scholarly journals Pancreatic-Polypeptide in the Human Pancreas: Expression and Quantitative Variation During Development and in Ductal Adenocarcinoma

2003 ◽  
Vol 46 (1) ◽  
pp. 9-14 ◽  
Author(s):  
Demetrio Tamiolakis ◽  
Constantine Simopoulos ◽  
Athanasia Kotini ◽  
Ioannis Venizelos ◽  
Theodoros Jivannakis ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Polypeptide ◽  
Pancreatic Tissue ◽  
Ductal Adenocarcinoma ◽  
Human Pancreas ◽  
Neoplastic Tissue ◽  
Mantle Zone ◽  
Tissue Sections ◽  
Ductal Pancreatic Adenocarcinoma ◽  
Significant Difference

Aim: To determine the immunoreactivity of pancreatic-polypeptide (PP) during the development of the human fetal pancreas and ductal pancreatic adenocarcinoma, given that, PP positive cells were demonstrated either into its embryonic anlage or into pancreatic cancer. Methods: Tissue sections from 15 pancreatic fetal specimens, and equal number of ductal adenocarcinoma specimens, were assessed. Results: The density of positive cells in the primitive exocrine ductal epithelium and endocrine epithelium was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal – endocrine) and pure ductal type (p1=0.001, p2<0.0005, p3 =0.046 and p4<0.0005 respectively). The above values were estimated during the 10th to 12th week. There was no significant difference in the density of positive cells in the mantle zone of the islets from the 13th to the 24th week, and the neoplastic tissue of mixed (p5=0.11) and pure ductal type (p6=0.23). Conclusion: The immunostaining for PP identifies a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component, initially considered as pure ductal tumors, and mixed ductal and neuroendocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, raising the question of therapeutic efficacy of PP and analogues as potential adjuvant treatment of pancreatic cancer.

scholarly journals Does Neoplastic Cholecystokinin Expression Reflect the Embryonal Pattern of the Protein? A Study in Human Pancreas

2004 ◽  
Vol 47 (2) ◽  
pp. 101-105 ◽  
Author(s):  
Demetrio Tamiolakis ◽  
Ioannis Venizelos ◽  
Constantine Simopoulos ◽  
Maria Lambropoulou ◽  
Athanasia Kotini ◽  
...  
Keyword(s):  
Protein A ◽  
Pancreatic Tissue ◽  
Nuclear Antigen ◽  
Ductal Adenocarcinoma ◽  
Endocrine Tumors ◽  
Human Pancreas ◽  
Neoplastic Tissue ◽  
New Therapeutic Approaches ◽  
Significant Difference ◽  
Poorly Differentiated

Aim: To determine the immunoreactivity of cholecystokinin (CCK) during the development of the human fetal pancreas and pancreatic adenocarcinoma, given that, CCK positive cells were demonstrated either in its embryonic anlage or in pancreatic cancer. In order to obtain possible parallels in the expression pattern of neoplastic cells in adults (well – moderately – poorly differentiated), we investigated the pattern of CCK expression in the pancreatic tissue during the various stages of development and compared these with the proliferation of tissue assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry. Experimental design: Tissue sections from 15 pancreatic fetal specimens, and equal number of ductal adenocarcinoma specimens, were assessed using immunohistochemical methods for CCK. Results: The density of positive cells in the primitive exocrine ductal walls and outgrowing buds was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal – endocrine) and pure ductal type (p1=0.004, p2<0.0005, p3<0.0005 and p4=0.023 respectively). The above values were estimated from 20th to 22nd weeks of gestation. There was no significant difference in the density of positive cells in the islet cell epithelium from 25–30 weeks, and the neoplastic tissue of mixed (p5=0.10) and pure ductal type (p6=0.15). Conclusions: The immunostaining for CCK identifies a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component (initially considered as pure ductal tumors), and mixed ductal-endocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, and may be important for the development of new therapeutic approaches with eventual clinical utility.

scholarly journals Chylous Ascites, Unusual Association with Ductal Pancreatic Adenocarcinoma with Plasmacytoid Morphology: A Case Report and Literature Review

2021 ◽  
Vol 07 (03) ◽  
pp. e158-e162
Author(s):  
Catalin Bogdan Satala ◽  
Ioan Jung ◽  
Tivadar Jr. Bara ◽  
Vlad Tudorache ◽  
Simona Gurzu
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Surgical Intervention ◽  
Chylous Ascites ◽  
Distal Portion ◽  
Ductal Adenocarcinoma ◽  
Lymph Vessels ◽  
Lymphangiosis Carcinomatosa ◽  
Ductal Pancreatic Adenocarcinoma ◽  
Tumor Emboli

AbstractChylous ascites represents a relatively uncommon condition. In this paper, we present a case of chyloperitoneum associated with pancreatic ductal adenocarcinoma (PDAC) and a review of literature regarding chylous ascites. A 76-year-old male patient was admitted in emergency department with acute abdomen. A pancreatic cancer was suspected. Subtotal spleno-pancreatectomy, for a nodular mass infiltrating the mild and distal portion of the pancreas, was necessary. During surgical intervention in the peritoneal cavity, a moderate quantity of whitish and thick consistency fluid with milk-like appearance was observed to be accumulated. After examination of the fluid, chyloperitoneum was diagnosed. The histologic examination showed a PDAC, with multiple emboli in lymph vessels, with tumor cells with plasmacytoid morphology, diagnosed as lymphangiosis carcinomatosa. The patient died at 3 weeks after surgical intervention. In patients with pancreatic cancer and chylous ascites, suspicion of tumor-related blockage of the lymphatic flow should be suspected. Prognosis of PDAC should be evaluated not only based on the number of lymph node metastases, but also considering the number of lymph vessels with tumor emboli and the architecture of tumor cells. This is the first reported case of a PDAC with plasmacytoid morphology of lymphangiosis carcinomatosa.

scholarly journals Mercury in Pancreatic Cells of People with and without Pancreatic Cancer

2020 ◽  
Vol 17 (23) ◽  
pp. 8990
Author(s):  
Roger Pamphlett ◽  
Andrew J. Colebatch ◽  
Philip A. Doble ◽  
David P. Bishop
Keyword(s):  
Pancreatic Cancer ◽  
Toxic Metals ◽  
Inductively Coupled Plasma ◽  
Islet Cells ◽  
Inorganic Mercury ◽  
Pancreatic Tissue ◽  
Human Pancreas ◽  
Inductively Coupled ◽  
Pancreatic Cells ◽  
Cadmium Lead

Toxic metals have been implicated in the pathogenesis of pancreatic cancer. Human exposure to mercury is widespread, but it is not known how often mercury is present in the human pancreas and which cells might contain mercury. We therefore aimed to determine, in people with and without pancreatic cancer, the distribution and prevalence of mercury in pancreatic cells. Paraffin-embedded sections of normal pancreatic tissue were obtained from pancreatectomy samples of 45 people who had pancreatic adenocarcinoma, and from autopsy samples of 38 people without pancreatic cancer. Mercury was identified using two methods of elemental bio-imaging: (1) With autometallography, inorganic mercury was seen in islet cells in 14 of 30 males (47%) with pancreatic cancer compared to two of 17 males (12%) without pancreatic cancer (p = 0.024), and in 10 of 15 females (67%) with pancreatic cancer compared to four of 21 females (19%) without pancreatic cancer (p = 0.006). Autometallographic mercury was present in acinar cells in 24% and in periductal cells in 11% of people with pancreatic cancer, but not in those without pancreatic cancer. (2) Laser ablation-inductively coupled plasma-mass spectrometry confirmed the presence of mercury in islets that stained with autometallography and detected cadmium, lead, chromium, iron, nickel and aluminium in some samples. In conclusion, the genotoxic metal mercury is found in normal pancreatic cells in more people with, than without, pancreatic cancer. These findings support the hypothesis that toxic metals such as mercury contribute to the pathogenesis of pancreatic cancer.

Amount and Distribution of Collagen in Pancreatic Tissue of Different Species in the Perspective of Islet Isolation Procedures

1995 ◽  
Vol 4 (6) ◽  
pp. 609-614 ◽  
Author(s):  
Paul T.R. van Suylichem ◽  
Jan-Erik H.M. van Deijnen ◽  
Gerrit H.J. Wolters ◽  
Reinout van Schilfgaarde
Keyword(s):  
Colorimetric Method ◽  
Pancreatic Tissue ◽  
Collagen Content ◽  
Human Pancreas ◽  
Islet Isolation ◽  
Secondary Importance ◽  
Enzymatic Dissociation ◽  
Tissue Sections ◽  
Dog Pancreas ◽  
General Experience

Because collagen is the major target in the enzymatic dissociation of the pancreas for islet isolation, we determined the amount of collagen and its distribution in a comparative study comprising normal pancreata of rat, dog, man, young pig, and adult pig. Collagen content was determined using a colorimetric method and its distribution was assessed in tissue sections stained with Sirius red. The collagen content is relatively low in the rat and adult pig pancreas, and the amount of collagen is relatively low in the septa of the rat and dog pancreas. Not the amount of collagen in the septa but collagen in the rest of the pancreas, mainly located between the acini, seems to determine the dissociation of the pancreatic tissue. This can be exemplified by the higher islet yields obtained from the adult vs. the young pig pancreas; the latter contains a higher total amount of collagen but a similar, relatively high, amount of collagen in the septa. A high amount of collagen surrounding the islets seems to be of secondary importance in islet isolations, because yields of the same magnitude are obtained from the canine and human pancreas containing a relatively low vs. high amount of collagen around the islets but a similar total collagen content. The rat pancreas contains both a low total amount of collagen and a high amount of collagen around the islets; therefore, the general experience that islet isolation procedures are effective in rats can be readily understood.

CRM1 expression in pancreatic carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15115-e15115 ◽  
Author(s):  
Amit Mahipal ◽  
Domenico Coppola ◽  
Shilpa Gupta ◽  
Barbara Centeno ◽  
Mokenge Peter Malafa
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Carcinoma ◽  
Anticancer Agents ◽  
Normal Tissue ◽  
Tissue Sample ◽  
Pancreatic Tissue ◽  
Ductal Adenocarcinoma ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Paired Samples

e15115 Background: Increased expression of chromosomal region maintenance (CRM1) protein, also known as exportin 1, has been described in several human cancers. It is an important regulator of subcellular localization of tumor suppressor proteins and growth regulatory proteins. Direct inhibition of CRM1 blocks cell proliferation and induces apoptosis leading to the current evaluation of CRM1 inhibitors as anticancer agents in early phase clinical trials. There is a paucity of data regarding the prevalence of CRM1 expression in pancreatic cancer. Methods: We analyzed the expression of CRM1 by immunohistochemistry (IHC) in pancreatic tissue microarray (TMA) samples (malignant and non-malignant) obtained from patients who underwent potentially curative resection for pancreatic ductal adenocarcinoma. CRM1 antibody (Santa Cruz Biotechnology) was used for immunostaining the formalin fixed paraffin embedded core sections in the TMA samples. The intensity of staining and percentage of cells stained were graded on a scale of 0 to 3, with 3 being highest. The final IHC score was obtained using the product of immunostain intensity and percentage of cells stained (Range: 0-9). Low and high CRM1 expression was considered if the IHC score was 0 to 4 and 6 to 9 respectively. Results: Seventy nonmalignant and 91 pancreatic carcinoma samples were evaluated in this study. The median IHC score was 6 (range: 0-9) and 3 (range: 1-9) in malignant and nonmalignant pancreatic tissue samples respectively (P<0.0001). High CRM1 expression was found in 11% (8/70) of normal tissue samples and 69% (63/91) of tumor samples (P<0.0001). There were 48 paired samples of pancreatic cancer tissue and normal tissue obtained from same patient. Among these patients, 33 (69%) patients had higher CRM1 expression, 7 (15%) patients had similar expression and 8 (17%) patients had lower expression in malignant tissue sample as compared to their adjacent normal tissues. Conclusions: Higher CRM1 expression occurs frequently in pancreatic cancer as compared to nonmalignant pancreatic tissue, reinforcing its putative tumor oncogenic activity, and raising the value of targeting it for pancreatic cancer therapy.

scholarly journals Evaluation of cancer invasion markers determining the risk of lymph node metastasis in pancreatic cancer

2020 ◽  
pp. 60-65
Author(s):  
M. V. Zavyalova ◽  
S. V. Vtorushin ◽  
N. V. Krakhmal ◽  
Yu. Yu. Rakina ◽  
A. P. Koshel
Keyword(s):  
Pancreatic Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Invasion ◽  
Ductal Adenocarcinoma ◽  
Morphological Parameters ◽  
Integrin Β1 ◽  
Node Metastasis ◽  
Ductal Pancreatic Adenocarcinoma ◽  
Immunohistochemical Studies

The aim of the study was to evaluate the expression features of cancer invasion markers in ductal pancreatic adenocarcinoma and determine their relationship with the frequency of lymph node metastasis.Materials and methods: 84 cases of pancreatic ductal adenocarcinoma were studied with morphological and immunohistochemical studies using antibodies MMP2, Integrin β1 and β3, β-catenin, Twist and Snail, which associated with increased invasive properties of the tumor according to the literature.Results: The study showed the presence of relationships between the expression indicators of the studied markers in different structures of the parenchymal component of the tumor with the frequency of lymph node metastasis in pancreatic cancer.Conclusion: The results of the study show the possibility of using these markers as additional morphological parameters that allow us to assess and predict the risk of lymphogenous dissemination of pancreatic cancer.

Effect of three-dimensional collagen I and global histone acetylation on gemcitabine resistance in pancreatic cancer cells.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14515-e14515
Author(s):  
Surabhi Dangi-Garimella ◽  
Vaibhav Sahai ◽  
Mario A. Shields ◽  
Hidayatullah G. Munshi
Keyword(s):  
Pancreatic Cancer ◽  
Histone Acetylation ◽  
High Mobility ◽  
Tissue Microarrays ◽  
Pancreatic Tissue ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
Collagen Gels ◽  
Pancreatic Cancer Cells ◽  
3D Collagen

e14515 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. PDAC is also associated with epigenetic changes. We have previously shown that PDAC cells are resistant to gemcitabine in the collagen microenvironment because of increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2) and increased ERK1/2 signaling. Methods: Pancreatic tissue microarrays were stained with trichrome and for histone H3K9, H3K27 acetylation (Ac), and histone acetyltransferase (HATs) expression. PDAC cells were plated onto tissue culture plastic or in 3D collagen gels and protein expression was assessed by Western blotting. DNA damage response was assessed by comet and clonogenic assays. Results: Human PDAC tumors display in areas of fibrosis higher histone H3K9Ac and H3K27Ac. Moreover, PDAC cells upregulate H3K9Ac and H3K27Ac along with GCN5, PCAF and p300 HATs when grown in 3D collagen. Inhibiting ERK1/2 activity and/or decreasing HMGA2 expression attenuates the effect of collagen on H3Ac and HAT expression. Human PDAC tumors with HMGA2 also demonstrate H3Ac and HAT expression. Additionally, cells in 3D collagen demonstrate reduced tailing with the comet assay, increased clonogenic potential and increased γH2AX following gemcitabine treatment, suggesting an increased repair response to damaged DNA in the collagen microenvironment. Significantly, downregulation of HATs along with inhibition of ERK1/2 activity attenuates gemcitabine-induced γH2AX detected in 3D collagen. Conclusions: Collagen microenvironment limits the effectiveness of gemcitabine through ERK1/2 and HMGA2-dependent HAT expression. HMGA2 expression is associated with histone acetylation and HAT expression in human PDAC tumors, particularly in area of fibrosis, suggesting that fibrosis may contribute to chemo-resistance through increased HMGA2-HAT signaling. Given that very little progress has been made in the treatment of pancreatic cancer, targeting HATs could be a novel approach to sensitize pancreatic tumors to chemotherapy.

scholarly journals Role of eosinophils in the initiation and progression of pancreatitis pathogenesis

2018 ◽  
Vol 314 (2) ◽  
pp. G211-G222 ◽  
Author(s):  
Murli Manohar ◽  
Alok K. Verma ◽  
Sathisha Upparahalli Venkateshaiah ◽  
Anil Mishra
Keyword(s):  
Chronic Pancreatitis ◽  
Mast Cells ◽  
Critical Role ◽  
Pancreatic Tissue ◽  
Experimental Models ◽  
Human Pancreas ◽  
Protein Levels ◽  
Tissue Sections ◽  
Tissue Eosinophilia

Eosinophilic pancreatitis (EP) is reported in humans; however, the etiology and role of eosinophils in EP pathogenesis are poorly understood and not well explored. Therefore, it is interesting to examine the role of eosinophils in the initiation and progression of pancreatitis pathogenesis. Accordingly, we performed anti-major basic protein immunostaining, chloroacetate esterase, and Masson’s trichrome analyses to detect eosinophils, mast cells, and collagen in the tissue sections of mouse and human pancreas. Induced eosinophils accumulation and degranulation were observed in the tissue sections of human pancreatitis, compared with no eosinophils in the normal pancreatic tissue sections. Similarly, we observed induced tissue eosinophilia along with mast cells and acinar cells atrophy in cerulein-induced mouse model of chronic pancreatitis. Additionally, qPCR and ELISA analyses detected induced transcript and protein levels of proinflammatory and profibrotic cytokines, chemokines like IL 5, IL-18, eotaxin-1, eotaxin-2, TGF-β1, collagen-1, collagen-3, fibronectin, and α-SMA in experimental pancreatitis. Mechanistically, we show that eosinophil-deficient GATA1 and endogenous IL-5-deficient mice were protected from the induction of proinflammatory and profibrotic cytokines, chemokines, tissue eosinophilia, and mast cells in a cerulein-induced murine model of pancreatitis. These human and experimental data indicate that eosinophil accumulation and degranulation may have a critical role in promoting pancreatitis pathogenesis including fibrosis. Taken together, eosinophil tissue accumulation needs appropriate attention to understand and restrict the progression of pancreatitis pathogenesis in humans.NEW & NOTEWORTHY The present study for the first time shows that eosinophils accumulate in the pancreas and promote disease pathogenesis, including fibrosis in earlier reported cerulein-induced experimental models of pancreatitis. Importantly, we show that GATA-1 and IL-5 deficiency protects mice form the induction of eosinophil active chemokines, and profibrotic cytokines, including accumulation of tissue collagen in an experimental model of pancreatitis. Additionally, we state that cerulein-induced chronic pancreatitis is independent of blood eosinophilia.

scholarly journals Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers

2012 ◽  
Vol 50 (4) ◽  
Author(s):  
Elad Sharon ◽  
Jingli Zhang ◽  
Kevin Hollevoet ◽  
Seth M. Steinberg ◽  
Ira Pastan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Stage ◽  
Pancreatic Disease ◽  
Ductal Adenocarcinoma ◽  
Biliary Carcinoma ◽  
Healthy Donors ◽  
Significant Difference ◽  
Individual Participant ◽  
Pair Wise Comparison

AbstractTumor mesothelin overexpression is present in different malignancies, including the majority of patients with pancreatic or biliary cancers. The objective of this study was to evaluate the use of shed serum mesothelin and megakaryocyte potentiating factor (MPF) concentrations as biomarkers for these cancers.A total of 151 individuals, divided into five groups, were retrospectively analyzed: healthy donors (n=15), patients with benign non-pancreatic conditions (n=52), benign pancreatic conditions (n=33), biliary carcinoma (n=9), and pancreatic ductal adenocarcinoma (n=42). Mesothelin and MPF concentrations were measured in serum with the Mesomark™ and Human MPF ELISA, respectively.Mesothelin and MPF concentrations did not significantly differ among the five individual participant groups (p=0.34, p=0.33, respectively), nor did any other combination and pair-wise comparison of the participant groups demonstrated a significant difference in biomarker concentrations. In patients with pancreatic cancer, mesothelin or MPF concentrations were not associated with tumor stage (p=0.87, p=0.48, respectively) or differentiation grade (p=0.73, p=0.52, respectively).Serum mesothelin and MPF concentrations, measured with standard available ELISAs, were not specific for benign or pancreatic disease. Both biomarkers were not elevated in patients with pancreatic or biliary cancers, and consequently do not appear to be useful biomarkers for these malignancies.

scholarly journals Efficacy And Safety Of EUS-Guided Multimode Ablation Compared With Conventional Chemotherapy In Unresectable Pancreatic Cancer Patients

2021 ◽  
Author(s):  
Xixian Ruan ◽  
Zinan Zhang ◽  
Xiuyan Long ◽  
Ning Fang ◽  
Xiaoyu Yu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Size ◽  
Ductal Adenocarcinoma ◽  
Unresectable Pancreatic Cancer ◽  
Efficacy And Safety ◽  
Conventional Chemotherapy ◽  
Significant Difference ◽  
Group A ◽  
Mean Size ◽  
Group B

Abstract Background & Aims: To compare the feasibility and safety between multimode endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) and conventional chemotherapy in unresectable pancreatic ductal adenocarcinoma (PDAC).Methods: All the pathologically confirmed unresectable PDAC located in the head of the pancreas patients who underwent multimode EUS-RFA or conventional chemotherapy were retrospectively enrolled from June 2018 and April 2019. Patients who underwent multimode EUS-RFA (Group A) was performed through HybridTherm probe(HTP). Patients in Group B accepted nab-Paclitaxel plus Gemcitabine or S-1 plus Gemcitabine. The comparison between efficacy and safety of multimode EUS-RFA and conventional chemotherapy were analyzed by T test and MannWhitney test. A multivariate analysis was performed for each prognostic factor using the Cox proportional hazards model.Results: A total of 10 unresectable PDAC patients were retrospectively enrolled in Group A (mean size 9.46±5.94 cm3, range 2.00-21.09 cm3) and 9 patients in Group B (mean size 14.02±5.81cm3, range 4.60–24.62 cm3). The tumor size was significantly reduced before and after undergoing multimode EUS-RFA (P = 0.005), with an average tumor volume reduction of 38.1%.The tumor size was not significantly changed in Group B (P = 0.452). Statistically significant difference was observed in tumor size between Group A and Group B after treatment (P = 0.033). All patients died because of the progress of the tumor. The median lifetime from Group A&B was 9 months ranged 3-18 months VS 7 months ranged 1-7 months (P = 0.001). Overall no severe adverse events occurred in both groups.Conclusion: EUS-guided multimode ablation has the more feasibility in the treatment of unresectable pancreatic cancer than conventional chemotherapy. In this article, the limited data seems to show the trend of tumor shrinkage, pain relief, lifetime prolongation. Further studies are needed, such as expanding the sample size of patients and comparing the feasibility and safety among all the treatment.

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