CD44 is a multistructural and multifunctional cell surface molecule involved in cell proliferation, cell differentiation, cell migration, angiogenesis, presentation of cytokines, chemokines, and growth factors to the corresponding receptors, and docking of proteases at the cell membrane, as well as in signaling for cell survival. All these biological properties are essential to the physiological activities of normal cells, but they are also associated with the pathologic activities of cancer cells. Experiments in animals have shown that targeting of CD44 by antibodies, antisense,and CD44-soluble proteins markedly reduces the malignant activities of various neoplasms, stressing the therapeutic potential of anti-CD44 agents. Furthermore, because alternative splicing and posttranslational modifications generate many different CD44 sequences, including, perhaps, tumor-specific sequences, the production of anti-CD44 tumor-specific agents may be a realistic therapeutic approach. However, in many cancers (renal cancer and non-Hodgkin's lymphomas are exceptions), a high level of CD44 expression is not always associated with an unfavorable outcome. On the contrary, in some neoplams CD44 upregulation is associated with a favorable outcome. Even worse, in many cases different research grows analyzing the same neoplastic disease reached contradictory conclusions regarding the correlation between CD44 expression and disease prognosis, possibly due to differences in methodology. These problems must be resolved before applying anti-CD44 therapy to human cancers.
These data demonstrate for the first time that the prophylactic administration of captopril is effective in preventing colonic fibrosis in TNBS-induced colitis. The antifibrotic action of captopril could be due to the blockade of TGFbeta-1 overexpression, and/or to a direct down-regulation of TGFbeta-1 transcript.
Introduction: Cartilage–hair hypoplasia (CHH) is a rare skeletal dysplasia that presents with various degrees of immunodeficiency, short stature, and a susceptibility to malignancies. Individuals with CHH can present with severe combined immunodeficiency or combined immunodeficiency and are at risk for severe and unusual infections irrespective of their laboratory findings. In addition, individuals with CHH can present with variable skeletal abnormalities, mainly involving the metaphysis of long bones. CHH is a rare disease and familiarity with the variable features is crucial for diagnosis. Methods: We report the clinical, radiological, and genetic findings for 5 patients with proven diagnoses of CHH. Results: In this study we describe a cohort of patients with CHH and present their clinical findings and progressions. In addition, we present the radiological images and the immunological investigations that were done in these patients. Although all the patients in our cohort had poor cellular immunity, they had a variable clinical course. Three out of 5 patients received a bone marrow transplant (BMT) and 2 out of 5 died at an early age (1 after BMT). Those who had poor humoral function had a worse prognosis compared with those with good humoral function. The skeletal findings were characteristic for CHH. Conclusion: CHH is a disease with a variable presentation. Clinicians should be aware of the characteristic skeletal and immunological findings to identify the disease as early as possible. Statement of novelty: We present novel clinical and radiological findings in patients with variable RMRP gene mutations.
(Suppl 1):A1Background Asthma is the most common chronic respiratory disease in childhood. However, it is quite difficult to make a prompt diagnosis of asthma in a child 5 years and younger, partly due to a lack of objective diagnostic means. Our previous studies on susceptibility gene of asthma showed that a gene-gene interaction among 4 single nucleotide polymorphisms including IL13 rs20541 and IL4 rs2243250, ADRB2 rs1042713 and FcER1B rs569108 had a predictable role for asthma in wheezing children. Objective The study was aimed to further investigate the predictive effects of the four-loci interaction model in Chinese preschool children with asthma. Methods A total of 212 wheezing children aged 6 months to 5 years were enrolled and followed up for at least one year at Shanghai Xinhua Hospital between Dec 2014 and Mar 2016. Clinical data and lab findings of atopy were collected. All the children were divided into the high-risk group and the low-risk group according to genotypes of the four-loci interaction model. The differences of clinical features were compared between the two groups. The predictive effects for asthma were analyzed among asthma predictive index (API), 2015 Canadian Diagnostic Criteria for Asthma in Preschoolers and our four-loci interaction model. Results Of all the enrolled 212 children, 117 (55.2%) were assigned into the high-risk group and 95 (44.8%) were the low-risk group. Compared with the low-risk group, the high-risk group had more yearly episodes of wheeze and a higher level of blood eosinophilia. More children in the high-risk group presented with afebrile wheeze, eczema and positive food or aero allergens and had a history of tobacco exposure. If the asthma-predictive effect of positive API was considered as 1, the four-loci interaction model had a sensitivity of 77.2%, a specificity of 80.0% and an AUC area of 0.786 with a modest consistency (P=0.22, Kappa=0.49), while the Canadian criteria had a sensitivity of 97.8%, a specificity of 53.3% and an AUC area of 0.539 with a low consistency (P<0.01, Kappa=0.265).
ConclusionsThe four-loci interaction model is associated with the phenotypes of wheezing in Chinese preschoolers. It has a consistent predictive effect with API for asthma and is more specific than the Canadian criteria in the diagnosis of asthma, which indicates that the four-loci interaction model may be developed as a new objective predictive tool for asthma in Chinese children 5 years and younger.
A2Loss of esophageal epithelial SPINK7 unleashes uncontrolled proteolytic activity, impaired epithelial barrier, defective differentiation and pro-inflammatory cytokine production Background Epithelial barrier impairment has been implicated in the development of allergic disease. However, the molecular mechanisms by which impaired epithelial barrier function induces Th2-type immune responses remain largely unknown. In this study, we examined the role of the serine peptidase inhibitor kazal type (SPINK)7 on epithelial barrier function and mucosal Th2-associated immune responses...
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