Targeting Signaling Pathway Networks in Several Malignant Tumors: Progresses and Challenges.

Malignant tumors remain the health problem of highest concern among people worldwide due to its high mortality and recurrence. Lung, gastric, liver, colon, and breast cancers are among the top five malignant tumors in terms of morbidity and mortality. In cancer biology, aberrant signaling pathway regulation is a prevalent theme that drives the generation, metastasis, invasion, and other processes of all malignant tumors. The Wnt/ß-catenin, PI3K/AKT/mTOR, Notch and NF-kB pathways are widely concerned and signal crosstalks exist in the five solid tumors. This review provides an innovative summary of the recent progress in research on these signaling pathways, the underlying mechanism of the molecules involved in these pathways, and the important role of some miRNAs in tumor-related signaling pathways. It also presents a brief review of the antitumor molecular drugs that target these signaling pathways. This review may provide a theoretical basis for the study of the molecular biological mechanism of malignant tumors and vital information for the development of new treatment strategies with a focus on efficacy and the reduction of side effects.

Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells generated in various pathologic conditions, which have been known to be key components of the tumor microenvironment (TME) involving in tumor immune tolerance. So MDSCs have been extensively researched recently. As its name suggests, immunosuppression is the widely accepted function of MDSCs. Aside from suppressing antitumor immune responses, MDSCs in the TME also stimulate tumor angiogenesis and metastasis, thereby promoting tumor growth and development. Therefore, altering the recruitment, expansion, activation, and immunosuppression of MDSCs could partially restore antitumor immunity. So, this view focused on the favorable TME conditions that promote the immunosuppressive effects of MDSCs and contribute to targeted therapies with increased precision for MDSCs.

[TGFBI gene mutation analysis in a Chinese family with Thiel-Behnke corneal dystrophy].

OBJECTIVE: To identify the gene mutation in autosomal dominant Thiel-Behnke corneal dystrophy affecting a five-generation Chinese family. To study the TGFBI gene mutation in Chinese patients with Thiel-Behnke corneal dystrophy by molecular genetic analysis. METHODS: Ophthalmologic examinations were performed in 10 patients and two normal family members in an autosomal dominant Thiel-Behnke corneal dystrophy family. Five ml peripheral blood was collected and Genomic DNA was extracted using salt fractionation. The exons 4, 7, 8, 11 and 12 of the TGFBI gene were amplified by PCR and mutation analysis was performed by direct sequencing. RESULTS: Mutation analysis of the exons 4, 7, 8, 11 and 12 of the TGFBI gene identified a G-->A missense mutation in the exon 12 by bidirectional sequencing. This mutation resulted in a substitution of glutamine for arginine at amino acid 555 (R555Q) of the protein. This mutation existed in all of the patients, but not in unaffected individuals. CONCLUSION: Thiel-Behnke corneal dystrophy in this family is caused by R555Q mutation of the TGFBI gene, the phenotypes of this corneal dystrophy are closely correlated with TGFBI mutation.

[A research on TGFBI gene mutations in Chinese families with corneal dystrophies].

OBJECTIVE: To identify what kind of TGFBI gene mutation happening to Chinese patients with corneal dystrophies. METHODS: Three Chinese families with stromal corneal dystrophies and one Chinese family with Thiel-Behnke corneal dystrophies were studied, of whom three were Han race and another was Mongolia race in China. All members of families were examined clinically and their genomic DNAs were extracted from blood leukocytes. Thirteen exons in TGFBI gene were amplified by polymerase chain reaction (PCR) and directly sequenced for molecular analysis. RESULTS: Mutations in TGFBI gene were detected from all the patients with corneal dystrophy, but not found in normal subjects of families. The mutation R555W was found and identified from the family with granular corneal dystrophy; R555Q from the family with Thiel-Behnke corneal dystrophy; and R124H from the other two families with Avellino corneal dystrophy. CONCLUSION: The above study results show that the amino acids R124 and R555, if their genetic codes result from the mutations, play an important role in the pathogenesis of autosomal dominant corneal dystrophy of Chinese patients, and the molecular genetic analysis can improve the accuracy of diagnosing corneal dystrophy. In China, the mutation R555Q found in the family with Thiel-Behnke corneal dystrophy is reported for the first time.