The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.     

Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance

Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad-) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad- cells. Similarly, proliferation of the 3+Ecad- cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3-Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad- subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad- cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics.     

Drain site evisceration of fallopian tube, another reason to discourage abdominal drain: report of a case and brief review of literature

Placement of a drain following abdominal surgery is common despite a lack of convincing evidence in the current literature to support this practice. The use of intra-abdominal drain is associated with many potential and serious complications. We report a drain site evisceration of the right fallopian tube after the removal of an intra-abdominal drain. The drain was placed in the right iliac fossa in a patient who underwent a lower segment Caesarean section (LSCS) for meconium liquor with fetal distress. The Pfannenstiel incision made for LSCS was reopened and the protruding inflamed fimbrial end of the right fallopian tube was excised. The patient made an uneventful recovery. Routine intra-abdominal prophylactic drain following an abdominal surgery including LSCS should be discouraged.     

The decision-to-delivery interval in emergency Caesarean sections and its correlation with perinatal outcome: evidence from 204 deliveries in a developing country

The international standard decision-to-delivery interval (DDI) for emergency Caesarean sections (CSs) is ≤ 30 minutes but there is little evidence to support this recommendation. The aim of this study was to evaluate DDI for emergency CS and its relationship to perinatal outcome. We undertook a prospective observational study of consecutive cases of emergency CS. Perinatal outcomes were recorded as: Apgar score; neonates requiring admission; and perinatal deaths. The relation between DDI and perinatal outcome was analysed using chi-square and one way analysis of variance (ANOVA). Of 204 pregnancies observed, 19% of deliveries were achieved in ≤ 30 minutes. The mean DDI was 42.5 ± 19.4 minutes. There was no difference between the perinatal outcome for babies with DDI of ≤ 30 versus 31-60 minutes. There was a significantly higher risk of poor perinatal outcome for babies with DDI > 60 minutes. The perinatal outcome between DDI of ≤ 30 and 31-60 minutes was statistically not different. However, the ≤ 30 minutes DDI should remain the gold standard.     

A Comparative Evaluation of the Vertical Root Fracture Resistance of Endodontically Treated Teeth using Different Root Canal Sealers: An in vitro Study

Objective: The objective of this study is to evaluate the vertical root fracture resistance of endodontically treated teeth obturated with - Tubli-Seal EWT/Gutta-percha, AH Plus/Gutta-percha, Epiphany SE sealer/Epiphany point. Study design: Sixty-five single rooted premolars were decoronated and root length was 14 mm for each specimen. Fifty five teeth were enlarged up to ISO size 40 master apical file with stainless steel K-files using standardized preparation and remaining ten teeth were served as negative control. Then teeth were randomly assigned into different groups depending on sealer used for obturation as follows: Group 1: Negative control-no instrumentation was performed. Group 2: Positive control-gutta-percha with out the use of any sealer. Group 3: Experimental group-gutta-percha and Tubli-Seal EWT root canal sealer. Group 4: Experimental group-gutta-percha and AH Plus. Group 5: Experimental group-epiphany SE sealer and epiphany points. After 72 hours, the specimens were embedded in autopolymerizing resin leaving 7 mm of each root exposed and were subjected to fracture testing under universal testing machine at a crosshead speed of 1.0 mm per minute until the root fractured. Results were statistically analyzed using one-way ANOVA and independent t-test. Results: Showed that Epiphany SE sealer/Epiphany points showed highest mean fracture resistance and Tubli-Seal EWT group showed the least fracture resistance of all the materials tested. There was no statistically significant difference among experimental groups. Conclusion: Epiphany SE sealer/Epiphany points demonstrated highest fracture resistance values than the other materials tested and intact tooth had highest resistance against vertical root fracture. Clinical significance: Epiphany SE sealer/Epiphany points may be one of the materials of choice in the endodontic treatment of teeth. Keywords: Epiphany sealer/Epiphany points, AH Plus/Guttapercha, Tubli-Seal EWT, Vertical root fracture. How to cite this article: Nagpal A, Annapoorna BM, Prashanth MB, Prashanth NT, Singla M, Deepak BS, Singh A, Tavane PN. A Comparative Evaluation of the Vertical Root Fracture Resistance of Endodontically Treated Teeth using Different Root Canal Sealers: An in vitro Study. J Contemp Dent Pract 2012;13(3):351-355. Source of support: Nil Conflict of interest: None declared.     

Influence of cigarette smoking on blood and salivary super oxide dismutase levels among smokers and non‐smokers

Aim: To determine the influence of smoking on the blood and salivary superoxide dismutase levels among smokers, and to demonstrate the significance in alterations in the levels of superoxide dismutase in association with patient age, periodontal disease status, and duration and smoking frequency. Methods: Sixty healthy male patients (aged 20–60 years) constituted the target population. Blood and saliva samples were collected, and the periodontal index was measured using a Community Periodontal Index probe. Blood and salivary superoxide dismutase levels were calculated with the reagents prepared, and values were measured in a UV spectrophotometer. Results: There was a significant decrease in mean superoxide dismutase levels with an increase in age and smoking duration and frequency (0.23–0.05 U/mL). There was a range of 0.31–0.06 U/mL variation in the mean superoxide dismutase levels as the periodontal disease condition deteriorated. Conclusions: There was a significant reduction in the superoxide dismutase levels in the blood and saliva of smokers with increased duration and frequency of smoking, and as the periodontal disease condition worsened. Thus, this study emphasizes the importance of saliva as an easy, non‐invasive procedure in the diagnosis of patients who are more prone to precancerous lesions and conditions, and its importance in patient education and motivation programs for smoking cessation.     

Spry1 as a novel regulator of erythropoiesis, EPO/EPOR target, and suppressor of JAK2

Sprouty proteins are established modifiers of receptor tyrosine kinase (RTK) signaling and play important roles in vasculogenesis, bone morphogenesis, and renal uteric branching. Little is understood, however, concerning possible roles for these molecular adaptors during hematopoiesis. Within erythroid lineage, Spry1 was observed to be selectively and highly expressed at CFU-e to erythroblast stages. In analyses of possible functional roles, an Mx1-Cre approach was applied to conditionally delete Spry1. At steady state, Spry1 deletion selectively perturbed erythroid development and led to reticulocytosis plus heightened splenic erythropoiesis. When challenged by hemolysis, Spry1-null mice exhibited worsened anemia and delayed recovery. During short-term marrow transplantation, Spry1-null donor marrow also failed to efficiently rescue the erythron. In each anemia model, however, hyperexpansion of erythroid progenitors was observed. Spry function depends on phosphorylation of a conserved N-terminal PY motif. Through an LC-MS/MS approach, Spry1 was discovered to be regulated via the erythropoietin receptor (EPOR), with marked EPO-induced Spry1-PY53 phosphorylation observed. When EPOR signaling pathways were analyzed within Spry1-deficient erythroid progenitors, hyperactivation of not only Erk1,2 but also Jak2 was observed. Studies implicate Spry1 as a novel regulator of erythropoiesis during anemia, transducer of EPOR signals, and candidate suppressor of Jak2 activity.     

No association between cigarette smoking and incidence of plasma cell myeloma: a meta-analysis of 17 observational studies

Plasma cell myeloma (PCM) is a lymphoproliferative disorder characterized by the malignant growth of monoclonal plasma cells within the bone marrow. Although risk factors for the development of PCM have been identified, the etiology on the majority of patients with PCM remains unclear. Cigarette smoking has been postulated as a potential risk factor for lymphoid malignancies; however, the association with PCM is inconclusive. We have carried out a meta-analysis of observational studies to assess the relationship, if any, between cigarette smoking and PCM. A literature search through December 2011 rendered 4 prospective cohort and 13 case–control studies evaluating such association. Our categorical meta-analysis showed that there is no association between ever, current, and former smokers and PCM.This lack of association was maintained when analyzing by study design, study quality, and geographical area of report. Similarly, meta regression analysis showed no association with the number of cigarettes smoked per day. In conclusion, our meta-analysis shows that there is no relationship between cigarette smoking and an increased incidence of PCM. Future studies should focus on other potential risk factors for PCM.     

Association of antibiotics with status epilepticus

The objective of this study is to evaluate clinical picture, radiological findings and response to treatment in patients with antibiotic associated status epilepticus (SE). In a retrospective review, 12 out of 117 (10%) patients with SE had temporal association with antibiotic administration. Their medical history, clinical findings, and duration and type of SE were recorded. Serum chemistry, blood counts, cranial MRI, EEG and CSF examination were carried out. The offending antibiotics were withdrawn and the patients were treated with phenytoin, lorazepam, sodium valproate or midazolam. The response to treatment was recorded and death during hospital stay noted. The median age of the patients was 36 (18 and 74) years and 5 were females. Eight patients had convulsive and four nonconvulsive SE. The median duration of status was 12 h. The antibiotics related to SE included intravenous cephalosporin (ceftazidime 5, amoxyclavulenic acid 2, piperacillin 2, cefepime 1) and quinolones (levofloxacin 3, ofloxacin 1, ciprofloxacin 2) in isolation or in combinations. Five patients had hepatic (41.7%) and 6 (50%) renal failure; the later received higher than the recommended dose of antibiotics. Cranial MRI was abnormal in 7 out of 9 (77.8%) patients that include cortical lesion in one, corticosubcortical in three and subcortical in three. SE responded to first antiepileptic drug in four and to second in five patients. Three patients (25%) had refractory SE. Eight (66.7%) patients died and death was related to SE in 2 patients. 10% SE patients may be related to antibiotics. Hence the antibiotic should be carefully chosen in patients with hepatic and renal failure, and the dose should be modified.