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Journal of the National Medical... Jun 1980Carcinoma of pancreas is not uncommon in Africa where the prognosis seems to be worse than in cases seen in Europe and North America. The reason for this poor prognosis...
Carcinoma of pancreas is not uncommon in Africa where the prognosis seems to be worse than in cases seen in Europe and North America. The reason for this poor prognosis is because patients with this disease are seen in medical institutions at late stages.There seems to be a rise also in the incidence of this disease in our environment. This increased incidence may be real or apparent, and may be related to the rise in hospital consciousness in the population.As seen in Ibadan, the pattern of the disease is not much different from that reported from other parts of Africa.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Male; Middle Aged; Nigeria; Pancreatic Neoplasms
PubMed: 7392077
DOI: No ID Found -
Cancer Imaging : the Official... Oct 2010Pancreatic carcinoma is the fourth cause of death from cancer in the United States, with a survival rate at 5 years of less than 5%. About 60% of tumors originate at the... (Review)
Review
Pancreatic carcinoma is the fourth cause of death from cancer in the United States, with a survival rate at 5 years of less than 5%. About 60% of tumors originate at the head of the pancreas, 15% in the body, 5% in the tail; 20% are diffuse within the pancreas. This article discusses the imaging and staging of pancreatic cancer.
Topics: Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Neoplasm Staging; Pancreatic Neoplasms; Positron-Emission Tomography; Tomography, X-Ray Computed
PubMed: 20880783
DOI: 10.1102/1470-7330.2010.9028 -
Gut and Liver Nov 2017Pancreatic cancer (PC) is the third most common cause of cancer-related death in the United States and the 12th most common worldwide. Mortality is high, largely due to... (Review)
Review
Pancreatic cancer (PC) is the third most common cause of cancer-related death in the United States and the 12th most common worldwide. Mortality is high, largely due to late stage of presentation and suboptimal treatment regimens. Approximately 10% of PC cases have a familial basis. The major genetic defect has yet to be identified but may be inherited by an autosomal dominant pattern with reduced penetrance. Several known hereditary syndromes or genes are associated with an increased risk of developing PC and account for approximately 2% of PCs. These syndromes include the hereditary breast-ovarian cancer syndrome, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma, Lynch syndrome, familial polyposis, ataxia-telangiectasia, and hereditary pancreatitis. Appropriate screening using methods such as biomarkers or imaging, with endoscopic ultrasound and magnetic resonance imaging, may assist in the early detection of neoplastic lesions in the high-risk population. If these lesions are detected and treated before the development of invasive carcinoma, PC disease morbidity and mortality may be improved. This review will focus on familial PC and other hereditary syndromes implicated in the increased risk of PC; it will also highlight current screening methods and the future of new screening modalities.
Topics: Carcinoma; Early Detection of Cancer; Female; Forecasting; Genetic Predisposition to Disease; Humans; Male; Neoplastic Syndromes, Hereditary; Pancreatic Neoplasms; Risk Assessment; Risk Factors
PubMed: 28609837
DOI: 10.5009/gnl16414 -
Cell Communication and Signaling : CCS May 2017This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma.... (Review)
Review
This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma. The aggressive nature of these tumor types is mainly due to metastatic dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor microenvironment and the ability of the tumor cells to undergo epithelial-mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These processes are controlled entirely or in part by TGF-β and the small RHO GTPase RAC1 with both proteins acting as tumor promoters in late-stage cancers. Data from our and other studies point to signaling crosstalk between TGF-β and RAC1 and the related isoform, RAC1b, in pancreatic and mammary carcinoma cells. Based on the exciting observation that RAC1b functions as an endogenous inhibitor of RAC1, we propose a model on how the relative abundance or activity of RAC1 and RAC1b in the tumor cells may determine their responses to TGF-β and, ultimately, the metastatic capacity of the tumor.
Topics: Animals; Breast Neoplasms; Humans; Pancreatic Neoplasms; Signal Transduction; Transforming Growth Factor beta; rac1 GTP-Binding Protein
PubMed: 28499439
DOI: 10.1186/s12964-017-0175-0 -
Chinese Medical Journal Nov 2019Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the leading causes of cancer-related death worldwide. Hence, the development of effective anti-PDAC therapies is... (Review)
Review
OBJECTIVE
Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the leading causes of cancer-related death worldwide. Hence, the development of effective anti-PDAC therapies is urgently required. Patient-derived xenograft (PDX) models are useful models for developing anti-cancer therapies and screening drugs for precision medicine. This review aimed to provide an updated summary of using PDX models in PDAC.
DATA SOURCES
The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms, including PDAC, pancreatic carcinoma, pancreatic cancer, patient-derived xenografts or PDX, and patient-derived tumor xenografts or PDTX.
STUDY SELECTION
Original articles and review articles relevant to the review's theme were selected.
RESULTS
PDX models are better than cell line-derived xenograft and other models. PDX models consistently demonstrate retained tumor morphology and genetic stability, are beneficial in cancer research, could enhance drug discovery and oncologic mechanism development of PDAC, allow an improved understanding of human cancer cell biology, and help guide personalized treatment.
CONCLUSIONS
In this review, we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches. PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.
Topics: Animals; Antineoplastic Agents; Carcinoma, Pancreatic Ductal; Disease Models, Animal; Humans; Pancreatic Neoplasms; Precision Medicine; Xenograft Model Antitumor Assays
PubMed: 31725451
DOI: 10.1097/CM9.0000000000000524 -
BMC Molecular Biology Aug 2017Nuclear factors of activated T-cells (NFATs) have been mainly characterized in the context of immune response regulation because, as transcription factors, they have the...
BACKGROUND
Nuclear factors of activated T-cells (NFATs) have been mainly characterized in the context of immune response regulation because, as transcription factors, they have the ability to induce gene transcription. NFAT proteins are found in several types of tumors, for instance, pancreatic carcinoma. The role of NFATs in carcinogenesis is regulating central genes in cell differentiation and cell growth. NFAT proteins are primarily located in cytoplasm and only transported to the cell nucleus after activation. Here, they interact with other transcription factors cooperating with NFAT proteins, thus influencing the selection and regulation of NFAT-controlled genes. To identify and characterize possible interaction partners of the transcription factor NFATc2 in pancreatic carcinoma cells PaTu 8988t.
METHODS
NFATc2 expression and the mode of action of Ionomycin in the pancreatic tumor cell lines PaTu 8988t were shown with Western blotting and immunofluorescence tests. Potential partner proteins were verified by means of immunoprecipitation and binding partners, their physical interactions with DNA pull-down assays, siRNA technologies, and GST pull-down assays. Functional evidence was complemented by reporter-promoter analyses.
RESULTS
NFATc2 and Sp1 are co-localized in cell nuclei and physically interact at the NFAT target sequence termed NFAT-responsive promotor construct. Sp1 increases the functional activity of its binding partner NFATc2. This interaction is facilitated by Ionomycin in the early stimulation phase (up to 60 min).
CONCLUSIONS
Oncological therapy concepts are becoming more and more specific, aiming at the efficient modulation of specific signal and transcription pathways. The oncogenic transcription partner Sp1 is important for the transcriptional and functional activity of NFATc2 in pancreatic carcinoma. The binding partners interact in cells. Further studies are necessary to identify the underlying mechanisms and establish future therapeutic options for treating this aggressive type of tumor.
Topics: Carrier Proteins; Cell Line, Tumor; Cell Nucleus; Gene Expression; Humans; NFATC Transcription Factors; Nigericin; Pancreatic Neoplasms; Promoter Regions, Genetic; Protein Binding; Protein Transport; Sp1 Transcription Factor
PubMed: 28774282
DOI: 10.1186/s12867-017-0097-9 -
World Journal of Gastroenterology Aug 2013To investigate the potential role of positron emission tomography (PET) in the diagnosis, staging and prognosis predicting of pancreatic carcinoma (PC). (Meta-Analysis)
Meta-Analysis
AIM
To investigate the potential role of positron emission tomography (PET) in the diagnosis, staging and prognosis predicting of pancreatic carcinoma (PC).
METHODS
A systematic review of relevant literatures in PubMed, Embase and Cochrane Library was performed. The sensitivity and specificity of diagnostic and staging studies, and HRs for prognosis predicting studies were pooled. The bivariate model was used for diagnostic studies and the random-effect model for prognostic studies. Heterogeneity between included studies was tested using χ(2) test, and subgroup analysis was performed to explain the heterogeneities. All of the calculations were performed using Stata version 11.0.
RESULTS
A total of 39 studies were included. The pooled sensitivity of PET in diagnosing PC (30 studies, 1582 patients), evaluating N stating (4 studies, 101 patients) and liver metastasis (7 studies, 316 patients) were 0.91 (95%CI: 0.88-0.93), 0.64 (95%CI: 0.50-0.76), and 0.67 (95%CI: 0.52-0.79), respectively; and the corresponding specificity was 0.81 (95%CI: 0.75-0.85), 0.81 (95%CI: 0.25-0.85), and 0.96 (95%CI: 0.89-0.98), respectively. In prognosis analysis (6 studies, 198 patients), significant difference of overall survival was observed between high and low standardized uptake value groups (HR = 2.39, 95%CI: 1.57-3.63). Subgroup analysis showed that PET/CT was more sensitive than PET alone in evaluating liver metastasis of PC, 0.82 (95%CI: 0.48-0.98) and 0.67 (95%CI: 0.52-0.79), respectively.
CONCLUSION
PET can be used as a valuable diagnostic and predictive tool for PC, but its effect in the staging of PC remains indeterminate.
Topics: Carcinoma; Chi-Square Distribution; Female; Fluorodeoxyglucose F18; Humans; Male; Neoplasm Staging; Pancreatic Neoplasms; Positron-Emission Tomography; Predictive Value of Tests; Prognosis; Radiopharmaceuticals
PubMed: 23922481
DOI: 10.3748/wjg.v19.i29.4808 -
Journal of Immunology Research 2021Acidosis in the tumor microenvironment (TME) is involved in tumor immune dysfunction and tumor progression. We attempted to develop an acidosis-related index (ARI)...
BACKGROUND
Acidosis in the tumor microenvironment (TME) is involved in tumor immune dysfunction and tumor progression. We attempted to develop an acidosis-related index (ARI) signature to improve the prognostic prediction of pancreatic carcinoma (PC).
METHODS
Differential gene expression analyses of two public datasets (GSE152345 and GSE62452) from the Gene Expression Omnibus database were performed to identify the acidosis-related genes. The Cancer Genome Atlas-pancreatic carcinoma (TCGA-PAAD) cohort in the TCGA database was set as the discovery dataset. Univariate Cox regression and the Kaplan-Meier method were applied to screen for prognostic genes. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish the optimal model. The tumor immune infiltrating pattern was characterized by the single-sample gene set enrichment analysis (ssGSEA) method, and the prediction of immunotherapy responsiveness was conducted using the tumor immune dysfunction and exclusion (TIDE) algorithm.
RESULTS
We identified 133 acidosis-related genes, of which 37 were identified as prognostic genes by univariate Cox analysis in combination with the Kaplan-Meier method ( values of both methods < 0.05). An acidosis-related signature involving seven genes (, , , , , , and ) was developed in TCGA-PAAD and further validated in GSE62452. Patients in the acidosis-related high-risk group consistently showed poorer survival outcomes than those in the low-risk group. The 5-year AUCs (areas under the curve) for survival prediction were 0.738 for TCGA-PAAD and 0.889 for GSE62452, suggesting excellent performance. The low-risk group in TCGA-PAAD showed a higher abundance of CD8+ T cells and activated natural killer cells and was predicted to possess an elevated proportion of immunotherapeutic responders compared with the high-risk counterpart.
CONCLUSIONS
We developed a reliable acidosis-related signature that showed excellent performance in prognostic prediction and correlated with tumor immune infiltration, providing a new direction for prognostic evaluation and immunotherapy management in PC.
Topics: Acidosis; Biomarkers, Tumor; Computational Biology; Databases, Genetic; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Humans; Pancreatic Neoplasms; Prognosis; Proportional Hazards Models; ROC Curve; Transcriptome; Tumor Microenvironment
PubMed: 34993253
DOI: 10.1155/2021/3821055 -
Clinical and Translational Science Aug 2023Pancreatic adenocarcinoma remains a leading cause of cancer-related deaths. In order to develop appropriate therapeutic and prognostic tools, a comprehensive mapping of...
Pancreatic adenocarcinoma remains a leading cause of cancer-related deaths. In order to develop appropriate therapeutic and prognostic tools, a comprehensive mapping of the tumor's molecular abnormalities is essential. Here, our aim was to integrate available transcriptomic data to uncover genes whose elevated expression is simultaneously linked to cancer pathogenesis and inferior survival. A comprehensive search was performed in GEO to identify clinical studies with transcriptome-level gene expression data of pancreatic carcinoma with overall survival data and normal pancreatic tissues. After quantile normalization, the entire database was used to identify genes with altered expression. Cox proportional hazard regression was employed to uncover genes most strongly correlated with survival with a Bonferroni corrected p < 0.01. Perturbed biological processes and molecular pathways were identified to enable the understanding of underlying processes. A total of 16 available datasets were combined. The aggregated database comprised data of 1640 samples for 20,443 genes. When comparing with normal pancreatic tissues, a total of 2612 upregulated and 1977 downregulated genes were uncovered in pancreatic carcinoma. Among these, we found 24 genes with higher expression which significantly correlated with overall survival length also. The most significant genes were ANXA8, FAM83A, KRT6A, MET, MUC16, NT5E, and SLC2A1. These genes remained significant after a multivariate analysis also including grade and stage. Here, we assembled a large-scale database of pancreatic carcinoma samples and used this cohort to identify carcinoma-specific genes linked to altered survival outcomes. As our analysis focused on genes with higher expression, these could serve as future therapy targets.
Topics: Humans; Pancreatic Neoplasms; Transcriptome; Prognosis; Adenocarcinoma; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Neoplasm Proteins
PubMed: 37260110
DOI: 10.1111/cts.13563 -
International Journal of Clinical and... 2015Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor invasion...
Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor invasion and metastasis. This study aims to investigate the correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma. Immunohistochemistry was used to evaluate MMP-2 and TFPI-2 expression in tumor tissues and corresponding non-tumor tissues from 122 patients with pancreatic carcinoma. The results showed that the expression of MMP-2 was significantly (P < 0.05) higher in tumor tissues (78.7%) than in adjacent non-tumor tissues (27.9%), whereas the expression of TFPI-2 was significantly (P < 0.001) lower in tumor tissues (27.9%) than in adjacent non-tumor tissues (79.5%). Spearman's rank correlation test showed a negative correlation between MMP-2 and TFPI-2 expression (r = -0.346, P < 0.001). Kaplan-Meier survival analysis showed that high MMP-2 expression was significantly correlated with decreased disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001), while high TFPI-2 expression was significantly associated with increased DFS (P < 0.001) and OS (P < 0.001) of the patients. Multivariate analysis showed that high MMP-2 expression can act as an independent predictive factor for poor DFS (P = 0.01); and low TFPI-2 expression as an independent prognostic factor for poor DFS (P < 0.001) and OS (P < 0.001). In conclusion, our findings suggested that the differential expression of MMP-2 and TFPI-2 have a negative correlation in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for prognosis of pancreatic carcinoma.
Topics: Adult; Aged; Biomarkers, Tumor; Disease-Free Survival; Female; Glycoproteins; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Matrix Metalloproteinase 2; Middle Aged; Pancreatic Neoplasms; Prognosis
PubMed: 25755762
DOI: No ID Found