BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be ea...BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors.We herein present a rare case of ES involving the gastric area.CASE SUMMARY We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d.Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach;the mass was connected to the gastric antrum.Then,the mass was surgically excised completely.Upon histopathological,immunophenotype and molecular analysis,the mass was identified to be a primary gastric ES.CONCLUSION EES is an aggressive tumor with poor prognosis.Therefore,early diagnosis and timely intervention are essential for a good prognosis.It is imperative for us to raise awareness about this rare tumor.Surgical resection is still the best treatment option.展开更多
AIM:To determine the expression characteristics of connective tissue growth factor(CTGF/CCN2) in human hepatocellular carcinoma(HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression a...AIM:To determine the expression characteristics of connective tissue growth factor(CTGF/CCN2) in human hepatocellular carcinoma(HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression and metastasis in vitro.METHODS:Liver samples from 36 patients(who underwent hepatic resection for the first HCC between 2006 and 2011) and 6 normal individuals were examined for transforming growth factor β1(TGF-β1) or CCN2 mRNA by in situ hybridization.Computer image analysis was performed to measure integrated optimal density of CCN2 mRNA-positive cells in carcinoma foci and the surrounding stroma.Fibroblast-specific protein-1(FSP-1) and E-cadherin were examined to evaluate the process of epithelial to mesenchymal transition,α-smooth muscle actin and FSP-1 were detected to identify hepatic stellate cells,and CD34 was measured to evaluate the extent of vascularization in liver tissues by immunohistochemical staining.CCN2 was assessed for its stimulation of HepG2 cell migration and invasion using commercial kits while flow cytometry was used to determine CCN2 effects on HepG2 cell-cycle.RESULTS:In situ hybridization analysis showed that TGF-β1 mRNA was mainly detected in connective tissues and vasculature around carcinoma foci.In comparison to normal controls,CCN2 mRNA was enhanced 1.9-fold in carcinoma foci(12.36 ± 6.08 vs 6.42 ± 2.35) or 9.4-fold in the surrounding stroma(60.27 ± 28.71 vs 6.42 ± 2.35),with concomitant expression of CCN2 and TGF-β1 mRNA in those areas.Epithelial-mesenchymal transition phenotype related with CCN2 was detected in 12/36(33.3%) of HCC liver samples at the edges between carcinoma foci and vasculature.Incubation of HepG2 cells with CCN2(100 ng/mL) resulted in more of the cells transitioning into S phase(23.85 ± 2.35 vs 10.94 ± 0.23),and induced a significant migratory(4.0-fold) and invasive(5.7-fold) effect.TGF-β1-induced cell invasion was abrogated by a neutralizing CCN2 antibody showing that CCN2 is a downstream mediator of TGF-β1-induced hepatoma cell invasion.CONCLUSION:These data support a role for CCN2 in the growth and metastasis of HCC and highlight CCN2 as a potential novel therapeutic target.展开更多
AIM To examine the role of micro RNA 1181 (miR-1181) in invasion and proliferation in pancreatic cancer.METHODS We analyzed the expression of mi R-1181 in several pancreatic cancer cell lines and gen...AIM To examine the role of micro RNA 1181 (miR-1181) in invasion and proliferation in pancreatic cancer.METHODS We analyzed the expression of mi R-1181 in several pancreatic cancer cell lines and generated stable MIA-Pa Ca-2 and PANC-1 cell lines with up-regulated mi R-1181 expression using an adenovirus delivery system. We then investigated mi R-1181's effect on invasion and proliferation of pancreatic cancer cells by transwell assay, wound healing assay, cell counting kit-8 assay and colony-forming assay, and explored any underlying mechanisms by western bolt. Beyond that, we observed the change of the PANC-1 cell's cytoskeleton by immunofluorescence staining.RESULTS Our data showed that mi R-1181 was relatively downregulated in pancreatic cancer cell lines compared with normal pancreatic ductal epithelial cells. And miR-1181 inhibited the migration, invasion and proliferation activities of MIA-Pa Ca-2 and PANC-1 cells. Notably,after over-expressing of mi R-1181 in PANC-1 cells, F-actin depolymerized. Immunofluorescence staining shows decreased F-actin and β-tubulin expression in PANC-1 cells over-expressing mi R-1181 compared with the control cells. Furthermore, we found that over-expressing mi R-1181 inhibited the expression of signal transducer and activator of transcription 3(STAT3) while knocking-down mi R-1181 up-regulated the expression of STAT3. Knocking-down mi R-1181 promoted the invasion and proliferation of pancreatic cancer cells. And inhibition of STAT3 blocked the promotion effects of knocking-down mi R-1181 on proliferation and invasion in pancreatic cancer. CONCLUSION Together our findings suggest that mi R-1181 may be involved in pancreatic cancer cell invasion and proliferation by targeting STAT3 and indicate that mi R-1181 may be a potential therapeutic agent for pancreatic cancer.展开更多
The expression levels of hypoxia-inducible factor 1alpha(HIF-1α) and HIF-2α in pancreatic cancer(PC) and their association with clinicopathologic characteristics were investigated in order to elucidate their roles i...The expression levels of hypoxia-inducible factor 1alpha(HIF-1α) and HIF-2α in pancreatic cancer(PC) and their association with clinicopathologic characteristics were investigated in order to elucidate their roles in the development of PC. HIF-1α and HIF-2α m RNA levels in 20 patients with PC were detected by quantitative real-time polymerase chain reaction. The expression of HIF-1α and HIF-2α protein in samples from other 90 patients with PC was measured by immunohistochemistry. Correlations between the expression of HIF-1α or HIF-2α and clinicopathologica features and prognosis were analyzed. The expression of both HIF-1α and HIF-2α m RNA was up-regulated in most cancer tissues(P<0.05). HIF-1α staining was weakly positive in most cancer tissues and strongly positive in adjacent pancreas tissues(P<0.05). Clinicopathologic analysis revealed that relatively strong HIF-1α expression in cancer tissues was related to greater invasion(P<0.05), higher tumor pathologic stage(P<0.05), higher American Joint Committee on Cancer(AJCC) stage(P<0.05) and shorter overall survival time(P<0.05). Conversely, HIF-2α staining was strongly positive in most cancer tissues and weakly positive in adjacent pancreas tissues. Clinicopathologic analysis revealed that relatively strong HIF-2α expression in cancer tissues was related to less invasion(P<0.05), lower tumor pathologic stage(P<0.05), lower AJCC stage(P<0.05) and longer overall survival time(P<0.05). Moreover, the HIF-1αhigh/HIF-2αlow group showed a shorter survival time than the HIF-1αlow/HIF-2αhigh group. In conclusion, although HIF-1α and HIF-2α m RNA expression patterns are the same, their protein expression patterns are significantly different and they play different roles in PC. Combined analysis of HIF-1α and HIF-2α expression might be useful to predict the prognosis of patients with PC.展开更多
Autoimmune pancreatitis(AIP)is a form of chronic pancreatitis that is categorized as type 1 or type 2according to the clinical profile.Type 1 AIP,which predominantly presents in a few Asian countries,is a hyper-IgG4-r...Autoimmune pancreatitis(AIP)is a form of chronic pancreatitis that is categorized as type 1 or type 2according to the clinical profile.Type 1 AIP,which predominantly presents in a few Asian countries,is a hyper-IgG4-related disease.We report a case of IgG4-related AIP overlapping with Mikulicz’s disease and lymphadenitis,which is rare and seldom reported in literature.A 63-year male from Northeast China was admitted for abdominal distension lasting for one year.He presented symmetric swelling of the parotid and submandibular glands with slight dysfunction of salivary secretion for 6 mo.He had a 2-year history of bilateral submandibular lymphadenopathy without pain.He underwent surgical excision of the right submandibular lymph node one year prior to admission.He denied any history of alcohol,tobacco,or illicit drug use.Serological examination revealed high fasting blood sugar level(8.8 mmol/L)and high level of IgG4(15.2 g/L).Anti-SSA or anti-SSB were negative.Computed tomography of the abdomen showed a diffusely enlarged pancreas with loss of lobulation.Immunohistochemical stain for IgG4 demonstrated diffuse infiltration of IgG4-positive plasma cells in labial salivary gland and lymph node biopsy specimens.The patient received a dose of 30 mg/d of prednisone for three weeks.At this three-week follow-up,the patient reported no discomfort and his swollen salivary glands,neck lymph node and pancreas had returned to normal size.The patient received a maintenance dose of 10mg/d of prednisone for 6 mo,after which his illness had not recurred.展开更多
Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer t...Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer treated in our hospital between June 2012 and May 2016 were collected, the expression of KLF9 in pancreatic cancer tissues and paracancerous tissues were measured and then patients were further divided into high KLF9 expression group and low KLF9 expression group, 29 cases in each group. Serum tumor marker levels as well as invasion gene and tumor suppressor gene expression in tumor tissue were compared between patients with different KLF9 expression.Results: KLF9 expression in pancreatic cancer tissue was significantly lower than that in paracancerous tissue;serum tumor markers CA19-9, CA242, CA50 and CEA levels of low KLF9 expression group were higher than those of high KLF9 expression group;focal invasion genes DKK-1, GSK3β and HOXB7 mRNA expression of low KLF9 expression group were higher than those of high KLF9 expression group while tumor suppressor genes Bach2, SIRT3, DPC4 and Kiss-1 mRNA expression were lower than those of high KLF9 expression group.Conclusion: The expression of KLF9 decreases in pancreatic cancer tissues, and the expression of KLF9 is negatively correlated with the malignant degree of tumor.展开更多
The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecu...The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.展开更多
基金Supported by the Science and Education Project of Neijiang First People’s Hospital。
文摘BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors.We herein present a rare case of ES involving the gastric area.CASE SUMMARY We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d.Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach;the mass was connected to the gastric antrum.Then,the mass was surgically excised completely.Upon histopathological,immunophenotype and molecular analysis,the mass was identified to be a primary gastric ES.CONCLUSION EES is an aggressive tumor with poor prognosis.Therefore,early diagnosis and timely intervention are essential for a good prognosis.It is imperative for us to raise awareness about this rare tumor.Surgical resection is still the best treatment option.
基金Supported by National Natural Scientific Foundation,No. 30872236,81070370,to Gao RPNIH 5R01AA016003,to Brigstock DR
文摘AIM:To determine the expression characteristics of connective tissue growth factor(CTGF/CCN2) in human hepatocellular carcinoma(HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression and metastasis in vitro.METHODS:Liver samples from 36 patients(who underwent hepatic resection for the first HCC between 2006 and 2011) and 6 normal individuals were examined for transforming growth factor β1(TGF-β1) or CCN2 mRNA by in situ hybridization.Computer image analysis was performed to measure integrated optimal density of CCN2 mRNA-positive cells in carcinoma foci and the surrounding stroma.Fibroblast-specific protein-1(FSP-1) and E-cadherin were examined to evaluate the process of epithelial to mesenchymal transition,α-smooth muscle actin and FSP-1 were detected to identify hepatic stellate cells,and CD34 was measured to evaluate the extent of vascularization in liver tissues by immunohistochemical staining.CCN2 was assessed for its stimulation of HepG2 cell migration and invasion using commercial kits while flow cytometry was used to determine CCN2 effects on HepG2 cell-cycle.RESULTS:In situ hybridization analysis showed that TGF-β1 mRNA was mainly detected in connective tissues and vasculature around carcinoma foci.In comparison to normal controls,CCN2 mRNA was enhanced 1.9-fold in carcinoma foci(12.36 ± 6.08 vs 6.42 ± 2.35) or 9.4-fold in the surrounding stroma(60.27 ± 28.71 vs 6.42 ± 2.35),with concomitant expression of CCN2 and TGF-β1 mRNA in those areas.Epithelial-mesenchymal transition phenotype related with CCN2 was detected in 12/36(33.3%) of HCC liver samples at the edges between carcinoma foci and vasculature.Incubation of HepG2 cells with CCN2(100 ng/mL) resulted in more of the cells transitioning into S phase(23.85 ± 2.35 vs 10.94 ± 0.23),and induced a significant migratory(4.0-fold) and invasive(5.7-fold) effect.TGF-β1-induced cell invasion was abrogated by a neutralizing CCN2 antibody showing that CCN2 is a downstream mediator of TGF-β1-induced hepatoma cell invasion.CONCLUSION:These data support a role for CCN2 in the growth and metastasis of HCC and highlight CCN2 as a potential novel therapeutic target.
基金Supported by The National Natural Science Foundation of China,No.81160311 and No.81572429 to Jiang JX
文摘AIM To examine the role of micro RNA 1181 (miR-1181) in invasion and proliferation in pancreatic cancer.METHODS We analyzed the expression of mi R-1181 in several pancreatic cancer cell lines and generated stable MIA-Pa Ca-2 and PANC-1 cell lines with up-regulated mi R-1181 expression using an adenovirus delivery system. We then investigated mi R-1181's effect on invasion and proliferation of pancreatic cancer cells by transwell assay, wound healing assay, cell counting kit-8 assay and colony-forming assay, and explored any underlying mechanisms by western bolt. Beyond that, we observed the change of the PANC-1 cell's cytoskeleton by immunofluorescence staining.RESULTS Our data showed that mi R-1181 was relatively downregulated in pancreatic cancer cell lines compared with normal pancreatic ductal epithelial cells. And miR-1181 inhibited the migration, invasion and proliferation activities of MIA-Pa Ca-2 and PANC-1 cells. Notably,after over-expressing of mi R-1181 in PANC-1 cells, F-actin depolymerized. Immunofluorescence staining shows decreased F-actin and β-tubulin expression in PANC-1 cells over-expressing mi R-1181 compared with the control cells. Furthermore, we found that over-expressing mi R-1181 inhibited the expression of signal transducer and activator of transcription 3(STAT3) while knocking-down mi R-1181 up-regulated the expression of STAT3. Knocking-down mi R-1181 promoted the invasion and proliferation of pancreatic cancer cells. And inhibition of STAT3 blocked the promotion effects of knocking-down mi R-1181 on proliferation and invasion in pancreatic cancer. CONCLUSION Together our findings suggest that mi R-1181 may be involved in pancreatic cancer cell invasion and proliferation by targeting STAT3 and indicate that mi R-1181 may be a potential therapeutic agent for pancreatic cancer.
基金supported by grants from the National Natural Science Foundation of China(No.81160311 and No.81101621)the Outstanding Young Training Project of Science and Education of Guizhou Province+1 种基金China(No.[2012]177)the Postdoctoral Science Foundation of China(No.2013M531983)
文摘The expression levels of hypoxia-inducible factor 1alpha(HIF-1α) and HIF-2α in pancreatic cancer(PC) and their association with clinicopathologic characteristics were investigated in order to elucidate their roles in the development of PC. HIF-1α and HIF-2α m RNA levels in 20 patients with PC were detected by quantitative real-time polymerase chain reaction. The expression of HIF-1α and HIF-2α protein in samples from other 90 patients with PC was measured by immunohistochemistry. Correlations between the expression of HIF-1α or HIF-2α and clinicopathologica features and prognosis were analyzed. The expression of both HIF-1α and HIF-2α m RNA was up-regulated in most cancer tissues(P<0.05). HIF-1α staining was weakly positive in most cancer tissues and strongly positive in adjacent pancreas tissues(P<0.05). Clinicopathologic analysis revealed that relatively strong HIF-1α expression in cancer tissues was related to greater invasion(P<0.05), higher tumor pathologic stage(P<0.05), higher American Joint Committee on Cancer(AJCC) stage(P<0.05) and shorter overall survival time(P<0.05). Conversely, HIF-2α staining was strongly positive in most cancer tissues and weakly positive in adjacent pancreas tissues. Clinicopathologic analysis revealed that relatively strong HIF-2α expression in cancer tissues was related to less invasion(P<0.05), lower tumor pathologic stage(P<0.05), lower AJCC stage(P<0.05) and longer overall survival time(P<0.05). Moreover, the HIF-1αhigh/HIF-2αlow group showed a shorter survival time than the HIF-1αlow/HIF-2αhigh group. In conclusion, although HIF-1α and HIF-2α m RNA expression patterns are the same, their protein expression patterns are significantly different and they play different roles in PC. Combined analysis of HIF-1α and HIF-2α expression might be useful to predict the prognosis of patients with PC.
基金Supported by National Natural Scientific FoundationNo.8107037081270544(to Gao RP)and NIH 5R01AA016003(to Brigstock D)
文摘Autoimmune pancreatitis(AIP)is a form of chronic pancreatitis that is categorized as type 1 or type 2according to the clinical profile.Type 1 AIP,which predominantly presents in a few Asian countries,is a hyper-IgG4-related disease.We report a case of IgG4-related AIP overlapping with Mikulicz’s disease and lymphadenitis,which is rare and seldom reported in literature.A 63-year male from Northeast China was admitted for abdominal distension lasting for one year.He presented symmetric swelling of the parotid and submandibular glands with slight dysfunction of salivary secretion for 6 mo.He had a 2-year history of bilateral submandibular lymphadenopathy without pain.He underwent surgical excision of the right submandibular lymph node one year prior to admission.He denied any history of alcohol,tobacco,or illicit drug use.Serological examination revealed high fasting blood sugar level(8.8 mmol/L)and high level of IgG4(15.2 g/L).Anti-SSA or anti-SSB were negative.Computed tomography of the abdomen showed a diffusely enlarged pancreas with loss of lobulation.Immunohistochemical stain for IgG4 demonstrated diffuse infiltration of IgG4-positive plasma cells in labial salivary gland and lymph node biopsy specimens.The patient received a dose of 30 mg/d of prednisone for three weeks.At this three-week follow-up,the patient reported no discomfort and his swollen salivary glands,neck lymph node and pancreas had returned to normal size.The patient received a maintenance dose of 10mg/d of prednisone for 6 mo,after which his illness had not recurred.
文摘Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer treated in our hospital between June 2012 and May 2016 were collected, the expression of KLF9 in pancreatic cancer tissues and paracancerous tissues were measured and then patients were further divided into high KLF9 expression group and low KLF9 expression group, 29 cases in each group. Serum tumor marker levels as well as invasion gene and tumor suppressor gene expression in tumor tissue were compared between patients with different KLF9 expression.Results: KLF9 expression in pancreatic cancer tissue was significantly lower than that in paracancerous tissue;serum tumor markers CA19-9, CA242, CA50 and CEA levels of low KLF9 expression group were higher than those of high KLF9 expression group;focal invasion genes DKK-1, GSK3β and HOXB7 mRNA expression of low KLF9 expression group were higher than those of high KLF9 expression group while tumor suppressor genes Bach2, SIRT3, DPC4 and Kiss-1 mRNA expression were lower than those of high KLF9 expression group.Conclusion: The expression of KLF9 decreases in pancreatic cancer tissues, and the expression of KLF9 is negatively correlated with the malignant degree of tumor.
基金Lei Zheng is supported by NIH grant R01 CA169702,NIH grant R01 CA197296,The Viragh Foundation and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins,National Cancer Institute Specialized Programs of Research Excellence in Gastrointestinal Cancers grant F50 CA062924,Sidney Kimmel Comprehensive Cancer Center grant P30 CA006973.
文摘The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.
