CAR­T cell therapy: A breakthrough in traditional cancer treatment strategies (Review).

Chimeric antigen receptor (CAR)­T cell therapy is an innovative approach to immune cell therapy that works by modifying the T cells of a patient to express the CAR protein on their surface, and thus induce their recognition and destruction of cancer cells. CAR­T cell therapy has shown some success in treating hematological tumors, but it still faces a number of challenges in the treatment of solid tumors, such as antigen selection, tolerability and safety. In response to these issues, studies continue to improve the design of CAR­T cells in pursuit of improved therapeutic efficacy and safety. In the future, CAR­T cell therapy is expected to become an important cancer treatment, and may provide new ideas and strategies for individualized immunotherapy. The present review provides a comprehensive overview of the principles, clinical applications, therapeutic efficacy and challenges of CAR­T cell therapy.

Erratum: Clinical and pathological characteristics of IgG4-related interstitial lung disease.

[This corrects the article DOI: 10.3892/etm.2017.5554.].

Pathogenicity of the MAGE family.

The melanoma antigen gene (MAGE) protein family is a group of highly conserved proteins that share a common homology domain. Under normal circumstances, numerous MAGE proteins are only expressed in reproduction-related tissues; however, abnormal expression levels are observed in a variety of tumor tissues. The MAGE family consists of type I and II proteins, several of which are cancer-testis antigens that are highly expressed in cancer and serve a critical role in tumorigenesis. Therefore, this review will use the relationship between MAGEs and tumors as a starting point, focusing on the latest developments regarding the function of MAGEs as oncogenes, and preliminarily reveal their possible mechanisms.

Prognostic Threshold of Neuroendocrine Differentiation in Gastric Carcinoma: a Clinicopathological Study of 945 Cases.

PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.

Clinical and pathological characteristics of IgG4-related interstitial lung disease.

IgG4-related interstitial lung disease (IgG4-RILD), which is characterized by increased IgG4 levels, IgG4+ plasma cell infiltration and irregular whorled fibrosis, is a recently described lung disorder that belongs to the group of systemic fibroinflammatory IgG4-related diseases (IgG4-RD). The aim of the present study was to improve the current knowledge regarding the specific clinical and histopathological characteristics of IgG4-RILD and to investigate its underlying immune mechanism in vivo. A total of 7 patients newly diagnosed with IgG4-RILD were enrolled in the present study (4 men and 3 women; mean age, 57 years; range, 29-71 years). Patients' clinical history was collected and serological indicators, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), antinuclear antibodies (ANAs) and tumor markers were measured. Serum immunoglobulin G (IgG), IgE and IgG4 levels were also evaluated. In addition, computed tomographic (CT) images and pathological examinations were used to determine the characteristics of lung lesions in all patients. The majority of patients presented with symptoms of fever, cough and dyspnea, while allergic symptoms were also encountered. The laboratory examination results revealed different degrees of increased CRP, ESR, tumor markers, ANA, serum IgE and IgG4. The CT images revealed diffuse ground glass opacities, bronchiectasis and thickened bronchovascular bundles. Histologically, the lung lesions were characterized by dense IgG4+ lymphoplasmacytic infiltrates intermixed with extensive fibrous tissue hyperplasia and an irregularly storiform pattern of fibrosis. The mean number of IgG4+ plasma cells was >10 cells/high power field. The ratio of IgG/IgG4+ plasma cells was >50% in inflamed lesions and the number of parenchymal cells was markedly reduced. Obliterative phlebitis or obliterative arteritis was observed in all patients. In conclusion, the clinicopathological similarities between IgG4-RILD and other IgG4-RD suggest that IgG4-related immunopathological processes may be associated with the pathogenesis of pulmonary lesions. Future studies based on the findings herein may elucidate the specific pathological process underlying the development of this fibroinflammatory disorder.