乳腺导管原位癌(ductal carcinoma in situ,DCIS)是一种局限于乳腺导管内的上皮增生性病变,不向周围浸润,不转移,部分病例不经治疗会发展成为浸润性导管癌。但是,由于肿块一般较小或未形成明显的可触及的肿块,多不易被发现。国外,随高...乳腺导管原位癌(ductal carcinoma in situ,DCIS)是一种局限于乳腺导管内的上皮增生性病变,不向周围浸润,不转移,部分病例不经治疗会发展成为浸润性导管癌。但是,由于肿块一般较小或未形成明显的可触及的肿块,多不易被发现。国外,随高质量的乳腺摄影技术的广泛开展,临床DCIS的发现率由过去的0.8%上升到5%左右,有的地区甚至占临床诊断病例的1/4。由于DCIS的临床治愈率可达100%,同时至少有一部分DCIS不经治疗会发展成为浸润性导管癌,此外,DCIS与乳腺良性病变——导管上皮异型增生的鉴别诊断问题等,有必要熟悉和掌握DCIS的病理诊断标准。展开更多
Objective: To study multi-directional derivation of cord blood mononuclear cells to CD3AK, LAK and CIK cells as well as changes of killing activity to gastric cancer cell strain in vitro. Methods: CD3mAb and IL-2 we...Objective: To study multi-directional derivation of cord blood mononuclear cells to CD3AK, LAK and CIK cells as well as changes of killing activity to gastric cancer cell strain in vitro. Methods: CD3mAb and IL-2 were used to induce CD3AK cells, and IL-2 was used to induce LAK cells; IFN-γ was used in the beginning, then IL-1, CD3mAb and IL-2 were used to induce CIK cells after 24 h for observing amplification and analyzing their relationship. The phenotypes of the cultured CIK cells were analyzed by flow cytometry. Subsequently, by using MGC-803 gastric cancer cell strain as target cells, the killing activity of CD3AK, LAK and CIK cells was evaluated by using MTT method. Results: The amplification activity of CD3AK and CIK cells was all far higher than LAK cells (P〈0.05). The amplification activity had no obvious difference between CIK cells and CD3AK cells at prophase, but that was far higher in CIK cells than CD3AK cells at about 20^th day (P〈0.05). The flow cytometry revealed that the amount of CD3^+ CD56^+ cells, major effector cells after CIK cells being cultured was significantly increased (P〈0.05), moreover, the amount of CD8^+ cells was significantly increased as well (P〈0.05). The killing activities of CD3AK and CIK cells to the MGC-803 gastric cancer cell strain were all significantly higher than LAK cells, while the killing activity of CIK cells was stronger than CD3AK cells (P〈0.05). Conclusion: CIK cells have stronger amplification activity and killing activity, and can be taken as more effective killing cells applied to the tumor adoptive immunotherapy.展开更多
Highly biocompatible superparamagnetic Fe3O4 nanoparticles were synthesized by amide of folic acid (FA) ligands and the NH2-group onto the surface of Fe3O4 nanoparticles. The as-synthesized folate-conjugated Fe3O4 n...Highly biocompatible superparamagnetic Fe3O4 nanoparticles were synthesized by amide of folic acid (FA) ligands and the NH2-group onto the surface of Fe3O4 nanoparticles. The as-synthesized folate-conjugated Fe3O4 nanoparticles were characterized by X-ray diffraction diffractometer, transmission electron microscope, FT-IR spectrometer, vibrating sample magnetometer, and dynamic light scattering instrument. The in vivo labeling effect of folate-conjugated Fe3O4 nanoparticles on the hepatoma cells was investigated in tumor-bearing rat. The results demonstrate that the as-prepared nanoparticles have cubic structure of Fe3O4 with a particle size of about 8 nm and hydrated diameter of 25.7 nm at a saturation magnetization of 51 A·m2/kg. These nanoparticles possess good physiological stability, low cytotoxicity on human skin fibroblasts and negligible effect on Wistar rats at the concentration as high as 3 mg/kg body mass. The folate-conjugated Fe3O4 nanoparticles could be effectively mediated into the human hepatoma Bel 7402 cells through the binding of folate and folic acid receptor, enhancing the signal contrast of tumor tissue and surrounding normal tissue in MRI imaging. It is in favor of the tumor cells labeling, tracing, magnetic resonance imaging (MRI) target detection and magnetic hyperthermia.展开更多
Trogocytosis is a rapid transfer between cells of membranes and associated proteins. Trogocytic exchanges have been investigated between different cell types, mainly in two-cell systems, involving one donor and one ac...Trogocytosis is a rapid transfer between cells of membranes and associated proteins. Trogocytic exchanges have been investigated between different cell types, mainly in two-cell systems, involving one donor and one acceptor cell type. Here, we studied trogocytosis in a more complex system, involving not only several immune cell subsets but also multiple tumor cells. We show that CD4~ T cells, CD8+ T cells and monocytes can acquire membrane patches and the intact proteins they contain from different tumor cells by multiple simultaneous trogocytoses. The trogocytic ca- pabilities of CD4~ and CD8~ T cells were found to be similar, but inferior to that of autologous monocytes. Activated peripheral-blood mononuclear cells (PBMCs) may also exchange membranes between themselves in an all-autolo- gous system. For this reason, monocytes are capable of acquiring membranes from multiple tumor cell sources, and transfer them again to autologous T cells, along with some of their own membranes (serial trogocytosis). Our data illustrate the extent of membrane exchanges between autologous activated immune effector cells and their environ- ment, and how the cellular content of the local environment, including "bystander" cells, may impact the functions of immune effector cells.展开更多
AIM: To explore the difference between cancer cells and normal cells, we investigated the Raman spectra of singlecells from gastrointestinal cancer patients. METHODS: All samples were obtained from 30 diagnosed as gas...AIM: To explore the difference between cancer cells and normal cells, we investigated the Raman spectra of singlecells from gastrointestinal cancer patients. METHODS: All samples were obtained from 30 diagnosed as gastrointestinal cancer patients. The flesh tumor specimen is located in the center of tumor tissue, while the normal ones were 5 cm away from the outside tumor section. The imprint was put under the microscope and a single cell was chosen for Raman measurement. All spectra were collected at confocal Raman micro-spectroscopy (British Renishaw) with NIR 780 nm laser.RESULTS: We measured the Raman spectra of several cells from gastrointestinal cancer patients. The result shows that there exists the strong line at 1 002/cm with less half-width assigned to the phenylalanine in several cells. The Raman lines of white cell were lower and less, while those of red cell were not only higher in intensity and more abundant, but also had a parti cular C-N breathing stretching band of pyrrole ring at 1 620-1 540/cm. The line at 1 084/cm assigned to phosphate backbone of DNA became obviously weaker in cancer cell. The Raman spectra of stomach cancer cells were similar to those of normal cells, but the Raman intensity of cancer cells was much lower than that of normal cells, and even some lines disappear. The lines of enteric cancer cells became weaker than spectra above and many lines disappeared, and the cancer cells in different position had different fluorescence intensity.CONCLUSION: The Raman spectra of several cells from cancer patients show that the structural changes of cancer cells happen and many bonds rupture so that the biological function of cells are lost. The results indicate that Raman spectra can offer the experiment basis for the cancer diagnosis and treatment.展开更多
Objective: The aim of our study was to observe the anti-tumor effect of silencing the expression of HIF-1α on cervical cancer in nude mice and to explore its mechanism of action. Methods: Human cervical cancer cell...Objective: The aim of our study was to observe the anti-tumor effect of silencing the expression of HIF-1α on cervical cancer in nude mice and to explore its mechanism of action. Methods: Human cervical cancer cell line Siha cells were divided into 3 groups: mock control group, control group transfected with scrambled sequence plasmid, and experimental group transfected with pU-HIF-la-shRNA eukaryotic expression plasmid. Cultured cells of the three groups were inoculated in nude mice to establish cervical cancer-bearing nude mice. HIF-la RNAi assay was performed to evaluate the tumor-suppressive effect of HIF-1α silencing on cervical cancer-bearing nude mice. Immunohistochemistry and Western blot were used to observe the distribution and protein expression of HIF-1α and GLUT1, while RT-PCR was adopted to detect the gene expression of HIF-1α, GLUTI and HK I1. The product of glycolysis (tactic acid) and apoptosis in tumor cells were detected by colorimetry and semi-quantitative TUNEL staining, respectively. Results: The tumor growth in experimental group was significantly slower than that in the two control groups (P 〈 0.05). In the 50th day after transplantation, the tumor weight in the experimental group was (1.90 ± 0.28) g, significantly lower than (2.95 ± 0.77) g in the control group and (2.54 ± 0.56) g in the mock group (P 〈 0.01). In the experimental group, the gene and protein levels of HIF-1α were 0.45 ± 0.04 and 1.25 ± 0.92, and the levels of GLUT1 were 0.32 ± 0.02 and 1.25 ± 0.48, respectively. Both indicators in HIF-la and GLUT1 were lower than that in the two control groups (P 〈 0.05). The expression levels of HK Ⅱ gene and lactic acid in the experimental group were lower than that in the two control groups (P 〈 0.05), but the apoptotic cells were much more numerous in the experimental group than that in matched control groups (P 〈 0.01). Conclusion: The 9ene therapy by siRNAtargeted silencing of HIF-1α may down-regulate its downstream genes GLUT1 and HK Ⅱ expression, therefore, to reduce the tumor glycolysis activity and promote tumor cell apoptosis, and exert a tumor-suppressing effect in vivo.展开更多
Our previous studies showed a predominance of high molecular weight protein group in tumor nuclear matrices. Contrary to normal cells, proteins of this group are preferentially phosphorylated. Phosphoproteins of hepat...Our previous studies showed a predominance of high molecular weight protein group in tumor nuclear matrices. Contrary to normal cells, proteins of this group are preferentially phosphorylated. Phosphoproteins of hepatoma nuclear matrix are selectively subjected to rapid proteolysis. By alkali treatment and a monoclonal antibody against phosphotyrosyl residue the presence of two high molecular weight bands of phosphotyrosyl-containing proteins was detected in nuclear matrices of tumor but not of normal liver cells. High molecular weight protein group of tumor nuclear matrices revealed also a rapid turnover and preferential incorporation of labeled amino acids selectively inhibited by chloramphenicol.展开更多
We present 2 cases of hepatocyte nuclear factor 1α (HNF1α)-mutated adenomatosis, discovered for reasons unrelated to this disease, and identified using immunohistochemical methods. These new tools may further our un...We present 2 cases of hepatocyte nuclear factor 1α (HNF1α)-mutated adenomatosis, discovered for reasons unrelated to this disease, and identified using immunohistochemical methods. These new tools may further our understanding of the link between adenomas/adenomatosis subtypes and their complications, and their association with other abnormalities.展开更多
文摘乳腺导管原位癌(ductal carcinoma in situ,DCIS)是一种局限于乳腺导管内的上皮增生性病变,不向周围浸润,不转移,部分病例不经治疗会发展成为浸润性导管癌。但是,由于肿块一般较小或未形成明显的可触及的肿块,多不易被发现。国外,随高质量的乳腺摄影技术的广泛开展,临床DCIS的发现率由过去的0.8%上升到5%左右,有的地区甚至占临床诊断病例的1/4。由于DCIS的临床治愈率可达100%,同时至少有一部分DCIS不经治疗会发展成为浸润性导管癌,此外,DCIS与乳腺良性病变——导管上皮异型增生的鉴别诊断问题等,有必要熟悉和掌握DCIS的病理诊断标准。
文摘Objective: To study multi-directional derivation of cord blood mononuclear cells to CD3AK, LAK and CIK cells as well as changes of killing activity to gastric cancer cell strain in vitro. Methods: CD3mAb and IL-2 were used to induce CD3AK cells, and IL-2 was used to induce LAK cells; IFN-γ was used in the beginning, then IL-1, CD3mAb and IL-2 were used to induce CIK cells after 24 h for observing amplification and analyzing their relationship. The phenotypes of the cultured CIK cells were analyzed by flow cytometry. Subsequently, by using MGC-803 gastric cancer cell strain as target cells, the killing activity of CD3AK, LAK and CIK cells was evaluated by using MTT method. Results: The amplification activity of CD3AK and CIK cells was all far higher than LAK cells (P〈0.05). The amplification activity had no obvious difference between CIK cells and CD3AK cells at prophase, but that was far higher in CIK cells than CD3AK cells at about 20^th day (P〈0.05). The flow cytometry revealed that the amount of CD3^+ CD56^+ cells, major effector cells after CIK cells being cultured was significantly increased (P〈0.05), moreover, the amount of CD8^+ cells was significantly increased as well (P〈0.05). The killing activities of CD3AK and CIK cells to the MGC-803 gastric cancer cell strain were all significantly higher than LAK cells, while the killing activity of CIK cells was stronger than CD3AK cells (P〈0.05). Conclusion: CIK cells have stronger amplification activity and killing activity, and can be taken as more effective killing cells applied to the tumor adoptive immunotherapy.
基金Project(2011JQ028)supported by the Fundamental Research Funds for the Central Universities,ChinaProjects(2008SK3114,2010SK3113)supported by Hunan Provincial Science&Technology Plan,China+2 种基金Project(B2007086)supported by Science&Research Funds of Hunan Health Department,ChinaProject(12JJ5057)supported by Natural Science Foundation of Hunan Province,ChinaProjects(XCX1119,XCX12073)supported by University Students Innovative Experiment Plan Project of Hunan Agricultural University,China
文摘Highly biocompatible superparamagnetic Fe3O4 nanoparticles were synthesized by amide of folic acid (FA) ligands and the NH2-group onto the surface of Fe3O4 nanoparticles. The as-synthesized folate-conjugated Fe3O4 nanoparticles were characterized by X-ray diffraction diffractometer, transmission electron microscope, FT-IR spectrometer, vibrating sample magnetometer, and dynamic light scattering instrument. The in vivo labeling effect of folate-conjugated Fe3O4 nanoparticles on the hepatoma cells was investigated in tumor-bearing rat. The results demonstrate that the as-prepared nanoparticles have cubic structure of Fe3O4 with a particle size of about 8 nm and hydrated diameter of 25.7 nm at a saturation magnetization of 51 A·m2/kg. These nanoparticles possess good physiological stability, low cytotoxicity on human skin fibroblasts and negligible effect on Wistar rats at the concentration as high as 3 mg/kg body mass. The folate-conjugated Fe3O4 nanoparticles could be effectively mediated into the human hepatoma Bel 7402 cells through the binding of folate and folic acid receptor, enhancing the signal contrast of tumor tissue and surrounding normal tissue in MRI imaging. It is in favor of the tumor cells labeling, tracing, magnetic resonance imaging (MRI) target detection and magnetic hyperthermia.
文摘Trogocytosis is a rapid transfer between cells of membranes and associated proteins. Trogocytic exchanges have been investigated between different cell types, mainly in two-cell systems, involving one donor and one acceptor cell type. Here, we studied trogocytosis in a more complex system, involving not only several immune cell subsets but also multiple tumor cells. We show that CD4~ T cells, CD8+ T cells and monocytes can acquire membrane patches and the intact proteins they contain from different tumor cells by multiple simultaneous trogocytoses. The trogocytic ca- pabilities of CD4~ and CD8~ T cells were found to be similar, but inferior to that of autologous monocytes. Activated peripheral-blood mononuclear cells (PBMCs) may also exchange membranes between themselves in an all-autolo- gous system. For this reason, monocytes are capable of acquiring membranes from multiple tumor cell sources, and transfer them again to autologous T cells, along with some of their own membranes (serial trogocytosis). Our data illustrate the extent of membrane exchanges between autologous activated immune effector cells and their environ- ment, and how the cellular content of the local environment, including "bystander" cells, may impact the functions of immune effector cells.
基金Supported by the National Natural Science Foundation of China,No. 60471049the Natural Science Foundation of Shandong Province of China, No. Y2004G09
文摘AIM: To explore the difference between cancer cells and normal cells, we investigated the Raman spectra of singlecells from gastrointestinal cancer patients. METHODS: All samples were obtained from 30 diagnosed as gastrointestinal cancer patients. The flesh tumor specimen is located in the center of tumor tissue, while the normal ones were 5 cm away from the outside tumor section. The imprint was put under the microscope and a single cell was chosen for Raman measurement. All spectra were collected at confocal Raman micro-spectroscopy (British Renishaw) with NIR 780 nm laser.RESULTS: We measured the Raman spectra of several cells from gastrointestinal cancer patients. The result shows that there exists the strong line at 1 002/cm with less half-width assigned to the phenylalanine in several cells. The Raman lines of white cell were lower and less, while those of red cell were not only higher in intensity and more abundant, but also had a parti cular C-N breathing stretching band of pyrrole ring at 1 620-1 540/cm. The line at 1 084/cm assigned to phosphate backbone of DNA became obviously weaker in cancer cell. The Raman spectra of stomach cancer cells were similar to those of normal cells, but the Raman intensity of cancer cells was much lower than that of normal cells, and even some lines disappear. The lines of enteric cancer cells became weaker than spectra above and many lines disappeared, and the cancer cells in different position had different fluorescence intensity.CONCLUSION: The Raman spectra of several cells from cancer patients show that the structural changes of cancer cells happen and many bonds rupture so that the biological function of cells are lost. The results indicate that Raman spectra can offer the experiment basis for the cancer diagnosis and treatment.
文摘Objective: The aim of our study was to observe the anti-tumor effect of silencing the expression of HIF-1α on cervical cancer in nude mice and to explore its mechanism of action. Methods: Human cervical cancer cell line Siha cells were divided into 3 groups: mock control group, control group transfected with scrambled sequence plasmid, and experimental group transfected with pU-HIF-la-shRNA eukaryotic expression plasmid. Cultured cells of the three groups were inoculated in nude mice to establish cervical cancer-bearing nude mice. HIF-la RNAi assay was performed to evaluate the tumor-suppressive effect of HIF-1α silencing on cervical cancer-bearing nude mice. Immunohistochemistry and Western blot were used to observe the distribution and protein expression of HIF-1α and GLUT1, while RT-PCR was adopted to detect the gene expression of HIF-1α, GLUTI and HK I1. The product of glycolysis (tactic acid) and apoptosis in tumor cells were detected by colorimetry and semi-quantitative TUNEL staining, respectively. Results: The tumor growth in experimental group was significantly slower than that in the two control groups (P 〈 0.05). In the 50th day after transplantation, the tumor weight in the experimental group was (1.90 ± 0.28) g, significantly lower than (2.95 ± 0.77) g in the control group and (2.54 ± 0.56) g in the mock group (P 〈 0.01). In the experimental group, the gene and protein levels of HIF-1α were 0.45 ± 0.04 and 1.25 ± 0.92, and the levels of GLUT1 were 0.32 ± 0.02 and 1.25 ± 0.48, respectively. Both indicators in HIF-la and GLUT1 were lower than that in the two control groups (P 〈 0.05). The expression levels of HK Ⅱ gene and lactic acid in the experimental group were lower than that in the two control groups (P 〈 0.05), but the apoptotic cells were much more numerous in the experimental group than that in matched control groups (P 〈 0.01). Conclusion: The 9ene therapy by siRNAtargeted silencing of HIF-1α may down-regulate its downstream genes GLUT1 and HK Ⅱ expression, therefore, to reduce the tumor glycolysis activity and promote tumor cell apoptosis, and exert a tumor-suppressing effect in vivo.
文摘Our previous studies showed a predominance of high molecular weight protein group in tumor nuclear matrices. Contrary to normal cells, proteins of this group are preferentially phosphorylated. Phosphoproteins of hepatoma nuclear matrix are selectively subjected to rapid proteolysis. By alkali treatment and a monoclonal antibody against phosphotyrosyl residue the presence of two high molecular weight bands of phosphotyrosyl-containing proteins was detected in nuclear matrices of tumor but not of normal liver cells. High molecular weight protein group of tumor nuclear matrices revealed also a rapid turnover and preferential incorporation of labeled amino acids selectively inhibited by chloramphenicol.
文摘We present 2 cases of hepatocyte nuclear factor 1α (HNF1α)-mutated adenomatosis, discovered for reasons unrelated to this disease, and identified using immunohistochemical methods. These new tools may further our understanding of the link between adenomas/adenomatosis subtypes and their complications, and their association with other abnormalities.