Dramatic advances in immune therapy have emerged as a promising strategy in cancer therapeutics. In addition to chemotherapy and radiotherapy, inhibitors targeting immune-checkpoint molecules such as ...cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death receptor-1 (PD-1) and its ligand (PD-L1) demonstrate impressive clinical benefits in clinical trials. In this review, we present background information about therapies involving PD-1/PD-L1 blockade and provide an overview of current clinical trials. Furthermore, we present recent advances involving predictive biomarkers associated with positive therapeutic outcomes in cancer immunotherapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Technology offers opportunities to revolutionize medicine and research but can threaten privacy and patient confidentiality. As the scale of patient data explodes, the safety and integrity of medical ...information are increasingly at stake. We highlight security and privacy issues associated with genomic research, medical devices, and wearable technology.
In the original publication of this article 1 the name of the fifth author is uncorrect. The correct name of the fifth author should be Wei-Chiao Chang rather than Wei-Chao Chang. The original ...publication has been corrected.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of ...cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer.
We searched public databases to explore associations between
gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with
gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets.
We found that
mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High
levels were correlated with estrogen receptor negativity (
<0.001), advanced tumor grade (
<0.001), and poor tumor differentiation (
<0.001). GSEA revealed that
-high breast cancers were enriched for gene sets associated with metastasis, progenitor-like phenotypes, and poor prognosis. Multivariable Cox proportional hazards regression analyses of microarray datasets verified that high
gene expression was associated with poor overall survival in a dose-response manner. The prognostic power of
was superior to that of TNM staging and comparable to that of multiple gene signatures.
These findings suggest that
may be a promising prognostic biomarker for patients with breast cancer.
Cholangiocarcinoma is the second most common primary malignant tumor in the liver. It is a tumor that is characteristically
composed of cells resembling those from the bile duct. The disease is ...difficult to diagnose and is usually fatal due to its
late clinical presentation, lack of effective non-operative therapy, and rapid turnover. Most patients have unresectable tumors
at the time of presentation and die within 12 months once diagnosis has been made. Prognosis of intrahepatic cholangiocarcinoma
(ICC) remains very poor. Currently, there is no established therapy once diagnosis is made. In this report, we provide a case
of a patient who presented with ICC and positive history of hepatitis C virus (HCV). The patient also had a strong family
history of cancer. Finally, we attempt to review some of the important developments in the study of ICC, with particular attention
to recent studies linking hepatitis with the disease.
Human mitochondrial pyrroline-5-carboxylate reductase (PYCR) is a house-keeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate to proline. This enzymatic cycle plays pivotal roles ...in amino acid metabolism, intracellular redox potential and mitochondrial integrity. Here, we hypothesize that PYCR1 might be a novel prognostic biomarker and therapeutic target for breast cancer. In this study, breast cancer tissue samples were obtained from Zhejiang University (ZJU set). Immunohistochemistry analysis was performed to detect the protein level of PYCR1, and Kaplan-Meier and Cox proportional analyses were employed in this outcome study. The prognostic significance and performance of PYCR1 mRNA were validated on 13 worldwide independent microarray data sets, composed of 2500 assessable breast cancer cases. Our findings revealed that both PYCR1 mRNA and protein expression were significantly associated with tumor size, grade and invasive molecular subtypes of breast cancers. Independent and pooled analyses verified that higher PYCR1 mRNA levels were significantly associated with poor survival of breast cancer patients, regardless of estrogen receptor (ER) status. For in vitro studies, inhibition of PYCR1 by small-hairpin RNA significantly reduced the growth and invasion capabilities of the cells, while enhancing the cytotoxicity of doxorubicin in breast cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative). Further population study also validated that chemotherapy significantly improved survival in early-stage breast cancer patients with low PYCR1 expression levels. Therefore, PYCR1 might serve as a prognostic biomaker for either ER-positive or ER-negative breast cancer subtypes and can also be a potential target for breast cancer therapy.
Abnormal spindle-like microcephaly-associated (
) protein is essential for mitotic spindle function during cell replication. The present study aimed to evaluate the hypothesis that
serves a critical ...role in cancer invasiveness and may act as a prognostic biomarker in bladder cancer. In total, 6 independent worldwide bladder cancer microarray mRNA expression datasets (n=1,355) with clinical and follow-up annotations were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Reverse transcription-quantitative polymerase chain reaction analysis revealed that
mRNA expression was higher in bladder cancer tissue compared with adjacent normal bladder mucosae in 10 paired human tissue samples (P=0.004).
overexpression in human bladder cancer samples was consistent with the mRNA expression datasets from GEO and TCGA. Bioinformatics analysis indicated that
mRNA expression was significantly associated with grade and tumor node metastasis (TNM) stage in bladder cancer, based on pooled GEO and TCGA datasets (P<0.05). Stratification analysis indicated that the clinical significance of
was particularly pronounced in low-grade or papillary subtypes of bladder cancer. Individual Cox and pooled Kaplan-Meier analyses suggested that
expression was significantly directly correlated with poor overall (OS) and progression-free survival (PFS) in bladder cancer. Multivariate and stratification analyses demonstrated that the prognostic significance of
was evident in low-grade or papillary bladder cancers, yet not in high-grade or non-papillary subgroups. Increased expression of
was associated with poor OS in muscle-invasive bladder cancer and with poor PFS in non-muscle-invasive bladder cancer (P<0.05). Bioinformatics analysis identified the top 11
-related genes on STRING-DB.org. The expression of the majority of these genes was associated with poor outcomes of bladder cancer with statistical significance. Gene set enrichment analysis indicated that the high expression of
could enrich gene signatures involved in mitosis, differentiation and metastasis in bladder cancer. Further analysis of TCGA datasets indicated that increased
expression was significantly associated with higher Gleason score, T stage, N stage and poor clinical outcome in prostate cancer. It was also significantly associated with late TNM stage and poor PFS in renal cell carcinoma. In summary,
may serve as a novel prognostic biomarker for low-grade or papillary bladder cancer.
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