The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform

Fred S Gorelick - One of the best experts on this subject based on the ideXlab platform.

  • Structure-Function Relationships in the Pancreatic Acinar Cell
    Physiology of the Gastrointestinal Tract, 2018
    Co-Authors: Fred S Gorelick, James D. Jamieson
    Abstract:

    Abstract The pancreatic Acinar Cell synthesizes, stores, and secretes the enzymes and enzyme precursors required for the digestion of dietary proteins, carbohydrates, and lipids. To meet the daily needs for digestion, the Acinar Cell has the highest average rates of protein synthesis in the body. Enzymes are stored in zymogen granules that are localized to the apical region of the Cell. Signals generated by food in the intestine reach the Acinar Cell by neural and hormonal routes stimulate the secretion of enzymes from zymogen granules by exocytosis into the pancreatic duct. The Acinar Cell has been a model system for examining mechanisms of protein synthesis and export. Thus, nascent digestive enzyme proteins are transported from the endoplasmic reticulum to the Golgi complex, segregated from lysosomal enzymes, and then directed to zymogen granules by vesicular transport in a time-dependent and vectorial manner. The exocrine pancreas has two major physiologic functions: it supplies the enzymes and enzyme precursors (zymogens) that are needed for digesting dietary lipids, carbohydrates, and proteins and secretes a bicarbonate-rich fluid that neutralizes acidic gastric secretions and thus provides the correct pH for intestinal digestion by pancreatic enzymes. Two major Cell types form the exocrine pancreas; Acinar Cells and duct Cells. The chapter focuses on the Acinar Cell which synthesizes, stores, and secretes digestive enzymes while duct Cells secrete chloride and bicarbonate. Reasons to focus on the Acinar Cell include its critical physiologic function and its history as the model for the scientific studies that described the steps responsible for regulating protein synthesis and export and Cell signaling. Thus, after electron microscopy was developed, Cell biologists first visualized Acinar Cell organelles, they often then determined their Cellular function by studying this Cell. Although this review is largely based on the data from rodent Acinar Cells, limited data from human Acinar Cells suggest they will exhibit the same fundamental responses.

  • tlr9 and the nlrp3 inflammasome link Acinar Cell death with inflammation in acute pancreatitis
    Gastroenterology, 2011
    Co-Authors: Rafaz Hoque, Fred S Gorelick, Sohail Z. Husain, Ahsan U. Shah, Muhammad A Sohail, Ahsan F Malik, Sherhayar Sarwar, Franck J Barrat, Richard A Flavell, Wajahat Z Mehal
    Abstract:

    Acute pancreatitis is characterized by a sequence of events that begins with intraCellular activation of stored zymogens within the Acinar Cell. This can lead to Acinar Cell death and subsequent pancreatic inflammation.1 This model has received support from experimental systems such as caerulein-induced pancreatitis in which each of these pathologic responses can be demonstrated.2 Clinical and experimental studies have documented that the extent of the subsequent inflammatory response is directly related to disease severity and survival.3 An important role for inflammation in the pathogenesis of pancreatitis is supported by systems which show a requirement for inflammatory components in the development of pancreatitis. For example, neutrophils contribute to injury through the generation of reactive oxygen species.4 Other inflammatory components which are required for maximal pancreatitis include the IL-1 receptor, caspase -1, and TNF-α.5 Collectively, these studies suggest that a complex cytokine and Cellular inflammatory response mediates injury in acute pancreatitis. However, whether Acinar Cell death could promote an inflammatory response has not been explored. A central feature of necrotic Cell death is the release of intraCellular contents. Some intraCellular molecules on release into the extraCellular compartment induce an immune response, and are known as damage associated molecular patterns (DAMPs).6 Over twenty DAMPs have been identified; they bind to a wide range of DAMP-receptors including members of the TOLL, and purinergic receptor families. Activation of DAMP-receptors results in up-regulation of pro-cytokines such as pro-IL-1β, and activation of Cellular proteases required for their cleavage to functional cytokines.7 Recently caspase-1 has been identified as a central component of a cytosolic complex termed the inflammasome which is required for the initiation of many types of sterile inflammatory responses. We demonstrate that the inflammasome is activated during acute pancreatitis, and components of the inflammasome are required for maximal pancreatitis. Furthermore, we identify the DAMP-receptors TLR9 and P2X7 as upstream of the inflammasome and vital for the development of pancreatic injury.

  • low extraCellular ph induces damage in the pancreatic Acinar Cell by enhancing calcium signaling
    Journal of Biological Chemistry, 2011
    Co-Authors: Anamika Reed, Fred S Gorelick, Edwin C Thrower, Sohail Z. Husain, Ahsan U. Shah, Martine Alexandre, Michael H Nathanson
    Abstract:

    Low extraCellular pH (pHe) occurs in a number of clinical conditions and sensitizes to the development of pancreatitis. The mechanisms responsible for this sensitization are unknown. Because abnormal Ca2+ signaling underlies many of the early steps in the pathogenesis of pancreatitis, we evaluated the effect of decreasing pHe from 7.4 to 7.0 on Ca2+ signals in the Acinar Cell. Low pHe significantly increased the amplitude of cerulein-induced Ca2+ signals. The enhancement in amplitude was localized to the basolateral region of the Acinar Cell and was reduced by pretreatment with ryanodine receptor (RYR) inhibitors. Because basolateral RYRs also have been implicated in the pathogenesis of pancreatitis, we evaluated the effects of RYR inhibitors on pancreatitis responses in acidic conditions. RYR inhibitors significantly reduced the sensitizing effects of low pHe on zymogen activation and Cellular injury. These findings suggest that enhanced RYR-mediated Ca2+ signaling in the basolateral region of the Acinar Cell is responsible for the injurious effects of low pHe on the exocrine pancreas.

  • the Acinar Cell and early pancreatitis responses
    Clinical Gastroenterology and Hepatology, 2009
    Co-Authors: Fred S Gorelick, Edwin C Thrower
    Abstract:

    Pathologic responses arising from the pancreatic Acinar Cell appear to have a central role in initiating acute pancreatitis. Environmental factors that sensitize the Acinar Cell to harmful stimuli likely have a critical role in many forms of pancreatitis, including that induced by alcohol abuse. Activation of zymogens within the Acinar Cell and an inhibition of secretion are critical, but poorly understood, early pancreatitis events. While there is firm evidence relating trypsinogen activation to pancreatitis, the importance of other zymogens has been less studied. Preliminary studies suggest that trypsin may be activated by mechanisms that are distinct from other zymogens. Further, unlike the small intestine, it may not catalyze the activation of other zymogens. These features could affect strategies aimed at inhibiting proteases to treat pancreatitis. Specific intraCellular signals are required to activate pancreatitis pathways in the Acinar Cell. The most important is calcium. Recent studies have suggested that calcium release through specific calcium channels in the endoplasmic reticulum is the means by which pathological elevations in cytosolic calcium occur. Although the targets of abnormal calcium signaling are unknown, calcineurin, a calcium-dependent phosphatase, may serve such a role. Finally, recent work suggests that an acute acid load might sensitize the Acinar Cell to pancreatitis responses. Therapies aimed at preventing or reversing the effects of an acid load on the pancreas may be important for treatment.

  • reducing extraCellular ph sensitizes the Acinar Cell to secretagogue induced pancreatitis responses in rats
    Gastroenterology, 2009
    Co-Authors: Madhavi Bhoomagoud, Edwin C Thrower, Thomas R. Kolodecik, Thomas Jung, Jorunn Atladottir, Christine Shugrue, Anamika Chaudhuri, Fred S Gorelick
    Abstract:

    Background & Aims Protease activation within the pancreatic Acinar Cell is a key early event in acute pancreatitis and may require low pH intraCellular compartments. Clinical studies suggest that acidosis may affect the risk for developing pancreatitis. We hypothesized that exposure to an acid load might sensitize the Acinar Cell to secretagogue-induced pancreatitis. Methods Secretagogues (cerulein, carbachol, and bombesin) can induce protease activation in Acinar Cells at high (100 nmol/L, 1 mmol/L, and 10 μmol/L, respectively) but not at physiologically relevant concentrations. The effects of decreasing extraCellular pH (pHe) in early secretagogue-induced pancreatitis (zymogen activation and injury) were examined in rats (1) in vitro with isolated acini and (2) in vivo with an acid challenge. Results In acini, lowering pHe from 7.6 to 6.8 enhanced secretagogue-induced zymogen activation and injury, but did not affect secretion. For cerulein, this sensitization was seen over a range of concentrations (0.01–100.00 nmol/L). However, reduced pHe alone had no effect on zymogen activation, amylase secretion, or Cell injury. We have reported that zymogen activation is mediated by the vacuolar ATPase (vATPase), a proton transporter. vATPase inhibition, using concanamycin (100 nmol/L), blocked the low pHe effects on zymogen activation. An acute acid load given in vivo enhanced cerulein-induced (50 μg/kg) trypsinogen activation and pancreatic edema. Conclusion These studies suggest that acid challenge sensitizes the pancreatic Acinar Cell to secretagogue-induced zymogen activation and injury and may increase the risk for the development and severity of acute pancreatitis.

Edwin C Thrower - One of the best experts on this subject based on the ideXlab platform.

  • low extraCellular ph induces damage in the pancreatic Acinar Cell by enhancing calcium signaling
    Journal of Biological Chemistry, 2011
    Co-Authors: Anamika Reed, Fred S Gorelick, Edwin C Thrower, Sohail Z. Husain, Ahsan U. Shah, Martine Alexandre, Michael H Nathanson
    Abstract:

    Low extraCellular pH (pHe) occurs in a number of clinical conditions and sensitizes to the development of pancreatitis. The mechanisms responsible for this sensitization are unknown. Because abnormal Ca2+ signaling underlies many of the early steps in the pathogenesis of pancreatitis, we evaluated the effect of decreasing pHe from 7.4 to 7.0 on Ca2+ signals in the Acinar Cell. Low pHe significantly increased the amplitude of cerulein-induced Ca2+ signals. The enhancement in amplitude was localized to the basolateral region of the Acinar Cell and was reduced by pretreatment with ryanodine receptor (RYR) inhibitors. Because basolateral RYRs also have been implicated in the pathogenesis of pancreatitis, we evaluated the effects of RYR inhibitors on pancreatitis responses in acidic conditions. RYR inhibitors significantly reduced the sensitizing effects of low pHe on zymogen activation and Cellular injury. These findings suggest that enhanced RYR-mediated Ca2+ signaling in the basolateral region of the Acinar Cell is responsible for the injurious effects of low pHe on the exocrine pancreas.

  • the Acinar Cell and early pancreatitis responses
    Clinical Gastroenterology and Hepatology, 2009
    Co-Authors: Fred S Gorelick, Edwin C Thrower
    Abstract:

    Pathologic responses arising from the pancreatic Acinar Cell appear to have a central role in initiating acute pancreatitis. Environmental factors that sensitize the Acinar Cell to harmful stimuli likely have a critical role in many forms of pancreatitis, including that induced by alcohol abuse. Activation of zymogens within the Acinar Cell and an inhibition of secretion are critical, but poorly understood, early pancreatitis events. While there is firm evidence relating trypsinogen activation to pancreatitis, the importance of other zymogens has been less studied. Preliminary studies suggest that trypsin may be activated by mechanisms that are distinct from other zymogens. Further, unlike the small intestine, it may not catalyze the activation of other zymogens. These features could affect strategies aimed at inhibiting proteases to treat pancreatitis. Specific intraCellular signals are required to activate pancreatitis pathways in the Acinar Cell. The most important is calcium. Recent studies have suggested that calcium release through specific calcium channels in the endoplasmic reticulum is the means by which pathological elevations in cytosolic calcium occur. Although the targets of abnormal calcium signaling are unknown, calcineurin, a calcium-dependent phosphatase, may serve such a role. Finally, recent work suggests that an acute acid load might sensitize the Acinar Cell to pancreatitis responses. Therapies aimed at preventing or reversing the effects of an acid load on the pancreas may be important for treatment.

  • Molecular and Cellular regulation of pancreatic Acinar Cell function.
    Current Opinion in Gastroenterology, 2009
    Co-Authors: Sohail Z. Husain, Edwin C Thrower
    Abstract:

    PURPOSE OF REVIEW: This review focuses on studies from the past year that have greatly advanced our understanding of molecular and Cellular regulation of pancreatic Acinar Cell function. RECENT FINDINGS: Recent advances focus on signals dictating pancreatic development, Acinar Cell fate, pancreatic growth, and secretion. Regeneration of Acinar Cells after pancreatitis depends on expression of embryonic signals in mature Acinar Cells. In this setting, Acinar Cells can also transdifferentiate into adipose Cells. With the forced induction of certain early and endocrine-driving transcription factors, Acinar Cells can also transdifferentiate into beta-Cells. There has also been an increased understanding of Acinar-to-ductal metaplasia and the subsequent formation of pancreatic intraepithelial neoplasia lesions. Multiple proteins involved in secretion have been characterized, including small guanosine triphosphate-binding proteins, soluble N-ethylmaleimide-sensitive factor attachment proteins, and ion channels. SUMMARY: These findings demonstrate the regenerative potential of the Acinar Cell to mitigate injurious states such as pancreatitis. The ability of Acinar Cells to transdifferentiate into beta-Cells could potentially provide a treatment for diabetes. Finally, the results might be helpful in preventing malignant transformation events arising from the Acinar Cell. Developments in proteomics and computer modeling could expand our view of proteins mediating Acinar Cell function.

  • reducing extraCellular ph sensitizes the Acinar Cell to secretagogue induced pancreatitis responses in rats
    Gastroenterology, 2009
    Co-Authors: Madhavi Bhoomagoud, Edwin C Thrower, Thomas R. Kolodecik, Thomas Jung, Jorunn Atladottir, Christine Shugrue, Anamika Chaudhuri, Fred S Gorelick
    Abstract:

    Background & Aims Protease activation within the pancreatic Acinar Cell is a key early event in acute pancreatitis and may require low pH intraCellular compartments. Clinical studies suggest that acidosis may affect the risk for developing pancreatitis. We hypothesized that exposure to an acid load might sensitize the Acinar Cell to secretagogue-induced pancreatitis. Methods Secretagogues (cerulein, carbachol, and bombesin) can induce protease activation in Acinar Cells at high (100 nmol/L, 1 mmol/L, and 10 μmol/L, respectively) but not at physiologically relevant concentrations. The effects of decreasing extraCellular pH (pHe) in early secretagogue-induced pancreatitis (zymogen activation and injury) were examined in rats (1) in vitro with isolated acini and (2) in vivo with an acid challenge. Results In acini, lowering pHe from 7.6 to 6.8 enhanced secretagogue-induced zymogen activation and injury, but did not affect secretion. For cerulein, this sensitization was seen over a range of concentrations (0.01–100.00 nmol/L). However, reduced pHe alone had no effect on zymogen activation, amylase secretion, or Cell injury. We have reported that zymogen activation is mediated by the vacuolar ATPase (vATPase), a proton transporter. vATPase inhibition, using concanamycin (100 nmol/L), blocked the low pHe effects on zymogen activation. An acute acid load given in vivo enhanced cerulein-induced (50 μg/kg) trypsinogen activation and pancreatic edema. Conclusion These studies suggest that acid challenge sensitizes the pancreatic Acinar Cell to secretagogue-induced zymogen activation and injury and may increase the risk for the development and severity of acute pancreatitis.

  • Protein kinase C in the pancreatic Acinar Cell
    Journal of Gastroenterology and Hepatology, 2008
    Co-Authors: Fred S Gorelick, Stephen J. Pandol, Edwin C Thrower
    Abstract:

    Pathological activation of selective signaling molecules within the pancreatic Acinar Cell mediates the development of acute pancreatitis. Some of the key early Acinar Cell events include activation of proteases, inhibition of apical secretion, and elaboration of inflammatory mediators. Previous studies have shown that supraphysiological concentrations of cholecystokinin (CCK) that can cause pancreatitis in vivo, also initiate these pathological responses in dispersed groups of Acinar Cells (acini). Protein kinase C (PKC) regulates many Cellular events and a role for this family of signaling molecules has been described in some of the pathological responses of pancreatitis. Notably, ethanol can activate specific PKC isoforms and sensitize the Acinar Cells to the pathological effects of CCK. Our preliminary studies in isolated pancreatic acini and a Cell-free reconstitution system suggest that PKC can mediate protease activation in the Acinar Cell. These findings may be relevant to the pathogenesis of pancreatitis from alcohol and other etiologies.

Jelena Todoric - One of the best experts on this subject based on the ideXlab platform.

  • basal autophagy maintains pancreatic Acinar Cell homeostasis and protein synthesis and prevents er stress
    Proceedings of the National Academy of Sciences of the United States of America, 2015
    Co-Authors: Laura Antonucci, Jelena Todoric, Ilya Gukovsky, Johan B Fagman, Mason R Mackey, Mark H Ellisman, Michael Karin
    Abstract:

    Pancreatic Acinar Cells possess very high protein synthetic rates as they need to produce and secrete large amounts of digestive enzymes. Acinar Cell damage and dysfunction cause malnutrition and pancreatitis, and inflammation of the exocrine pancreas that promotes development of pancreatic ductal adenocarcinoma (PDAC), a deadly pancreatic neoplasm. The Cellular and molecular mechanisms that maintain Acinar Cell function and whose dysregulation can lead to tissue damage and chronic pancreatitis are poorly understood. It was suggested that autophagy, the principal Cellular degradative pathway, is impaired in pancreatitis, but it is unknown whether impaired autophagy is a cause or a consequence of pancreatitis. To address this question, we generated Atg7Δpan mice that lack the essential autophagy-related protein 7 (ATG7) in pancreatic epithelial Cells. Atg7Δpan mice exhibit severe Acinar Cell degeneration, leading to pancreatic inflammation and extensive fibrosis. Whereas ATG7 loss leads to the expected decrease in autophagic flux, it also results in endoplasmic reticulum (ER) stress, accumulation of dysfunctional mitochondria, oxidative stress, activation of AMPK, and a marked decrease in protein synthetic capacity that is accompanied by loss of rough ER. Atg7Δpan mice also exhibit spontaneous activation of regenerative mechanisms that initiate Acinar-to-ductal metaplasia (ADM), a process that replaces damaged Acinar Cells with duct-like structures.

  • loss of Acinar Cell ikkα triggers spontaneous pancreatitis in mice
    Journal of Clinical Investigation, 2013
    Co-Authors: Ning Li, Xuefeng Wu, Ryan G Holzer, Jelena Todoric, Eek Joong Park, Hisanobu Ogata, Anna S Gukovskaya, Ilya Gukovsky, Donald P Pizzo
    Abstract:

    Chronic pancreatitis is an inflammatory disease that causes progressive destruction of pancreatic Acinar Cells and, ultimately, loss of pancreatic function. We investigated the role of I?B kinase ? (IKK?) in pancreatic homeostasis. Pancreas-specific ablation of IKK? (Ikk?(?pan)) caused spontaneous and progressive Acinar Cell vacuolization and death, interstitial fibrosis, inflammation, and circulatory release of pancreatic enzymes, clinical signs resembling those of human chronic pancreatitis. Loss of pancreatic IKK? causes defective autophagic protein degradation, leading to accumulation of p62-mediated protein aggregates and enhanced oxidative and ER stress in Acinar Cells, but none of these effects is related to NF-?B. Pancreas-specific p62 ablation prevented ER and oxidative stresses and attenuated pancreatitis in Ikk?(?pan) mice, suggesting that Cellular stress induced by p62 aggregates promotes development of pancreatitis. Importantly, downregulation of IKK? and accumulation of p62 aggregates were alsoobserved in chronic human pancreatitis. Our studies demonstrate that IKK?, which may control autophagic protein degradation through its interaction with ATG16L2, plays a critical role in maintaining pancreatic Acinar Cell homeostasis, whose dysregulation promotes pancreatitis through p62 aggregate accumulation.

Catherine E Ovitt - One of the best experts on this subject based on the ideXlab platform.

  • Intrinsic mitotic activity supports the human salivary gland Acinar Cell population.
    FEBS Letters, 2019
    Co-Authors: Matthew H. Ingalls, Andrew J. Hollomon, Shawn D. Newlands, Andrew Mcdavid, Catherine E Ovitt
    Abstract:

    : To develop treatments for salivary gland dysfunction, it is important to understand how human salivary glands are maintained under normal homeostasis. Previous data from our lab demonstrated that murine salivary Acinar Cells maintain the Acinar Cell population through self-duplication under conditions of homeostasis, as well as after injury. Early studies suggested that human Acinar Cells are mitotically active, but the identity of the resultant daughter Cells was not clear. Using markers of Cell cycle activity and mitosis, as well as an ex vivo 5-Ethynyl-2´-deoxyuridine assay, we show that human salivary gland Acinar Cells divide to generate daughter Acinar Cells. As in mouse, our data indicate that human salivary gland homeostasis is supported by the intrinsic mitotic capacity of Acinar Cells.

  • salivary gland homeostasis is maintained through Acinar Cell self duplication
    Developmental Cell, 2015
    Co-Authors: Marit H Aure, Stephen F Konieczny, Catherine E Ovitt
    Abstract:

    Summary Current dogma suggests that salivary gland homeostasis is stem Cell dependent. However, the extent of stem Cell contribution to salivary gland maintenance has not been determined. We investigated Acinar Cell replacement during homeostasis, growth, and regeneration, using an inducible CreER T2 expressed under the control of the Mist1 gene locus. Genetic labeling, followed by a chase period, showed that Acinar Cell replacement is not driven by the differentiation of unlabeled stem Cells. Analysis using R26 Brainbow2.1 reporter revealed continued proliferation and clonal expansion of terminally differentiated Acinar Cells in all major salivary glands. Induced injury also demonstrated the regenerative potential of pre-labeled Acinar Cells. Our results support a revised model for salivary gland homeostasis based predominantly on self-duplication of Acinar Cells, rather than on differentiation of stem Cells. The proliferative capacity of differentiated Acinar Cells may prove critical in the implementation of Cell-based strategies to restore the salivary glands.

David S Klimstra - One of the best experts on this subject based on the ideXlab platform.

  • cytomorphologic and immunophenotypical features of Acinar Cell neoplasms of the pancreas
    Cancer Cytopathology, 2013
    Co-Authors: Carlie S Sigel, David S Klimstra
    Abstract:

    BACKGROUND Acinar Cell neoplasms of the pancreas are rare but when encountered, the diagnosis is often established based on cytology specimens. Diagnostic accuracy is important because Acinar Cell carcinomas are aggressive yet may mimic tumors with different outcomes and management. METHODS The authors identified all patients with a diagnosis of Acinar Cell neoplasm in the institutional database; assessed cytomorphology and immunocytochemistry for trypsin, chymotrypsin, synaptophysin, chromogranin A, and MIB-1; and compared all cytology and final histological diagnoses for diagnostic discrepancies. RESULTS Cytological features were described for 16 histologically proven malignant Acinar Cell neoplasms: Acinar Cell carcinoma (8 cases), mixed Acinar-neuroendocrine carcinoma (6 cases), mixed Acinar-ductal carcinoma (1 case), and pancreatoblastoma (1 case).The majority of aspirates from Acinar Cell cystadenomas were nondiagnostic or negative (5 of 6 cases; 83%). Acinar and neuroendocrine differentiation that was detected by immunocytochemistry in >20% of tumor Cells was found to be correlated with mixed Acinar-neuroendocrine carcinoma histology. Cytohistological correlation included 32 patients with 17 discordant diagnoses (53%). The following preoperative cytology diagnoses proved to be Acinar Cell neoplasms on resection: neuroendocrine tumor (5 cases), adenocarcinoma (5 cases), atypical ductal Cells (2 cases), solid pseudopapillary neoplasm, and hepatoCellular carcinoma. Three aspirates diagnosed as Acinar Cell carcinoma by cytology proved to be chronic pancreatitis (2 cases) and ductal adenocarcinoma (1 case). CONCLUSIONS Acinar Cell carcinoma has a distinctive cytological appearance but is frequently misdiagnosed on cytology. Immunocytochemistry is useful for identifying Acinar differentiation. Cancer (Cancer Cytopathol) 2013;121:459–70. © 2013 American Cancer Society.

  • Acinar Cell carcinoma of the pancreas new genetic and treatment insights into a rare malignancy
    Oncologist, 2011
    Co-Authors: Maeve A Lowery, David S Klimstra, Jinru Shia, Kenneth H Yu, Peter J Allen, Murray F Brennan, Eileen M Oreilly
    Abstract:

    Background. Acinar Cell carcinoma (ACC) of the pancreas is a rare neoplasm, accounting for 1% of all pancreatic neoplasms. There remains a lack of data regarding the use of systemic therapy in this disease. We present a series of 40 consecutive cases of ACC of the pancreas treated at Memorial Sloan-Kettering Cancer Center, with an emphasis on evaluation of activity of new therapeutic agents.

  • pancreatic Acinar Cell carcinomas with prominent ductal differentiation mixed Acinar ductal carcinoma and mixed Acinar endocrine ductal carcinoma
    The American Journal of Surgical Pathology, 2010
    Co-Authors: Edward B Stelow, Ruthy Shacolevy, Joaquin J Garcia, David S Klimstra
    Abstract:

    BackgroundPancreatic Acinar Cell carcinomas (ACCs) are clinically and pathologically distinct from pancreatic ductal adenocarcinomas (PDAs). Whereas endocrine differentiation has been well shown in ACCs, significant ductal components are rare. This paper reviews the clinicopathologic features of a s

  • Acinar Cell cystadenoma of the pancreas a new entity
    The American Journal of Surgical Pathology, 2002
    Co-Authors: Giuseppe Zamboni, David S Klimstra, Benoit Terris, Aldo Scarpa, Markus Kosmahl, Paola Capelli, Gunter Kloppel
    Abstract:

    This report describes a newly observed cystic lesion of the pancreas showing Acinar Cell differentiation. The patients affected by this lesion included seven women and three men (age range 16–66 years). In six patients, all of whom were female and all but one of whom suffered from abdominal pain, th

  • Acinar Cell carcinoma of the pancreas a clinicopathologic study of 28 cases
    The American Journal of Surgical Pathology, 1992
    Co-Authors: David S Klimstra, Clara S Heffess, James E Oertel, Juan Rosai
    Abstract:

    We have examined the microscopic appearance, immunohistochemical staining properties, and clinical behavior of 28 cases of Acinar Cell carcinoma of the pancreas. Two of the tumors occurred in children. The adult patients ranged in age from 40 to 81 years (mean, 62 years). Males greatly outnumbered f