thymosin and Kidney-Neoplasms

Topics: Humans; Immunization, Passive; Immunotherapy; Interferons; Interleukin-2; Kidney Neoplasms; Killer Cells, Natural; Lymphokines; Thymosin; Tumor Necrosis Factor-alpha

Thymosin b10 (TMSB10), a member of the thymosin family, is mainly located in cells and participates in the assembly and occurrence of cytoskeleton. We aimed to investigate the regulatory mechanism of TMSB10 in ccRCC.. In this study, Xiantao Academic Tools were taken to perform the pan-cancer expression and immune infiltration analysis of TMSB10. Furthermore, it is found that there is a binding site for JUN in the promoter region of TMSB10 through the JASPAR database predictive analysis. The CHIP experiment is used to confirm that JUN regulates the expression of TMSB10 through transcription, and to further detect the mRNA expression level of TMSB10 and JUN in ccRCC cell lines by qRT-PCR. Proliferation and apoptosis function analysis was also carried out to determine the functional changes of ccRCC cell lines after the expression of TMSB10 was regulated by JUN transcription.. The results show that TMSB10 is significantly up-regulated in a variety of cancers. Moreover, JUN regulates the high expression of TMSB10 through transcription and further promotes the proliferation of ccRCC cells and inhibits their apoptosis.. In conclusion, this study shows that JUN transcription regulates the high expression of TMSB10 and promotes the progress of ccRCC.

Topics: Apoptosis; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Prognosis; Thymosin

Clear cell renal cell carcinoma (ccRCC) is one of the most common urological malignancies. Identifying novel biomarkers and investigating the underlying mechanism of ccRCC development will be crucial to the management and treatment of ccRCC in patients. Thymosin b10 (TMSB10), a member of the thymosin family, is involved in various physiological processes, including tissue regeneration and inflammatory regulation. Moreover, it has been found to be upregulated in many types of carcinoma. However, its roles in ccRCC remain to be elucidated. The present study aimed to explore the expression of TMSB10 in ccRCC through mining The Cancer Genome Atlas (TCGA) and Oncomine databases, and to investigate the association between TMSB10 expression and clinicopathological factors. Furthermore, immunohistochemistry assays and western blotting were conducted to verify TMSB10 expression levels in human ccRCC tissues and cell lines. Functional analyses were also performed to identify the roles of TMSB10 in vitro. The results revealed that TMSB10 was significantly upregulated in RCC tissues and cell lines. The expression of TMSB10 was closely associated with various clinicopathological parameters. In addition, high expression of TMSB10 predicted poor clinical outcome. The receiver operating characteristic curve revealed that TMSB10 could sufficiently distinguish the tumor from normal kidney (area under the curve = 0.9543, P<0.0001). Furthermore, knockdown of TMSB10 impaired the proliferation of ccRCC cells, and attenuated cell and invasion in vitro. In addition, TMSB10 knockdown downregulated reduced the phosphorylation of PI3K and the expression of vascular endothelial growth factor. In conclusion, the present study demonstrated that high expression of TMSB10 could serve as a useful diagnostic and prognostic biomarker and a potential therapeutic target for ccRCC.

Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Kidney Neoplasms; Male; Neoplasm Staging; Prognosis; Survival Analysis; Thymosin; Up-Regulation

To determine the plasma levels of thymosin-α1 (TA1) and prothymosin-α (PTMA) proteins in renal cell carcinoma (RCC) or urothelial carcinoma (UC) patients, and explore the potential of these 2 molecules as biomarkers.. Blood samples were taken from 50 consecutive patients with RCC, 97 with UC, and 55 with benign urologic diseases before surgery. Their clinical characteristics were obtained from medical record review. Plasma TA1 and PTMA levels were measured using enzyme-linked immunosorbent assay and their correlation with tumor grade, pathologic stage, and survival were explored.. Plasma TA1 levels were significantly lower in RCC patients than in UC or benign patients, particularly in UC of the renal pelvis patients (P < 0.0001). Plasma PTMA levels were also significantly lower in UC patients compared with RCC patients and benign patients (P < 0.05). Plasma TA1 levels inversely correlated with pathologic stage both in bladder cancer and RCC patients (P = 0.03 and 0.02, respectively). Both plasma TA1 and PTMA did not correlate with tumor grade. Plasma TA1 was a prognostic indicator for progression-free and disease-specific overall survival in bladder cancer patients (P = 0.008 and 0.04, respectively).. Plasma TA1 level may be a biomarker for differentiating between UC and RCC. It may also be a prognostic factor for disease progression and disease-specific survival in bladder cancer patients. These findings warrant more studies for validation.

Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Diagnosis, Differential; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Kidney Neoplasms; Neoplasm Grading; Neoplasm Staging; Prognosis; Protein Precursors; Thymalfasin; Thymosin; Urinary Bladder Neoplasms

To investigate the prognostic role of prothymosin-alpha (PTMA) expression in human upper urinary tract transitional cell carcinoma (UUT-TCC).. Paraffin-embedded tissues were collected from 91 patients with UUT-TCC and from 15 paired normal renal cortex and 13 paired urothelial walls. The primary antibody for PTMA (2F11) used was validated in 4 human urothelial cancer cell lines before assessing the surgical specimen. Immunohistochemistry was then conducted to determine the expression intensity of PTMA, the calculation of immunostaining density using imaging analysis, and for immunostaining localization. The correlates with clinicopathologic characteristics and patient survival were explored.. The expression intensity of PTMA demonstrated a significant enhancement of PTMA expression in UUT-TCCs compared with both paired normal tissues (P = .0002 and P = .0004 for UUT-TCC vs the urothelial wall and vs the renal cortex, respectively). As for the localization of PTMA immunoreactivity, of the 91 tumor specimens, 33 (36.3%) were cytoplasmic PTMA-expressing, 51 (56.0%) were nuclear PTMA-expressing, and 7 (7.7%) were PTMA-negative tumors. On univariate and multivariate analyses, PTMA expression localization was the sole independent prognostic indicator for recurrence-free survival (hazard ratio 4.90, 95% confidence interval 1.73-13.9; P = .003), although pathologic staging was an independent prognostic indicator for both progression-free survival (hazard ratio 22.6, 95% confidence interval 2.56-198; P = .005) and disease-specific overall survival (hazard ratio 5.60, 95% confidence interval 1.48-21.2; P = .011). The limitations of our study included small patient numbers and short follow-up.. The results of our study have shown that PTMA is overexpressed in UUT-TCCs and that cytoplasmic PTMA expression can provide significant prognostic information for subsequent tumor recurrence in the residual urinary tract after nephroureterectomy.

Topics: Aged; Aged, 80 and over; Carcinoma, Transitional Cell; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Prognosis; Protein Precursors; Thymosin; Ureteral Neoplasms

Topics: Carcinoma, Transitional Cell; Humans; Kidney Neoplasms; Nephrectomy; Prognosis; Protein Precursors; Thymosin; Ureteral Neoplasms

The structurally related small (< 5 kD) polypeptides, namely thymosins beta-4 and beta-10, were originally defined in the rat immune system. Previously it was shown that both the beta-4 and beta-10 genes are constitutively expressed at higher levels in neoplastic human kidney. Also, it was shown that human embryonic kidney contained more of these proteins than the adult tissue. The present study used a human thymosin beta-10 cDNA to examine the possibility that overexpression of the beta-10 mRNA in renal cell carcinoma was due to gene amplification. Southern blot analysis of genomic DNA extracted from normal and neoplastic tissue indicated no amplification of the thymosin beta-10 gene in RCC. No amplification or rearrangements were found in the human RAR-alpha gene in normal versus RCC tissue. Decreased expression of both the thymosin beta-4 and beta-10 proteins in the normal adult human kidney was found to be derived from a corresponding decrease in levels of the cognate mRNAs. These findings suggest that the thymosin beta-10 gene is deregulated in renal cell carcinoma.

Topics: Adult; Blotting, Southern; Carcinoma, Renal Cell; Gene Amplification; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Receptors, Retinoic Acid; RNA, Messenger; Thymosin

Thymosins beta 4 and beta 10 are 2 structurally related polypeptides originally defined in the rat immune system. To date, no truly unambiguous functions have been formally ascribed to these small (less than 4.9 kDa) acidic proteins. Previous research has demonstrated relationships between expression of these genes and cell growth/differentiation. These observations prompted the present study which has used cDNA and synthetic oligonucleotide probes in combination with high-performance liquid chromatography (HPLC) to examine the differential expression of these 2 genes in normal and neoplastic human tissues and in the developing human kidney. Low levels of beta 4 and beta 10 mRNA species prevailed in normal tissues; in contrast, these gene transcripts were notably more abundant in malignant renal tumors and in the normal human embryonic kidney. These findings show that the thymosin beta 4 and beta 10 genes are constitutively expressed at higher levels in embryonic/neoplastic as compared to normal/benign tissues and that thymosin in beta 10 in particular may be a new molecular marker for renal-cell carcinoma as well as other malignancies.

Topics: Aging; Base Sequence; Blotting, Northern; Breast Neoplasms; Chromatography, High Pressure Liquid; Cloning, Molecular; Female; Gene Expression; Humans; Infant; Kidney; Kidney Neoplasms; Middle Aged; Molecular Sequence Data; Neoplasm Proteins; Neoplasms; Nucleic Acid Hybridization; Oligonucleotide Probes; Ovarian Neoplasms; Reference Values; RNA, Messenger; Thymosin

Topics: Aged; Carcinoma, Renal Cell; Drug Evaluation; Humans; Hyperglycemia; Kidney Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Thymosin

Partially purified thymosin fraction 5 ( TF5 ) was administered to 21 patients with advanced renal cancer. Two different loading dose schedules and doses (60 and 120 mg/m2) of SQ TF5 were employed in 10 patients each. Of 20 evaluable patients, three exhibited partial responses and two exhibited stable disease. All five of these patients had had prior nephrectomies and lung metastases as the dominant site of disease. Toxicity was minimal but included one probable systemic allergic reaction. We could not identify any specific relationship between TF5 dose/schedule or pretreatment immune abnormalities and tumor responsiveness. Our results indicate that the administration of TF5 alone can induce regressions of renal cancer. Additional trials with larger numbers of patients appear to be justified.

Topics: Adult; Aged; Drug Evaluation; Female; Humans; Kidney Neoplasms; Leukocyte Count; Male; Middle Aged; T-Lymphocytes; Thymosin

Topics: Adult; B-Lymphocytes; Breast Neoplasms; Dose-Response Relationship, Immunologic; Humans; Kidney Neoplasms; Melanoma; Middle Aged; Neoplasms; Rosette Formation; T-Lymphocytes; Thymosin; Thymus Hormones