• minimally invasive surgery
• necrosectomy
• necrotising pancreatitis
• pancreatic necrosis
• step-up approach

• Combined immunotherapy
• Immunotherapy
• Pancreatic cancer
• Resistance
• Tumor microenvironment
• manipulation

• chemotherapy
• inflammation
• pancreatic cancer
• toll-like receptor

• Animals
• Humans
• Inflammation/complications
• Inflammation/metabolism
• Pancreatic Neoplasms/etiology
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Signal Transduction
• Toll-Like Receptors/metabolism

• pancreatic cancer
• pancreatic cancer diagnosis
• pancreatic cancer immunotherapies
• serological markers

• biomarker
• genomics
• glycomics
• metabolomics
• metagenomics
• omics
• pancreatic cancer
• personalized medicine
• proteomics
• systems biology
• transcriptomics

MicroRNAs (miRNAs) are a family of small non-coding (18–22 nucleotide) RNA molecules. These molecules regulate gene expression by either inhibiting mRNA translation or by degrading mRNA. A single miRNA can control the expression of target genes, and the expression of a target gene can be regulated by multiple miRNAs. They are key regulators of various biological and pathological processes. These include cell proliferation, development and tumorigenesis. Novel studies have discovered definite signature miRNAs in the initiation and progression of cancers. Interestingly, miRNAs have also been found in fragile genomic sites that are associated with increased cancer risk.

These micro RNAs regulate the expression of several genes that play a crucial role in the transition of normal oral mucosa through dysplasia to malignancy. The aim of this review is to recapitulate the current understanding of the many miRNAs that have been identified, the genes that they target and the role that they play in the carcinogenic pathway. The review also highlights the prospective role of miRNAs in the diagnosis, prognosis and treatment of oral cancers.

• Downregulation
• Dysplasia
• Invasion and metastasis
• Proliferation
• Tumorigenesis
• miRNAs

• Ant colony clustering
• Bipartite network
• LncRNA–protein interaction
• Predicting

• HIF-α/VEGF pathway
• MTA1
• Pancreatic cancer
• invasion
• migration

• Animals
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Gene Expression Regulation, Neoplastic
• Histone Deacetylases/genetics
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics
• Mice
• Neoplasm Invasiveness/genetics
• Neoplasm Invasiveness/pathology
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Repressor Proteins/genetics
• Trans-Activators
• Vascular Endothelial Growth Factor A/genetics
• Xenograft Model Antitumor Assays

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• China/epidemiology
• Female
• Geography
• Humans
• Incidence
• Male
• Middle Aged
• Mortality/ethnology
• Mortality/trends
• Pancreatic Neoplasms/epidemiology
• Pancreatic Neoplasms/ethnology
• Pancreatic Neoplasms/mortality
• Rural Population/statistics & numerical data
• Socioeconomic Factors
• Urban Population/statistics & numerical data

• DNA repair pathways
• Targeted therapy
• pancreas cancer
• personalized therapy
• tumor microenvironment

• Adenocarcinoma/pathology
• Adenocarcinoma/therapy
• Animals
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Carcinoma, Pancreatic Ductal/pathology
• Carcinoma, Pancreatic Ductal/therapy
• Humans
• Molecular Targeted Therapy
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/therapy
• Precision Medicine/methods
• Survival Rate
• Tumor Microenvironment

• R21 CA188818 NCI NIH HHS

• immune checkpoint
• immunotherapy
• pancreatic cancer
• pancreatic ductal adenocarcinoma
• precision medicine
• tumor microenvironment
• vaccine

• P50 CA062924 NCI NIH HHS
• P30 CA006973 NCI NIH HHS
• K23 CA148964 NCI NIH HHS
• R01 CA197296 NCI NIH HHS
• R01 CA169702 NCI NIH HHS

• T cells
• Trabectedin
• epigenetics
• pancreatic cancer
• tumor microenvironment

• diagnosis
• driver mutations
• genomic variations
• pancreatic cancer
• therapy

• Drug resistance
• Gemcitabine
• Genes
• MicroRNAs
• Pancreatic ductal adenocancinoma

Altered expression of miR-503 has been linked to human carcinogenesis. In this present study, we aimed to detect the potential for miR-503 as a novel biomarker for gastric cancer (GC) patients.

The relative mRNA level of miR-503 in serum and tissue of 68 GC patients and serum of 32 healthy volunteers was determined by real-time reverse transcription quantitative polymerase chain reaction.

The miR-503 level was significantly lower in the tissue and serum of GC than their counterparts (all P<0.01). Downregulation of miR-503 was found to be corrected with more aggressive tumor. Patients in the high-miR-503 group showed significantly better overall survival compared to the low-miR-503 group (P=0.021). The serum miR-503 level in GC was inversely correlated with carcinoembryonic antigen (CEA) (r=−0.624, P<0.001). Furthermore, the area under the receiver operating characteristic curve for miR-503 discriminating GC patients from healthy individuals was 0.889 (P=0.006), with a sensitivity of 96.8% and a specificity of 79.4%, higher than that of CEA (area under the receiver operating characteristic curve =0.681, P=0.048).

The present study suggests that the expression level of miR-503 may serve as prognostic and diagnostic biomarker for GC.

• biomarker
• diagnosis
• gastric cancer
• microRNA
• prognosis

Mitochondria have long been recognized as the main source of energy production for the eukaryotic cell. Recent studies have found that the mitochondria have a variety of dynamic functions aside from the production of energy. It communicates bidirectionally with other organelles in order to modulate its energy balance efficiently, as well as maintain homeostasis, ultimately prolonging its own and the cell’s longevity. The mitochondria achieves this level of regulation via specific and common bidirectional chemical messengers, especially involving the endoplasmic/sarcoplasmic reticulum (ER/SR), deoxyribonucleoside triphosphates (dNTP’s), ATP and the generation of reactive oxygen species (ROS). Its communication network is also involved in stress associated events. In this regard, the activation of the Bax family proteins and the release of cytochrome c occurs during cellular stress. The communication can also promote apoptosis of the cell. When mitochondrial abnormalities cannot be dealt with, there is an increased chance that major illnesses like type 2 diabetes, Alzheimer’s disease, and cancer may occur. Importantly, functioning chloroplasts can be found in animals, suggesting conserved chemical messengers during its evolutionary path. The dynamic capacity of mitochondria is also noted by their ability to function anaerobically. Indeed, this latter phenomenon may represent a return to an earlier developmental stage of mitochondria, suggesting certain disorders result from its untimely appearance.

• Cervical cancer
• microRNA-26b
• overall survival
• quantitative RT-PCR
• recurrence-free survival

• Adenocarcinoma/genetics
• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Adenocarcinoma/therapy
• Biomarkers, Tumor/genetics
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/mortality
• Carcinoma, Squamous Cell/secondary
• Carcinoma, Squamous Cell/therapy
• Chi-Square Distribution
• Disease-Free Survival
• Down-Regulation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Lymphatic Metastasis
• MicroRNAs/genetics
• Middle Aged
• Multivariate Analysis
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Proportional Hazards Models
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors
• Time Factors
• Treatment Outcome
• Uterine Cervical Neoplasms/genetics
• Uterine Cervical Neoplasms/mortality
• Uterine Cervical Neoplasms/pathology
• Uterine Cervical Neoplasms/therapy

Altered miR-148/152 family expression contributes to human carcinogenesis. This study was designed to detect the potential for using miR-148/152 family as biomarkers for NSCLC patients.

The relative expression levels of miR-148/152 family (miR-148a, miR-148b, and miR-152) in serum of 36 non-small-cell lung carcinoma (NSCLC) patients, 20 patients with benign pulmonary diseases (BPD), and 10 healthy individuals were assessed by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).

The expression of all three miRNAs were significantly lower in the serum of NSCLC than that of BPD and healthy controls (all p<0.01), and their expression levels were strongly correlated with each other (r=0.781, 0.720, and 0.645, respectively). Downregulation of miR-148/152 family was found to be corrected with more aggressive tumors. The area under the receiver operating characteristic curves (AUCs) for miR-148a, miR-148b, and miR-152 discriminating NSCLC from BPD were 0.775, 0.725, and 0.774, respectively, all higher than that of CEA (0.506). Combining the three miRNAs increased the discrimination performance, yielding an AUC of 0.789 (95% confidence interval, 0.643 to 0.895), with a sensitivity of 72.2% and a specificity of 90.0%.

The results of present study suggest that the expression levels of circulating miR-148/152 family may serve as biomarkers for NSCLC.

• micrornas
• mouth neoplasms
• prognosis

• Aged
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Case-Control Studies
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Mouth Neoplasms/genetics
• Mouth Neoplasms/pathology
• Multivariate Analysis
• Prognosis
• Real-Time Polymerase Chain Reaction

Personalized medicine’s foundation rests on the use of molecular technologies, which are being used to identify genetic mutations, polymorphisms, and variants that can be associated with an individual’s genetic make up, revealing risk factors and predictive data. Needless to say this same analysis can be performed on various types of cancers, including samples stored for many years under the right conditions. For the most part, these technologies employ microarray and RNA-Seq methodologies, which examine large numbers of gene expressions at a time, providing clustering and patterns of this expression. The methodologies and their evaluative outcomes further demonstrate that more than a single gene is involved with various phenomena. However, given the mass of data emerging from this analysis, and commonalities they reveal between various phenomena/disorders, achieving 100% certainty may not be that easy. Another outcome from this massive store of molecular data is the concept of one medicine. This field has been developed by researchers in a variety of disciplines (e.g., medical and veterinary science) that advocate for greater integration of animal and human health. One medicine takes advantage of the fact that molecular commonalities in major biochemical pathways occur because of evolutionary conservation, which is dependent on stereospecificity. In this regard, the foci of personalized medicine and one medicine are quite broad and require trained professionals, as well as a lowering of cost in order to be better integrated into mainstream medical practice.

• Diagnosis
• Pancreatic cancer
• Pathogenesis
• Therapy
• miRNA

• biomarkers
• cancer
• companion diagnostics
• epidemiology
• epigenetics
• genomics
• omics technologies
• outcome
• personalized medicine
• pharmacogenomics

Pancreatic ductal adenocarcinoma (PDAC) is a type of highly lethal malignant tumor. PDAC is locally invasive and is surrounded by a dense desmoplasia or fibrosis, which can involve adjacent vital structures. Previously, the effect of pancreatic stellate cells (PSCs) of stroma in the progression of PDAC has received more attention, and most in vitro and in vivo studies revealed that PSCs appear to confer biological aggressiveness. However, clinical trials targeting desmoplasia or PSCs showed disappointing results. Recent studies found that stromal components, especially activated PSCs, are able to inhibit the occurrence and progression of PDAC. Inhibition of the stroma or desmoplasia through genetic regulations or drugs accelerates the formation and progression of PDAC. Thus, we hypothesized that in various times and spaces, there is a balance between the tumor epithelia and stroma; once the balance is upset, the tumor traits may undergo certain changes. Therefore, finding the key changing points of this relationship to corrupt or influence it, instead of blindly inhibiting the stroma motivation or simply maintaining stroma activation, will destroy the cooperation or promote the competition and antagonism among cells. This approach may render tumors more vulnerable and thus unable to resist anti-cancer therapies.

• Chemotherapy
• FOLFIRINOX
• Pancreatic cancer
• Pancreatic oncology
• Pancreatic resection
• Pancreaticoduodenectomy
• Treatment advances

• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Early Detection of Cancer/trends
• Gastroenterology/trends
• Humans
• Medical Oncology/trends
• Molecular Diagnostic Techniques/trends
• Molecular Targeted Therapy/trends
• Neoadjuvant Therapy/trends
• Pancreatectomy/adverse effects
• Pancreatectomy/mortality
• Pancreatectomy/trends
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/therapy
• Patient Selection
• Precancerous Conditions/genetics
• Precancerous Conditions/metabolism
• Precancerous Conditions/mortality
• Precancerous Conditions/pathology
• Precancerous Conditions/therapy
• Precision Medicine/trends
• Predictive Value of Tests
• Risk Factors
• Treatment Outcome

Pancreatic cancer is one of the most lethal cancers. Increasing incidence and mortality indicates that there is still much lacking in detection and management of the disease. This is partly due to a lack of specific symptoms during early stages of the disease. Several growth factor receptors have been associated with pancreatic cancer. Here, we have investigated if an RNA interference approach targeted to IGF-IR could be effective and efficient against pancreatic cancer growth and metastasis. For that, we evaluated the effects of IGF-1R inhibition using small interfering RNA (siRNAs) on tumor growth and metastasis in HPAC and PANC-1 pancreatic cancer cell lines. We found that silencing IGF-1R inhibits pancreatic cancer growth and metastasis by blocking key signaling pathways such AKT/PI3K, MAPK, JAK/STAT and EMT. Silencing IGF-1R resulted in an anti-proliferative effect in PANC-1 and HPAC pancreatic cancer cell lines. Matrigel invasion, transwell migration and wound healing assays also revealed a role for IGF-1R in metastatic properties of pancreatic cancer. These results were further confirmed using Western blotting analysis of key intermediates involved in proliferation, epithelial mesenchymal transition, migration, and invasion. In addition, soft agar assays showed that silencing IGF-1R also blocks the colony forming capabilities of pancreatic cancer cells in vitro. Western blots, as well as, flow cytometric analysis revealed the induction of apoptosis in IGF-1R silenced cells. Interestingly, silencing IGF-1R also suppressed the expression of insulin receptor β. All these effects together significantly control pancreatic cancer cell growth and metastasis. To conclude, our results demonstrate the significance of IGF-1R in pancreatic cancer.

• Apoptosis/genetics
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation
• Epithelial-Mesenchymal Transition/genetics
• Gene Knockdown Techniques
• Humans
• MAP Kinase Signaling System/genetics
• Molecular Targeted Therapy
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• RNA Interference
• RNA, Small Interfering/genetics
• Receptor, IGF Type 1/deficiency
• Receptor, IGF Type 1/genetics

Despite progresses in diagnosis and treatment, pancreatic cancer continues to have the worst prognosis of all solid malignant tumors. Recent evidences suggest that the metastasis-promoting protein S100P stimulates pancreatic tumor proliferation, survival, invasion and metastasis progression through extracellular functions. Moreover, its expression is strongly correlated with poor prognosis in patients with several types of cancer although the entire molecular mechanism responsible for the diverse biological functions is not fully understood. We showed that extracellular S100P stimulates pancreatic carcinoma BxPC3 cell line by promoting cell proliferation. We also demonstrated that S100P induces, in this cell line, the phosphorylation of IκBα and the secretion of matrix metalloproteinase 9 (MMP-9). In addition, treatment with S100P protected cells from injuries induced by the cytotoxic agent Gemcitabine. On the basis of these results, we developed function-blocking anti-S100P monoclonal antibodies (mAbs) that abolished all of its in vitro activities. Furthermore, in vivo treatment with the candidate 2H8 antibody decreased tumor growth and liver metastasis formation in a subcutaneous and orthotopic BxPC3 tumor model. We conclude here that a therapeutic strategy blocking the extracellular activity of S100P by means of specific mAbs could be an attractive therapeutic approach as a single agent or in combination with target-directed or chemotherapeutic drugs to treat pancreatic cancer.

• Female
• Humans
• Male
• MicroRNAs/blood
• Pancreatic Neoplasms/diagnosis
• Pancreatitis, Chronic/diagnosis

• P20 CA101955 NCI NIH HHS
• P50 CA101955 NCI NIH HHS
• U01 CA152758 NCI NIH HHS