A deficiency ofγδT cells has been described in Crohn's disease(CD).AIM To analyze the gene expression of interleukin 7(IL-7)and its receptors in the tissues of patients with CD.METHODS We studied the peripheral ...A deficiency ofγδT cells has been described in Crohn's disease(CD).AIM To analyze the gene expression of interleukin 7(IL-7)and its receptors in the tissues of patients with CD.METHODS We studied the peripheral blood of 80 patients with CD,comparing them with a group of 80 healthy subjects.The number and apoptosis ofαβandγδT cells in peripheral blood and the proportion ofαβandγδT cells in the intestinal tissues of patients with CD(n=25)were studied.The gene and protein expression of IL-7,IL-2 receptor subunitγ[cluster of differentiation 132(CD132)],receptorα(CD127),and caspase-3 in tissues was analyzed by quantitative PCR.Serum IL-7 levels were also analyzed.RESULTS In patients with CD,a decreased number ofγδT cells and an increase in the apoptosis of CD56+αβandγδT cells in peripheral blood was observed(P<0.0001 and P<0.01)respectively,and there was an inverse correlation among T subsets and their apoptosis.In addition,IL-7 gene expression and IL-7 protein in the tissues of these patients were increased.The titers of caspase-3 in tissues were low vs control group(P>0.01).The percentage of CD8+γδT cells decreased in tissues(P<0.01),and was directly related to IL-7 levels in peripheral blood.The expression of IL-2 receptor subunitγ(CD132)was greatly decreased in the tissues of patients with CD(P<0.05).CONCLUSION There may be a cause-effect relationship between the lower gene expression of the IL-2 receptor subunitγ(CD132)in tissues of patients with CD andγδT cells immunodeficiency.展开更多
AIM: To investigate the clinical course of untreatable hepatocellular carcinoma (HCC) identified at any stage and to identify factors associated with mortality. METHODS: From January 1999 to December 2010, 320 out of ...AIM: To investigate the clinical course of untreatable hepatocellular carcinoma (HCC) identified at any stage and to identify factors associated with mortality. METHODS: From January 1999 to December 2010, 320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatments were followed and managed with supportive therapy. Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated according to Child-Pugh score. The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging. Data were collected for each patient including all clinical, laboratory and imaging variables necessary for the outcome prediction staging systems considered. HCC staging was performed according Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program scores. Follow-up time was defined as the number of months from the diagnosis of HCC to death. Prognostic baseline variables were analyzed by multivariate Cox analysis to identify the independent predictors of survival. RESULTS: Seventy-five per cent of patients had hepatitis C. Ascites was present in 169 patients (53%), while hepatic encephalopathy was present in 49 patients (15%). The Child-Pugh score was class A in 105 patients (33%), class B in 142 patients (44%), and class C in 73 patients (23%). One hundred patients (31%) had macroscopic vascular invasion and/or extra-hepatic spread of the tumor. A single lesion > 10 cm was observed in 34 patients (11%), while multinodular HCC was present in 189 patients (59%). Thirty nine patients (12%) were BCLC early (A) stage, 55 (17%) were BCLC intermediate (B) stage, 124 (39%) were BCLC advanced (C) stage, and 102 (32%) were end-stage BCLC (D). At the time of this analysis (July 2011), 28 (9%) patients were still alive. Six (2%) patients who were lost during follow-up were censored at the last visit. The overall median survival was 6.8 mo, and the 1-year survival was 32%. The 1-year survival according to BCLC classes was 100%, 79%, 12% and 0%, for BCLC A, B, C and D, respectively. There was a significant difference in survival between each BCLC class. The median survival of patients of BCLC stages A, B, C and D was 33, 17.4, 6.9, and 1.8 mo, respectively (P < 0.05 for comparison between stages). The median survival of Child-Pugh A, B and C classes were 9.8 mo (range 6.4-13), 6.1 (range 4.9-7.3), and 3.7 (range 1.5-6), respectively (P < 0.05 for comparison between stages). By univariate analysis, the variables significantly associated to an increased liklihood of mortality were Eastern Cooperative Oncology Group performance status (PS), presence of ascites, low level of albumin, elevated level of bilirubin, international normalized ratio (INR) and Log-[(α fetoprotein (AFP)]. At multivariate analysis, mortality was independently predicted by bad PS (P < 0.0001), high INR values (P = 0.0001) and elevated Log-(AFP) levels (P = 0.009). CONCLUSION: This study confirms the heterogeneous behavior of untreated HCC. BCLC staging remains an important prognostic guide and may be important in decision-making for palliative treatment.展开更多
As all branches of science grow and new experimental techniques become readily accessible,our knowledge of medicine is likely to increase exponentially in the coming years.Recently developed technologies have revoluti...As all branches of science grow and new experimental techniques become readily accessible,our knowledge of medicine is likely to increase exponentially in the coming years.Recently developed technologies have revolutionized our analytical capacities,leading to vast knowledge of many genes or genomic regions involved in the pathogenesis of congenital heart diseases,which are often associated with other genetic syndromes,coronary artery disease and non-ischemic cardiomyopathies and channelopathies.The knowledge-base of the genesis of cardiovascular diseases is likely going to be further revolutionized in this new era of genomic medicine.Here,we review the advances that have been made over the last several years in this field and discuss different genetic mechanisms that have been shown to underlie a variety of cardiovascular diseases.展开更多
Modern liver ultrasonography(US)has become a“one-stop shop”able to provide not only anatomic and morphologic but also functional information about vascularity,stiffness and other various liver tissue properties.Mode...Modern liver ultrasonography(US)has become a“one-stop shop”able to provide not only anatomic and morphologic but also functional information about vascularity,stiffness and other various liver tissue properties.Modern US techniques allow a quantitative assessment of various liver diseases.US scanning is no more limited to the visualized plane,but three-dimensional,volumetric acquisition and consequent post-processing are also possible.Further,US scan can be consistently merged and visualized in real time with Computed Tomography and Magnetic Resonance Imaging examinations.Effective and safe microbubble�based contrast agents allow a real time,dynamic study of contrast kinetic for the detection and characterization of focal liver lesions.Ultrasound can be used to guide loco-regional treatment of liver malignancies and to assess tumoral response either to interventional procedures or medical therapies.Microbubbles may also carry and deliver drugs under ultrasound exposure.US plays a crucial role in diagnosing,treating and monitoring focal and diffuse liver disease.On the basis of personal experience and literature data,this paper is aimed to review the main topics involving recent advances in the field of liver ultrasound.展开更多
Introduction: Granulomatous mastitis (GM) is a rare benign histopathologic lesion, associated with tissue inflammation, architectural distortions and heterogeneous parenchymal inflammation upon radiological evaluation...Introduction: Granulomatous mastitis (GM) is a rare benign histopathologic lesion, associated with tissue inflammation, architectural distortions and heterogeneous parenchymal inflammation upon radiological evaluation. The treatment of GM is controversial, and currently, there is no consensus about the most appropriate therapy. Case Presentation: We presented a unique, atypical GM case with a prolonged disease course that ultimately led to a bilateral mastectomy. A conservative therapeutic approach and limited or wide surgical excisions have failed to prevent unfavorable outcomes in both the initial presentation and recurrent disease. Conclusions: There’re no clear data in the literature delineating persistent recurrences of GM after conservative treatment and multiple surgeries. Obtaining a disease-free surgical margin might be an important prognostic factor for a lasting relapse-free clinical resolution.展开更多
To the editor Soft-tissue sarcomas(STS)represent a very heterogeneous group of rare tumors including more than 100 different subtypes[1].Surgery and neo/adjuvant radiation therapy represent the cornerstone of treatmen...To the editor Soft-tissue sarcomas(STS)represent a very heterogeneous group of rare tumors including more than 100 different subtypes[1].Surgery and neo/adjuvant radiation therapy represent the cornerstone of treatment for STS.However,despite an optimal resection of the tumor,up to 40%of patients will develop metastatic relapse and will die from the disease[1].Doxorubicin represents the first-line standard of care for patients with advanced disease since the 1970s,despite several attempts to identify better regimens.The median overall survival(OS)of patients with metastatic disease is<18 months and has only modestly improved over the past 20 years[2].展开更多
Theγδcells are a unique population of T lymphocytes that combine innate-like features and adaptive-type responses and play an important role in the early host response to infections and malignancies.Different fromα...Theγδcells are a unique population of T lymphocytes that combine innate-like features and adaptive-type responses and play an important role in the early host response to infections and malignancies.Different fromαβT cells,γδT cells recognize a limited set of antigens,which are shared by a variety of microbial pathogens and tumor cells in a non-MHC restricted manner;1 thus,these cells use the TCR in a manner similar to a pattern recognition receptor(PRR).Moreover,whereasαβT cells require antigen-and cytokine-driven clonal expansion,γδT cells are equipped with immediate effector functions.1 However,the potentialγδrepertoire with junctional diversity is estimated at∼10^(18),which is much greater than theαβrepertoire(∼10^(16)),thus raising questions concerning the forces governing the selection of such a huge TCR repertoire during ontogeny and whether and how theγδTCR repertoire is shaped under physiological and pathological conditions.展开更多
1(NUTM1)gene rearrangements(15q14).In 1991,two independent research teams reported NC cases characterized by the t(15;19)translo-cation.1,2 In vitro studies by French et al.3 led to the pivotal discovery of NC in 2003...1(NUTM1)gene rearrangements(15q14).In 1991,two independent research teams reported NC cases characterized by the t(15;19)translo-cation.1,2 In vitro studies by French et al.3 led to the pivotal discovery of NC in 2003 as a distinct disease entity driven by the fusion of bromodo-main and extraterminal domain(BET)protein 4(BRD4)and NUTM1.In 2004,the World Health Organization(WHO)classified tumors with t(15;19)translocation as a thymic malignancy and designated it“NUT midline carcinoma,”due to its predominant occurrence in midline organs.4 However,subsequent reports revealed NC’s emergence in numerous nonmidline organs,leading to its reclassification as the independent entity“NUT carcinoma of the thorax”by the WHO in 2015.5 NC exhibits rapid progression and profound resistance to conventional radiotherapy and chemotherapy.展开更多
文摘A deficiency ofγδT cells has been described in Crohn's disease(CD).AIM To analyze the gene expression of interleukin 7(IL-7)and its receptors in the tissues of patients with CD.METHODS We studied the peripheral blood of 80 patients with CD,comparing them with a group of 80 healthy subjects.The number and apoptosis ofαβandγδT cells in peripheral blood and the proportion ofαβandγδT cells in the intestinal tissues of patients with CD(n=25)were studied.The gene and protein expression of IL-7,IL-2 receptor subunitγ[cluster of differentiation 132(CD132)],receptorα(CD127),and caspase-3 in tissues was analyzed by quantitative PCR.Serum IL-7 levels were also analyzed.RESULTS In patients with CD,a decreased number ofγδT cells and an increase in the apoptosis of CD56+αβandγδT cells in peripheral blood was observed(P<0.0001 and P<0.01)respectively,and there was an inverse correlation among T subsets and their apoptosis.In addition,IL-7 gene expression and IL-7 protein in the tissues of these patients were increased.The titers of caspase-3 in tissues were low vs control group(P>0.01).The percentage of CD8+γδT cells decreased in tissues(P<0.01),and was directly related to IL-7 levels in peripheral blood.The expression of IL-2 receptor subunitγ(CD132)was greatly decreased in the tissues of patients with CD(P<0.05).CONCLUSION There may be a cause-effect relationship between the lower gene expression of the IL-2 receptor subunitγ(CD132)in tissues of patients with CD andγδT cells immunodeficiency.
文摘AIM: To investigate the clinical course of untreatable hepatocellular carcinoma (HCC) identified at any stage and to identify factors associated with mortality. METHODS: From January 1999 to December 2010, 320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatments were followed and managed with supportive therapy. Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated according to Child-Pugh score. The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging. Data were collected for each patient including all clinical, laboratory and imaging variables necessary for the outcome prediction staging systems considered. HCC staging was performed according Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program scores. Follow-up time was defined as the number of months from the diagnosis of HCC to death. Prognostic baseline variables were analyzed by multivariate Cox analysis to identify the independent predictors of survival. RESULTS: Seventy-five per cent of patients had hepatitis C. Ascites was present in 169 patients (53%), while hepatic encephalopathy was present in 49 patients (15%). The Child-Pugh score was class A in 105 patients (33%), class B in 142 patients (44%), and class C in 73 patients (23%). One hundred patients (31%) had macroscopic vascular invasion and/or extra-hepatic spread of the tumor. A single lesion > 10 cm was observed in 34 patients (11%), while multinodular HCC was present in 189 patients (59%). Thirty nine patients (12%) were BCLC early (A) stage, 55 (17%) were BCLC intermediate (B) stage, 124 (39%) were BCLC advanced (C) stage, and 102 (32%) were end-stage BCLC (D). At the time of this analysis (July 2011), 28 (9%) patients were still alive. Six (2%) patients who were lost during follow-up were censored at the last visit. The overall median survival was 6.8 mo, and the 1-year survival was 32%. The 1-year survival according to BCLC classes was 100%, 79%, 12% and 0%, for BCLC A, B, C and D, respectively. There was a significant difference in survival between each BCLC class. The median survival of patients of BCLC stages A, B, C and D was 33, 17.4, 6.9, and 1.8 mo, respectively (P < 0.05 for comparison between stages). The median survival of Child-Pugh A, B and C classes were 9.8 mo (range 6.4-13), 6.1 (range 4.9-7.3), and 3.7 (range 1.5-6), respectively (P < 0.05 for comparison between stages). By univariate analysis, the variables significantly associated to an increased liklihood of mortality were Eastern Cooperative Oncology Group performance status (PS), presence of ascites, low level of albumin, elevated level of bilirubin, international normalized ratio (INR) and Log-[(α fetoprotein (AFP)]. At multivariate analysis, mortality was independently predicted by bad PS (P < 0.0001), high INR values (P = 0.0001) and elevated Log-(AFP) levels (P = 0.009). CONCLUSION: This study confirms the heterogeneous behavior of untreated HCC. BCLC staging remains an important prognostic guide and may be important in decision-making for palliative treatment.
基金Supported by Italian Ministry of Health and FILAS Regione Lazio
文摘As all branches of science grow and new experimental techniques become readily accessible,our knowledge of medicine is likely to increase exponentially in the coming years.Recently developed technologies have revolutionized our analytical capacities,leading to vast knowledge of many genes or genomic regions involved in the pathogenesis of congenital heart diseases,which are often associated with other genetic syndromes,coronary artery disease and non-ischemic cardiomyopathies and channelopathies.The knowledge-base of the genesis of cardiovascular diseases is likely going to be further revolutionized in this new era of genomic medicine.Here,we review the advances that have been made over the last several years in this field and discuss different genetic mechanisms that have been shown to underlie a variety of cardiovascular diseases.
文摘Modern liver ultrasonography(US)has become a“one-stop shop”able to provide not only anatomic and morphologic but also functional information about vascularity,stiffness and other various liver tissue properties.Modern US techniques allow a quantitative assessment of various liver diseases.US scanning is no more limited to the visualized plane,but three-dimensional,volumetric acquisition and consequent post-processing are also possible.Further,US scan can be consistently merged and visualized in real time with Computed Tomography and Magnetic Resonance Imaging examinations.Effective and safe microbubble�based contrast agents allow a real time,dynamic study of contrast kinetic for the detection and characterization of focal liver lesions.Ultrasound can be used to guide loco-regional treatment of liver malignancies and to assess tumoral response either to interventional procedures or medical therapies.Microbubbles may also carry and deliver drugs under ultrasound exposure.US plays a crucial role in diagnosing,treating and monitoring focal and diffuse liver disease.On the basis of personal experience and literature data,this paper is aimed to review the main topics involving recent advances in the field of liver ultrasound.
文摘Introduction: Granulomatous mastitis (GM) is a rare benign histopathologic lesion, associated with tissue inflammation, architectural distortions and heterogeneous parenchymal inflammation upon radiological evaluation. The treatment of GM is controversial, and currently, there is no consensus about the most appropriate therapy. Case Presentation: We presented a unique, atypical GM case with a prolonged disease course that ultimately led to a bilateral mastectomy. A conservative therapeutic approach and limited or wide surgical excisions have failed to prevent unfavorable outcomes in both the initial presentation and recurrent disease. Conclusions: There’re no clear data in the literature delineating persistent recurrences of GM after conservative treatment and multiple surgeries. Obtaining a disease-free surgical margin might be an important prognostic factor for a lasting relapse-free clinical resolution.
基金MSD(Merck Sharp and Dohme)AVENIR.Grant Number:HEART。
文摘To the editor Soft-tissue sarcomas(STS)represent a very heterogeneous group of rare tumors including more than 100 different subtypes[1].Surgery and neo/adjuvant radiation therapy represent the cornerstone of treatment for STS.However,despite an optimal resection of the tumor,up to 40%of patients will develop metastatic relapse and will die from the disease[1].Doxorubicin represents the first-line standard of care for patients with advanced disease since the 1970s,despite several attempts to identify better regimens.The median overall survival(OS)of patients with metastatic disease is<18 months and has only modestly improved over the past 20 years[2].
文摘Theγδcells are a unique population of T lymphocytes that combine innate-like features and adaptive-type responses and play an important role in the early host response to infections and malignancies.Different fromαβT cells,γδT cells recognize a limited set of antigens,which are shared by a variety of microbial pathogens and tumor cells in a non-MHC restricted manner;1 thus,these cells use the TCR in a manner similar to a pattern recognition receptor(PRR).Moreover,whereasαβT cells require antigen-and cytokine-driven clonal expansion,γδT cells are equipped with immediate effector functions.1 However,the potentialγδrepertoire with junctional diversity is estimated at∼10^(18),which is much greater than theαβrepertoire(∼10^(16)),thus raising questions concerning the forces governing the selection of such a huge TCR repertoire during ontogeny and whether and how theγδTCR repertoire is shaped under physiological and pathological conditions.
基金supported by the China Postdoctoral Science Foundation(grant number 2022M723207)the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2023KY666)+8 种基金Zhejiang Traditional Chinese Medicine Science Fund Project(grant number 2024ZL372)Qiantang Cross Fund Project(grant number 2023-16)the National Natural Science Foundation of China of Zhejiang Cancer Hospital Cultivation Project(grant number PY2023006)the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2024KY812)the Natural Science Foundation of Zhejiang Province(grant number Q24H160110)the National Natural Science Foundation of China(grant number NSFC82371851)the Science and Technology Foundation of Guizhou Province(Outstanding Young Scientists of Guizhou Province)(grant number Qiankeherencai-YQK(2023)021)the Science and Technology Foundation of Guizhou Province(grant number Qiankehejichu-ZK(2023)General 212)the Science and Technology Foundation of Guizhou Province(grant number Qiankehechengguo-LC(2025)General 068).
文摘1(NUTM1)gene rearrangements(15q14).In 1991,two independent research teams reported NC cases characterized by the t(15;19)translo-cation.1,2 In vitro studies by French et al.3 led to the pivotal discovery of NC in 2003 as a distinct disease entity driven by the fusion of bromodo-main and extraterminal domain(BET)protein 4(BRD4)and NUTM1.In 2004,the World Health Organization(WHO)classified tumors with t(15;19)translocation as a thymic malignancy and designated it“NUT midline carcinoma,”due to its predominant occurrence in midline organs.4 However,subsequent reports revealed NC’s emergence in numerous nonmidline organs,leading to its reclassification as the independent entity“NUT carcinoma of the thorax”by the WHO in 2015.5 NC exhibits rapid progression and profound resistance to conventional radiotherapy and chemotherapy.
