Epigenetic regulators have been implicated in tumorigenesis of many types of cancer;however,their roles in endothelial cell cancers such as canine hemangiosarcoma(HSA)have not been studied.In this study,we find that l...Epigenetic regulators have been implicated in tumorigenesis of many types of cancer;however,their roles in endothelial cell cancers such as canine hemangiosarcoma(HSA)have not been studied.In this study,we find that lysine-specific demethylase 2 b(KDM2 B)is highly expressed in HSA cell lines compared with normal canine endothelial cells.Silencing of KDM2 B in HSA cells results in increased cell death in vitro compared with the scramble control by inducing apoptosis through the inactivation of the DNA repair pathways and accumulation of DNA damage.Similarly,doxycycline-induced KDM2 B silencing in tumor xenografts results in decreased tumor sizes compared with the control.Furthermore,KDM2 B is also highly expressed in clinical cases of HSA.We hypothesize that pharmacological KDM2 B inhibition can also induce HSA cell death and can be used as an alternative treatment for HSA.We treat HSA cells with GSK-J4,a histone demethylase inhibitor,and find that GSK-J4 treatment also induces apoptosis and cell death.In addition,GSK-J4 treatment decreases tumor size.Therefore,we demonstrate that KDM2 B acts as an oncogene in HSA by enhancing the DNA damage response.Moreover,we show that histone demethylase inhibitor GSK-J4 can be used as a therapeutic alternative to doxorubicin for HSA treatment.展开更多
This study investigated the role of mast cells in canine cutaneous vascular tumors, and is the first such study to distinguish between tumors arising in the dermis versus the subcutis. Mast cell numbers in canine cuta...This study investigated the role of mast cells in canine cutaneous vascular tumors, and is the first such study to distinguish between tumors arising in the dermis versus the subcutis. Mast cell numbers in canine cutaneous hemangiomas (HA) and hemangiosarcomas (HSA) were evaluated to identify a relationship between mast cells, tumor type (HA, HSA), histologic location (dermis, subcutis) and tumor recurrence. One hundred and sixty-seven biopsies from 148 dogs were evaluated. Using only one biopsy from each dog, mast cell counts (MCC) for each tumor (n = 148) were obtained by averaging the number of mast cells counted in ten 400× fields. A significant difference in mean MCC was found only between tumor types, with HA having more mast cells than HSA (4.2 ± 4.2 vs. 2.2 ± 2.6;p < 0.001). No significant difference in mean MCC existed between tumors that recurred and those that did not. There was no difference in recurrence rate between tumor type or histologic location. Our results indicate that benign HA contain more mast cells than malignant endothelial cell tumors, regardless of histologic location;whether this is a cause or effect relationship remains to be determined.展开更多
Formation of new blood vessels is paramount for tumour growth and metastatic dissemination and vascular endothelial growth factor (VEGF) is one of the key regulators of this process. The purpose of this study was to e...Formation of new blood vessels is paramount for tumour growth and metastatic dissemination and vascular endothelial growth factor (VEGF) is one of the key regulators of this process. The purpose of this study was to evaluate the immunohistochemical expression of VEGF in 23 splenic hemangiosarcomas and 7 splenic hemangiomas in dogs. Blood tests performed previous to splenectomy were analysed for correlation with tumour VEGF expression. Results showed significantly higher VEGF expression in hemangiosarcomas than hemangiomas and lower hematocrit values and red cell count in dogs affected with malignant neoplasia (P < 0.05). These findings suggest the presence of high VEGF levels may be related to the malignant vascular proliferation seen in hemangiosarcomas.展开更多
Primary hepatic angiosarcoma （PHA） is a raremalignancy that carries a poor prognosis. Of 1500patients who underwent hepatectomy for primaryhepatic tumors between 1994 and 2013 at our center,two patients were patholo...Primary hepatic angiosarcoma （PHA） is a raremalignancy that carries a poor prognosis. Of 1500patients who underwent hepatectomy for primaryhepatic tumors between 1994 and 2013 at our center,two patients were pathologically diagnosed withPHA. Clinical characteristics, treatment modalities,and outcomes of the two patients were collectedand analyzed. Both patients underwent hepatectomyand had a postoperative survival time of 8 and 16mo, respectively. A search of PubMed yielded eightreferences reporting 35 cases of PHA publishedbetween 2004 and 2013. On the basis of the presentedcases and review of the literature, we endorse completesurgical resection as the mainstay definitive treatmentof PHA, with adjuvant postoperative chemotherapypotentially improving survival. Palliative chemotherapyis an option in advanced hepatic angiosarcoma.展开更多
BACKGROUND: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract and occur rarely in the duodenum. Splenic angiosarcoma is an aggressive neoplasm with an extremely poor ...BACKGROUND: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract and occur rarely in the duodenum. Splenic angiosarcoma is an aggressive neoplasm with an extremely poor prognosis. METHODS: We report a case of a 70-year-old man hospitalized for abdominal pain in the upper quadrants, dyspepsia and nausea, previously treated for Hodgkin lymphoma 30 years ago. Abdominal CT showed a solid nodular lesion in the third portion of the duodenum, the presence of retropancreatic, aortic and caval lymph nodes, and four nodular splenic masses. 111 In-octreotide scintigraphy revealed pathological tissue accumulation in the duodenal region, and in the retropancreatic, retroduodenal, aortic and caval lymph nodes, suggesting a nonfunctioning neuroendocrine peripancreatic tumor. RESULTS: At exploratory laparotomy, an exophytic soft tumor was found originating from the third portion of the duodenum. Pancreas-preserving duodenectomy with duodenojejunostomy, splenectomy and lymphnodectomy of retropancreatic aortic and caval lymph nodes were performed. Pathological evaluation and immunohistochemical studies showed the presence of a duodenal gastrointestinal stromal tumor with low mitotic activity and a well-differentiated angiosarcoma localized to the spleen and invading lymph nodes.CONCLUSIONS: We speculated that the angiosarcoma and duodenal gastrointestinal stromal tumors of this patient were due to the treatment of Hodgkin lymphoma with radiotherapy 30 years ago. Pancreas-preserving segmental duodenectomy can be used to treat non-malignant neoplasms of the duodenum and avoid extensive surgery. Splenectomy is the treatment of choice for localized angiosarcomas but a strict follow-up is mandatory because of the possibility of recurrence.展开更多
基金supported by the Sasakawa Scientific Research Grant(KG,Research No.2019-4111)provided by the Japan Science Society and the KAKENHI Grant-in-Aid for Young Scientist(KA,Number 18K14575,20K15654)provided by Japan Society for the Promotion of Science。
文摘Epigenetic regulators have been implicated in tumorigenesis of many types of cancer;however,their roles in endothelial cell cancers such as canine hemangiosarcoma(HSA)have not been studied.In this study,we find that lysine-specific demethylase 2 b(KDM2 B)is highly expressed in HSA cell lines compared with normal canine endothelial cells.Silencing of KDM2 B in HSA cells results in increased cell death in vitro compared with the scramble control by inducing apoptosis through the inactivation of the DNA repair pathways and accumulation of DNA damage.Similarly,doxycycline-induced KDM2 B silencing in tumor xenografts results in decreased tumor sizes compared with the control.Furthermore,KDM2 B is also highly expressed in clinical cases of HSA.We hypothesize that pharmacological KDM2 B inhibition can also induce HSA cell death and can be used as an alternative treatment for HSA.We treat HSA cells with GSK-J4,a histone demethylase inhibitor,and find that GSK-J4 treatment also induces apoptosis and cell death.In addition,GSK-J4 treatment decreases tumor size.Therefore,we demonstrate that KDM2 B acts as an oncogene in HSA by enhancing the DNA damage response.Moreover,we show that histone demethylase inhibitor GSK-J4 can be used as a therapeutic alternative to doxorubicin for HSA treatment.
文摘This study investigated the role of mast cells in canine cutaneous vascular tumors, and is the first such study to distinguish between tumors arising in the dermis versus the subcutis. Mast cell numbers in canine cutaneous hemangiomas (HA) and hemangiosarcomas (HSA) were evaluated to identify a relationship between mast cells, tumor type (HA, HSA), histologic location (dermis, subcutis) and tumor recurrence. One hundred and sixty-seven biopsies from 148 dogs were evaluated. Using only one biopsy from each dog, mast cell counts (MCC) for each tumor (n = 148) were obtained by averaging the number of mast cells counted in ten 400× fields. A significant difference in mean MCC was found only between tumor types, with HA having more mast cells than HSA (4.2 ± 4.2 vs. 2.2 ± 2.6;p < 0.001). No significant difference in mean MCC existed between tumors that recurred and those that did not. There was no difference in recurrence rate between tumor type or histologic location. Our results indicate that benign HA contain more mast cells than malignant endothelial cell tumors, regardless of histologic location;whether this is a cause or effect relationship remains to be determined.
文摘Formation of new blood vessels is paramount for tumour growth and metastatic dissemination and vascular endothelial growth factor (VEGF) is one of the key regulators of this process. The purpose of this study was to evaluate the immunohistochemical expression of VEGF in 23 splenic hemangiosarcomas and 7 splenic hemangiomas in dogs. Blood tests performed previous to splenectomy were analysed for correlation with tumour VEGF expression. Results showed significantly higher VEGF expression in hemangiosarcomas than hemangiomas and lower hematocrit values and red cell count in dogs affected with malignant neoplasia (P < 0.05). These findings suggest the presence of high VEGF levels may be related to the malignant vascular proliferation seen in hemangiosarcomas.
基金Supported by Science and Technology Department of Zhejiang Province,No.2011C13038Department of Education of Zhejiang Province,No.N20130411
文摘Primary hepatic angiosarcoma （PHA） is a raremalignancy that carries a poor prognosis. Of 1500patients who underwent hepatectomy for primaryhepatic tumors between 1994 and 2013 at our center,two patients were pathologically diagnosed withPHA. Clinical characteristics, treatment modalities,and outcomes of the two patients were collectedand analyzed. Both patients underwent hepatectomyand had a postoperative survival time of 8 and 16mo, respectively. A search of PubMed yielded eightreferences reporting 35 cases of PHA publishedbetween 2004 and 2013. On the basis of the presentedcases and review of the literature, we endorse completesurgical resection as the mainstay definitive treatmentof PHA, with adjuvant postoperative chemotherapypotentially improving survival. Palliative chemotherapyis an option in advanced hepatic angiosarcoma.
文摘BACKGROUND: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract and occur rarely in the duodenum. Splenic angiosarcoma is an aggressive neoplasm with an extremely poor prognosis. METHODS: We report a case of a 70-year-old man hospitalized for abdominal pain in the upper quadrants, dyspepsia and nausea, previously treated for Hodgkin lymphoma 30 years ago. Abdominal CT showed a solid nodular lesion in the third portion of the duodenum, the presence of retropancreatic, aortic and caval lymph nodes, and four nodular splenic masses. 111 In-octreotide scintigraphy revealed pathological tissue accumulation in the duodenal region, and in the retropancreatic, retroduodenal, aortic and caval lymph nodes, suggesting a nonfunctioning neuroendocrine peripancreatic tumor. RESULTS: At exploratory laparotomy, an exophytic soft tumor was found originating from the third portion of the duodenum. Pancreas-preserving duodenectomy with duodenojejunostomy, splenectomy and lymphnodectomy of retropancreatic aortic and caval lymph nodes were performed. Pathological evaluation and immunohistochemical studies showed the presence of a duodenal gastrointestinal stromal tumor with low mitotic activity and a well-differentiated angiosarcoma localized to the spleen and invading lymph nodes.CONCLUSIONS: We speculated that the angiosarcoma and duodenal gastrointestinal stromal tumors of this patient were due to the treatment of Hodgkin lymphoma with radiotherapy 30 years ago. Pancreas-preserving segmental duodenectomy can be used to treat non-malignant neoplasms of the duodenum and avoid extensive surgery. Splenectomy is the treatment of choice for localized angiosarcomas but a strict follow-up is mandatory because of the possibility of recurrence.
