This study investigated the effects of miRNA-155 on malignant biological characteristics of NK/T-cell lymphoma cell lines and the possible mechanism. The expression of miRNA-155 was detected in lymphoma cell lines fro...This study investigated the effects of miRNA-155 on malignant biological characteristics of NK/T-cell lymphoma cell lines and the possible mechanism. The expression of miRNA-155 was detected in lymphoma cell lines from different sources （SNK-6, YTS, Jurkat and DOHH2） by real-time PCR. Lentiviral vectors （pLL3.7） that could overexpress or downexpress miRNA-155 were constructed. Recombinant lentiviral particles were prepared and purified, and their titers determined. The expression of miRNA-155 in the infected SNK-6 cells and the cell proliferation were detected by PCR and CCK-8, respectively. Flow cytometry was used to determine the apoptosis of infected SNK-6 cells. The target of miRNA155 was predicted from Targetscan website. The effect of miRNA155 on FOXO3a expression was examined by Western blotting. The results showed that among the human NK/T-cell lymphoma cell lines SNK-6, YTS, Jurkat and DOHH2, the expression of miRNA-155 was highest in SNK-6. The infection efficiency of the recombinant lentivirns in SNK-6 was more than 70% at multiplicity of infection （MOI） of 100. The expression of miRNA-155 was significantly increased in SNK-6 cells infected by lentivirus vectors with high expression of miRNA-155 （4 times higher than the control group）, and profoundly decreased in those infected with lentivirnses with low expression of miRNA-155. The proliferation of letivirns-infected SNK-6 cells was decreased as the expression of miRNA-155 reduced. The apoptosis rate was increased with the reduction in the expression of miRNA-155. FOXO3a was found to be a possible target of miRNA155, as suggested by Targetscan website. Western blotting showed that the expression of FOXO3a was significantly elevated in SNK-6 cells with miRNA-155 inhibition. It was concluded that reduction in miRNA-155 expression can inhibit the proliferation of SNK-6 lymphoma cells and promote their apoptosis, which may be associated with regulation of FOXO3a gene.展开更多
AIM To provide the overall spectrum of gastrosplenic fistula(GSF) occurring in lymphomas through a systematic review including a patient at our hospital.METHODS A comprehensive literature search was performed in the M...AIM To provide the overall spectrum of gastrosplenic fistula(GSF) occurring in lymphomas through a systematic review including a patient at our hospital.METHODS A comprehensive literature search was performed in the MEDLINE database to identify studies of GSF occurring in lymphomas. A computerized search of our institutional database was also performed. In all cases, we analyzed the clinicopathologic/radiologic features, treatment and outcome of GSF occurring in lymphomas. RESULTS A literature search identified 25 relevant studies with 26 patients. Our institutional data search added 1 patient. Systematic review of the total 27 cases revealed that GSF occurred mainly in diffuse, large B-cell lymphoma(n = 23), but also in diffuse, histiocytic lymphoma(n = 1), Hodgkin's lymphoma(n = 2), and NK/T-cell lymphoma(n = 1, our patient). The common clinical presentations are constitutional symptoms(n = 20) and abdominal pain(n = 17), although acute gastrointestinal bleeding(n = 6) and infection symptoms due to splenic abscess(n = 3) are also noted. In all patients, computed tomography scanning was very helpful for diagnosing GSF and for evaluating the lymphoma extent. GSF could occur either post-chemotherapy(n = 10) or spontaneously(n = 17). Surgical resection has been the most common treatment. Once patients have recovered from the acute illness status after undergoing surgery, their long-term outcome has been favorable. CONCLUSION This systematic review provides an overview of GSF occurring in lymphomas, and will be helpful in making physicians aware of this rare disease entity.展开更多
Primary testicular NK/T-cell lymphoma is an extremely rare entity progressed rapidly.The aim of this study was to examine clinical and pathological features of primary testicular NK/T-cell lymphoma and to investigate ...Primary testicular NK/T-cell lymphoma is an extremely rare entity progressed rapidly.The aim of this study was to examine clinical and pathological features of primary testicular NK/T-cell lymphoma and to investigate the effective diagnosis and prognosis.In this paper,the two cases of primary testicular NK/T-cell lymphoma were observed by light microscopy,immunohistochemistry and examined by in situ hybridization for Epstein-Barr Virus（EBV） DNA and the literatures were reviewed.The two patients respectively present with bilateral and right-side painless testicular enlargement.The morphology of neoplastic cells of case 1 were small to medium,tumor cells of case 2 were small,medium and large mixed.The tumor cells grew diffusely with irregular and distort nuclear,destructed the organizational structure of the normal testis,and damaged blood vessels,meanwhile,coagulation necrosis was exist.Immunohistochemical staining of neoplastic cells showed positive for CD45,CD2,CD56,CD3ε（cytoplasm staining pattern）,CD45RO and Granzyme B,and negative for CD57,CD20,CD79α,CD30,CK,MPO,TdT,Bcl-2 and PLAP were negative.In addition,the EBV DNA was detected in the lymphoma by In situ hybridization.In conclusion,the expression of CD56,CD3ε,and Granzyme B associated proteins and EBV examination by in situ hybridization play a vital role in diagnosis and differential diagnosis of primary testicular NK/T-cell lymphoma.展开更多
AIM:To investigate the clinical features,diagnosis,treatment and prognosis of intestinal T-cell lymphomas(ITCL)by retrospective analysis.METHODS:Sixty-eight patients who were diagnosed with ITCL in case reports in the...AIM:To investigate the clinical features,diagnosis,treatment and prognosis of intestinal T-cell lymphomas(ITCL)by retrospective analysis.METHODS:Sixty-eight patients who were diagnosed with ITCL in case reports in the Chinese literature were compiled and reviewed.Age,gender,CD56 expression,surgical management,multifocal nature,perforation and cyclophosphamide chemotherapy were analyzed as the prognostic factors.The Kaplan-Meier method was adopted for the univariate analysis and the cumulative survival curve analysis.RESULTS:The male-to-female ratio was 1.52 to 1.The median age was 41.7 years.Twenty-seven patients had symptoms of abdominal pain or diarrhea.Thirty-six of60 patients with temperature records had high fevers at the onset of the illness.Twenty-six of 34 patients who underwent fiberoptic colonoscopy were misdiagnosed with Crohn’s disease,intestinal tuberculosis or cancer.Sixty-one patients underwent surgery.Twelve of 61 surgical patients required a second operation for anastomotic leakage or secondary perforation.The sites of lesion involvement were the jejunum(8.82%),ileum(29.41%),ileum and colon(4.41%),colon(55.88%)and appendix(1.47%).The median cumulative survival rate was 3 mo(3.00±0.48).CONCLUSION:Efforts should be made to correctly diagnose ITCL and select the proper operative approach that may reduce serious complications and create opportunities for further treatment.展开更多
Background Extranodal natural killer/T-cell （NK/T cell） lymphoma, nasal-type, is a rare lymphoma. Skin is the second most common site of involvement after the nasal cavity/nasalpharynx. The aim of this study was to ...Background Extranodal natural killer/T-cell （NK/T cell） lymphoma, nasal-type, is a rare lymphoma. Skin is the second most common site of involvement after the nasal cavity/nasalpharynx. The aim of this study was to investigate the clinicopathologic features, immunophenotype, T cell receptor （TCR） gene rearrangement, the association with Epstein-Barr virus （EBV） infection and p53 gene mutations of the lymphoma. Methods The clinicopathologic analysis, immunohistochemistry, in situ hybridization for EBERI/2, TCR gene rearrangement by polymerase chain reaction （PCR）, mutations of p53 gene analyzed by PCR and sequence analysis were employed in this study. Results In the 19 cases, the tumor primarily involved the dermis and subcutaneous layer. Immunohistochemical staining showed that most of the cases expressed CD45RO, CD56, CD3E, TIA-1 and GrB. Three cases were positive for CD3 and two cases were positive for CD30. Monoclonal TCRy gene rearrangement was found in 7 of 18 cases. The positive rate of EBERI/2 was 100%. No p53 gene mutation was detected on the exon 4-9 in the 18 cases. Fifteen cases showed Pro （proline）/Arg （arginine） single nucleotide polymorphisms （SNPs） on the exon 4 at codon 72. The expression of p53 protein was 72% （13/18）immunohistochemically. Conclusions Cutaneous NK/T-cell lymphoma is a rare but highly aggressive lymphoma with poor prognosis. No p53 gene mutation was detected on the exon 4-9, and Pro/Arg SNPs on p53 codon 72 were detected in the cutaneous NK/T-cell lymphoma. The overexpression of p53 protein may not be the result of p53 gene mutation.展开更多
As the chemotherapeutic resistance of extranodal NK/T-cell lymphoma(ENKTL) rises year by year, searching for novel chemoprevention compounds has become imminent. Gambogic acid(GA) has recently been shown to have anti-...As the chemotherapeutic resistance of extranodal NK/T-cell lymphoma(ENKTL) rises year by year, searching for novel chemoprevention compounds has become imminent. Gambogic acid(GA) has recently been shown to have anti-tumor effects, but its role and underling mechanism in ENKTL are rather elusive. In the present study, we showed that GA inhibited the cell growth and potently induced the apoptosis of ENKTL cells in vitro in a time-and concentration-dependent manner. Furthermore, GA induced cell death through endoplasmic reticulum stress(ERS) mediated suppression of Akt signaling pathways and finally the release of the caspase-3 proteases. Overall, our data provided evidences supporting GA as a potential therapeutic agent for ENKTL, which may facilitate further preclinical development of anti-tumor drugs.展开更多
The important role of lncRNAs and miRNAs in directing immune responses has become increasingly clear.Recent evidence conforms that miRNAs and lncRNAs are involved in NK cell biology and diseases through RNAeprotein,RN...The important role of lncRNAs and miRNAs in directing immune responses has become increasingly clear.Recent evidence conforms that miRNAs and lncRNAs are involved in NK cell biology and diseases through RNAeprotein,RNAeRNA,or RNAeDNA interactions.In this view,we summarize the contribution of miRNAs and lncRNAs to NK cell lineage devel-opment,activation and function,highlight the biological significance of functional miRNAs or lncRNAs in NKTL and discuss the potential of these miRNAs and lncRNAs as innovative bio-markers/targets for NKTL early diagnosis,target treatment and prognostic evaluations.展开更多
Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr...Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr virus and are prevalent in East Asia and Latin America.Except for that of limited-stage ENKL,the prognosis of both diseases was poor in the previous decade.The advent of non-anthracycline-based chemoradiotherapy has contributed to an improvement in ENKL prognosis,but there is still room for further treatment progress.Recently,the high efficacy of PD-1 antibody was reported in relapsed or refractory ENKL patients.This was later supported by the finding that PD-L1/PD-L2 genetic alterations are frequently observed in ENKL and ANKL patients.Due to the rarity of the disease,a standard treatment for ANKL remains to be established.Currently,allogeneic stem cell transplantation is the only curative treatment,and this is even applicable to chemo-resistant ANKL patients.In this review,we focus on recent treatment approaches for NK/T cell lymphomas including novel agents.展开更多
文摘This study investigated the effects of miRNA-155 on malignant biological characteristics of NK/T-cell lymphoma cell lines and the possible mechanism. The expression of miRNA-155 was detected in lymphoma cell lines from different sources （SNK-6, YTS, Jurkat and DOHH2） by real-time PCR. Lentiviral vectors （pLL3.7） that could overexpress or downexpress miRNA-155 were constructed. Recombinant lentiviral particles were prepared and purified, and their titers determined. The expression of miRNA-155 in the infected SNK-6 cells and the cell proliferation were detected by PCR and CCK-8, respectively. Flow cytometry was used to determine the apoptosis of infected SNK-6 cells. The target of miRNA155 was predicted from Targetscan website. The effect of miRNA155 on FOXO3a expression was examined by Western blotting. The results showed that among the human NK/T-cell lymphoma cell lines SNK-6, YTS, Jurkat and DOHH2, the expression of miRNA-155 was highest in SNK-6. The infection efficiency of the recombinant lentivirns in SNK-6 was more than 70% at multiplicity of infection （MOI） of 100. The expression of miRNA-155 was significantly increased in SNK-6 cells infected by lentivirus vectors with high expression of miRNA-155 （4 times higher than the control group）, and profoundly decreased in those infected with lentivirnses with low expression of miRNA-155. The proliferation of letivirns-infected SNK-6 cells was decreased as the expression of miRNA-155 reduced. The apoptosis rate was increased with the reduction in the expression of miRNA-155. FOXO3a was found to be a possible target of miRNA155, as suggested by Targetscan website. Western blotting showed that the expression of FOXO3a was significantly elevated in SNK-6 cells with miRNA-155 inhibition. It was concluded that reduction in miRNA-155 expression can inhibit the proliferation of SNK-6 lymphoma cells and promote their apoptosis, which may be associated with regulation of FOXO3a gene.
文摘AIM To provide the overall spectrum of gastrosplenic fistula(GSF) occurring in lymphomas through a systematic review including a patient at our hospital.METHODS A comprehensive literature search was performed in the MEDLINE database to identify studies of GSF occurring in lymphomas. A computerized search of our institutional database was also performed. In all cases, we analyzed the clinicopathologic/radiologic features, treatment and outcome of GSF occurring in lymphomas. RESULTS A literature search identified 25 relevant studies with 26 patients. Our institutional data search added 1 patient. Systematic review of the total 27 cases revealed that GSF occurred mainly in diffuse, large B-cell lymphoma(n = 23), but also in diffuse, histiocytic lymphoma(n = 1), Hodgkin's lymphoma(n = 2), and NK/T-cell lymphoma(n = 1, our patient). The common clinical presentations are constitutional symptoms(n = 20) and abdominal pain(n = 17), although acute gastrointestinal bleeding(n = 6) and infection symptoms due to splenic abscess(n = 3) are also noted. In all patients, computed tomography scanning was very helpful for diagnosing GSF and for evaluating the lymphoma extent. GSF could occur either post-chemotherapy(n = 10) or spontaneously(n = 17). Surgical resection has been the most common treatment. Once patients have recovered from the acute illness status after undergoing surgery, their long-term outcome has been favorable. CONCLUSION This systematic review provides an overview of GSF occurring in lymphomas, and will be helpful in making physicians aware of this rare disease entity.
基金supported by a grant from the Foundation of Chongqing Medical University(No.XBYB2007085)
文摘Primary testicular NK/T-cell lymphoma is an extremely rare entity progressed rapidly.The aim of this study was to examine clinical and pathological features of primary testicular NK/T-cell lymphoma and to investigate the effective diagnosis and prognosis.In this paper,the two cases of primary testicular NK/T-cell lymphoma were observed by light microscopy,immunohistochemistry and examined by in situ hybridization for Epstein-Barr Virus（EBV） DNA and the literatures were reviewed.The two patients respectively present with bilateral and right-side painless testicular enlargement.The morphology of neoplastic cells of case 1 were small to medium,tumor cells of case 2 were small,medium and large mixed.The tumor cells grew diffusely with irregular and distort nuclear,destructed the organizational structure of the normal testis,and damaged blood vessels,meanwhile,coagulation necrosis was exist.Immunohistochemical staining of neoplastic cells showed positive for CD45,CD2,CD56,CD3ε（cytoplasm staining pattern）,CD45RO and Granzyme B,and negative for CD57,CD20,CD79α,CD30,CK,MPO,TdT,Bcl-2 and PLAP were negative.In addition,the EBV DNA was detected in the lymphoma by In situ hybridization.In conclusion,the expression of CD56,CD3ε,and Granzyme B associated proteins and EBV examination by in situ hybridization play a vital role in diagnosis and differential diagnosis of primary testicular NK/T-cell lymphoma.
文摘AIM:To investigate the clinical features,diagnosis,treatment and prognosis of intestinal T-cell lymphomas(ITCL)by retrospective analysis.METHODS:Sixty-eight patients who were diagnosed with ITCL in case reports in the Chinese literature were compiled and reviewed.Age,gender,CD56 expression,surgical management,multifocal nature,perforation and cyclophosphamide chemotherapy were analyzed as the prognostic factors.The Kaplan-Meier method was adopted for the univariate analysis and the cumulative survival curve analysis.RESULTS:The male-to-female ratio was 1.52 to 1.The median age was 41.7 years.Twenty-seven patients had symptoms of abdominal pain or diarrhea.Thirty-six of60 patients with temperature records had high fevers at the onset of the illness.Twenty-six of 34 patients who underwent fiberoptic colonoscopy were misdiagnosed with Crohn’s disease,intestinal tuberculosis or cancer.Sixty-one patients underwent surgery.Twelve of 61 surgical patients required a second operation for anastomotic leakage or secondary perforation.The sites of lesion involvement were the jejunum(8.82%),ileum(29.41%),ileum and colon(4.41%),colon(55.88%)and appendix(1.47%).The median cumulative survival rate was 3 mo(3.00±0.48).CONCLUSION:Efforts should be made to correctly diagnose ITCL and select the proper operative approach that may reduce serious complications and create opportunities for further treatment.
文摘Background Extranodal natural killer/T-cell （NK/T cell） lymphoma, nasal-type, is a rare lymphoma. Skin is the second most common site of involvement after the nasal cavity/nasalpharynx. The aim of this study was to investigate the clinicopathologic features, immunophenotype, T cell receptor （TCR） gene rearrangement, the association with Epstein-Barr virus （EBV） infection and p53 gene mutations of the lymphoma. Methods The clinicopathologic analysis, immunohistochemistry, in situ hybridization for EBERI/2, TCR gene rearrangement by polymerase chain reaction （PCR）, mutations of p53 gene analyzed by PCR and sequence analysis were employed in this study. Results In the 19 cases, the tumor primarily involved the dermis and subcutaneous layer. Immunohistochemical staining showed that most of the cases expressed CD45RO, CD56, CD3E, TIA-1 and GrB. Three cases were positive for CD3 and two cases were positive for CD30. Monoclonal TCRy gene rearrangement was found in 7 of 18 cases. The positive rate of EBERI/2 was 100%. No p53 gene mutation was detected on the exon 4-9 in the 18 cases. Fifteen cases showed Pro （proline）/Arg （arginine） single nucleotide polymorphisms （SNPs） on the exon 4 at codon 72. The expression of p53 protein was 72% （13/18）immunohistochemically. Conclusions Cutaneous NK/T-cell lymphoma is a rare but highly aggressive lymphoma with poor prognosis. No p53 gene mutation was detected on the exon 4-9, and Pro/Arg SNPs on p53 codon 72 were detected in the cutaneous NK/T-cell lymphoma. The overexpression of p53 protein may not be the result of p53 gene mutation.
基金supported by the National Natural Science Foundation of China(Nos.81502588 and 81370673)Agency of Jiangsu Province Science and Technology(Nos.2013035 and BK20151018)+2 种基金the Key Medical subjects of Jiangsu Province(No.BL2014078)Research Office of Jiangsu Cancer Hospital(No.ZK201401)the Key Discipline of Jiangsu Province(2016-2020)
文摘As the chemotherapeutic resistance of extranodal NK/T-cell lymphoma(ENKTL) rises year by year, searching for novel chemoprevention compounds has become imminent. Gambogic acid(GA) has recently been shown to have anti-tumor effects, but its role and underling mechanism in ENKTL are rather elusive. In the present study, we showed that GA inhibited the cell growth and potently induced the apoptosis of ENKTL cells in vitro in a time-and concentration-dependent manner. Furthermore, GA induced cell death through endoplasmic reticulum stress(ERS) mediated suppression of Akt signaling pathways and finally the release of the caspase-3 proteases. Overall, our data provided evidences supporting GA as a potential therapeutic agent for ENKTL, which may facilitate further preclinical development of anti-tumor drugs.
文摘The important role of lncRNAs and miRNAs in directing immune responses has become increasingly clear.Recent evidence conforms that miRNAs and lncRNAs are involved in NK cell biology and diseases through RNAeprotein,RNAeRNA,or RNAeDNA interactions.In this view,we summarize the contribution of miRNAs and lncRNAs to NK cell lineage devel-opment,activation and function,highlight the biological significance of functional miRNAs or lncRNAs in NKTL and discuss the potential of these miRNAs and lncRNAs as innovative bio-markers/targets for NKTL early diagnosis,target treatment and prognostic evaluations.
文摘Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr virus and are prevalent in East Asia and Latin America.Except for that of limited-stage ENKL,the prognosis of both diseases was poor in the previous decade.The advent of non-anthracycline-based chemoradiotherapy has contributed to an improvement in ENKL prognosis,but there is still room for further treatment progress.Recently,the high efficacy of PD-1 antibody was reported in relapsed or refractory ENKL patients.This was later supported by the finding that PD-L1/PD-L2 genetic alterations are frequently observed in ENKL and ANKL patients.Due to the rarity of the disease,a standard treatment for ANKL remains to be established.Currently,allogeneic stem cell transplantation is the only curative treatment,and this is even applicable to chemo-resistant ANKL patients.In this review,we focus on recent treatment approaches for NK/T cell lymphomas including novel agents.
