Additional file 3: Figure S3. of Epidermal growth factor receptor inhibitor with fluorouracil, leucovorin, and irinotecan as an alternative treatment for advanced upper tract urothelial carcinoma: a case report

Electropherogram of exon 2 of the KRAS gene. (TIF 3851 kb

Additional file 2: Figure S2. of Epidermal growth factor receptor inhibitor with fluorouracil, leucovorin, and irinotecan as an alternative treatment for advanced upper tract urothelial carcinoma: a case report

Electropherogram of the telomerase reverse transcriptase (TERT) promoter region. (TIF 3855 kb

Additional file 1: Figure S1. of Epidermal growth factor receptor inhibitor with fluorouracil, leucovorin, and irinotecan as an alternative treatment for advanced upper tract urothelial carcinoma: a case report

(A) Photomicrograph of the rectum showed the presence of neoplastic cells resembling adenocarcinoma (arrow). (B) Microscopic features of renal pelvis revealed infiltrating urothelial carcinoma, high grade (arrow). (C) Microscopic features of ureter revealed infiltrating urothelial carcinoma, high grade (arrow). (D) Microscopic features of bladder revealed infiltrating urothelial carcinoma, high grade (arrow). A–D show hematoxylin and eosin stain, magnification ×200. (TIF 2307 kb

Genetic Variants in <em>CASP3</em>, <em>BMP5</em>, and <em>IRS2</em> Genes May Influence Survival in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy

<div><p>Several genome-wide association studies (GWAS) have been conducted to identify the common single nucleotide polymorphisms (SNPs) that influence the risk of prostate cancer. It was hypothesized that some prostate cancer-associated SNPs might relate to the clinical outcomes in patients treated for prostate cancer using androgen-deprivation therapy (ADT). A cohort of 601 patients who have received ADT for prostate cancer was genotyped for 29 SNPs that have been associated with prostate cancer in Cancer Genetic Markers of Susceptibility GWAS, and within the genes that have been implicated in cancer. Prognostic significance of these SNPs on the disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan-Meier analysis and Cox regression model. Three SNPs, namely <em>CASP3</em> rs4862396, <em>BMP5</em> rs3734444 and <em>IRS2</em> rs7986346, were found to be closely associated with the ACM (<em>P</em>≤0.042), and <em>BMP5</em> rs3734444 and <em>IRS2</em> rs7986346 were also noted to be significantly related to the PCSM (<em>P</em>≤0.032) after adjusting for the known clinicopathologic predictors. Moreover, patients carrying a greater number of unfavorable genotypes at the loci of interest had a shorter time to ACM and PCSM during ADT (<em>P</em> for trend <0.001). Our results suggest that <em>CASP3</em> rs4862396, <em>BMP5</em> rs3734444 and <em>IRS2</em> rs7986346 may affect the survival in patients after ADT for prostate cancer, and the analysis of these SNPs can help identify patients at higher risk of poor outcome.</p> </div

Genotyping frequencies and the association of genotype with PCSM during ADT.

<p>Abbreviations: ADT, androgen-deprivation therapy; HR, hazard ratio; 95% CI, 95% confidence interval; PSA, prostate-specific antigen.</p>*<p><i>P</i> values were calculated using the log-rank test.</p>†<p>HRs were adjusted for age, clinical stage, Gleason score, PSA at ADT initiation, PSA nadir, and time to PSA nadir.</p>‡<p>Unfavorable genotypes refer to GG in BMP5 rs3734444 and TG+GG in IRS2 rs7986346.</p><p><i>P</i>≤0.05 are in boldface.</p

Genotyping frequencies and the association of genotype with disease progression during ADT.

<p>Abbreviations: ADT, androgen-deprivation therapy; HR, hazard ratio; 95% CI, 95% confidence interval; PSA, prostate-specific antigen.</p>*<p><i>P</i> values were calculated using the log-rank test.</p>†<p>HRs were adjusted for age, clinical stage, Gleason score, PSA at ADT initiation, PSA nadir, and time to PSA nadir.</p

The mRNA expressions of endogenous <i>CASP3</i>, <i>BMP5</i> and <i>IRS2</i> in human prostate cancer cell lines.

<p>Total RNAs were prepared from LNCaP, DU 145 and PC-3 cells, and gene expressions were analyzed using real-time RT-PCR. Relative gene expression represents the fold changes in gene expression relative to LNCaP cells set at 1.0. Numbers on the bars represent the difference in threshold cycles between genes of interest and internal control gene. Data are expressed as the mean ± SE of three independent experiments.</p

Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer

<div><p>Although most advanced prostate cancer patients respond to androgen-deprivation therapy (ADT), the efficacy is widely variable. We investigated whether the host genetic variations in sex hormone pathway genes are associated with the efficacy of ADT. A cohort of 645 patients with advanced prostate cancer treated with ADT was genotyped for 18 polymorphisms across 12 key genes involved in androgen and estrogen metabolism. We found that after adjusting for known risk factors in multivariate Cox regression models, <em>AKR1C3</em> rs12529 and <em>AR</em>-CAG repeat length remained significantly associated with prostate cancer-specific mortality (PCSM) after ADT (<em>P</em>≤0.041). Furthermore, individuals carrying two unfavorable genotypes at these loci presented a 13.7-fold increased risk of PCSM compared with individuals carrying zero (<em>P</em><0.001). Our results identify two candidate molecular markers in key genes of androgen and estrogen pathways associated with PCSM after ADT, establishing the role of pharmacogenomics in this therapy.</p> </div

The influence of the genetic loci of interest on prostate cancer prognosis.

<p>Kaplan-Meier curves of (A) time to PCSM during ADT for patients with 0, 1, or 2 unfavorable genotypes at the 2 genetic loci of interest, and (B) time to ACM during ADT for patients with 0, 1, or >1 unfavorable genotypes at the 3 genetic loci of interest; measured in all patients (left), in patients without distant metastasis (middle), or in patients with distant metastases (right). Numbers in parentheses indicate the number of patients.</p

Means ± standard deviations of the baseline characteristics and biochemical variables in the subjects with and without MetS.

<p>BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; DM: diabetes mellitus; CVD: cardiovascular disease; TG: triglyceride; HDL: high density lipoprotein; CHOL(T): total cholesterol; E2: estradiol; SHBG: sex hormone–binding globulin;</p>*<p>: Significant difference (P<0.05).</p