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1.
Front Immunol ; 15: 1426620, 2024.
Article in English | MEDLINE | ID: mdl-39035010

ABSTRACT

The nucleotide-binding and oligomerization domain-like receptors (NLRs) NLR family CARD domain-containing protein 5 (NLRC5) and Class II Major Histocompatibility Complex Transactivator (CIITA) are transcriptional regulators of major histocompatibility complex (MHC) class I and class II genes, respectively. MHC molecules are central players in our immune system, allowing the detection of hazardous 'non-self' antigens and, thus, the recognition and elimination of infected or transformed cells from the organism. Recently, CIITA and NLRC5 have emerged as regulators of selected genes of the butyrophilin (BTN) family that interestingly are located in the extended MHC locus. BTNs are transmembrane proteins exhibiting structural similarities to B7 family co-modulatory molecules. The family member BTN2A2, which indeed contributes to the control of T cell activation, was found to be transcriptionally regulated by CIITA. NLRC5 emerged instead as an important regulator of the BTN3A1, BTN3A2, and BTN3A3 genes. Together with BTN2A1, BTN3As regulate non-conventional Vγ9Vδ2 T cell responses triggered by selected metabolites of microbial origin or accumulating in hematologic cancer cells. Even if endogenous metabolites conform to the canonical definition of 'self', metabolically abnormal cells can represent a danger for the organism and should be recognized and controlled by immune system cells. Collectively, new data on the role of NLRC5 in the expression of BTN3As link the mechanisms regulating canonical 'non-self' presentation and those marking cells with abnormal metabolic configurations for immune recognition, an evolutionary parallel that we discuss in this perspective review.


Subject(s)
Butyrophilins , Intracellular Signaling Peptides and Proteins , Humans , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Butyrophilins/metabolism , Butyrophilins/genetics , Butyrophilins/immunology , Animals , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Trans-Activators/genetics , Trans-Activators/metabolism , Gene Expression Regulation , Lymphocyte Activation/immunology , Antigens, CD
2.
Anticancer Agents Med Chem ; 17(7): 955-960, 2017.
Article in English | MEDLINE | ID: mdl-27539314

ABSTRACT

BACKGROUND: Studies have shown that the renin angiotensin system via angiogenesis is involved in tumor development. OBJECTIVE: Therefore, objective of the present study was to examine the effect of perindopril on tumor growth and angiogenesis in animal models of breast cancer. METHODS: In the present study, the effect of perindopril on tumor development of mammary gland cancer induced by 7,12-dimethylbenz[a]anthracene, mouse tumor xenograft and corneal micropocket model has been investigated. Anti-angiogenic effect by chick yolk sac membrane assay has also been studied. RESULTS: In the present study, it has been found that perindopril produced a significant inhibition of tumor growth, in DMBA induced breast cancer. Treatment also produced significant suppression of cancer biomarkers such as lactate dehydrogenase, gamma glutamyl transferase and inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate. Histopathological analysis also showed that perindopril was able to inhibit tumor development by the inhibition of hyperplastic lesions. Perindopril produced significant inhibition of tumor growth, in a mouse xenograft model and caused inhibition of neovascularization in the corneal micropocket model. In chick yolk sac membrane assay, perindopril showed inhibition of vascular growth and reduced blood vessel formation. CONCLUSION: Therefore, perindopril is widely used in clinical practice, may represent a neo-adjuvant therapy for treatment of breast cancer.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Breast Neoplasms/drug therapy , Breast/drug effects , Neovascularization, Pathologic/drug therapy , Perindopril/therapeutic use , Animals , Breast/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Chick Embryo , Chickens , Cornea/blood supply , Cornea/metabolism , Cornea/pathology , Disease Models, Animal , Disease Progression , Female , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolism
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