scholarly journals Metastatic pancreatic ductal adenocarcinoma in a teenage girl: A rare disease

2020 ◽  
Vol 60 (6) ◽  
pp. 341-4
Author(s):  
Sutaryo Sutaryo ◽  
Scolastika Dita Kristian
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Acinar Cell Carcinoma ◽  
Abdominal Discomfort ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
Solid Pseudopapillary Tumor ◽  
Teenage Girl ◽  
Pancreatic Endocrine Neoplasm ◽  
Pancreatic Cells ◽  
Tumor Types

Pancreatic ductal adenocarcinoma (PDAC) is highly uncommon in patients < 20 years of age, at less than 0.1% of population.1 Pancreatic tumors in children and adolescents can develop from endocrine or exocrine cells. The tumor types include solid pseudopapillary tumor, ductal adenocarcinoma, pancreatoblastoma, acinar cell carcinoma, and pancreatic endocrine neoplasm (malignant and benign).2 Other types of tumors may be attached to it or secondarily engage the gland or emerge from other kinds of non-pancreatic cells inside the pancreas. The prevalent type of classic PDAC in adults is highly uncommon in children.  We report here on a fifteen-year old girl with metastatic pancreatic ductal adenocarcinoma (mPDAC), who presented with abdominal discomfort and jaundice.

scholarly journals From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 21 (11) ◽  
pp. 4067 ◽  
Author(s):  
Christopher Montemagno ◽  
Shamir Cassim ◽  
Jacques Pouyssegur ◽  
Alexis Broisat ◽  
Gilles Pagès
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Malignant Progression ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
Therapeutic Targeting ◽  
Normal Tissues ◽  
Attractive Candidate ◽  
Rising Incidence ◽  
Resistance To Chemotherapy

Pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of all pancreatic tumors, is a highly devastating disease with poor prognosis and rising incidence. The lack of available specific diagnostics tests and the limited treatment opportunities contribute to this pejorative issue. Over the last 10 years, a growing interest pointing towards mesothelin (MSLN) as a promising PDAC-associated antigen has emerged. The limited expression of MSLN in normal tissues (peritoneum, pleura and pericardium) and its overexpression in 80 to 90% of PDAC make it an attractive candidate for therapeutic management of PDAC patients. Moreover, its role in malignant progression related to its involvement in tumor cell proliferation and resistance to chemotherapy has highlighted the relevance of its targeting. Hence, several clinical trials are investigating anti-MSLN efficacy in PDAC. In this review, we provide a general overview of the different roles sustained by MSLN during PDAC progression. Finally, we also summarize the different MSLN-targeted therapies that are currently tested in the clinic.

scholarly journals Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia

2020 ◽  
Vol 21 (22) ◽  
pp. 8823
Author(s):  
Justin F. Creeden ◽  
Khaled Alganem ◽  
Ali S. Imami ◽  
Nicholas D. Henkel ◽  
F. Charles Brunicardi ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tyrosine Kinases ◽  
Tumor Development ◽  
Review Literature ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
Desmoplastic Stroma ◽  
B Lymphoid ◽  
Therapeutic Research ◽  
Lymphocyte Cell

Kinase drug discovery represents an active area of therapeutic research, with previous pharmaceutical success improving patient outcomes across a wide variety of human diseases. In pancreatic ductal adenocarcinoma (PDAC), innovative pharmaceutical strategies such as kinase targeting have been unable to appreciably increase patient survival. This may be due, in part, to unchecked desmoplastic reactions to pancreatic tumors. Desmoplastic stroma enhances tumor development and progression while simultaneously restricting drug delivery to the tumor cells it protects. Emerging evidence indicates that many of the pathologic fibrotic processes directly or indirectly supporting desmoplasia may be driven by targetable protein tyrosine kinases such as Fyn-related kinase (FRK); B lymphoid kinase (BLK); hemopoietic cell kinase (HCK); ABL proto-oncogene 2 kinase (ABL2); discoidin domain receptor 1 kinase (DDR1); Lck/Yes-related novel kinase (LYN); ephrin receptor A8 kinase (EPHA8); FYN proto-oncogene kinase (FYN); lymphocyte cell-specific kinase (LCK); tec protein kinase (TEC). Herein, we review literature related to these kinases and posit signaling networks, mechanisms, and biochemical relationships by which this group may contribute to PDAC tumor growth and desmoplasia.

Update on Pancreatic Endocrine Tumors

2006 ◽  
Vol 130 (7) ◽  
pp. 963-966 ◽  
Author(s):  
Wendy L. Frankel
Keyword(s):  
Mass Effect ◽  
Acinar Cell Carcinoma ◽  
Ductal Adenocarcinoma ◽  
Solid Pseudopapillary Tumor ◽  
Endocrine Tumors ◽  
Term Survival ◽  
Pancreatic Endocrine Tumors ◽  
Adjacent Structures

Abstract Endocrine tumors of the pancreas represent 1% to 2% of all pancreatic neoplasms. The tumors tend to have an indolent behavior, and long-term survival is common. There is no gender or age predilection. Patients can present with symptoms due to hormonal excess or a local mass effect or be asymptomatic. The tumors tend to be solid and well circumscribed. Typical microscopic findings include an organoid pattern of growth, with cells containing scant to moderate amounts of cytoplasm, and nuclei with dispersed chromatin and inconspicuous nucleoli. The morphologic spectrum of these tumors can be variable, and the differential diagnosis includes chronic pancreatitis with neuroendocrine hyperplasia, ductal adenocarcinoma, solid pseudopapillary tumor, acinar cell carcinoma, and pancreatoblastoma. The classification of these tumors remains controversial, and prognosis is difficult to predict, but important features include metastasis and invasion of adjacent structures. Resection remains the mainstay of surgical treatment. It is important to be aware that unusual morphologic variants of pancreatic endocrine tumors are common, and immunohistochemical stains can help avoid misdiagnosis.

Influence of IP-10/CXCL10 induction in human pancreatic cancer stroma on lymphocytes recruitment and correlation with survival.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 290-290 ◽  
Author(s):  
Thomas B Brunner ◽  
Serena Lunardi ◽  
Nigel B Jamieson ◽  
Su Yin Lim ◽  
Kristin L Griffiths ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Patients ◽  
Mononuclear Cells ◽  
Pancreatic Stellate Cells ◽  
Human Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
Pancreatic Cancer Cells

290 Background: Pancreatic ductal adenocarcinoma is characterized by an abundant desmoplastic reaction driven by pancreatic stellate cells (PSCs) that contributes to tumor progression. Here we sought to characterize the interactions between pancreatic cancer cells (PCCs) and PSCs that affect the inflammatory and immune response in pancreatic tumors. Methods: Conditioned media from mono- and cocultures of PSCs and PCCs were assayed for expression of cytokines, chemokines and growth factors. Gene expression analysis of human pancreatic ductal adenocarcinoma samples was used to verify expression of cytokines and their correlation with markers of immunoresponse and with clinical outcome. Finally, we tested chemotaxis of leukocytes isolated from peripheral blood mononuclear cells of pancreatic cancer patients. Results: IP-10/CXCL10 was the most highly induced chemokine in coculture of PSCs and PCCs. Its expression was induced in the PSCs by PCCs. IP-10 expression was consistently upregulated in human pancreatic cancer specimens, and positively correlated with high stroma content. Furthermore, expression of IP-10 and its receptor CXCR3 were significantly associated with the intratumoral presence of regulatory T cells (Tregs). In an independent cohort of 48 patients with resectable pancreatic ductal adenocarcinoma, the survival of patients with high IP-10 levels was 18.1 months less than those with low IP-10 levels (HR=2.14, 95% CI 1.05 -4.42). Importantly, IP-10 stimulated the ex vivo recruitment of CXCR3+ effector T cells as well as CXCR3+ Tregs derived from patients with pancreatic cancer. Conclusions: Our findings suggest that, in pancreatic cancer patients, CXCR3+ Tregs are recruited by IP-10 expressed by PSCs in the tumor stroma, leading to immunosuppressive and tumor-promoting effects.

scholarly journals Overcoming Immunological Resistance Enhances the Efficacy of A Novel Anti-tMUC1-CAR T Cell Treatment against Pancreatic Ductal Adenocarcinoma

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1070 ◽  
Author(s):  
Yazdanifar ◽  
Zhou ◽  
Grover ◽  
Williams ◽  
Bose ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
Indoleamine 2 ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Chimeric antigen receptor (CAR) T cells have shown remarkable success in treating hematologic cancers. However, this efficacy has yet to translate to treatment in solid tumors. Pancreatic ductal adenocarcinoma (PDA) is a fatal malignancy with poor prognosis and limited treatment options. We have developed a second generation CAR T cell using the variable fragments of a novel monoclonal antibody, TAB004, which specifically binds the tumor-associated-MUC1 (tMUC1). tMUC1 is overexpressed on ~85% of all human PDA. We present data showing that TAB004-derived CAR T cells specifically bind to tMUC1 on PDA cells and show robust killing activity; however, they do not bind or kill normal epithelial cells. We further demonstrated that the tMUC1-CAR T cells control the growth of orthotopic pancreatic tumors in vivo. We witnessed that some PDA cells (HPAFII and CFPAC) were refractory to CAR T cell treatment. qPCR analysis of several genes revealed overexpression of indoleamine 2, 3-dioxygenases-1 (IDO1), cyclooxygenase 1 and 2 (COX1/2), and galectin-9 (Gal-9) in resistant PDA cells. We showed that combination of CAR T cells and biological inhibitors of IDO1, COX1/2, and Gal-9 resulted in significant enhancement of CAR T cell cytotoxicity against PDA cells. Overcoming PDA resistance is a significant advancement in the field.

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