Carcinoma‐associated fibroblasts,its implication in head and neck squamous cell carcinoma: a mini review

The communication between tumor stromal and parenchymal cells provides an insight to tumor progression. One of the main elements of the stroma, a major contributor to the extracellular environment of tumors, is carcinoma‐associated fibroblasts. They can originate from either normal fibroblasts in the immediate vicinity of the tumor or from circulating bone marrow–derived mesenchymal stem cells. These myofibroblasts can arise locally from an endothelial–mesenchymal transformation at the invasive edge of the cancer and are physically associated with carcinoma cells, that is, in the development of high‐grade malignancies and poor prognosis. These carcinoma‐associated fibroblasts feed the epithelial tumor cells in a host–parasite relationship establishing its role in head and neck squamous cell carcinoma progression.     

燕滨扶正胶囊治疗代偿期及失代偿期肝硬化临床疗效观察研究

目的 研究中药燕滨扶正胶囊治疗肝硬化（代偿期或失代偿期）临床疗效。方法 选择代偿期及失代偿期肝硬化患者41例,随机分为治疗组（21例）及对照组（20例）。治疗组给予燕滨扶正胶囊1500 mg/次,口服,2次/日。对照组给予扶正化瘀胶囊2500 mg/次,3次/日。两组疗程均为48周。两组依据病情给予抗病毒,护肝降酶、对症支持等一般治疗（替比夫定、甘利欣、消炎利胆片、茵栀黄胶囊等）,观察两组患者症状、血常规、肝功能、门静脉宽度、腹水、肝脏及脾脏形态。结果 中药燕滨扶正胶囊联合抗病毒药物可使代偿期及失代偿期肝硬化患者门静脉宽度、脾肿大回缩或复常,可使纤维化指标复常或大幅下降且肝脏功能好转或复常。结论 燕滨扶正胶囊可改善肝硬化。     

前后路联合手术治疗髋臼双柱骨折疗效分析

目的:探讨前后路联合手术治疗髋臼双柱骨折的效果并分析影响疗效的相关因素。方法:2007年8月至2009年7月收治髋臼双柱骨折患者19例,男13例,女6例;年龄27～52岁,平均39.6岁。高位双柱骨折11例,低位双柱骨折8例,双柱骨折累及骶髂关节1例。受伤至手术时间4～11 d,平均5.8 d。患者均采用前后联合入路手术,重建钢板和螺钉内固定。结果:除1例死亡外本组全部获随访,随访时间12～18个月,平均13.6个月。关节功能根据Harris评分标准,术后功能优9例,良7例,可2例。结论:经前后路联合切开复位内固定治疗髋臼双柱骨折疗效满意。     

Role of the B domain for factor VIII and factor V expression and function

Factor V and factor VIII are homologous cofactors in the blood coagulation cascade that have the domain structure A1-A2-B-A3-C1-C2, of which the B domain has extensively diverged. In transfected COS-1 monkey cells, expression of factor VIII is approximately 10-fold less efficient than that of factor V, primarily because of inefficient protein secretion and, to a lesser extent, reduced mRNA expression. To study the functional significance and effect of the B domain on expression and activity, chimeric cDNAs were constructed in which the B domains of factor V and factor VIII were exchanged. Expression of a factor VIII chimera harboring the B-domain of factor V yielded a fully functional factor VIII molecule that was expressed twofold more efficiently than wild-type factor VIII because of increased mRNA expression. Thus, sequences within the factor VIII B domain were not responsible for the inefficient secretion of factor VIII compared with factor V. Expression of a factor V chimera harboring the B domain of factor VIII was slightly reduced compared with wild-type factor V, although the secreted molecule had significantly reduced procoagulant activity correlating with dissociated heavy and light chains and resistance to thrombin activation. Interestingly, the factor V chimera containing the factor VIII B domain was efficiently activated by Russell's viper venum (RVV). A factor V B domain deletion (residues 710- 1545) molecule also exhibited significantly reduced procoagulant activity caused by resistance to thrombin cleavage and activation, although this molecule was activatable by RVV. These results show that, in contrast to factor VIII, thrombin activation of factor V requires sequences within the B domain. In addition, thrombin activation of factor V occurs through a different mechanism than activation by RVV.     

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.     

Transfected leukocyte integrin CD11b/CD18 (Mac-1) mediates phorbol ester-activated, homotypic cell:cell adherence in the K562 cell line

The CD11b/CD18 leukocyte integrin molecule mediates diverse neutrophil adherence-related functions, including cell:cell and cell:extracellular matrix attachments. To study the individual role of this leukocyte integrin in cell adherence in hematopoietic cells, we expressed the CD11b/CD18 complex on the surface of K562 cells, a cell line derived from an individual with chronic myelogenous leukemia in blast crisis. We used an amphotrophic retroviral vector designated LCD18SN, harboring the complete coding sequence for the CD18 subunit, to transfer the CD18 cDNA into K562 cells and select stable cell lines. The CD11b subunit in the expression plasmid pREP4 was transfected into these K562/CD18 cells by electroporation and stable cell clones were selected. These K562 cells possessed RNA and intracellular protein for each subunit, and they expressed the CD11b/CD18 heterodimer on the cell surface. When CD11b/CD18 expressing K562 cells were stimulated with phorbol myristate acetate (50 ng/mL) for 24 to 48 hours, these K562 cells formed dense cell:cell aggregates. This homotypic aggregation required both activation of the CD11b/CD18 complex and the induction of the counter- receptor for CD11b/CD18 on the conjugate cell. This cell line will (1) enable the structure-function relationships between cell activation and homotypic adherence to be assessed, (2) provide the opportunity to identify accessory molecules required for activation of the CD11b/CD18 complex, and (3) facilitate the identification of novel ligands for the CD11b/CD18 complex.     

The Role of 1N-Ethenoadenosine Triphosphate and 1N-Ethenoadenosine Monophosphate in Firefly Luminescence

1,N⁶-Ethenoadenosine triphosphate (ε-ATP) has been found to be inactive as a substrate for firefly luciferase. However, chemically synthesized luciferyl-εAMP is oxidized by luciferase and light is emitted. The color of the light is red in contrast to the normal yellow-green observed with luciferyladenylate. Although εATP will not serve as a substrate in the activation reaction, the reversal of the activation, pyrophosphorolysis of dehydroluciferyladenylate, will occur with the ethenoadenosine analog.     

Whites and African-Americans in headache specialty clinics respond equally well to treatment

This study sought to determine if Whites and African-Americans respond similarly to headache treatment administered in 'real-world' headache specialty treatment clinics. Using a naturalistic, longitudinal design, 284 patients receiving treatment for headache disorders completed 30-day daily diaries that assessed headache frequency and severity at pretreatment and 6-month follow-up and also provided data on their headache disability and quality of life at pretreatment and 1-, 2- and 6-month follow-up. Controlling for socioeconomic status and psychiatric comorbidity, hierarchical linear models found that African-Americans and Whites reported significant reductions in headache frequency and disability and improvements in life quality over the 6-month treatment period. African-Americans, unlike Whites, also reported significant decreases in headache severity. Nevertheless, Africans-Americans had significantly more frequent and disabling headaches and lower quality of life after treatment relative to Whites. Although Whites and African Americans responded favourably to headache treatments, more efficacious treatments are needed given the elevated level of headache frequency that remained in both racial groups following treatment.     

A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.