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BMC Cancer Jun 2012Pancreatic carcinoma is a significant cause of cancer-related death in developed countries. As the level of circulating endothelial cells (CECs) is known to increase in... (Clinical Trial)
Clinical Trial
BACKGROUND
Pancreatic carcinoma is a significant cause of cancer-related death in developed countries. As the level of circulating endothelial cells (CECs) is known to increase in response to various cancers, we investigated the predictive potential of CEC levels and the association of these levels with the expression of proangiogenic factors in pancreatic carcinoma patients.
METHODS
Pancreatic carcinoma patients receiving gemcitabine chemotherapy were prospectively assigned to this study. CEC levels were measured using the CellTracks system, and the plasma levels of several angiogenesis factors were measured using multiplex immunoassay. Associations between clinical outcomes and the levels of these factors were evaluated.
RESULTS
Baseline CEC levels were markedly higher in pancreatic carcinoma patients (n = 37) than in healthy volunteers (n = 53). Moreover, these high CEC levels were associated with decreased overall survival (median, 297 days versus 143 days, P < 0.001) and progression-free survival (median, 150 days versus 64 days, P = 0.008), as well as with high vascular endothelial growth factor, interleukin (IL)-8, and IL-10 expression in the pancreatic carcinoma patients.
CONCLUSIONS
Several chemokines and proangiogenic factors correlate with the release of CECs, and the number of CECs detected may be a useful prognostic marker in pancreatic carcinoma patients undergoing gemcitabine chemotherapy.
TRIAL REGISTRATION
UMIN000002323.
Topics: Aged; Aged, 80 and over; Angiogenesis Inducing Agents; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Carcinoma; Deoxycytidine; Endothelial Cells; Female; Humans; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Prognosis; Gemcitabine
PubMed: 22731825
DOI: 10.1186/1471-2407-12-268 -
Clinical Cancer Research : An Official... Aug 2012Cancer stem cells (CSC) have been identified in an ever-increasing number of human malignancies on the basis of their ability to recapitulate tumors in the ectopic... (Review)
Review
Cancer stem cells (CSC) have been identified in an ever-increasing number of human malignancies on the basis of their ability to recapitulate tumors in the ectopic setting and maintain long-term tumorigenic potential. In addition, in pancreatic adenocarcinoma, CSCs may display additional properties, such as relative drug resistance and enhanced invasive and migratory potential that implicate a role in disease pathogenesis spanning initial tumor formation to metastatic disease progression. Importantly, these findings also indicate that the development of novel therapeutic strategies capable of inhibiting or eliminating CSCs will improve clinical outcomes. Preclinical studies have already described a wide array of potential approaches that target CSC-specific surface antigens and cellular pathways involved in cell survival, adhesion, self-renewal, and differentiation. Further, progress in this area should continue to move forward as the unique biology of CSCs is better understood. All preclinical studies to date have focused on targeting specific and phenotypically defined CSCs, but multiple cell populations with the ability to form tumors and self-renew have been identified in pancreatic carcinoma. As the clinical efficacy of CSC-directed therapies will depend on the inhibition of all sources of tumor self-renewal, better understanding of how specific CSC populations are related to one another and whether each possesses specific functional properties will be critical. In this CCR Focus article, we discuss the potential relationships between different pancreatic CSC populations and strategies to identify novel targeting approaches.
Topics: Animals; Antineoplastic Agents; Carcinoma, Pancreatic Ductal; Humans; Molecular Targeted Therapy; Neoplastic Stem Cells; Pancreatic Neoplasms
PubMed: 22896694
DOI: 10.1158/1078-0432.CCR-11-3112 -
BMC Ophthalmology Mar 2022Orbital metastasis from pancreatic tumors is extremely rare, and its clinical characteristics are still unclear. (Review)
Review
BACKGROUND
Orbital metastasis from pancreatic tumors is extremely rare, and its clinical characteristics are still unclear.
CASE PRESENTATION
Our case was a 73-year-old female who noticed diplopia on right gaze 3 months before referral to us. Imaging studies demonstrated a mass involving the lateral rectus muscle in the right orbit. The results of pathological examination of an excised specimen corresponded to poorly differentiated adenocarcinoma. Systemic work-up revealed pancreatic carcinoma with peritoneal metastasis. The patient underwent chemotherapy. We reviewed literature on similar cases and found 19 reported cases of pancreatic tumors metastasizing to the orbit. The results of our review indicate a tendency for formation of solitary mass without bony erosion, delayed detection of the primary pancreatic carcinoma, and poorer prognosis of such tumors, compared to metastatic orbital tumors from other lesions.
CONCLUSIONS
We report a rare case of metastatic orbital tumor from an unknown primary pancreatic carcinoma. Clinical characteristics of cases with metastatic pancreatic tumors seem to be different from those with metastatic tumors from the other lesions. Pancreatic tumors are frequently asymptomatic in an early stage, leading to delayed detection of the primary pancreatic carcinoma and poorer prognosis.
Topics: Adenocarcinoma; Aged; Diplopia; Female; Humans; Orbital Neoplasms; Pancreatic Neoplasms
PubMed: 35279125
DOI: 10.1186/s12886-022-02337-7 -
Bosnian Journal of Basic Medical... Aug 2009The aim of this work was investigate the association of P120 catenin expression with the clinicopathologic features and prognosis of pancreatic carcinoma. RT-PCR was...
The aim of this work was investigate the association of P120 catenin expression with the clinicopathologic features and prognosis of pancreatic carcinoma. RT-PCR was performed to investigate the expression of P120 catenin mRNA and western blotting were performed to investigate the expression of P120 catenin protein in 52 patients with pancreatic carcinoma. The relationships between P120 catenin expression and clinicopathological characteristics and prognosis were analyzed. The mRNA and protein expression of P120 catenin detected by RT-PCR and western blotting in pancreatic carcinoma was significantly lower than that in normal pancreatic tissues (0.227+/-0.067 vs 0.793+/-0.162, t=9.157, P =0.000; 0.665+/-0.192 vs 0.936+/-0.251, t=3.857, P=0.002). Reduced expression of P120 catenin mRNA and protein was significantly correlated with lymph node metastasis (P =0.004, P =0.006), vascular invasion (P =0.022, P =0.039 ), distant metastasis (P =0.037 , P =0.025), differentiated (P =0.033, P =0.013) and pTNM stage (P =0.003, P =0.022) of tumours. Additionally, reduced expression of P120 catenin mRNA and protein in tumour correlated with a worse prognosis and normal expression with a better survival rate (P=0.022, P=0.007). The reduced expression of both P120 catenin mRNA and protein in pancreatic carcinoma suggest that low expressions relate to pancreatic carcinoma development. P120 catenin may be related to pancreatic carcinoma behaviour and be a potential prognostic molecule.
Topics: Biomarkers, Tumor; Blotting, Western; Catenins; Cell Adhesion Molecules; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Pancreatic Neoplasms; Phosphoproteins; Predictive Value of Tests; Prognosis; RNA, Messenger; Delta Catenin
PubMed: 19754472
DOI: 10.17305/bjbms.2009.2805 -
Biomedicine & Pharmacotherapy =... Jan 2019Pancreatic carcinoma (PC), one of the most prevalent and malignant tumors, has a poor prognosis and a high mortality rate. EG-VEGF, a vascular endothelial growth factor...
OBJECTIVE
Pancreatic carcinoma (PC), one of the most prevalent and malignant tumors, has a poor prognosis and a high mortality rate. EG-VEGF, a vascular endothelial growth factor from endocrine glands, also termed as PROK1, has a high positive expression rate in PC tissues and is involved in the pathogenesis of various tumors. However, the expression and potential role of EG-VEGF in PC has not been thoroughly explored. The aim of this study was to better clarify the expression and potential role of EG-VEGF in pancreatic carcinoma.
METHODS
Immunohistochemical staining, western blotting, and RT-qPCR analysis were performed to detect the EG-VEGF level in PC tissues and cells. Subsequently, two short hairpin RNA (shRNA) lentiviral expression vector, shPROK1-1/shPROK1-2, were transfected into PANC-1 and BxPC-3 PC cell lines. MTT assay was used to determine cell proliferation. Meanwhile, flow cytometry assay was conducted to measure cell cycle and cell apoptosis. The protein levels of PI3K/AKT/mTOR pathway-related genes were also determined by western blotting.
RESULTS
EG-VEGF was aberrantly expressed in PC samples, as compared with paracancerous samples. Knockdown of PROK1 notably decreased the protein level of EG-VEGF, indicating a successful downregulation model of EG-VEGF. EG-VEGF silencing remarkably attenuated cell proliferation, while also induced G0/G1 arrest and magnified the extent of cell apoptosis. Further, EG-VEGF knockdown significantly inhibited PI3K/AKT/mTOR signaling pathway by downregulating p-PI3K, p-AKT, and p-mTOR levels.
CONCLUSION
This study identified the high-expression of EG-VEGF in pancreatic carcinoma tissues and cells, and demonstrated that EG-VEGF silencing inhibits the proliferation of PC cells and promotes apoptosis via regulating PI3K/AKT/mTOR pathway. Thus, EG-VEGF may become an essential target for the therapy of pancreatic cancer in the future.
Topics: Aged; Apoptosis; Cell Line; Cell Proliferation; Female; Gene Silencing; Humans; Male; Middle Aged; Pancreatic Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived
PubMed: 30551529
DOI: 10.1016/j.biopha.2018.10.125 -
Journal of Cancer Research and... 2018Pancreatic cancer, also known as exocrine pancreatic carcinoma or pancreatic ductal adenocarcinoma, is one of the most challenging tumor entities worldwide, which is... (Review)
Review
Pancreatic cancer, also known as exocrine pancreatic carcinoma or pancreatic ductal adenocarcinoma, is one of the most challenging tumor entities worldwide, which is characterized as a highly aggressive disease with dismal overall prognosis. Treatment options for patients with locally advanced pancreatic cancer include surgery, chemotherapy, and radiotherapy. In many cases, surgical resection is not possible due to the advanced stage at diagnosis and poor responses to current treatments, therefore, treatment alternatives have to be performed. However, brachytherapy through radioactive I seeds (RIS) implantation into pancreatic cancer has been first applied in unresectable carcinoma and made accuracy curative effects. Therapeutic procedures of RIS implantation for pancreatic carcinoma were not identical in domestic medical centers, making it hard to achieve homogeneity and affecting the efficacy seriously at last. To maximize the benefits of RIS for patients with pancreatic cancer, Chinese Medical Doctor Association of Radioactive Seed Implantation Technology Expert Committee and Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association, Radioactive Seed Therapy Branch organized and helped establish China expert consensus on RIS implantation for the treatment of pancreatic cancer, to provide a reference for clinical practices.
Topics: Brachytherapy; Consensus Development Conferences as Topic; Female; Humans; Intraoperative Care; Iodine Radioisotopes; Male; Pancreatic Neoplasms; Radiotherapy, Adjuvant; Radiotherapy, Image-Guided; Treatment Outcome
PubMed: 30589023
DOI: 10.4103/jcrt.JCRT_96_18 -
BioMed Research International 2014Pancreatic cancer is still a dismal disease. The high mortality rate is mainly caused by the lack of highly sensitive and specific diagnostic tools, and most of the... (Review)
Review
Pancreatic cancer is still a dismal disease. The high mortality rate is mainly caused by the lack of highly sensitive and specific diagnostic tools, and most of the patients are diagnosed in an advanced and incurable stage. Knowledge about precursor lesions for pancreatic cancer has grown significantly over the last decade, and nowadays we know that mainly three lesions (PanIN, and IPMN, MCN) are responsible for the development of pancreatic cancer. The early detection of these lesions is still challenging but provides the chance to cure patients before they might get an invasive pancreatic carcinoma. This paper focuses on PanIN, IPMN, and MCN lesions and reviews the current level of knowledge and clinical measures.
Topics: Adenocarcinoma, Mucinous; Carcinoma in Situ; Carcinoma, Pancreatic Ductal; Cell Transformation, Neoplastic; Humans; Pancreatic Neoplasms; Precancerous Conditions
PubMed: 24783207
DOI: 10.1155/2014/474905 -
Radiation Oncology (London, England) Jul 2010Pancreatic ductal carcinoma is one of the most lethal malignancies, but in recent years a number of positive developments have occurred in the management of pancreatic... (Review)
Review
Pancreatic ductal carcinoma is one of the most lethal malignancies, but in recent years a number of positive developments have occurred in the management of pancreatic carcinoma. This article aims to give an overview of the current knowledge regarding the role of radiotherapy in the treatment of pancreatic ductal adenocarcinoma (PDAC). The results of meta-analyses, phase III-studies, and phase II-studies using chemoradiotherapy and chemotherapy for resectable and non-resectable PDAC were reviewed. The use of radiotherapy is discussed in the neoadjuvant and adjuvant settings as well as in the locally advanced situation. Whenever possible, radiotherapy should be performed as simultaneous chemoradiotherapy. Patients with PDAC should be offered entry into clinical trials to identify optimal treatment results.
Topics: Antineoplastic Agents; Carcinoma, Pancreatic Ductal; Clinical Trials as Topic; Combined Modality Therapy; Humans; Neoadjuvant Therapy; Pancreatectomy; Pancreatic Neoplasms; Radiotherapy, Adjuvant
PubMed: 20615227
DOI: 10.1186/1748-717X-5-64 -
Journal of B.U.ON. : Official Journal... 2020
Topics: Cell Line, Tumor; Humans; Pancreatic Neoplasms; TOR Serine-Threonine Kinases
PubMed: 33099966
DOI: No ID Found -
Oxidative Medicine and Cellular... 2022As a refractory tumor, pancreatic carcinoma is more vulnerable to ferroptosis, a novel regulated cell death mode. However, the exact role of pancreatic stellate cells...
As a refractory tumor, pancreatic carcinoma is more vulnerable to ferroptosis, a novel regulated cell death mode. However, the exact role of pancreatic stellate cells (PSCs) in pancreatic cancer ferroptosis is still unclear. Using the coculture system, we revealed that activated PSCs promote pancreatic cancer cell ferroptosis resistance. Mechanistically, activated PSCs secreted HGF, which further activated the HGF receptor, c-MET, in pancreatic cancer cells, prevented lipid peroxidation, and ultimately triggered pancreatic cancer cell ferroptosis resistance and . TCGA and GEPIA databases also revealed a strong correlation between c-MET and antiferroptosis indicators. Our study supplied the evidence for the cross-talk between activated PSCs and pancreatic cancer cells in ferroptosis, which suggested a strategy to inhibit PSC paracrine signaling for preventing pancreatic carcinoma ferroptosis resistance.
Topics: Cell Line, Tumor; Ferroptosis; Hepatocyte Growth Factor; Humans; Pancreatic Neoplasms; Pancreatic Stellate Cells
PubMed: 35693705
DOI: 10.1155/2022/2985249