Endoscopic US FNA and FNB provided similar NGS adequacy rates. Metastatic lesions accessible by percutaneous biopsy may be preferable to EUS FNB/A of primary lesions for obtaining tissue for NGS. All biopsies, including EUS FNB, were more likely to be successful using larger-gauge needles.
Targeted agents have improved the efficacy of chemotherapy for cancer patients, however, there remains a lack of understanding of how these therapies affect the unsuspecting bystanders of the stromal microenvironment. Cetuximab, a monoclonal antibody therapy targeting the epidermal growth factor receptor (EGFR), is given in combination with chemotherapy as the standard of care for a subset of metastatic colorectal cancer patients. The overall response to this treatment is underwhelming and, while genetic mutations that confer resistance have been identified, it is still not known why this drug is ineffective for some patients. We discovered that cancer-associated fibroblasts (CAFs), a major cellular subset of the tumor stroma, can provide a source of cancer cell resistance. Specifically, we observed that upon treatment with cetuximab, CAFs increased their secretion of EGF, which was sufficient to render neighboring cancer cells resistant to cetuximab treatment through sustained mitogen-activated protein kinases (MAPK) signaling. Furthermore, we show the cetuximab-induced EGF secretion to be specific to CAFs and not to cancer cells or normal fibroblasts. Altogether, this work emphasizes the importance of the tumor microenvironment and considering the potential unintended consequences of therapeutically targeting cancer-driving proteins on non-tumorigenic cell types.
Calcifying fibrous tumor is a benign mass lesion classically described as a soft tissue tumor. However, a thorough review of the literature reveals that it can occur virtually anywhere, including the tubular gastrointestinal (GI) tract. Its clinical manifestations are variable in the GI tract, and its imaging findings are nonspecific. However, it has unique histologic and immunophenotypical features that must be recognized by GI pathologists to differentiate it from an assortment of other rare mesenchymal lesions of the abdomen and GI tract. Calcifying fibrous tumor is composed of a paucicellular collagen matrix, interspersed calcified bodies, and a sparse inflammatory infiltrate. Although calcifying fibrous tumor is benign, pathologists must be aware that it may occur in the GI tract to differentiate it from other potentially more aggressive, rare mesenchymal lesions.
Chronic pancreatitis is a prominent risk factor for the development of pancreatic ductal adenocarcinoma. In both conditions, the activation of myofibroblast-like pancreatic stellate cells (PSCs) plays a predominant role in the formation of desmoplastic reaction through the synthesis of connective tissue and extracellular matrix, inducing local pancreatic fibrosis and an inflammatory response. Yet the signaling events involved in chronic pancreatitis and pancreatic cancer progression and metastasis remain poorly defined. Cadherin-11 (Cad-11, also known as OB cadherin or CDH11) is a cell-to-cell adhesion molecule implicated in many biological functions, including tissue morphogenesis and architecture, extracellular matrix-mediated tissue remodeling, cytoskeletal organization, epithelial-to-mesenchymal transition, and cellular migration. In this study, we show that, in human chronic pancreatitis and pancreatic cancer tissues, Cad-11 expression was significantly increased in PSCs and pancreatic cancer cells. In particular, an increased expression of Cad-11 can be detected on the plasma membrane of activated PSCs isolated from chronic pancreatitis tissues and in pancreatic cancer cells metastasized to the liver. Moreover, knockdown of Cad-11 in cancer cells reduced pancreatic cancer cell migration. Taken together, our data underline the potential role of Cad-11 in PSC activation and pancreatic cancer metastasis.
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