MicroRNAs have key roles in tumor metastasis. Here, we describe the regulation and function of miR-34a and miR-34c (miR-34a/c) in breast cancer metastasis. Expression analysis verified that miR-34a/c expression is significantly decreased in metastatic breast cancer cells and human primary breast tumors with lymph node metastases. Overexpression of miR-34a/c could inhibit breast cancer cell migration and invasion in vitro and distal pulmonary metastasis in vivo. Further studies revealed that Fos-related antigen 1 (Fra-1 or Fosl1) is a downstream target of miR-34a/c as miR-34a/c bound directly to the 3'untranslated region of Fra-1, subsequently reducing both the mRNA and protein levels of Fra-1. Silencing of Fra-1 recapitulated the effects of miR-34a/c overexpression, whereas enforced expression of Fra-1 reverses the suppressive effects of miR-34a/c. Moreover, significant downregulation of miR-34a in metastatic breast cancer tissues was found to be inversely correlated with Fra-1 expression. Our results demonstrate that miR-34a/c functions as a metastasis suppressor to regulate breast cancer migration and invasion through targeting Fra-1 oncogene and suggest a therapeutic application of miR-34 in breast cancer.
We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.
Background
Diagnosing persistent pulmonary consolidation still faces challenges. The purpose of this study is to compare the diagnostic yield and the complication rate between percutaneous transthoracic CT-guided coaxial needle biopsy (PTCNB) and transbronchial lung biopsy (TBLB) of persistent pulmonary consolidation.
Materials
From January 1, 2016, to December 31, 2020, we have retrospectively enrolled a total of 155 consecutive patients (95 males, 60 females) with persistent pulmonary consolidation who underwent both TBLB and PTCNB. According to the standard reference, the diagnostic yield, accuracy, sensitivity and specificity of PTCNB and TBLB were assessed and compared.
Results
According to the standard reference, the final biopsy diagnoses of 11 cases were confirmed true malignant based on the surgical resections, the remaining were confirmed by clinical and imaging follow-up for at least 12 months. The overall diagnostic accuracy, sensitivity and specificity of PTCNB for malignant diagnosis were 91.61%, 72.34% and 100%, whereas of TBLB were 87.74%, 59.57% and 100%. The diagnostic yield of PTCNB and TBLB were 50.32% and 25.16%, respectively. For the TBLB-based negative cases, PTCNB provided a definite diagnostic yield of 37.93%. There were 45 (29.03%), 22 (14.19%) and 13 (8.39%) patients who experienced pneumothorax, intrapulmonary hemorrhage and hemoptysis, respectively, in PTCNB, while there were only 5 (3.22%) cases of mild intraprocedural bleeding occurring in TBLB.
Conclusions
CT-guided co-axial needle biopsy is an effective and safe modality, associated with higher diagnostic yield and better diagnostic accuracy compared to transbronchial lung biopsy for malignancy presenting as persistent consolidation, especially as the complementary method for TBLB-based negative lung lesions.
Key Points
Both PTCNB and TBLB showed high diagnostic accuracy for malignancy.
PTCNB had a higher diagnostic yield than TBLB for persistent pulmonary consolidation.
PTCNB could provide a complementary diagnosis for TBLB-based negative lung consolidation.
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