Fusobacterium nucleatum induces chemoresistance in colorectal cancer by inhibiting pyroptosis via the Hippo pathway.

Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific environmental risk factor. In this study, enrichment of F. nucleatum was elucidated to be significantly associated with CRC recurrence after chemotherapy. Functional experiments showed that F. nucleatum could inhibit pyroptosis induced by chemotherapy drugs, thereby inducing chemoresistance. Furthermore, mechanistic investigation demonstrated that F. nucleatum could regulate the Hippo pathway and promote the expression of BCL2, thereby inhibiting the Caspase-3/GSDME pyroptosis-related pathway induced by chemotherapy drugs and mediating CRC cell chemoresistance. Taken together, these results validated the significant roles of F. nucleatum in CRC chemoresistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of CRC.

Spindle cell metaplastic carcinoma of breast: A clinicopathological and immunohistochemical analysis.

AIM: To better characterize spindle cell metaplastic carcinoma (SpCMC) of breast, a rare variant of breast cancer that has been classified under the broad rubric of metaplastic carcinoma. METHODS: We presented herein 19 cases of metaplastic breast carcinoma with dominant spindle cell component. All cases were clinically of breast origin, showed more than 80% spindle morphology, 10 cases exhibited pure spindled morphology, 8 contained invasive ductal carcinoma (IDC) and 1 presented with ductal carcinoma in situ elements. RESULTS: Immunohistochemical studies showed evidence suggesting myoepithelial and epithelial differentiation as exhibited by immunoreactivity for at least one myoepithelial and epithelial markers in all pure spindle cell components. IDC group showed 21.7% of axillary lymph nodes metastasis rate, whereas the axillary lymph node metastasis rate of the SpCMC group was 1.3%, significantly lower than that of the IDC group (P < 0.001). Immunohistochemical staining of IDC exhibited higher degrees of positivity for ER, PR and Her2 (90, 60 and 30%, respectively) when compared with the SpCMC group, which showed a positive degree of 5.2, 5.2 and 10.5% for ER, PR and Her2, respectively (P < 0.001). CONCLUSION: Based on this series, SpCMC is a rare variant of metaplastic breast carcinoma with the distinct histopathological and immunohistochemical features. The biological behaviors of SpCMC, like axillary lymph node status, were quite different from that of IDC, suggesting that it may act as an independent pathologic subtype. Immunohistochemical analysis of a panel of epithelial and myoepithelial markers could contribute to the pathologic diagnosis of SpCMC.

Two novel mutations on exon 8 and intron 65 of COL7A1 gene in two Chinese brothers result in recessive dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa is an inherited bullous dermatosis caused by the COL7A1 gene mutation in autosomal dominant or recessive mode. COL7A1 gene encodes type VII collagen - the main component of the anchoring fibrils at the dermal-epidermal junction. Besides the 730 mutations reported, we identified two novel COL7A1 gene mutations in a Chinese family, which caused recessive dystrophic epidermolysis bullosa (RDEB). The diagnosis was established histopathologically and ultrastructurally. After genomic DNA extraction from the peripheral blood sample of all subjects (5 pedigree members and 136 unrelated control individuals), COL7A1 gene screening was performed by polymerase chain reaction amplification and direct DNA sequencing of the whole coding exons and flanking intronic regions. Genetic analysis of the COL7A1 gene in affected individuals revealed compound heterozygotes with identical novel mutations. The maternal mutation is a 2-bp deletion at exon 8 (c.1006_1007delCA), leading to a subsequent reading frame-shift and producing a premature termination codon located 48 amino acids downstream in exon 9 (p.Q336EfsX48), consequently resulting in the truncation of 2561 amino acids downstream. This was only present in two affected brothers, but not in the other unaffected family members. The paternal mutation is a 1-bp deletion occurring at the first base of intron 65 (c.IVS5568+1delG) that deductively changes the strongly conserved GT dinucleotide at the 5' donor splice site, results in subsequent reading-through into intron 65, and creates a stop codon immediately following the amino acids encoded by exon 65 (GTAA→TAA). This is predicted to produce a truncated protein lacking of 1089 C-terminal amino acids downstream. The latter mutation was found in all family members except one of the two unaffected sisters. Both mutations were observed concurrently only in the two affected brothers. Neither mutation was discovered in 136 unrelated Chinese control individuals. This study reveals novel disease-causing mutations in the COL7A1 gene.

Human leukocyte antigen-G (HLA-G) expression in cervical lesions: association with cancer progression, HPV 16/18 infection, and host immune response.

Human leukocyte antigen-G (HLA-G) expression in 55 cervical intraepithelial neoplasia (CIN) patients with or without human papillomavirus (HPV) infection and 116 patients with squamous cell cervical cancer were examined using immunohistochemistry. Host immune response was assessed by estimating the number of intratumoral lymphocyte infiltration (TIL) in all lesions and counting CD57-expressing cells in the neoplasm lesions. The means of HLA-G immunoreactive scores were compared by the Mann-Whitney test and 1-way analysis of variance (ANOVA). The association of HLA-G expression with disease progression, HPV infection and host immune response was calculated using the Pearson Chi-square test. It was found that HLA-G expression increasingly progressed from patients with CIN 1 to CIN 2/3 and was highest in patients with cervical cancer. Human leukocyte antigen-G expression was also significantly higher in CIN and cancer patients with HPV 16/18 than in CIN patients without HPV. A significant correlation between HLA-G expression and TIL score or the counting of CD57-expressing cells was also evident in CIN patients with HPV infection and cervical cancer cases. These results suggest that HLA-G expression in cervical lesions is associated with carcinogenesis, HPV infection, and host immune response.