Erratum to "Synergistic Effect of Garcinol and Curcumin on Antiproliferative and Apoptotic Activity in Pancreatic Cancer Cells".

[This corrects the article DOI: 10.1155/2012/709739.].

Association Between Programmed Death-Ligand 1 Expression and the Vascular Endothelial Growth Factor Pathway in Angiosarcoma.

Angiosarcoma is a vascular malignancy associated with a poor prognosis and chemotherapy resistance. The tumor immune microenvironment of angiosarcoma has not been characterized. We investigated the expression of programmed death-ligand 1 (PD-L1) and programmed death 1 (PD-1) in angiosarcoma and correlated these findings with vascular endothelial growth factor (VEGF)-related gene expression and survival.

Validation of Gene Expression Signatures to Identify Low-risk Clear-cell Renal Cell Carcinoma Patients at Higher Risk for Disease-related Death.

Background: Approximately 5-10% of patients with "low-risk" clear cell renal cell carcinoma (ccRCC), as stratified by externally validated clinicopathologic prognostic algorithms, eventually have disease relapse and die. Improving prognostic algorithms for these low-risk patients could help to provide improved individualized surveillance recommendations.

Objective: To identify genes that are differentially expressed in patients with low-risk ccRCC who did and did not die of their disease.

Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury.

Hepatic ischemia/reperfusion injury (IRI) and associated inflammation contributes to liver dysfunction and complications after liver surgery and transplantation. Mesenchymal stem cells (MSCs) have been reported to reduce hepatic IRI because of their reparative immunomodulatory effects in injured tissues. Recent studies have highlighted beneficial effects of extracellular vesicles from mesenchymal stem cells (MSC-EV) on tissue injury.

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma.

Background: Genetic alterations in chromatin modulators such as BRCA-1 associated protein-1 (BAP1) are the most frequent genetic alteration in intrahepatic cholangiocarcinomas (CCA). We evaluated the contribution of BAP1 expression on tumor cell behavior and therapeutic sensitivity to identify rationale therapeutic strategies.

Methods: The impact of BAP1 expression on sensitivity to therapeutic agents was evaluated in CCA cells with a 7-fold difference in BAP1 expression (KMBC-low, HuCCT1-high) and genetically engineered haplo-insufficient BAP1 knockout cells.

Extracellular vesicles in liver diseases.

Extracellular vesicles (EVs) are membrane-bound vesicles that are released by cells into their extracellular environment, have selective enrichment of specific proteins and RNA, and can mediate intercellular communication. In this review we highlight recent observations of the role of EVs in liver injury, viral hepatitis, alcoholic or nonalcoholic liver disease, biliary tract disease, and liver cancers. Potential applications as markers of diseases or for therapeutic applications are outlined to emphasize the new opportunities that are arising from the study of EVs.

MicroRNAs as paracrine signaling mediators in cancers and metabolic diseases.

The contribution of microRNAs to the regulation of mRNA expression during physiological and developmental processes are well-recognized. These roles are being expanded by recent observations that emphasize the capability of miRNA to participate in inter-cellular signaling and communication. Several factors support a functional role for miRNA as mediators of cell-to-cell signaling.

Clear Cell Type A and B Molecular Subtypes in Metastatic Clear Cell Renal Cell Carcinoma: Tumor Heterogeneity and Aggressiveness.

Background: Intratumor molecular heterogeneity has been reported for primary clear cell renal cell carcinoma (ccRCC) tumors; however, heterogeneity in metastatic ccRCC tumors has not been explored.

Objective: To evaluate intra- and intertumor molecular heterogeneity in resected metastatic ccRCC tumors.

Design, Setting, And Participants: We identified 111 patients who had tissue available from their primary tumor and at least one metastasis.

In vitro toxicology studies of extracellular vesicles.

Extracellular vesicles (EVs) are membrane-bound vesicles released from cells into the extracellular environment. There is emerging interest in the use of EVs as potential therapeutic interventions. We sought to evaluate the safety of EVs that may be therapeutically used by performing in vitro toxicological assessments.

Long non-coding RNA regulation of liver cancer stem cell self-renewal offers new therapeutic targeting opportunities.

Long non-coding RNAs (lncRNA) are critical regulators of gene expression, and can reprogram the transcriptome to modulate cellular processes involved in cellular growth and differentiation, and thereby contribute to tumorigenesis. In addition to effects on tumor cell growth, survival and cell signaling, lncRNA can modulate cancer stem cell (CSC) behavior, including the expression of pluripotency factors. The identification of lncRNA that are mechanistically linked to cancer stem cell self-renewal and differentiation, or aberrant signaling pathways associated with tumor growth or progression, offer new opportunities for therapeutic intervention.

Long non-coding RNAs as novel targets for therapy in hepatocellular carcinoma.

The recognition of functional roles for transcribed long non-coding RNA (lncRNA) has provided a new dimension to our understanding of cellular physiology and disease pathogenesis. LncRNAs are a large group of structurally complex RNA genes that can interact with DNA, RNA, or protein molecules to modulate gene expression and to exert cellular effects through diverse mechanisms. The emerging knowledge regarding their functional roles and their aberrant expression in disease states emphasizes the potential for lncRNA to serve as targets for therapeutic intervention.

Clear Cell Renal Cell Carcinoma Subtypes Identified by BAP1 and PBRM1 Expression.

Purpose: In clear cell renal cell carcinoma BAP1 and PBRM1 are 2 of the most commonly mutated genes (10% to 15% and 40% to 50%, respectively). We sought to determine the prognostic significance of PBRM1 and BAP1 expression in clear cell renal cell carcinoma.

Materials And Methods: We used immunohistochemistry to assess PBRM1 protein expression in 1,479 primary clear cell renal cell carcinoma tumors that were previously stained for BAP1.

Loss of PBRM1 and BAP1 expression is less common in non-clear cell renal cell carcinoma than in clear cell renal cell carcinoma.

Background: Recurrent mutations in polybromo-1 (PBRM1, ~40%) and BRCA1-associated protein-1 (BAP1, ~10%) occur in clear cell renal cell carcinoma (ccRCC), but their prevalence in non-ccRCC or renal oncocytoma (RO) is unknown. We evaluated loss of PBRM1 and BAP1 staining in ccRCC, papillary RCC (pRCC), chromophobe RCC (chRCC), and RO tumors using an immunohistochemistry assay in which negative staining was associated with loss-of-function mutations.

Methods: We identified 458 patients treated surgically for ccRCC, pRCC, chRCC, and RO between 2004 and 2012.

Inverse association between programmed death ligand 1 and genes in the VEGF pathway in primary clear cell renal cell carcinoma.

Increased angiogenesis and tumor-induced immune evasion are two mechanisms by which clear cell renal cell carcinoma (ccRCC) proliferate and metastasize; however, the relationship between these pathways in human ccRCC is poorly understood. We conducted a nested case-control study using 98 archived tumor samples from patients diagnosed with primary ccRCC between 1990 and 2006, half of which were identified by immunohistochemistry (IHC) as either programmed death ligand 1 (PDL-1)-positive or PDL-1-negative. RNAs were extracted from the formalin-fixed paraffin-embedded tumor slides and the expression of the VEGFA, VEGFR1, VEGFR2, and PDL-1 genes was quantified.

Higher expression of topoisomerase II alpha is an independent marker of increased risk of cancer-specific death in patients with clear cell renal cell carcinoma.

Background: Tumor-based biomarkers of outcome for patients with clear cell renal cell carcinoma (ccRCC) remain limited, especially for those with low-risk disease. Type IIa topoisomerase (TOPOIIa) is a well-known biomarker of DNA replication and a target for antineoplastic agents, but it has not been evaluated as a biomarker of ccRCC outcome.

Objective: To evaluate the association of TOPOIIa expression in ccRCC and risk of cancer-specific death following surgery.

Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low-risk clear cell renal cell carcinoma.

Background: The majority of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have low-risk disease with a < 10% chance of ccRCC-specific death. DNA sequencing revealed that mutations in BAP1 (BRCA1 associated protein-1) occur in 5% to 15% of ccRCC cases and are associated with poor outcomes. The vast majority of BAP1 mutations abolish protein expression.

Garcinol sensitizes human pancreatic adenocarcinoma cells to gemcitabine in association with microRNA signatures.

Background: Alterations in microRNA (miRNA/miR) genes are of biological importance in the pathophysiology of cancers, including pancreatic cancer (PaCa). Although growing evidence supports the role of miRNA in cancer, their response to dietary phytochemicals is less known. Previously, we showed that garcinol induces PaCa cell growth arrest and apoptosis in vitro.

A role for low-abundance miRNAs in colon cancer: the miR-206/Krüppel-like factor 4 (KLF4) axis.

Background: MicroRNAs (miRNAs or miRs) are short non-coding RNAs that affect the expression of genes involved in normal physiology, but that also become dysregulated in cancer development. In the latter context, studies to date have focused on high-abundance miRNAs and their targets. We hypothesized that among the pool of low-abundance miRNAs are some with the potential to impact crucial oncogenic signaling networks in colon cancer.

Synergistic effect of garcinol and curcumin on antiproliferative and apoptotic activity in pancreatic cancer cells.

Pancreatic cancer (PaCa) is a major health concern due to its aggressiveness and early metastasis. Current treatments for PaCa are limited by development of resistance against therapy. As an alternative strategy, we assessed the combinatorial effect of dietary compounds, garcinol and curcumin, on human PaCa cells (BxPC-3 and Panc-1).

MicroRNA profiling of carcinogen-induced rat colon tumors and the influence of dietary spinach.

Scope: MicroRNA (miRNA) profiles are altered in chronic conditions such as cardiovascular disease, diabetes, neurological disorders, and cancer. A systems biology approach was used to examine, for the first time, miRNAs altered in rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine carcinogen from cooked meat.

Methods And Results: Among the most highly dysregulated miRNAs were those belonging to the let-7 family.

MicroRNAs, diet, and cancer: new mechanistic insights on the epigenetic actions of phytochemicals.

There is growing interest in the epigenetic mechanisms that impact human health and disease, including the role of microRNAs (miRNAs). These small (18-25 nucleotide), evolutionarily conserved, non-coding RNA molecules regulate gene expression in a post-transcriptional manner. Several well-orchestered regulatory mechanisms involving miRNAs have been identified, with the potential to target multiple signaling pathways dysregulated in cancer.

Garcinol inhibits cell proliferation and promotes apoptosis in pancreatic adenocarcinoma cells.

Garcinol, or polyisoprenylated benzophenone, isolated from the rind of fruiting bodies of Garcinia indica, has been used in traditional medicine for its potential antiinflammatory and antioxidant properties. The objective of this study was to investigate the effect of garcinol on pancreatic cancer (PaCa) cell viability and proliferation. For this, 2 human PaCa cell lines, BxPC-3 and Panc-1, with wild and mutant k-ras, respectively, were treated with garcinol (0-40 μM).