The gastrointestinal peptide cholecystokinin (CCK) is released from the duodenum in response to dietary fat to aid in digestion, and plasma CCK levels are elevated with the consumption of high-fat diets. CCK is also a trophic peptide for the pancreas and has also been shown to stimulate growth of pancreatic cancer. In the current investigation, we studied the influence of a diet high in saturated fat on the growth of pancreatic cancer in syngeneic murine models before the mice became obese to exclude the confounding factors associated with obesity. The high-fat diet significantly increased growth and metastasis of pancreatic cancer compared with the control diet, and the stimulatory effect was blocked by the CCK-receptor antagonist proglumide. We then selectively knocked out the CCK receptor on the pancreatic cancer cells using clustered regularly interspaced short palindromic repeats technology and showed that without CCK-receptors, dietary fat was unable to stimulate cancer growth. We next demonstrated that dietary fat failed to influence pancreatic cancer xenograft growth in genetically engineered CCK peptide knockout mice. The tumor-associated fibrosis that is so prevalent in the pancreatic cancer microenvironment was significantly decreased with CCK-receptor antagonist therapy because fibroblasts also have CCK receptors. The CCK-receptor antagonist proglumide also altered tumor metalloprotease expression and increased tumor suppressor genes by a PCR array. Our studies confirm that a diet high in saturated fat promotes growth of pancreatic cancer and the action is mediated by the CCK-receptor pathway. NEW & NOTEWORTHY Diets high in long-chain saturated fats promote growth of pancreatic cancer independent of obesity. The mechanism through which dietary fat promotes cancer is mediated through the cholecystokinin (CCK) receptor pathway. Therapy with a CCK-receptor antagonist altered the tumor microenvironment by reducing fibrosis, increasing cluster of differentiation 8 lymphocytes, increasing tumor suppressor genes, and thus decreasing metastases. Use of CCK-receptor antagonist therapy with standard chemotherapy for pancreatic cancer may improve response by altering the tumor microenvironment.
Eosinophilic gastrointestinal disorders are a rare and complex group of disorders that are characterized by eosinophilic infiltration of the gastrointestinal tract. Patients often present with a wide range of signs and symptoms as any length or layer of the GI tract can be involved such as mucosal, muscular, or serosal. As a part of the workup, patients frequently undergo computed tomography scans and multiple endoscopies before the diagnosis is finally made as was true in our case of a 59-year-old male patient presenting with 2 months of nausea, abdominal pain, and weight loss. He underwent esophagogastroduodenoscopies, colonoscopies, video capsule study, and balloon enteroscopy before the diagnosis was confirmed histologically. Endoscopic and radiographic findings can be variable and are usually unpredictable. The diagnosis is confirmed on histopathological examination of biopsies that must show >15-50 eosinophils/high-power field based on the location in the GI tract. In our patient, erythema, scalloping, whitish exudate, and patches of villous blunting were noted in the duodenum to proximal ileum endoscopically with >50 eosinophils/high-power field confirming the diagnosis of eosinophilic enteritis. This class of diseases is often found in patients with a history of allergic disorders suggestive of hypersensitivity in the etiology of the disease although our patient had no such known history. Elimination diets and steroids are the mainstay of therapy and often lead to complete resolution of symptoms as well as endoscopic and radiographic findings in up to 90% of patients as was seen in our patient, although some patients have a chronic remitting course.
A 77-year-old woman with history of lung adenocarcinoma and bone metastasis presented with intractable nausea, nonbloody emesis, and abdominal pain. The patient was taking high doses of nonsteroidal anti-inflammatory drugs for pain from bone metastasis. Computed tomography demonstrated a duode-Marrache Mohamad K et al. EUS-guided rendezvous ERCP with steerable access device … Endoscopy 2020; 52: E355-E356 E355 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Eosinophilic gastrointestinal disorders are a rare and complex group of disorders that are characterized by eosinophilic infiltration of the gastrointestinal tract. Patients often present with a wide range of signs and symptoms as any length or layer of the GI tract can be involved such as mucosal, muscular, or serosal. As a part of the workup, patients frequently undergo computed tomography scans and multiple endoscopies before the diagnosis is finally made as was true in our case of a 59-year-old male patient presenting with 2 months of nausea, abdominal pain, and weight loss. He underwent esophagogastroduodenoscopies, colonoscopies, video capsule study, and balloon enteroscopy before the diagnosis was confirmed histologically. Endoscopic and radiographic findings can be variable and are usually unpredictable. The diagnosis is confirmed on histopathological examination of biopsies that must show >15-50 eosinophils/high-power field based on the location in the GI tract. In our patient, erythema, scalloping, whitish exudate, and patches of villous blunting were noted in the duodenum to proximal ileum endoscopically with >50 eosinophils/high-power field confirming the diagnosis of eosinophilic enteritis. This class of diseases is often found in patients with a history of allergic disorders suggestive of hypersensitivity in the etiology of the disease although our patient had no such known history. Elimination diets and steroids are the mainstay of therapy and often lead to complete resolution of symptoms as well as endoscopic and radiographic findings in up to 90% of patients as was seen in our patient, although some patients have a chronic remitting course.
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