RESUMO
The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1-8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member's chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment.
Assuntos
Quimiocinas , Proteínas com Domínio MARVEL , Neoplasias , Humanos , Quimiocinas/genética , Proteínas com Domínio MARVEL/genética , Transdução de Sinais , Neoplasias/genéticaRESUMO
Common variants of the transcription factor 7-like 2 (TCF7L2) gene were identified as one of the few genetic polymorphisms with powerful effects on the risk of type 2 diabetes (T2D). Given the genetic overlap between polycystic ovary syndrome (PCOS) and T2D, the present study was undertaken to investigate whether the TCF7L2 variants are also associated with PCOS. We analyzed single nucleotide polymorphisms (SNPs) rs11196218 and rs290487 of the TCF7L2 gene, which showed robust associations with T2D in Chinese population, in 430 PCOS patients and 360 control subjects by pyrosequencing, and also assessed the effect of genotype on clinical and biochemical traits in the PCOS group. We found no evidence for association between SNP rs11196218 and PCOS. The SNP rs290487 showed marginal differences in genotype frequencies between the PCOS and control group, with the minor C allele being the at-risk allele for PCOS. In PCOS women, the C allele carriers of rs290487 had higher levels of 2h blood glucose but lower insulinogenic index than noncarriers, suggesting impaired insulin secretion. Our data suggested that the TCF7L2 variants may confer an increased risk for early impairment of glucose homeostasis in PCOS.
Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Adulto , Alelos , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Heterozigoto , Hospitais Universitários , Humanos , Hiperglicemia/etiologia , Infertilidade Feminina/etiologia , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Adulto JovemRESUMO
In the crystal of the title compound, C(17)H(17)N(3)O(2), the mol-ecules exist in the keto-enamine form. The pyrazole ring is oriented at 10.59â (4) and 57.98â (5)° to the phenyl and furyl rings, respectively, and the dihedral angle between phenyl and furyl rings is 73.30â (11)°. An intra-molecular N-Hâ¯O hydrogen bond occurs between imino and carbonyl groups. In the crystal, weak C-Hâ¯O hydrogen bonds link the mol-ecules into supra-molecular chains along the b axis.
RESUMO
Docetaxel-mediated chemotherapy is the first line therapy for metastatic castration-resistant prostate cancer (CRPC) patients, but its therapeutic benefit is limited by the development of resistance. Although Forkhead box protein M1 (FOXM1) has been implicated in prostate tumorigenesis and metastasis, its role in docetaxel resistance has not been studied. Here, we showed that FOXM1 expression was upregulated in the docetaxel resistant CRPC cell lines (PC3-DR and VCaP-DR) and knockdown of FOXM1 sensitized the cells to docetaxel both in vitro and in vivo. In addition, autophagy was found to be significantly enhanced in resistant cells. Moreover, FOXM1 overexpression cells showed increased autophagic flux and higher numbers of autophagosomes. Knockdown of ATG7, beclin-1 or cotreatment with chloroquine, partly restored sensitivity to docetaxel in the FOXM1-overexpressing cells. Mechanistically, FOXM1 targeted AMPK/mTOR to activate the autophagy pathway and altered docetaxel response in CRPC. These findings identify the role of FOXM1 as well as the mechanism underlying FOXM1 action in docetaxel sensitivity and may, therefore, aid in design of CRPC therapies.
Assuntos
Proteína 7 Relacionada à Autofagia/genética , Docetaxel/farmacologia , Proteína Forkhead Box M1/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Serina-Treonina Quinases TOR/genética , Quinases Proteína-Quinases Ativadas por AMP , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína 7 Relacionada à Autofagia/antagonistas & inibidores , Proteína Beclina-1/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cloroquina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Proteína Forkhead Box M1/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Proteínas Quinases/genéticaRESUMO
In the title compound, C(11)H(10)ClN(3)S, the dihedral angle between the benzene and pyrimidine rings is 3.99â (4)°. In the crystal, inter-molecular N-Hâ¯N hydrogen bonds link the mol-ecules into ribbons of R(2) (2)(8) rings parallel to [100]. Weak C-Hâ¯S contacts connect adjacent ribbons into a two-dimensional undulating layer-like structure extending parallel to (110). The benzene and pyrimidine rings of adjacent mol-ecules have the offset face-to-face π-π stacking inter-actions in a zigzag fashion along the c axis, with perpendicular ring distances of 3.463 and 3.639â Å, and a dihedral angle between the planes of 3.99â (2)°. The distance between the ring centroids is 4.420â (2)â Å.
RESUMO
The title complex, [Cu(C(7)H(3)NO(4))(H(2)O)(2)](n), was prepared under hydro-thermal reaction conditions. In the crystal structure, the Cu(II) cation is located on a twofold rotation axis and is coordinated by two carboxyl-ate O atoms and one N atom from three pyridine-3,5-dicarboxyl-ate (PDA) anions and two water mol-ecules with a distorted trigonal-bipyramidal geometry. The tridentate PDA anion is also located on the twofold rotation axis and bridges the Cu(II) cations to form a two-dimensional polymeric layer. O-Hâ¯O hydrogen bonding between layers links the two-dimensional layers into a three-dimensional supra-molecular framework.
RESUMO
In the title mononuclear complex, [Zn(N(3))(2)(C(8)H(8)N(6))(2)], the Zn(II) atom, lying on a twofold rotation axis, is six-coordinated in a distorted octa-hedral environment by four N atoms from two 2,4-diamino-6-(2-pyrid-yl)-1,3,5-triazine ligands and two N atoms from two end-on-coordinated azide ions. N-Hâ¯N hydrogen bonds between the ligand and azide ion link the complex mol-ecules into a three-dimensional network.
RESUMO
The title compound, [Eu(C(12)H(9.33)N(2)O)(3)]NO(3), was obtained by the reaction of Eu(NO(3))·3H(2)O and the Schiff base ligand 2-(2-pyridylimino-meth-yl)phenol. The Eu atom is located on a threefold rotation axis and is nine-coordinated by three tridentate Schiff base ligands in a distorted tricapped trigonal-prismatic geometry. The O atom at the phenol hydr-oxy group is partially deprotonated and the H atoms are modelled with one-third occupancy according to the space group R. Offset face-to-face π-π [centroid-centroid distance = 3.886â (3)â Å] and edge-to-face C-Hâ¯π inter-actions are found between adjacent mol-ecules. An intra-molecular O-Hâ¯N hydrogen bond is also present.
RESUMO
OBJECTIVE: To investigate the effects of Artesunate(Art) on the LX-2 cell. METHODS: The cultured hepatic stellate cells were divided into control group and Art-treated groups with 250,350,450 µmol/L. The rate of cellular proliferation was detected by MIT assay, the content of ceramide (Cer)was determined by HPLC method, the content of hydroxyproline (Hyp) was determined by enzyme digestion method, the expressions of PPAR-γ, p53 and Caspase 3 were detected by Western blot. RESULTS: Compared with control group, IX-2 treated with Art were inhibited in a concentration-dependent manner(P < 0.01). Art could significantly increase the content of cerarnide in LX-2 ( P <0.01), and the content of Hyp was significantly decreased (P <0.05, P <0.01). The expressions of PPAR-γ, p53 and Caspase 3 were increased compared with that of control group(P < 0.01). CONCLUSION: Artesunate could inhibit the proliferation and induce apoptosis of hepatic stellate cells through upregulating ceramide.