Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protons provide the basis for superior distribution of radiation dose due to the physical characteristics of protons. Proton beams used in radiation therapy can be designed to yield a uniform dose across the target and then virtually zero deep to the target and lower dose proximal to the target (for non-superficial lesions). Such beams can be employed in comparable number, direction, weighting, angulation, intensity modulation as is feasible for photon beams. The result is a smaller treatment volume, and hence a lower incidence and frequency of treatment-related morbidity. Importantly, the reduction in treatment volume permits a higher dose to the tumour. This means an improved tumour control probability and lower normal tissue complication probability. Clinical gains appear to have been realized in the treatment of patient with uveal melanoma, skull-base sarcoma, para-nasal sinus carcinomas, selected stages of lung carcinoma and hepatocellular carcinoma. There are now three proton therapy centres with gantry systems with seven more being built. Further, there are seven additional centres in active planning. At present, prospective clinical evaluations are in progress for tumours at many anatomical sites.
 ...
PMID:Protons to replace photons in external beam radiation therapy? 1260 61

Invariant NKT cells (iNKT cells) recognize glycolipid Ags via an invariant TCR alpha-chain and play a central role in various immune responses. Although human CD4(+) and CD4(-) iNKT cell subsets both produce Th1 cytokines, the CD4(+) subset displays an enhanced ability to secrete Th2 cytokines and shows regulatory activity. We performed an ex vivo analysis of blood, liver, and tumor iNKT cells from patients with hepatocellular carcinoma and metastases from uveal melanoma or colon carcinoma. Frequencies of Valpha24/Vbeta11 iNKT cells were increased in tumors, especially in patients with hepatocellular carcinoma. The proportions of CD4(+), double negative, and CD8alpha(+) iNKT cell subsets in the blood of patients were similar to those of healthy donors. However, we consistently found that the proportion of CD4(+) iNKT cells increased gradually from blood to liver to tumor. Furthermore, CD4(+) iNKT cell clones generated from healthy donors were functionally distinct from their CD4(-) counterparts, exhibiting higher Th2 cytokine production and lower cytolytic activity. Thus, in the tumor microenvironment the iNKT cell repertoire is modified by the enrichment of CD4(+) iNKT cells, a subset able to generate Th2 cytokines that can inhibit the expansion of tumor Ag-specific CD8(+) T cells. Because CD4(+) iNKT cells appear inefficient in tumor defense and may even favor tumor growth and recurrence, novel iNKT-targeted therapies should restore CD4(-) iNKT cells at the tumor site and specifically induce Th1 cytokine production from all iNKT cell subsets.
 ...
PMID:Enrichment of human CD4+ V(alpha)24/Vbeta11 invariant NKT cells in intrahepatic malignant tumors. 2063 16

The potential benefits of proton therapy have been established in pediatric cancer, skull base tumor, uveal melanoma, and other types of cancers. Western and Asian countries, however, have differences in the pattern of cancer incidence; this leads to the difference in patient demographics for proton therapy. Furthermore, the advancement of the scanning beam technique in proton therapy greatly expands the capability of proton therapy in disease sites with great complexity. In this review, we focus on the cancers with high incidence in Taiwan, based on the Cancer Registry Annual Report, 2011, Taiwan. The potential case number and clinical benefits from proton therapy are evaluated and discussed. Two endemic cancers, hepatocellular carcinoma and head and neck cancer, are considered to be the major disease types appropriate for proton therapy in Taiwan. Primary lung cancer and left side breast cancer, which are popular in western countries as well as in Taiwan, are included for discussion. The issue of cost-effectiveness for proton therapy is also reviewed. Finally, we point out the clinical trials that should be conducted for proton therapy in Taiwan.
...
PMID:What are the potential benefits of using proton therapy in Taiwanese cancer patients? 2576 24

The cancers are the leading cause of disease-related deaths worldwide with a high risk of morbidity and mortality. Long noncoding RNAs (lncRNAs) play a critical role in a wide range of biological processes, including tumorigenesis. HOXA11-AS (NCRNA00076), the antisense strands of HOXA11 gene, was initially revealed in a mouse embryonic cDNA library in 2009 and it was a fairly novel lncRNA. This review summarized the advanced research progression concerning the expression and role of HOXA11-AS in different human malignancies. The expression of HOXA11-AS is aberrantly altered in many cancers, either as a tumor suppressor or as a tumor accelerator. The different underlying mechanism of HOXA11-AS in different cancers (including, nonsmall cell lung cancers, osteosarcoma, uveal melanoma, glioma, hepatocellular carcinoma, gastric cancer, breast cancer, cervical cancer, ovarian cancer, colorectal cancer, ovarian cancer, and glioblastoma) was also detailed. These findings lead us to conclude that HOXA11-AS participate in the complex network of cancers and plays an important role in the tumorigenesis and progression. Functional HOXA11-AS could be a promising biomarker for early detection as well as prognosis evaluation in cancer patients. Future HOXA11-AS-targeted intervention may become a valuable novel therapeutic tool, improving the clinical management of cancers.
 ...
PMID:HOXA11 antisense long noncoding RNA (HOXA11-AS): A promising lncRNA in human cancers. 2999 90

In recent years, immune checkpoint inhibitor has achieved remarkable success in multiple cancer treatment. However, how to pre-judge which patients are suitable for immune checkpoint inhibitor is a difficult problem. We use the existing public bioinformatics database to comprehensively analyze the relationship between clinical data of various cancers with immune checkpoint blocking molecules and long non-coding RNAs (lncRNAs), and try to find the potential predictive value of lncRNA for immunotherapy with checkpoint inhibitors. In this study, we found that: (a) high expression of lncRNA MIR155 host gene (MIR155HG) was closely related to better overall survival (OS) in cholangiocarcinoma (CHOL), lung adenocarcinoma (LUAD), and skin cutaneous melanoma (SKCM), and have better disease-free survival (DFS) in CHOL. Meanwhile, the high level of MIR155HG was associated with poorer OS in glioblastoma multiforme (GBM), kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and uveal melanoma (UVM). (b) The expression of MIR155HG was significantly correlated with infiltrating levels of immune cells and immune molecules, especially with immune checkpoint molecules such as programmed cell death protein 1 (PD-1), PD-1 ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) in most kinds of cancers. (c) Detection of clinical CHOL and liver hepatocellular carcinoma tissues confirmed that there was a strong positive correlation between MIR155HG expression and the levels of CTLA4 and PD-L1. MIR155 host gene can be used as a prognostic marker in multiple cancers, and of great value in predicting the curative effect of immune checkpoint inhibitor therapy owing to it is closely related with immune cells infiltration and immune checkpoint molecules expression.
 ...
PMID:MIR155HG is a prognostic biomarker and associated with immune infiltration and immune checkpoint molecules expression in multiple cancers. 3156

Non-coding RNAs occupy a significant fraction of the human genome. Their biological significance is backed up by a plethora of emerging evidence. One of the most robust approaches to demonstrate non-coding RNA's biological relevance is through their prognostic value. Using the rich gene expression data from The Cancer Genome Altas (TCGA), we designed Advanced Expression Survival Analysis (AESA), a web tool which provides several novel survival analysis approaches not offered by previous tools. In addition to the common single-gene approach, AESA computes the gene expression composite score of a set of genes for survival analysis and utilizes permutation test or cross-validation to assess the significance of log-rank statistic and the degree of over-fitting. AESA offers survival feature selection with post-selection inference and utilizes expanded TCGA clinical data including overall, disease-specific, disease-free, and progression-free survival information. Users can analyse either protein-coding or non-coding regions of the transcriptome. We demonstrated the effectiveness of AESA using several empirical examples. Our analyses showed that non-coding RNAs perform as well as messenger RNAs in predicting survival of cancer patients. These results reinforce the potential prognostic value of non-coding RNAs. AESA is developed as a module in the freely accessible analysis suite MutEx. Abbreviation: ACC: Adrenocortical Carcinoma (n = 92); BLCA: Bladder Urothelial Carcinoma (n = 412); BRCA: Breast Invasive Carcinoma (n = 1098); CESC: Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (n = 307); CHOL: Cholangiocarcinoma (n = 51); COAD: Colon Adenocarcinoma (n = 461); DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (n = 58); ESCA: Oesophageal Carcinoma (n = 185); GBM: Glioblastoma Multiforme (n = 617); HNSC: Head and Neck Squamous Cell Carcinoma (n = 528); KICH: Kidney Chromophobe (n = 113); KIRC: Kidney Renal Clear Cell Carcinoma (n = 537); KIRP: Kidney Renal Papillary Cell Carcinoma (n = 291); LAML: Acute Myeloid Leukaemia (n = 200); LGG: Brain Lower Grade Glioma (n = 516); LIHC: Liver Hepatocellular Carcinoma (n = 377); LUAD: Lung Adenocarcinoma (n = 585); LUSC: Lung Squamous Cell Carcinoma (n = 504); MESO: Mesothelioma (n = 87); OV: Ovarian Serous Cystadenocarcinoma (n = 608) PAAD: Pancreatic Adenocarcinoma (n = 185); PCPG: Pheochromocytoma and Paraganglioma (n = 179); PRAD: Prostate Adenocarcinoma (n = 500); READ: Rectum Adenocarcinoma (n = 172); SARC: Sarcoma (n = 261); SKCM: Skin Cutaneous Melanoma (n = 470); STAD: Stomach Adenocarcinoma (n = 443); TGCT: Testicular Germ Cell Tumours (n = 150); THCA: Thyroid Carcinoma (n = 507) THYM: Thymoma (n = 124); UCEC: Uterine Corpus Endometrial Carcinoma (n = 560); UCS: Uterine Carcinosarcoma (n = 57); UVM: Uveal Melanoma (n = 80).
 ...
PMID:Advancing Pan-cancer Gene Expression Survial Analysis by Inclusion of Non-coding RNA. 3160 16

Background: The tumor microenvironment (TME) consists of heterogeneous cell populations, including malignant cells and nonmalignant cells that support tumor proliferation, invasion, and metastasis through extensive cross talk. The intra-tumor immune landscape is a critical factor influencing patient survival and response to immunotherapy. Methods: Gene expression data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Immune cell infiltration was determined by single-sample Gene Set Enrichment Analysis (ssGSEA) depending on the integrated immune gene sets from published studies. Univariate analysis was used to determine the prognostic value of the infiltrated immune cells. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen for the most survival-relevant immune cells. An immune-cell characteristic score (ICCS) model was constructed by using multivariate Cox regression analysis. Results: The immune cell infiltration patterns across 32 cancer types were identified, and patients in the high immune cell infiltration cluster had worse overall survival (OS) but better progression-free interval (PFI) compared to the low immune cell infiltration cluster. However, immune cell infiltration showed inconsistent prognostic value depending on the cancer type. High immune cell infiltration (High CI) indicated a worse prognosis in brain lower grade glioma (LGG), glioblastoma multiforme (GBM), and uveal melanoma (UVM), and favorable prognosis in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), cholangiocarcinoma (CHOL), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), sarcoma (SARC), and skin cutaneous melanoma (SKCM). LUAD prognosis was significantly influenced by the infiltration of 13 immune cell types, with high infiltration of all but Type 2 T helper (Th2) cells correlating with a favorable prognosis. The ICCS model based on six most survival-relevant immune cell populations was generated that classified patients into low- and high-ICCS groups with good and poor prognoses, respectively. The multivariate and stratified analyses further revealed that the ICCS was an independent prognostic factor for LUAD. Conclusions: The infiltration of immune cells in 32 cancer types was quantified, and considerable heterogeneity was observed in the prognostic relevance of these cells in different cancer types. An ICCS model was constructed for LUAD with competent prognostic performance, which can further deepen our understanding of the TME of LUAD and can have implications for immunotherapy.
 ...
PMID:Pan-Cancer Analysis of Immune Cell Infiltration Identifies a Prognostic Immune-Cell Characteristic Score (ICCS) in Lung Adenocarcinoma. 3271 16

Combination therapy with inhibitors of cytotoxic T lymphocyte-associated protein (CTLA)4 and programmed death (PD)-1 has demonstrated efficacy in cancer patients. However, there is little information on CTLA4 and PD-1 expression levels and their clinical significance across diverse cancers. In this study, we addressed this question by analyzing PD-1 and CTLA4 levels in 33 different types of cancer along with their prognostic significance using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia datasets. Liver hepatocellular carcinoma (LIHC) patients receiving cytokine-induced killer cell (CIK) immunotherapy at Sun Yat-sen University cancer center were enrolled for survival analysis. The correlation between PD-1/CTLA4 expression and cancer immunity was also analyzed. The results showed that PD-1 and CTLA4 transcript levels varied across cancer cell lines, with aberrant expression detected in certain cancer types; Kaplan-Meier analysis with the Cox proportional hazards model showed that this was closely related to overall survival in breast invasive carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, acute myeloid leukemialymphoma, uterine corpus endometrial carcinoma, and uveal melanoma in TCGA. High serum PD-1 and CTLA4 levels predicted better survival in LIHC patients receiving CIK therapy. PD-1 and CTLA4 levels were found to be significantly correlated with the degree of tumor cell infiltration using Tumor Immune Estimation Resource, Estimating Relative Subsets of RNA Transcripts, and Estimation of Stromal and immune Cells in Malignant Tumor Tissues Using Expression Data as well as with tumor-infiltrating lymphocyte marker expression; they were also related to tumor mutation burden, microsatellite instability, mismatch repair, and the expression of DNA methyltransferases in some cancer types. Gene set enrichment analysis of 33 cancer types provided further evidence for associations between PD-1/CTLA4 levels and cancer development and immunocyte infiltration. Thus, PD-1 and CTLA4 play important roles in tumorigenesis and tumor immunity and can serve as prognostic biomarkers in different cancer types.
 ...
PMID:Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study. 3307 70