevant concentrations of COX-2 inhibitors fail to inhibit proliferation in standard in vitro assays. In pilot experiments, different culture conditions [standard monolayer, modified monolayer, soft agar, collagen, and poly(2-hydroxyethyl methacrylate)-coated plates] were assessed to determine conditions suitable for the study of COX inhibitor growth-inhibitory effects. This was followed by studies of the effects of clinically relevant concentrations of a selective COX-2 inhibitor (celecoxib) on urinary bladder cancer cell lines (HT1376, TCCSUP, and UMUC3). Celecoxib (相似文献   

Black Hawk Down: The evolution of resuscitation strategies in massive traumatic hemorrhage

Citation

Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB: The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007, 63: 805–813 [1].

Background

Patients with severe traumatic injuries often present with coagulopathy and require massive transfusion. The risk of death from hemorrhagic shock increases in this population. To treat the coagulopathy of trauma, some have suggested early, aggressive correction using a 1:1 ratio of plasma to red blood cell (RBC) units.

Methods

Objective

To determine whether the ratio of plasma to RBCs transfused would affect survival by decreasing death from hemorrhage.

Design

Retrospective chart review.

Setting

United States Army combat support hospital in Iraq.

Subjects

246 patients who received a massive transfusion (≥10 units of RBCs in 24 hours) from November 2003 to September 2005. Three groups of patients were constructed according to the plasma to RBC ratio transfused during massive transfusion.

Intervention

None.

Outcome

Hospital mortality rates and the cause of death were compared among groups. Multivariable logistic regression was used to determine the independent association between plasma to RBC ratio and hospital mortality.

Results

For the low ratio group the plasma to RBC median ratio was 1:8 (interquartile range (IQR), 0:12–1:5), for the medium ratio group, 1:2.5 (IQR, 1:3.0–1:2.3), and for the high ratio group, 1:1.4 (IQR, 1:1.7–1:1.2) (p < 0.001). Median Injury Severity Score (ISS) was 18 for all groups (IQR, 14–25). For low, medium, and high plasma to RBC ratios, overall mortality rates were 65%, 34%, and 19%, (p < 0.001); and hemorrhage mortality rates were 92.5%, 78%, and 37%, respectively (p < 0.001). Upon logistic regression, plasma to RBC ratio was independently associated with survival (odds ratio 8.6, 95% confidence interval 2.1–35.2).

Conclusion

In patients with combat-related trauma requiring massive transfusion, a high 1:1.4 plasma to RBC ratio is independently associated with improved survival to hospital discharge, primarily by decreasing death from hemorrhage. For practical purposes, massive transfusion protocols should utilize a 1:1 ratio of plasma to RBCs for all patients who are hypocoagulable with traumatic injuries.     

Cystic lung lesions in Sjogren syndrome: analysis of lymphocyte subsets in tissue with clinico-radiologic-pathologic correlation

Pulmonary complications associated with Sjögren syndrome (SS) have attracted attention in recent years. Sjögren syndrome has been associated with small cyst formation in salivary glands, thymus, and lungs and has been recently brought to the forefront by radiologists due to high-resolution techniques. However, pathologists are less aware of this finding unless clinico-radiologic-pathologic correlation is sought. Formation of large bullae in SS is a rare complication with potential for confusion with other diseases. Here, we present the clinical, radiologic, and pathologic findings in 3 patients with SS associated with multiple pulmonary cystic lesions. All 3 patients had a variable mixed restrictive and obstructive component of the disease. There was good correlation with the pulmonary function tests (PFTs), high-resolution computed tomographic scan, and morphology with regard to the restrictive component. The small cysts appear to correlate with the extent of obstructive changes on the PFTs. However, the large bullae do not, implying noncommunication with the conducting airways. This noncorrelation between the PFTs and extent of bullous disease with predominant involvement of lower lobes in SS enables distinction from bullous emphysema. The mechanism of bulla formation in SS appears to be different from bullous emphysema. A check valve mechanism has been proposed previously in SS, which does not explain cyst formation in the thymus. Alternately, inflammation may play a role with the key suspects being CD4 T-helper cells and perhaps NK cells. This is the first report of a clinico-radiologic-pathologic correlation with analysis of lymphocyte subsets.     

Differential requirements for hematopoietic commitment between human and rhesus embryonic stem cells

Progress toward clinical application of ESC-derived hematopoietic cellular transplantation will require rigorous evaluation in a large animal allogeneic model. However, in contrast to human ESCs (hESCs), efforts to induce conclusive hematopoietic differentiation from rhesus macaque ESCs (rESCs) have been unsuccessful. Characterizing these poorly understood functional differences will facilitate progress in this area and likely clarify the critical steps involved in the hematopoietic differentiation of ESCs. To accomplish this goal, we compared the hematopoietic differentiation of hESCs with that of rESCs in both EB culture and stroma coculture. Initially, undifferentiated rESCs and hESCs were adapted to growth on Matrigel without a change in their phenotype or karyotype. Subsequent differentiation of rESCs in OP9 stroma led to the development of CD34(+)CD45(-) cells that gave rise to endothelial cell networks in methylcellulose culture. In the same conditions, hESCs exhibited convincing hematopoietic differentiation. In cytokine-supplemented EB culture, rESCs demonstrated improved hematopoietic differentiation with higher levels of CD34(+) and detectable levels of CD45(+) cells. However, these levels remained dramatically lower than those for hESCs in identical culture conditions. Subsequent plating of cytokine-supplemented rhesus EBs in methylcellulose culture led to the formation of mixed colonies of erythroid, myeloid, and endothelial cells, confirming the existence of bipotential hematoendothelial progenitors in the cytokine-supplemented EB cultures. Evaluation of four different rESC lines confirmed the validity of these disparities. Although rESCs have the potential for hematopoietic differentiation, they exhibit a pause at the hemangioblast stage of hematopoietic development in culture conditions developed for hESCs.     

In Vitro Selection of Cell Lines in Punica granatum L. (Daru) Against Bacterial Blight

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Disease resistant cell lines of wild pomegranate were selected against bacterial blight caused by Xanthomonas...     

Monoclonal antibodies against recombinant GAPDH of Edwardsiella tarda reveal the conserved nature of the protein

The outer membrane protein, encoded by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, of Edwardsiella tarda is a highly conserved immunogenic protein. The GAPDH was cloned and expressed in Escherichia coli. The purified protein was used to produce mouse monoclonal antibodies (MAbs). Four stable hybridomas producing MAbs (3G12, 4E9, 5A11 and 9G1) against rGAPDH were obtained. The heavy chains of antibodies produced by the hybridomas were of the isotypes IgG1 and IgM. Cross reactivity of MAbs (3G12 and 9G1) was observed with GAPDH of Aeromonas hydrophila and Micrococcus luteus. MAbs 3G12 and 4E9 reacted with Vibrio cholerae, Salmonella enterica and Penaeus monodon tissues but not with vertebrate GAPDH. None of the MAbs reacted with Staphylococcus aureus. The results indicate that the level of conservation of GAPDH is high among evolutionarily close species. The MAbs developed will be a useful tool to study the evolutionarily conserved and functionally diverse GAPDH.     

Relationship between mobility, violence and HIV/STI among female sex workers in Andhra Pradesh, India

ABSTRACT: BACKGROUND: Violence and mobility have been identified as critical factors contributing to the spread of HIV worldwide. This study aimed to assess the independent and combined associations of mobility and violence with sexual risk behaviors and HIV, STI prevalence among female sex workers (FSWs) in India. METHODS: Data were drawn from a cross-sectional, bio-behavioral survey conducted among 2042 FSWs across five districts of southern India in 2005--06. Regression models were used to estimate odds ratios and 95% confidence intervals (CIs) for sexual risk behaviors and HIV infection based on experience of violence and mobility after adjusting for socio-demographic and sex work related characteristics. RESULTS: One-fifth of FSWs (19%) reported experiencing violence; 68% reported travelling outside their current place of residence at least once in the past year and practicing sex work during their visit. Mobile FSWs were more likely to report violence compared to their counterparts (23% vs. 10%, p < 0.001). Approximately 1 in 5 tested positive for HIV. In adjusted models, FSWs reporting both mobility and violence as compared to their counterparts were more likely to be infected with HIV (Adjusted odds ratio (adjusted OR): 2.07, 95% CI: 1.42--3.03) and to report unprotected sex with occasional (adjusted OR: 2.86, 95% CI: 1.76--4.65) and regular clients (adjusted OR: 2.07, 95% CI: 1.40--3.06). CONCLUSIONS: The findings indicate that mobility and violence were independently associated with HIV infection. Notably, the combined effect of mobility and violence posed greater HIV risk than their independent effect. These results point to the need for the provision of an enabling environment and safe spaces for FSWs who are mobile, to augment existing efforts to reduce the spread of HIV/AIDS.