BACKGROUND Transient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is ac... more BACKGROUND Transient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is activated by capsaicin, a pungent ingredient of hot pepper. Previous studies have suggested a link between obesity and capsaicin-associated pathways, and activation of TRPV1 may provide an alternative approach for obesity treatment. However, data on the TRPV1 distribution in human gastric mucosa are limited, and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown. AIM To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals. METHODS Forty-six patients with a body mass index (BMI) of > 40 kg/m2 and 20 patients with a BMI between 18-25 kg/m2 were included. Simultaneous biopsies from the fundus, antrum, and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy. Age, sex, history of alcohol and cigarette consumption, and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly. Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus, antrum, and duodenum tissues using an immunoreactivity score. Data were analyzed using SPSS 17.0. RESULTS TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum. Unlike foveolar cells in the antrum, TRPV1 was relatively low in foveolar cells in the fundus (4.92 ± 0.49 vs 0.48 ± 0.16, P < 0.01, Mann-Whitney U test). Additionally, the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum (1.33 ± 0.31 vs 2.95 ± 0.46, P < 0.01, Mann-Whitney U test). TRPV1 expression levels of different cell types in the fundus, antrum, and duodenum tissues of the morbidly obese group were similar to those of the control group. Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged ≥ 45 years than in patients < 45 years (3.03 ± 0.42, 4.37 ± 0.76, 2.28 ± 0.55 vs 1.9 ± 0.46, 1.58 ± 0.44, 0.37 ± 0.18, P = 0.03, P < 0.01, P < 0.01, respectively, Mann-Whitney U test). The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension (diabetes: 2.11 ± 0.67 vs 1.02 ± 0.34, P = 0.04; hypertension: 2.42 ± 0.75 vs 1.02 ± 0.33, P < 0.01 Mann-Whitney U test). CONCLUSION The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.
AIMS The aim of the study was to assess changes in levels of substance P (SP), vasoactive intesti... more AIMS The aim of the study was to assess changes in levels of substance P (SP), vasoactive intestinal peptide (VIP) and ghrelin in the gastroduodenal mucosa of obese individuals, which has not been studied before. METHODS Forty-six patients with a body mass index (BMI) of >40 kg/m2 and 20 patients with a BMI of 18-25 kg/m2 were included in the study. VIP and SP levels in the fundus, antrum and duodenal mucosa were measured in freshly frozen tissues using enzyme-linked immunosorbent assay (ELISA). Fasting levels of ghrelin in blood were also measured with ELISA. Tissue levels of ghrelin were assessed by immunohistochemical staining, and immunoreactivity scores were used for ghrelin evaluation in tissues. RESULTS Antrum SP levels were higher in the obese group than in the control group. A significant number of obese patients had low VIP levels in the fundus and antrum. Intense ghrelin staining was observed in a limited number of cells in the mucosal area of the gastric fundus that was similar in the control and patient groups. In the antrum and duodenum, ghrelin staining was low in all the samples examined. CONCLUSION Here, we found that SP levels are increased, while VIP levels are decreased in the antrum of morbidly obese individuals. Previous studies show that SP increases gastroduodenal motility, that VIP slows it down, and that the gastric emptying rate is higher in obese individuals, preventing negative feedback mechanisms upon food intake. Therefore, increases in SP and decreases in VIP levels in the antrum may contribute to obesity by accelerating gastric emptying.
Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the digestive tract are a rare heter... more Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment. Over the years, the diagnostic criteria, classification, and clinical behavior of these tumors have been the subjects of ongoing debate, and the various changes in their nomenclature have strengthened the challenges associated with MiNENs. This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as MiNEN, highlight the current diagnostic criteria, summarize the latest data on pathogenesis and provide information on available treatments. Moreover, this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system (GIS). Currently, the MiNEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma, depending on the organ of origin. Diagnosis is based on the presence of both morphological components in more than 30% of the tumor. However, this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of MiNEN by biopsy. Furthermore, available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of MiNEN is not supportive and warrants further investigation. The diagnosis of these tumors is not solely based on immunohistochemical findings. They are not hybrid tumors and both components can act independently; thus, careful grading of each component separately is required. In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection, the aggressive potential of both components has paramount importance in the choice of treatment. Regardless of the organ of origin within the GIS, almost MiNENs are tumors with poor prognosis and are frequently encountered in the elderly and men. They are most frequently reported in the colorectum, where data from molecular studies indicate a monoclonal origin; however, further studies are required to provide additional support for this origin.
Inflammatory myofibroblastic tumor of the liver is an uncommon lesion of uncertain pathogenesis t... more Inflammatory myofibroblastic tumor of the liver is an uncommon lesion of uncertain pathogenesis that has a unique histological appearance. Symptomatology and clinical findings in most cases suggest malignancy, and despite the advances in imaging techniques, the preoperative diagnosis of this tumor is difficult. We describe herein a case of inflammatory myofibroblastic tumor of the liver with a review of the literature. A mass occupying the right lobe of the liver was excised in a 48-year-old woman, who previously presented with weakness, fever, progressive weight loss, and right upper abdominal pain. The lesion was an unencapsulated light brown tumor (largest diameter 6 cm) without necrosis or hemorrhage. The characteristic histopathological features and the presence of spindle cells expressing smooth muscle actin and anaplastic lymphoma kinase allowed the diagnosis of inflammatory myofibroblastic tumor. The present case and the review revealed that inflammatory myofibroblastic tumor of the liver is not limited to younger age groups and males. Moreover, the rare occurrence of inflammatory myofibroblastic tumor of the liver and the lack of diagnostic clinical signs and symptoms do not exclude consideration of inflammatory myofibroblastic tumor in the differential diagnosis of liver tumors, especially in patients with tumor markers in normal ranges.
Turkiye Klinikleri Journal of Gastroenterohepatology, 2012
Objective: Midkine (MK) is a heparin-binding growth factor that plays important roles in cell tra... more Objective: Midkine (MK) is a heparin-binding growth factor that plays important roles in cell transformation and angiogenesis. Recent studies indicated that MK was involved in genesis and development of colorectal carcinomas (CRC). However in these tumors the relationship among MK expression, angiogenesis and prognosis has not been evaluated. The purpose of this study was to investigate whether MK expression was associated with angiogenesis and survival in patients with CRC. Material and Methods: Tumor specimens from 61 patients diagnosed as CRC were included in this study. Serial sections from paraffin embedded tissues were stained with anti-midkine and anti-CD34 antibodies. Angiogenesis was assessed as microvessel density (MVD). Chi-square test, Kaplan-Meier method and Cox regression analysis were used for statistical analysis. Results: MK expression was observed in 36 of the cases. Non-neoplastic mucosa was consistently negative. Any relationship was not observed between MK expression and clinicopathologic parameters, so MK expression failed to predict tumor behavior. Moreover MK expression was not associated with MVD. On the other hand the prognosis was significantly worse in patients with high MVD (>5.8). Survival analysis revealed that although MK expression had no impact on prognosis, MVD was an independent prognostic variable. Conclusion: Our results revealed that MK expression has no prognostic relevance in CRC. However MVD could be reliable indicator of prognosis. Although our data needs to be clarified with further molecular studies, the lack of correlation between MK expression and MVD suggests that MK has no impact on CRC related angiogenesis.
In this editorial, the roles of orosomucoid (ORM) in the diagnoses and follow-up assessments of b... more In this editorial, the roles of orosomucoid (ORM) in the diagnoses and follow-up assessments of both nonneoplastic diseases and liver tumors are discussed with respect to the publication by Zhu et al presented in the previous issue of World Journal of Gastroenterology (2020; 26(8): 840-817). ORM, or alpha-1 acid glycoprotein (AGP), is an acute-phase protein that constitutes 1% to 3% of plasma proteins in humans and is mainly synthesized in the liver. ORM exists in serum as two variants: ORM1 and ORM2. Although the variants share 89.6% sequence identity and have similar biological properties, ORM1 constitutes the main component of serum ORM. An interesting feature of ORM is that its biological effects differ according to variations in glycosylation patterns. This variable feature makes ORM an attractive target for diagnosing and monitoring many diseases, including those of the liver. Recent findings suggest that a sharp decrease in ORM level is an important marker for HBV-associated acute liver failure (ALF), and ORM1 plays an important role in liver regeneration. In viral hepatitis, increases in both ORM and its fucosylated forms and the correlation of these increases with fibrosis progression suggest that this glycoprotein can be used with other markers as a noninvasive method in the follow-up assessment of diseases. In addition, similar findings regarding the level of the asialylated form of ORM, called asialo-AGP (AsAGP), have been reported in a follow-up assessment of fibrosis in chronic liver disease. An increase in ORM in serum has also been shown to improve hepatocellular carcinoma (HCC) diagnosis performance when combined with other markers. In addition, determination of the ORM level has been useful in the diagnosis of HCC with AFP concentrations less than 500 ng/mL. For monitoring patients with AFP-negative HCC, a unique trifucosylated tetra-antennary glycan of ORM may also be used as a new potential marker. The fact that there are very few studies investigating the expression of this glycoprotein and its variants in liver tissues constitutes a potential limitation, especially in terms of revealing all the effects of ORM on carcinogenesis and tumor behavior. Current findings indicate that ORM2 expression is decreased in tumors, and this is related to the aggressive course of the disease. Parallel to this finding, in HCC cell lines, ORM2 decreases HCC cell migration and invasion, supporting reports of its tumor suppressor role. In conclusion, the levels of ORM and its different glycosylated variants are promising additional biomarkers for identifying ALF, for monitoring fibrosis in viral hepatitis, and for diagnosing early HCC. Although there is evidence that the loss of ORM2 expression in HCC is associated with poor prognosis, further studies are needed to support these findings. Additionally, investigations of ORM expression in borderline dysplastic nodules and hepatocellular adenomas, which pose diagnostic problems in the differential diagnosis of HCC, especially in biopsy samples, may shed light on whether ORM can be used in histopathological differential diagnosis.
Angiogenesis progresses together with fibrogenesis during chronic liver injury. Hypoxia‐inducible... more Angiogenesis progresses together with fibrogenesis during chronic liver injury. Hypoxia‐inducible factor‐1α (HIF‐1α), a master regulator of homeostasis, plays a pivotal role in hypoxia‐induced angiogenesis through its regulation of vascular endothelial growth factor (VEGF). The association between hypoxia, angiogenesis and VEGF expression has been demonstrated in experimental cirrhosis. However, expression of HIF‐1α has yet to be reported. The aim of this study was to investigate the significance of HIF‐1α expression during experimental liver fibrosis and the relationships between HIF‐1α expression, VEGF expression and angiogenesis. Cirrhosis was induced in male Wistar rats by intraperitoneal administration of diethyl nitrosamine (DEN) (100 mg/kg, once a week). The serial sections from liver tissues were stained with anti‐HIF‐1α, anti‐VEGF and anti‐CD34 antibodies before being measured by light microscopy. Our results showed that HIF‐1α expression gradually increases according to the severity of fibrosis (p&lt;0.01). Moreover, its expression was found to be correlated with angiogenesis (r=0.916) and VEGF expression (r=0.969). The present study demonstrates that HIF‐1α might have a role in the development of angiogenesis via regulation of VEGF during experimental liver fibrogenesis and suggests that this factor could be a potential target in the manipulation of angiogenesis in chronic inflammatory diseases of the liver.
In a preliminary study, the possibility that local inhibition of postaglandin formation may inhib... more In a preliminary study, the possibility that local inhibition of postaglandin formation may inhibit preterm labour was examined. An intravaginal cyclo-oxygenase inhibitor, naproxen sodium, 500 mg was used in cases of preterm labour. The gestational ages of the patients were between 27 and 34 weeks, and they included a triplet pregnancy unresponsive to beta-sympathomimetic therapy. Treatment with intravaginal naproxen sodium was associated with prolongation of pregnancy for more than 6 days in five out of seven patients. No untoward fetal or maternal side-effects were detected.
BACKGROUND Transient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is ac... more BACKGROUND Transient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is activated by capsaicin, a pungent ingredient of hot pepper. Previous studies have suggested a link between obesity and capsaicin-associated pathways, and activation of TRPV1 may provide an alternative approach for obesity treatment. However, data on the TRPV1 distribution in human gastric mucosa are limited, and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown. AIM To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals. METHODS Forty-six patients with a body mass index (BMI) of > 40 kg/m2 and 20 patients with a BMI between 18-25 kg/m2 were included. Simultaneous biopsies from the fundus, antrum, and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy. Age, sex, history of alcohol and cigarette consumption, and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly. Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus, antrum, and duodenum tissues using an immunoreactivity score. Data were analyzed using SPSS 17.0. RESULTS TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum. Unlike foveolar cells in the antrum, TRPV1 was relatively low in foveolar cells in the fundus (4.92 ± 0.49 vs 0.48 ± 0.16, P < 0.01, Mann-Whitney U test). Additionally, the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum (1.33 ± 0.31 vs 2.95 ± 0.46, P < 0.01, Mann-Whitney U test). TRPV1 expression levels of different cell types in the fundus, antrum, and duodenum tissues of the morbidly obese group were similar to those of the control group. Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged ≥ 45 years than in patients < 45 years (3.03 ± 0.42, 4.37 ± 0.76, 2.28 ± 0.55 vs 1.9 ± 0.46, 1.58 ± 0.44, 0.37 ± 0.18, P = 0.03, P < 0.01, P < 0.01, respectively, Mann-Whitney U test). The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension (diabetes: 2.11 ± 0.67 vs 1.02 ± 0.34, P = 0.04; hypertension: 2.42 ± 0.75 vs 1.02 ± 0.33, P < 0.01 Mann-Whitney U test). CONCLUSION The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.
AIMS The aim of the study was to assess changes in levels of substance P (SP), vasoactive intesti... more AIMS The aim of the study was to assess changes in levels of substance P (SP), vasoactive intestinal peptide (VIP) and ghrelin in the gastroduodenal mucosa of obese individuals, which has not been studied before. METHODS Forty-six patients with a body mass index (BMI) of >40 kg/m2 and 20 patients with a BMI of 18-25 kg/m2 were included in the study. VIP and SP levels in the fundus, antrum and duodenal mucosa were measured in freshly frozen tissues using enzyme-linked immunosorbent assay (ELISA). Fasting levels of ghrelin in blood were also measured with ELISA. Tissue levels of ghrelin were assessed by immunohistochemical staining, and immunoreactivity scores were used for ghrelin evaluation in tissues. RESULTS Antrum SP levels were higher in the obese group than in the control group. A significant number of obese patients had low VIP levels in the fundus and antrum. Intense ghrelin staining was observed in a limited number of cells in the mucosal area of the gastric fundus that was similar in the control and patient groups. In the antrum and duodenum, ghrelin staining was low in all the samples examined. CONCLUSION Here, we found that SP levels are increased, while VIP levels are decreased in the antrum of morbidly obese individuals. Previous studies show that SP increases gastroduodenal motility, that VIP slows it down, and that the gastric emptying rate is higher in obese individuals, preventing negative feedback mechanisms upon food intake. Therefore, increases in SP and decreases in VIP levels in the antrum may contribute to obesity by accelerating gastric emptying.
Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the digestive tract are a rare heter... more Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment. Over the years, the diagnostic criteria, classification, and clinical behavior of these tumors have been the subjects of ongoing debate, and the various changes in their nomenclature have strengthened the challenges associated with MiNENs. This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as MiNEN, highlight the current diagnostic criteria, summarize the latest data on pathogenesis and provide information on available treatments. Moreover, this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system (GIS). Currently, the MiNEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma, depending on the organ of origin. Diagnosis is based on the presence of both morphological components in more than 30% of the tumor. However, this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of MiNEN by biopsy. Furthermore, available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of MiNEN is not supportive and warrants further investigation. The diagnosis of these tumors is not solely based on immunohistochemical findings. They are not hybrid tumors and both components can act independently; thus, careful grading of each component separately is required. In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection, the aggressive potential of both components has paramount importance in the choice of treatment. Regardless of the organ of origin within the GIS, almost MiNENs are tumors with poor prognosis and are frequently encountered in the elderly and men. They are most frequently reported in the colorectum, where data from molecular studies indicate a monoclonal origin; however, further studies are required to provide additional support for this origin.
Inflammatory myofibroblastic tumor of the liver is an uncommon lesion of uncertain pathogenesis t... more Inflammatory myofibroblastic tumor of the liver is an uncommon lesion of uncertain pathogenesis that has a unique histological appearance. Symptomatology and clinical findings in most cases suggest malignancy, and despite the advances in imaging techniques, the preoperative diagnosis of this tumor is difficult. We describe herein a case of inflammatory myofibroblastic tumor of the liver with a review of the literature. A mass occupying the right lobe of the liver was excised in a 48-year-old woman, who previously presented with weakness, fever, progressive weight loss, and right upper abdominal pain. The lesion was an unencapsulated light brown tumor (largest diameter 6 cm) without necrosis or hemorrhage. The characteristic histopathological features and the presence of spindle cells expressing smooth muscle actin and anaplastic lymphoma kinase allowed the diagnosis of inflammatory myofibroblastic tumor. The present case and the review revealed that inflammatory myofibroblastic tumor of the liver is not limited to younger age groups and males. Moreover, the rare occurrence of inflammatory myofibroblastic tumor of the liver and the lack of diagnostic clinical signs and symptoms do not exclude consideration of inflammatory myofibroblastic tumor in the differential diagnosis of liver tumors, especially in patients with tumor markers in normal ranges.
Turkiye Klinikleri Journal of Gastroenterohepatology, 2012
Objective: Midkine (MK) is a heparin-binding growth factor that plays important roles in cell tra... more Objective: Midkine (MK) is a heparin-binding growth factor that plays important roles in cell transformation and angiogenesis. Recent studies indicated that MK was involved in genesis and development of colorectal carcinomas (CRC). However in these tumors the relationship among MK expression, angiogenesis and prognosis has not been evaluated. The purpose of this study was to investigate whether MK expression was associated with angiogenesis and survival in patients with CRC. Material and Methods: Tumor specimens from 61 patients diagnosed as CRC were included in this study. Serial sections from paraffin embedded tissues were stained with anti-midkine and anti-CD34 antibodies. Angiogenesis was assessed as microvessel density (MVD). Chi-square test, Kaplan-Meier method and Cox regression analysis were used for statistical analysis. Results: MK expression was observed in 36 of the cases. Non-neoplastic mucosa was consistently negative. Any relationship was not observed between MK expression and clinicopathologic parameters, so MK expression failed to predict tumor behavior. Moreover MK expression was not associated with MVD. On the other hand the prognosis was significantly worse in patients with high MVD (>5.8). Survival analysis revealed that although MK expression had no impact on prognosis, MVD was an independent prognostic variable. Conclusion: Our results revealed that MK expression has no prognostic relevance in CRC. However MVD could be reliable indicator of prognosis. Although our data needs to be clarified with further molecular studies, the lack of correlation between MK expression and MVD suggests that MK has no impact on CRC related angiogenesis.
In this editorial, the roles of orosomucoid (ORM) in the diagnoses and follow-up assessments of b... more In this editorial, the roles of orosomucoid (ORM) in the diagnoses and follow-up assessments of both nonneoplastic diseases and liver tumors are discussed with respect to the publication by Zhu et al presented in the previous issue of World Journal of Gastroenterology (2020; 26(8): 840-817). ORM, or alpha-1 acid glycoprotein (AGP), is an acute-phase protein that constitutes 1% to 3% of plasma proteins in humans and is mainly synthesized in the liver. ORM exists in serum as two variants: ORM1 and ORM2. Although the variants share 89.6% sequence identity and have similar biological properties, ORM1 constitutes the main component of serum ORM. An interesting feature of ORM is that its biological effects differ according to variations in glycosylation patterns. This variable feature makes ORM an attractive target for diagnosing and monitoring many diseases, including those of the liver. Recent findings suggest that a sharp decrease in ORM level is an important marker for HBV-associated acute liver failure (ALF), and ORM1 plays an important role in liver regeneration. In viral hepatitis, increases in both ORM and its fucosylated forms and the correlation of these increases with fibrosis progression suggest that this glycoprotein can be used with other markers as a noninvasive method in the follow-up assessment of diseases. In addition, similar findings regarding the level of the asialylated form of ORM, called asialo-AGP (AsAGP), have been reported in a follow-up assessment of fibrosis in chronic liver disease. An increase in ORM in serum has also been shown to improve hepatocellular carcinoma (HCC) diagnosis performance when combined with other markers. In addition, determination of the ORM level has been useful in the diagnosis of HCC with AFP concentrations less than 500 ng/mL. For monitoring patients with AFP-negative HCC, a unique trifucosylated tetra-antennary glycan of ORM may also be used as a new potential marker. The fact that there are very few studies investigating the expression of this glycoprotein and its variants in liver tissues constitutes a potential limitation, especially in terms of revealing all the effects of ORM on carcinogenesis and tumor behavior. Current findings indicate that ORM2 expression is decreased in tumors, and this is related to the aggressive course of the disease. Parallel to this finding, in HCC cell lines, ORM2 decreases HCC cell migration and invasion, supporting reports of its tumor suppressor role. In conclusion, the levels of ORM and its different glycosylated variants are promising additional biomarkers for identifying ALF, for monitoring fibrosis in viral hepatitis, and for diagnosing early HCC. Although there is evidence that the loss of ORM2 expression in HCC is associated with poor prognosis, further studies are needed to support these findings. Additionally, investigations of ORM expression in borderline dysplastic nodules and hepatocellular adenomas, which pose diagnostic problems in the differential diagnosis of HCC, especially in biopsy samples, may shed light on whether ORM can be used in histopathological differential diagnosis.
Angiogenesis progresses together with fibrogenesis during chronic liver injury. Hypoxia‐inducible... more Angiogenesis progresses together with fibrogenesis during chronic liver injury. Hypoxia‐inducible factor‐1α (HIF‐1α), a master regulator of homeostasis, plays a pivotal role in hypoxia‐induced angiogenesis through its regulation of vascular endothelial growth factor (VEGF). The association between hypoxia, angiogenesis and VEGF expression has been demonstrated in experimental cirrhosis. However, expression of HIF‐1α has yet to be reported. The aim of this study was to investigate the significance of HIF‐1α expression during experimental liver fibrosis and the relationships between HIF‐1α expression, VEGF expression and angiogenesis. Cirrhosis was induced in male Wistar rats by intraperitoneal administration of diethyl nitrosamine (DEN) (100 mg/kg, once a week). The serial sections from liver tissues were stained with anti‐HIF‐1α, anti‐VEGF and anti‐CD34 antibodies before being measured by light microscopy. Our results showed that HIF‐1α expression gradually increases according to the severity of fibrosis (p&lt;0.01). Moreover, its expression was found to be correlated with angiogenesis (r=0.916) and VEGF expression (r=0.969). The present study demonstrates that HIF‐1α might have a role in the development of angiogenesis via regulation of VEGF during experimental liver fibrogenesis and suggests that this factor could be a potential target in the manipulation of angiogenesis in chronic inflammatory diseases of the liver.
In a preliminary study, the possibility that local inhibition of postaglandin formation may inhib... more In a preliminary study, the possibility that local inhibition of postaglandin formation may inhibit preterm labour was examined. An intravaginal cyclo-oxygenase inhibitor, naproxen sodium, 500 mg was used in cases of preterm labour. The gestational ages of the patients were between 27 and 34 weeks, and they included a triplet pregnancy unresponsive to beta-sympathomimetic therapy. Treatment with intravaginal naproxen sodium was associated with prolongation of pregnancy for more than 6 days in five out of seven patients. No untoward fetal or maternal side-effects were detected.
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