Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts(MFs). MFs are spindle-shaped...Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts(MFs). MFs are spindle-shaped cells with stress fibres and welldeveloped fibronexus,and they display α-smooth muscle actin immunohistochemically and smoothmuscle myofilaments ultrastructurally. MFs play a crucial role in physiological and pathological processes. Derived from various sources,they play pivotal roles not only by synthesizing and producing extracellular matrix components,such as other connective tissue cells,but also are involved in force production. In the tissue remodelling phase of wound closure,integrinmediated interactions between MFs and type I collagen result in scar tissue formation. The tumour stroma in oral cancer actively recruits various cell types into the tumour mass,where they act as different sources of MFs. This article reviews the importance of MFs and its role in pathological processes such as wound healing,odontogenic cysts and tumours,salivary gland tumours,oral preneoplasia,and oral squamous cell carcinoma. Research oriented on blocking the transdifferentiation of fibroblasts into MFs can facilitate the development of noninvasive therapeutic strategies for the treatment of fibrosis and/or cancer.展开更多
AIM To determine whether it is possible to identify different immune phenotypic subpopulations of cancer-associated fibroblasts (CAFs) in pancreatic cancer (PC). METHODS We defined four different stromal compartments ...AIM To determine whether it is possible to identify different immune phenotypic subpopulations of cancer-associated fibroblasts (CAFs) in pancreatic cancer (PC). METHODS We defined four different stromal compartments in surgical specimens with PC: The juxtatumoural, peripheral, lobular and septal stroma. Tissue microarrays were produced containing all pre-defined PC compartments, and the expression of 37 fibroblast (FB) and 8 extracellular matrix (ECM) markers was evaluated by immunohistochemistry, immunofluorescence (IF), double-IF, and/or in situ hybridization. The compartment-specific mean labelling score was determined for each marker using a four-tiered scoring system. DOG1 gene expression was examined byquantitative reverse transcription PCR (qPCR). RESULTS CD10, CD271, cytoglobin, DOG1, miR-21, nestin, and tenascin C exhibited significant differences in expression profiles between the juxtatumoural and peripheral compartments. The expression of CD10, cytoglobin, DOG1, nestin, and miR-21 was moderate/strong in juxtatumoural CAFs (j-CAFs) and barely perceptible/weak in peripheral CAFs (p-CAFs). The upregulation of DOG1 gene expression in PC compared to normal pancreas was verified by qPCR. Tenascin C expression was strong in the juxtatumoural ECM and barely perceptible/weak in the peripheral ECM. CD271 expression was barely perceptible in j-CAFs but moderate in the other compartments. Galectin-1 was stronger expressed in j-CAFs vs septal fibroblasts, PDGFRβ, tissue transglutaminase 2, and hyaluronic acid were stronger expressed in lobular fibroblasts vs p-CAFs, and plectin-1 was stronger expressed in j-CAFs vs l-FBs. The expression of the remaining 33 markers did not differ significantly when related to the quantity of CAFs/FBs or the amount of ECM in the respective compartments.CONCLUSION Different immune phenotypic CAF subpopulations can be identified in PC, using markers such as cytoglobin, CD271, and miR-21. Future studies should determine whether CAF subpopulations have different functional properties.展开更多
Tumour induced osteomalacia(TIO) is a rare and often unrecognized cause of hypophosphatemia. We report on a case of TIO due to a hemangiopericytoma originating from the left nasal sinus. The patient was a 55-year-old ...Tumour induced osteomalacia(TIO) is a rare and often unrecognized cause of hypophosphatemia. We report on a case of TIO due to a hemangiopericytoma originating from the left nasal sinus. The patient was a 55-year-old male with a 3-year history of left hip pain and an undisplaced left hip fracture. Biochemical testing demonstrated low levels of serum phosphate and serum 1,25-dihydroxyvitamin D, and an elevated level of fibroblast growth factor 23. Octreotide scanning demonstrated uptake in the left nasal sinus area and a computed tomography scan revealed a left nasal sinus mass. The patient underwent surgical resection of the mass and histology was consistent with a sinonasal hemangiopericytoma. His serum phosphate levels normalized almost immediately after surgery and he had complete resolution of hip pain. Our case highlights the importance of considering TIO when assessing patients with low serum phosphate.展开更多
BACKGROUND Fibroblast growth factor 19(FGF-19)is one of the founding members of the endocrine FGF subfamily.Recently,it has been the subject of much interest owing to its role in various physiological processes affect...BACKGROUND Fibroblast growth factor 19(FGF-19)is one of the founding members of the endocrine FGF subfamily.Recently,it has been the subject of much interest owing to its role in various physiological processes affecting glucose and lipid metabolism and the regulation of bile acid secretion as well as cell proliferation,differentiation,and motility.Additionally,FGF-19 secretion in an autocrine style has reportedly contributed to cancer progression in various types of malignancies including hepatocellular carcinoma(HCC).AIM To estimate the serum FGF-19 concentrations in HCC cases and assess its diagnostic performance for the detection of HCC.METHODS We recruited 90 adult participants and divided them into three equal groups:Healthy controls,cirrhosis patients,and HCC patients.Serum FGF-19 concentrations were measured using the Human FGF-19 ELISA kit.RESULTS We detected a high statistically significant difference in serum FGF-19 levels among the three groups.The highest level was observed in the HCC group,followed by the cirrhosis and control groups(236.44±40.94 vs 125.63±31.54 vs 69.60±20.90 pg/mL,respectively,P≤0.001).FGF-19 was positively correlated with alpha fetoprotein(AFP;r=0.383,P=0.003)and international normalised ratio(r=0.357,P=0.005),while it was negatively correlated with albumin(r=-0.500,P≤0.001).For the detection of HCC,receiver operating characteristic curve analysis showed that the best cut-off point of AFP was>8.2 ng/mL with an area under the curve(AUC)of 0.78,sensitivity of 63.33%,specificity of 83.33%,positive predictive value(PPV)of 79.2%,negative predictive value(NPV)of 69.4%,and total accuracy of 78%.However,FGF-19 at a cut-off point>180 pg/mL had an AUC of 0.98,sensitivity of 100%,specificity of 90.0%,PPV of 90.0%,NPV of 100%,and total accuracy of 98%.CONCLUSION FGF-19 represents a possible novel non-invasive marker for HCC.It may improve the prognosis of HCC patients due to its utility in several aspects of HCC detection and management.展开更多
文摘Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts(MFs). MFs are spindle-shaped cells with stress fibres and welldeveloped fibronexus,and they display α-smooth muscle actin immunohistochemically and smoothmuscle myofilaments ultrastructurally. MFs play a crucial role in physiological and pathological processes. Derived from various sources,they play pivotal roles not only by synthesizing and producing extracellular matrix components,such as other connective tissue cells,but also are involved in force production. In the tissue remodelling phase of wound closure,integrinmediated interactions between MFs and type I collagen result in scar tissue formation. The tumour stroma in oral cancer actively recruits various cell types into the tumour mass,where they act as different sources of MFs. This article reviews the importance of MFs and its role in pathological processes such as wound healing,odontogenic cysts and tumours,salivary gland tumours,oral preneoplasia,and oral squamous cell carcinoma. Research oriented on blocking the transdifferentiation of fibroblasts into MFs can facilitate the development of noninvasive therapeutic strategies for the treatment of fibrosis and/or cancer.
基金Supported by Aase-and-Ejnar Danielsen’s Foundation,No.10-001452Brodrene Hartmann’s Foundation,No.A28308+5 种基金the Foundation of 17.12.1981,No.19024005Karen S.Jensens Grant,No.27-A1433University of Southern Denmark Faculty ScholarshipOdense University Hospital Free Research Fund,No.29-A1500,22-A1133 and 49-A2379Odense University Hospital Ph.D.stipend,No.1032Odense Pancreas Center(OPAC)
文摘AIM To determine whether it is possible to identify different immune phenotypic subpopulations of cancer-associated fibroblasts (CAFs) in pancreatic cancer (PC). METHODS We defined four different stromal compartments in surgical specimens with PC: The juxtatumoural, peripheral, lobular and septal stroma. Tissue microarrays were produced containing all pre-defined PC compartments, and the expression of 37 fibroblast (FB) and 8 extracellular matrix (ECM) markers was evaluated by immunohistochemistry, immunofluorescence (IF), double-IF, and/or in situ hybridization. The compartment-specific mean labelling score was determined for each marker using a four-tiered scoring system. DOG1 gene expression was examined byquantitative reverse transcription PCR (qPCR). RESULTS CD10, CD271, cytoglobin, DOG1, miR-21, nestin, and tenascin C exhibited significant differences in expression profiles between the juxtatumoural and peripheral compartments. The expression of CD10, cytoglobin, DOG1, nestin, and miR-21 was moderate/strong in juxtatumoural CAFs (j-CAFs) and barely perceptible/weak in peripheral CAFs (p-CAFs). The upregulation of DOG1 gene expression in PC compared to normal pancreas was verified by qPCR. Tenascin C expression was strong in the juxtatumoural ECM and barely perceptible/weak in the peripheral ECM. CD271 expression was barely perceptible in j-CAFs but moderate in the other compartments. Galectin-1 was stronger expressed in j-CAFs vs septal fibroblasts, PDGFRβ, tissue transglutaminase 2, and hyaluronic acid were stronger expressed in lobular fibroblasts vs p-CAFs, and plectin-1 was stronger expressed in j-CAFs vs l-FBs. The expression of the remaining 33 markers did not differ significantly when related to the quantity of CAFs/FBs or the amount of ECM in the respective compartments.CONCLUSION Different immune phenotypic CAF subpopulations can be identified in PC, using markers such as cytoglobin, CD271, and miR-21. Future studies should determine whether CAF subpopulations have different functional properties.
文摘Tumour induced osteomalacia(TIO) is a rare and often unrecognized cause of hypophosphatemia. We report on a case of TIO due to a hemangiopericytoma originating from the left nasal sinus. The patient was a 55-year-old male with a 3-year history of left hip pain and an undisplaced left hip fracture. Biochemical testing demonstrated low levels of serum phosphate and serum 1,25-dihydroxyvitamin D, and an elevated level of fibroblast growth factor 23. Octreotide scanning demonstrated uptake in the left nasal sinus area and a computed tomography scan revealed a left nasal sinus mass. The patient underwent surgical resection of the mass and histology was consistent with a sinonasal hemangiopericytoma. His serum phosphate levels normalized almost immediately after surgery and he had complete resolution of hip pain. Our case highlights the importance of considering TIO when assessing patients with low serum phosphate.
文摘BACKGROUND Fibroblast growth factor 19(FGF-19)is one of the founding members of the endocrine FGF subfamily.Recently,it has been the subject of much interest owing to its role in various physiological processes affecting glucose and lipid metabolism and the regulation of bile acid secretion as well as cell proliferation,differentiation,and motility.Additionally,FGF-19 secretion in an autocrine style has reportedly contributed to cancer progression in various types of malignancies including hepatocellular carcinoma(HCC).AIM To estimate the serum FGF-19 concentrations in HCC cases and assess its diagnostic performance for the detection of HCC.METHODS We recruited 90 adult participants and divided them into three equal groups:Healthy controls,cirrhosis patients,and HCC patients.Serum FGF-19 concentrations were measured using the Human FGF-19 ELISA kit.RESULTS We detected a high statistically significant difference in serum FGF-19 levels among the three groups.The highest level was observed in the HCC group,followed by the cirrhosis and control groups(236.44±40.94 vs 125.63±31.54 vs 69.60±20.90 pg/mL,respectively,P≤0.001).FGF-19 was positively correlated with alpha fetoprotein(AFP;r=0.383,P=0.003)and international normalised ratio(r=0.357,P=0.005),while it was negatively correlated with albumin(r=-0.500,P≤0.001).For the detection of HCC,receiver operating characteristic curve analysis showed that the best cut-off point of AFP was>8.2 ng/mL with an area under the curve(AUC)of 0.78,sensitivity of 63.33%,specificity of 83.33%,positive predictive value(PPV)of 79.2%,negative predictive value(NPV)of 69.4%,and total accuracy of 78%.However,FGF-19 at a cut-off point>180 pg/mL had an AUC of 0.98,sensitivity of 100%,specificity of 90.0%,PPV of 90.0%,NPV of 100%,and total accuracy of 98%.CONCLUSION FGF-19 represents a possible novel non-invasive marker for HCC.It may improve the prognosis of HCC patients due to its utility in several aspects of HCC detection and management.