Access to Piperazine-Fused Pyrrolocarbazoles Enabled by Acid-Catalyzed Stereoselective Hydroarylation of Ynamide-Indoles and Subsequent Diels-Alder Reactions/Aromatizations.

Pyrrolocarbazole skeletons are well known to possess a variety of biological activities that might be therapeutically useful in the treatment of cancers. Herein, an acid-catalyzed stereoselective hydroarylation/Diels-Alder cycloaddition/aromatization of ynamide-indoles is described. We newly designed and synthesized a variety of piperazine-fused pyrrolocarbazole derivatives that could be further applied to the synthesis of potent Wee1 inhibitors.

Rhodium(III)-Catalyzed Intramolecular Cyclization and Sequential Aromatization of Ynamides with Propargyl Esters: Access to 2,5-Dihydropyrroles and Pyrroles.

Disclosed herein is a rhodium(III)-catalyzed intramolecular cyclization of ynamides with propargyl esters. A variety of highly functionalized 2,5-dihydropyrroles were obtained in moderate to good yields with high / selectivities. Subsequent oxidation of the products gave valuable pyrrole derivatives.

Rhodium(III)-catalyzed intermolecular [3+3] annulation of benzoxazines with quinone compounds: access to spiro-heterocyclic scaffolds.

A rhodium(III)-catalyzed redox-neutral spiroannulation approach to access the spiro[benzo[][1,4]oxazine-benzo[]chromene skeleton is described in this contribution. A variety of spiro[5.5]-heterocyclic scaffolds were obtained in moderate to excellent yields under mild conditions.

Functional variants in the low-density lipoprotein receptor gene are associated with clear cell renal cell carcinoma susceptibility.

Recent studies indicate that abnormal levels of low-density lipoprotein (LDL), which is an important component of dyslipidaemia, are associated with alterations to cancer risk, including that of renal cell carcinoma (RCC). Single nucleotide polymorphisms at microRNA-binding sites contribute to cancer susceptibility and progression by affecting the messenger RNA (mRNA) function of target genes. In this case-control study, we examined the frequency of six potentially functional single nucleotide polymorphisms in the LDL receptor gene (LDLR) in 1004 clear cell RCC (ccRCC) patients and 1065 cancer-free subjects.

MDM4 genetic variants and risk of gastric cancer in an Eastern Chinese population.

MDM4 is a p53-interacting protein and plays an important role in carcinogenesis. In this study of 1,077 gastric cancer (GCa) cases and 1,173 matched cancer-free controls, we investigated associations between three tagging single nucleotide polymorphisms (SNPs) (rs11801299 G>A, rs1380576 C>G and rs10900598 G>T) in MDM4 and gastric cancer risk in an Eastern Chinese Population. In logistic regression analysis, a significantly decreased GCa risk was associated with the rs1380576 GG variant genotype (adjusted odds ratio [OR] =0.

Associations of genotypes and haplotypes of IL-17 with risk of gastric cancer in an eastern Chinese population.

Interleukin-17 plays a crucial role in inflammation-related carcinogenesis. We hypothesize that genetic variants in IL-17 are associated with gastric cancer (GCa) risk, and we genotyped five potentially functional single nucleotide polymorphisms (SNPs) (rs1974226 G > A, rs2275913 A > G, rs3819024 A > G, rs4711998 A > G, and rs8193036 C > T) of IL-17 in 1121 GCa patients and 1216 cancer-free controls in an eastern Chinese population. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI).

Associations of potentially functional variants in IL-6, JAKs and STAT3 with gastric cancer risk in an eastern Chinese population.

The interleukin-6 (IL-6)/JAK/STAT3 signaling pathway plays a central role in inflammation-mediated cancers, including gastric cancer (GCa). We evaluated associations between 10 potentially functional single nucleotide polymorphisms (SNPs) of four essential genes in the pathway and GCa risk in a study of 1,125 GCa cases and 1,221 cancer-free controls. We found that a significant higher GCa risk was associated with IL-6 rs2069837G variant genotypes [adjusted odds ratios (OR) = 1.

PSCA polymorphisms and gastric cancer susceptibility in an eastern Chinese population.

The prostate stem cell antigen (PSCA) gene, which encodes a prostate-specific antigen (PSA), was identified as a gene involved in cell adhesion and proliferation. The associations between the PSCA rs2294008 and rs2976392 single nucleotide polymorphisms (SNPs) and gastric cancer (GCa) susceptibility were still controversial. To derive a more precise estimation of the associations, we conducted a case-control study of 1,124 cases and 1,192 controls in an eastern Chinese population.

A Functional Polymorphism (rs2494752) in the AKT1 Promoter Region and Gastric Adenocarcinoma Risk in an Eastern Chinese Population.

AKT is an important signal transduction protein that plays a crucial role in cancer development. Therefore, we evaluated associations between single nucleotide polymorphisms (SNPs) in the AKT promoter region and gastric cancer (GCa) risk in a case-control study of 1,110 GCa patients and 1,114 matched cancer-free controls. We genotyped five SNPs (AKT1 rs2494750G >C, AKT1 rs2494752A >G, AKT1 rs10138227C >T, AKT2 rs7254617G>A and AKT2 rs2304186G >T) located in the 5' upstream regulatory, first intron or promoter regions.

Genetic variant of PRKAA1 and gastric cancer risk in an eastern Chinese population.

Published data on the association between PRKAA1 rs13361707 T > C polymorphism and gastric cancer (GCa) susceptibility were inconclusive. To derive a more precise estimation of the association, we conducted a large-scale GCa study of 1,124 cases and 1,194 controls to confirm this association in an eastern Chinese population. Our results showed that the C allele of PRKAA1 rs13361707 increased the GC risk in the study population [CT vs.

Genetic variations in the mTOR gene contribute toward gastric adenocarcinoma susceptibility in an Eastern Chinese population.

Background And Aim: Genetic variants in the mammalian target of rapamycin (mTOR) gene have become an interesting topic for the study of genetic susceptibility to cancer, but their associations with the risk of gastric cancer have not been fully investigated.

Materials And Methods: In a hospital-based case-control study of 1002 gastric cancer patients and 1003 cancer-free controls, we genotyped four potentially functional single nucleotide polymorphisms (SNPs) (rs1034528G>C, rs17036508T>C, rs3806317A>G, and rs2295080T>G) of mTOR and assessed their associations with the risk of gastric cancer using univariate and multivariate logistic regression analyses. We also used the multifactorial dimension reduction analysis to explore possible interactions and the false-positive report probabilities to assess significant findings.

Potentially functional polymorphisms in the ERCC2 gene and risk of esophageal squamous cell carcinoma in Chinese populations.

ERCC2 is indispensable for nucleotide excision repair pathway, and its functional polymorphisms may be associated with cancer risk. In a large case-control study of 1126 esophageal squamous cell carcinomas (ESCC) patients and 1131 controls, we genotyped two SNPs in ERCC2 (rs238406 G > T and rs13181 T > G) and assessed their associations with ESCC risk. We found a significantly elevated ESCC risk associated with the rs238406 T variant genotypes (adjusted OR = 1.

Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis.

Background: Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations.

Methods: We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications.

No association between TGFB1 polymorphisms and late radiotherapy toxicity: a meta-analysis.

Background: Transforming growth factor-beta 1 (TGF-β1) protein may be multifunctional and related to the development of fibrosis, induction of apoptosis, extracellular signaling and inhibition of proliferation in response to radiation-induced DNA damage. Several studies have investigated associations between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late radiation-induced injury of normal tissue, but the conclusions remain controversial.

Methods: We searched three electronic databases (i.

Potentially functional polymorphisms in the CASP7 gene contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population.

Background: Caspase 7 (CASP7) is an important regulator and executioner in the apoptosis pathway and plays a crucial role in cancer development and progression. However, few studies have evaluated associations between functional single nucleotide polymorphisms (SNPs) in the 3' untranslational region (UTR) of CASP7 and risk of gastric cancer.

Methods: In a case-control study of 1117 patients with gastric cancer and 1146 cancer-free controls with frequency matching on age and sex, we genotyped four potentially functional SNPs (rs4353229T>C, rs10787498T>G, rs1127687G>A and rs12247479G>A) located in the microRNA binding sites of the CASP7 3' UTR by using Taqman assays and evaluated their associations with risk of gastric cancer by using logistic regression analyses as well as multifactorial dimension reduction (MDR) analysis.

ERCC1 and ERCC2 variants predict survival in gastric cancer patients.

Purpose: ERCC1 and ERCC2 play critical roles in the nucleotide excision repair pathway that effectively repairs DNA damage induced by chemotherapeutic agents. Therefore, functional single nucleotide polymorphisms (SNPs) in these genes could have an impact on clinical outcomes in cancer patients who received chemotherapy. However, few studies have simultaneously investigated the roles of ERCC1 and ERCC2 SNPs in clinical outcomes in gastric cancer patients.

Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations.

Introduction: Mammalian target of rapamycin complex 1 (mTORC1) is an evolutionary conserved multiprotein complex that functions as a key regulator of gene transcription, protein translation, and autophagy. No studies have assessed associations between functional single nucleotide polymorphisms (SNPs) in mTORC1 genes and risk of esophageal squamous cell carcinoma (ESCC).

Methods: : In a case-control study of 1126 ESCC patients and 1131 cancer-free controls, we genotyped eight SNPs in mTORC1 (mTOR rs1883965 G>A and rs2536 T>C, mLST8 rs3160 C>T and rs26865 G>A, RPTOR rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A) and assessed their associations with risk of ESCC.

Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population.

Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk.

Associations of Lys939Gln and Ala499Val polymorphisms of the XPC gene with cancer susceptibility: a meta-analysis.

XPC polymorphisms may alter DNA repair capacity, thus leading to genetic instability and carcinogenesis. Numerous studies have investigated the associations of XPC Lys939Gln (rs2228001) and Ala499Val (rs2228000) polymorphisms with cancer susceptibility; however, the findings are inconclusive. We searched literature from MEDLINE and EMBASE for eligible publications that assessed the associations between these two polymorphisms and cancer risk.

Polymorphisms in ERCC1 and XPF genes and risk of gastric cancer in an eastern Chinese population.

Background: Inherited functional single nucleotide polymorphisms (SNPs) in DNA repair genes may alter DNA repair capacity and thus contribute to cancer risk.

Methods: Three ERCC1 functional SNPs (rs2298881C>A, rs3212986C>A and rs11615G>A) and two XPF/ERCC4 functional SNPs (rs2276466C>G and rs6498486A>C) were genotyped for 1125 gastric adenocarcinoma cases and 1196 cancer-free controls by Taqman assays. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate risk associations, and false-positive report probabilities (FPRP) were calculated for assessing significant findings.

Tyrosinase inhibitory effects and antioxidative activities of novel cinnamoyl amides with amino acid ester moiety.

Nine cinnamoyl amides with amino acid ester (CAAE) moiety were synthesized by the conjugation of the corresponding cinnamic acids (cinnamic acid, 4-hydroxy cinnamic acid, ferulic acid and caffeic acid) with amino acid esters, and their inhibitory effects on the activities of mushroom tyrosinase were investigated, using l-3,4-dihydroxyl-phenylalanine (l-DOPA) as the substrate. Among these CAAE amides, ethyl N-[3-(4-hydroxy-3-methoxyphenyl)-1-oxo-2-propen-1-yl]-l-phenylalaninate (b(4)) showed the strongest inhibitory activity; the IC(50) was 0.18 μM.