International journal of clinical and experimental pathology, 2018
AIMS Human papillomavirus (HPV) viral load and genotype are the primary determinants for the deve... more AIMS Human papillomavirus (HPV) viral load and genotype are the primary determinants for the development of cervical neoplasia. We aim to identify the prevalent HPV genotypes in the women of Shanghai, China and investigate the association between the HPV viral load and the severity of cervical neoplasia. METHODS Formalin-fixed, paraffin-embedded tissue samples were obtained from 20 cases of histologically normal cervix, 52 cases of low grade squamous intraepithelial lesion (LSIL), 46 cases of high grade squamous intraepithelial lesion (HSIL), and 29 cases of cervical squamous cervical cancer (SCC). A polymerase chain reaction reverse dot blot (PCR-RDB) genotyping chip was used to examine 23 HPV genotypes. Real-time quantitative PCR was used to detect the viral load of HPV in the fresh tissue of 80 cases. RESULTS The HPV infection rate in the 147 cases of cervical biopsies was 73.5%. Fourteen HPV genotypes were detected, including 12 high risk (HR)-HPVs and 2 low-risk (LR)-HPVs. HPV-...
Chemokine CXCL12 is an extracellular chemokine, which binds to its cell surface receptor CXCR4. H... more Chemokine CXCL12 is an extracellular chemokine, which binds to its cell surface receptor CXCR4. High expressions of CXCR4 and CXCL12 are associated with biological malignant potential in colon cancers. We aimed to investigate the roles of the CXCR4/CXCL12 axis in activation of the Wnt/β-catenin pathway in the development of colon cancers. Using colon cancer cell line, we performed the RNA interference assay to downregulate the expression of CXCR4. Cells were exposed to CXCL12 and their growth and metastatic activity were examined. Matrix metalloproteinases (MMPs) activity were analyzed by the gelatin zymography assay. Cell migration ability was estimated by assays of scratch wound and transwell chamber. The expression of CXCR4 and molecules relevant to the Wnt/β-catenin pathway were analyzed by the western blotting and real-time PCR assays. Human colon cancer HT-29 cells identified high expression of CXCR4. HT-29 cells highly responded to CXCL12 stimulation, showing the increase of ...
Haishengsu (HSS) is a seashell protein extracted from Tegillarca L. granosa, a type of Malaysian ... more Haishengsu (HSS) is a seashell protein extracted from Tegillarca L. granosa, a type of Malaysian shellfish. Previous in vitro studies showed that HSS might possess biological anticancer activity. In this combined in vitro and in vivo study, we investigated the inhibitory effects of HSS on tumor growth, invasion, and metastasis using human lung carcinoma cell lines A549 and NCI-H292, both
Abstract The chemokine CXCL12 (SDF-1) is an extracellular chemokine which binds to its cell surfa... more Abstract The chemokine CXCL12 (SDF-1) is an extracellular chemokine which binds to its cell surface receptor CXCR4. The axis of CXCL12/CXCR4 has been considered to play an important role for cancer cell migration. Recently, the aberrant expression of CXCR4 has been found during the malignancy of colorectal cancer (CRC), where it plays a crucial role in, among others, the proliferation, angiogenesis and metastatic spread. Various intracellular signal transduction cascades and effectors related to the CXCR4/CXCL12 axis have been determined, such as MAPK, PI-3K/Akt and Wnt. Currently, the potential role of CXCR4/CXCL12 as the therapeutic target for treatment of CRC has been focused. In this review, we summarized recent research on CXCL12/CXCR4 axis in the development of CRC.
cAMP responsive element binding protein 1 (CREB1) has been reported to be implicated in tumor dev... more cAMP responsive element binding protein 1 (CREB1) has been reported to be implicated in tumor development and progression of human cancers. However, the clinical significance and regulatory mechanisms of CREB1 expression in gastric cancer remain largely unknown. In the present study, immunohistochemistry was performed to detect the expression of CREB1 protein in 185 primary gastric cancer tissues, 50 secondary lymph node metastatic foci and 50 nontumorous gastric tissues. A prognostic model combining CREB1 expression with TNM tumor stage was constructed by logistic regression analysis. Regulation of CREB1 by miRNAs was investigated by luciferase reporter assay and Western blot. It was shown that CREB1 was highly expressed and correlated with lymph node metastasis, distant metastasis and tumor stage and poor outcome in gastric cancer. The prognostic model was proven to be an independent prognosis predictor and performed better than CREB1 or tumor stage alone. CREB1 was identified as ...
Sphingosine kinase 2 (SphK2) is a type of sphingosine kinase, which express highly in most of can... more Sphingosine kinase 2 (SphK2) is a type of sphingosine kinase, which express highly in most of cancers. SphK2 produce sphingosine-1-phosphate (S1P) and then accumulate in cancer cells. Our previous study showed that S1P antagonized the effects of all-trans-retinoic acid (ATRA) via the receptor-dependent and independent pathway. In this study, we aimed to investigate the roles of SphK2 in affecting ATRA's activity in human colon cancer cells. Cell proliferation was estimated by the clonogenic assay. The distribution of cell cycle was analyzed by flow cytometry assay. The apoptotic cells were determined by Annexin V-FITC/PI staining method. Western blotting assay was performed to analyze the levels of the proteins related to apoptosis and cell cycle. The mRNA levels of SphK2 and RARβ were evaluated by real-time PCR assay. RNA interference assay was performed to evaluate SphK2 activity. S1P antagonized the effect of ATRA on HT-29 cell proliferation, the ATRA-induced RARβ expression,...
CD98-mediated β1 and β3 integrins activation can induce Fak phosphorylation which eventually prom... more CD98-mediated β1 and β3 integrins activation can induce Fak phosphorylation which eventually promotes cell survival, proliferation, and migration. We evaluated the expression of CD98, integrin β1, integrin β3 and Fak in 45 cases of matched colorectal cancer (CRC) and liver metastases as well as 35 cases of CRC without liver metastases. There was a gradual increase of the expression of CD98, integrin β1, integrin β3 and Fak as tumor progressed from normal colon to carcinoma to budding tumor cells at the invasive front and to liver metastases. The expression of CD98 and integrin β1 in CRC with liver metastases was significantly higher than that in CRC without liver metastases. Furthermore, for those liver metastases with desmoplastic growth pattern, expression of CD98, integrin β1, integrin β3 and Fak at the metastases center was as strong as that at the metastases periphery. For those liver metastases with pushing or replacement growth patterns, more intense expression of these marke...
Integrins are a large family of cell surface receptors that bind extracellular matrix proteins. T... more Integrins are a large family of cell surface receptors that bind extracellular matrix proteins. The interaction of integrins with extracellular matrix activates a number of intracellular signaling pathways involved in cell proliferation, differentiation, motility, and other essential cell functions. Integrins are critically important to both health and disease. In this review, we first describe the structure, functions, and signaling characteristics of integrins. We then discuss the roles of integrins in cancer progression. Finally, we recapitulate the laboratory and clinical efforts of targeting integrins as effective means of cancer therapy and diagnosis. This comprehensive review could help scientists and clinicians gain a complete understanding of integrins. It could also contribute toward the development of new drugs, new methods of diagnostics, and new treatment of cancers to benefit the patients in clinical practice.
Solitary rectal ulcer syndrome (SRUS) is associated with erythema and ulceration of the rectal wa... more Solitary rectal ulcer syndrome (SRUS) is associated with erythema and ulceration of the rectal wall. Serrated lesions of the colon are divided into conventional hyperplastic polyps and a new set of lesions that are variably called sessile serrated polyps (SSPs) and sessile serrated adenomas. The SSPs are epithelial proliferative lesions that appear to act as a unique pathway to colorectal carcinogenesis. No association between SRUS and SSPs has been previously reported. To assess a possible association between SRUS and morphologic features that mimic SSPs. Twenty-six patients with SRUS, who presented to our institution between January 1, 1999, and November 14, 2004, were retrospectively reviewed for SSP-type morphologic features by 3 pathologists. Ki-67 and hMLH1 immunohistochemical stains were used. Control tissues included 10 conventional left-sided hyperplastic polyps, 10 right-sided large SSPs, 7 adenocarcinomas with known loss of hMLH1 gene expression, and 4 normal human tonsil...
The proliferative response of human lymphocytes to stimuli such as foreign histocompatibility ant... more The proliferative response of human lymphocytes to stimuli such as foreign histocompatibility antigens or mitogens is generally assessed by measuring the amount of tritiated thymidine which the cells incorporated in culture. In this paper, the possibility of assessing lymphocyte proliferation and viability by an empirical assay, using measurement of light absorbance on a ELISA reader in the yellow wave length (450 nm/air-550 nm/air), has been studied. The correlation of these measurements with a colormetric viability assay using MTS/PMS, with tritiated thymidine incorporation and with trypan blue exclusion viability counting, was determined. The results showed that the light absorbance assay correlated well with cell proliferation during 48-120 hours culture period and with cell viability after a 72 hour period. The MTS/PMS colormetric assay as well as trypan blue exclusion cell counting confirmed that the light absorbance assay was not merely caused by dead cells. This data confirm that the light absorbance assay is sufficiently sensitive to low levels of proliferation to allow detection of such responses at least as effectively as thymidine incorporation. The light absorbance assay procedure avoids the expense, time and hazards associated with scintillation counting, and is simple to perform without the necessity for reagents and preparative steps required by other assays.
Angiogenesis is essential to the survival, growth, invasion, and metastasis of various human soli... more Angiogenesis is essential to the survival, growth, invasion, and metastasis of various human solid tumors. We compared the microvessel density (MVD) and clinicopathologic features of two different groups of hepatocellular carcinoma (HCC), namely HCC with cirrhosis (HCC-C) and without cirrhosis (HCC-NC). A tissue microarray composed of 20 normal livers, 20 cirrhotic livers, tumor and adjacent background non-neoplastic liver tissues from 20 HCC-C and 20 HCC-NC were constructed and stained immunohistochemically with antibodies against the antigen CD34. The MVD was determined by the measurement of the area and density of CD34 positive sinusoidal endothelial cells using the Image Pro Plus software. There was a trend of increased MVD in cirrhotic liver compared to normal liver and in cirrhotic background non-neoplastic liver adjacent to the tumor compared to the non-cirrhotic background non-neoplastic liver. Tumor tissue of HCC-C and HCC-NC both showed significantly higher MVD than their ...
Riccardin D, a liverwort-derived naturally occurring macrocyclic bisbibenzyl, has been found to e... more Riccardin D, a liverwort-derived naturally occurring macrocyclic bisbibenzyl, has been found to exert anticancer effects in multiple cancer cell types. In this study, we investigated the effect and mechanism of Riccardin D on human breast cancer. Experiments were performed on human breast cancer MCF-7 and MDA-MB-231 cells. The antitumour effects of Riccardin D were assessed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and human breast cancer xenografts mice model. TRAPeze(®) XL Telomerase Detection assay was used for the detection of telomerase activity. γ-H2 AX foci formation was tested for the induction of DNA damage response. Cell cycle distribution was analysed by flow cytometry, and cell apoptosis was determined by annexin V-FITC/PI staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay and Western blotting. Riccardin D effectively inhibited the growth of MCF-7 and MDA-MB-231 cells in vitro. And Riccardin D also effectively delayed the growth of MCF-7 and MDA-MB-231-luc-D3H2LN xenografts without significant loss of body-weight. Further analysis suggested that Riccardin D's effects may arise from its suppression of telomerase activity, which led to telomere dysfunction. Telomerase inhibition and telomere dysfunction could activate the canonical ataxia telangiectasia-mutated (ATM) kinase-mediated DNA damage response, as shown by elevated expression of γ-H2 AX, p-ATM and p-Chk2. This is finally followed by the induction of cell cycle arrest and apoptosis, as shown by the increase of TUNEL-stained cells, caspase activation, PARP cleavage and the increase of bax/bcl-2 ratio. Moreover, Riccardin D induced p53-proficient MCF-7 cells to arrest in G1 phase and p53-deficient MDA-MB-231 cells to arrest in G2/M phase. Overall, these results demonstrate that Riccardin D may inhibit human breast cancer growth through suppression of telomerase activity.
Pneumatosis cystoides intestinalis (PCI) is a condition with multiple gas-filled cysts within the... more Pneumatosis cystoides intestinalis (PCI) is a condition with multiple gas-filled cysts within the bowel wall, associated with diverse background diseases. Its pathogenesis is still a mystery. Some previous observations scattered in the literature have suggested an association of the cystic spaces in PCI with the lymphatics. To further investigate whether PCI results from the ballooning of gas-filled lymphatic channels. We did immunostaining of podoplanin, a mucoprotein preferentially expressed in lymphatic endothelial cells, in 13 cases (8 men, 5 women; age range, 18-80 years) of PCI. Ten cases were diagnosed in resected segments of bowel and 3 in biopsies. Pneumatosis was seen in the right side of the colon (9 cases), transverse colon (1 case), sigmoid colon (1 case), and small bowel (2 cases). In addition, immunostaining for CD31, calretinin, WT1, CD68, smooth muscle actin, desmin, vimentin, and cytokeratins was also performed for comparison and correlation. A strong immunopositiv...
Although glucocorticoids and cyclosporine are frequently used to treat patients with various type... more Although glucocorticoids and cyclosporine are frequently used to treat patients with various types of glomerulopathy, clinical responses to treatment vary considerably. Considerable interindividual heterogeneity in the suppressive effects of glucocorticoids on lymphocyte proliferation in vitro has been previously reported, suggesting that differences in the pharmacodynamic responsiveness of the immune system to these agents might be an important determinant of how well an individual patient responds to treatment. It also has been shown that methylprednisolone is significantly more suppressive than prednisolone. To identify cellular mechanisms by which these drugs act, a study of the suppressive effects of prednisolone, methylprednisolone, and cyclosporine on lymphocyte proliferation and the expression of the cell surface receptor for interleukin-2 (IL-2R) was conducted using phytohemagglutin-stimulated peripheral blood mononuclear cells (PBMCs) from 13 patients with glomerulopathy and 12 control subjects. Heterogeneity among individuals in both parameters of lymphocyte responsiveness to these drugs was again found, and the significantly greater suppressive effect of methylprednisolone was confirmed for both proliferation and IL-2R expression in patients and control subjects. Cyclosporine alone was moderately suppressive. For most individuals, the greatest degree of suppression occurred when cells were exposed to both cyclosporine and glucocorticoid. Further studies are being conducted to determine whether pretreatment assessment of in vitro lymphocyte responsiveness has any predictive value regarding therapeutic efficacy of each drug in individual patients and to identify of those patients likely to require a more intensive or multidrug immunosuppressive regimen.
International journal of clinical and experimental pathology, 2018
AIMS Human papillomavirus (HPV) viral load and genotype are the primary determinants for the deve... more AIMS Human papillomavirus (HPV) viral load and genotype are the primary determinants for the development of cervical neoplasia. We aim to identify the prevalent HPV genotypes in the women of Shanghai, China and investigate the association between the HPV viral load and the severity of cervical neoplasia. METHODS Formalin-fixed, paraffin-embedded tissue samples were obtained from 20 cases of histologically normal cervix, 52 cases of low grade squamous intraepithelial lesion (LSIL), 46 cases of high grade squamous intraepithelial lesion (HSIL), and 29 cases of cervical squamous cervical cancer (SCC). A polymerase chain reaction reverse dot blot (PCR-RDB) genotyping chip was used to examine 23 HPV genotypes. Real-time quantitative PCR was used to detect the viral load of HPV in the fresh tissue of 80 cases. RESULTS The HPV infection rate in the 147 cases of cervical biopsies was 73.5%. Fourteen HPV genotypes were detected, including 12 high risk (HR)-HPVs and 2 low-risk (LR)-HPVs. HPV-...
Chemokine CXCL12 is an extracellular chemokine, which binds to its cell surface receptor CXCR4. H... more Chemokine CXCL12 is an extracellular chemokine, which binds to its cell surface receptor CXCR4. High expressions of CXCR4 and CXCL12 are associated with biological malignant potential in colon cancers. We aimed to investigate the roles of the CXCR4/CXCL12 axis in activation of the Wnt/β-catenin pathway in the development of colon cancers. Using colon cancer cell line, we performed the RNA interference assay to downregulate the expression of CXCR4. Cells were exposed to CXCL12 and their growth and metastatic activity were examined. Matrix metalloproteinases (MMPs) activity were analyzed by the gelatin zymography assay. Cell migration ability was estimated by assays of scratch wound and transwell chamber. The expression of CXCR4 and molecules relevant to the Wnt/β-catenin pathway were analyzed by the western blotting and real-time PCR assays. Human colon cancer HT-29 cells identified high expression of CXCR4. HT-29 cells highly responded to CXCL12 stimulation, showing the increase of ...
Haishengsu (HSS) is a seashell protein extracted from Tegillarca L. granosa, a type of Malaysian ... more Haishengsu (HSS) is a seashell protein extracted from Tegillarca L. granosa, a type of Malaysian shellfish. Previous in vitro studies showed that HSS might possess biological anticancer activity. In this combined in vitro and in vivo study, we investigated the inhibitory effects of HSS on tumor growth, invasion, and metastasis using human lung carcinoma cell lines A549 and NCI-H292, both
Abstract The chemokine CXCL12 (SDF-1) is an extracellular chemokine which binds to its cell surfa... more Abstract The chemokine CXCL12 (SDF-1) is an extracellular chemokine which binds to its cell surface receptor CXCR4. The axis of CXCL12/CXCR4 has been considered to play an important role for cancer cell migration. Recently, the aberrant expression of CXCR4 has been found during the malignancy of colorectal cancer (CRC), where it plays a crucial role in, among others, the proliferation, angiogenesis and metastatic spread. Various intracellular signal transduction cascades and effectors related to the CXCR4/CXCL12 axis have been determined, such as MAPK, PI-3K/Akt and Wnt. Currently, the potential role of CXCR4/CXCL12 as the therapeutic target for treatment of CRC has been focused. In this review, we summarized recent research on CXCL12/CXCR4 axis in the development of CRC.
cAMP responsive element binding protein 1 (CREB1) has been reported to be implicated in tumor dev... more cAMP responsive element binding protein 1 (CREB1) has been reported to be implicated in tumor development and progression of human cancers. However, the clinical significance and regulatory mechanisms of CREB1 expression in gastric cancer remain largely unknown. In the present study, immunohistochemistry was performed to detect the expression of CREB1 protein in 185 primary gastric cancer tissues, 50 secondary lymph node metastatic foci and 50 nontumorous gastric tissues. A prognostic model combining CREB1 expression with TNM tumor stage was constructed by logistic regression analysis. Regulation of CREB1 by miRNAs was investigated by luciferase reporter assay and Western blot. It was shown that CREB1 was highly expressed and correlated with lymph node metastasis, distant metastasis and tumor stage and poor outcome in gastric cancer. The prognostic model was proven to be an independent prognosis predictor and performed better than CREB1 or tumor stage alone. CREB1 was identified as ...
Sphingosine kinase 2 (SphK2) is a type of sphingosine kinase, which express highly in most of can... more Sphingosine kinase 2 (SphK2) is a type of sphingosine kinase, which express highly in most of cancers. SphK2 produce sphingosine-1-phosphate (S1P) and then accumulate in cancer cells. Our previous study showed that S1P antagonized the effects of all-trans-retinoic acid (ATRA) via the receptor-dependent and independent pathway. In this study, we aimed to investigate the roles of SphK2 in affecting ATRA's activity in human colon cancer cells. Cell proliferation was estimated by the clonogenic assay. The distribution of cell cycle was analyzed by flow cytometry assay. The apoptotic cells were determined by Annexin V-FITC/PI staining method. Western blotting assay was performed to analyze the levels of the proteins related to apoptosis and cell cycle. The mRNA levels of SphK2 and RARβ were evaluated by real-time PCR assay. RNA interference assay was performed to evaluate SphK2 activity. S1P antagonized the effect of ATRA on HT-29 cell proliferation, the ATRA-induced RARβ expression,...
CD98-mediated β1 and β3 integrins activation can induce Fak phosphorylation which eventually prom... more CD98-mediated β1 and β3 integrins activation can induce Fak phosphorylation which eventually promotes cell survival, proliferation, and migration. We evaluated the expression of CD98, integrin β1, integrin β3 and Fak in 45 cases of matched colorectal cancer (CRC) and liver metastases as well as 35 cases of CRC without liver metastases. There was a gradual increase of the expression of CD98, integrin β1, integrin β3 and Fak as tumor progressed from normal colon to carcinoma to budding tumor cells at the invasive front and to liver metastases. The expression of CD98 and integrin β1 in CRC with liver metastases was significantly higher than that in CRC without liver metastases. Furthermore, for those liver metastases with desmoplastic growth pattern, expression of CD98, integrin β1, integrin β3 and Fak at the metastases center was as strong as that at the metastases periphery. For those liver metastases with pushing or replacement growth patterns, more intense expression of these marke...
Integrins are a large family of cell surface receptors that bind extracellular matrix proteins. T... more Integrins are a large family of cell surface receptors that bind extracellular matrix proteins. The interaction of integrins with extracellular matrix activates a number of intracellular signaling pathways involved in cell proliferation, differentiation, motility, and other essential cell functions. Integrins are critically important to both health and disease. In this review, we first describe the structure, functions, and signaling characteristics of integrins. We then discuss the roles of integrins in cancer progression. Finally, we recapitulate the laboratory and clinical efforts of targeting integrins as effective means of cancer therapy and diagnosis. This comprehensive review could help scientists and clinicians gain a complete understanding of integrins. It could also contribute toward the development of new drugs, new methods of diagnostics, and new treatment of cancers to benefit the patients in clinical practice.
Solitary rectal ulcer syndrome (SRUS) is associated with erythema and ulceration of the rectal wa... more Solitary rectal ulcer syndrome (SRUS) is associated with erythema and ulceration of the rectal wall. Serrated lesions of the colon are divided into conventional hyperplastic polyps and a new set of lesions that are variably called sessile serrated polyps (SSPs) and sessile serrated adenomas. The SSPs are epithelial proliferative lesions that appear to act as a unique pathway to colorectal carcinogenesis. No association between SRUS and SSPs has been previously reported. To assess a possible association between SRUS and morphologic features that mimic SSPs. Twenty-six patients with SRUS, who presented to our institution between January 1, 1999, and November 14, 2004, were retrospectively reviewed for SSP-type morphologic features by 3 pathologists. Ki-67 and hMLH1 immunohistochemical stains were used. Control tissues included 10 conventional left-sided hyperplastic polyps, 10 right-sided large SSPs, 7 adenocarcinomas with known loss of hMLH1 gene expression, and 4 normal human tonsil...
The proliferative response of human lymphocytes to stimuli such as foreign histocompatibility ant... more The proliferative response of human lymphocytes to stimuli such as foreign histocompatibility antigens or mitogens is generally assessed by measuring the amount of tritiated thymidine which the cells incorporated in culture. In this paper, the possibility of assessing lymphocyte proliferation and viability by an empirical assay, using measurement of light absorbance on a ELISA reader in the yellow wave length (450 nm/air-550 nm/air), has been studied. The correlation of these measurements with a colormetric viability assay using MTS/PMS, with tritiated thymidine incorporation and with trypan blue exclusion viability counting, was determined. The results showed that the light absorbance assay correlated well with cell proliferation during 48-120 hours culture period and with cell viability after a 72 hour period. The MTS/PMS colormetric assay as well as trypan blue exclusion cell counting confirmed that the light absorbance assay was not merely caused by dead cells. This data confirm that the light absorbance assay is sufficiently sensitive to low levels of proliferation to allow detection of such responses at least as effectively as thymidine incorporation. The light absorbance assay procedure avoids the expense, time and hazards associated with scintillation counting, and is simple to perform without the necessity for reagents and preparative steps required by other assays.
Angiogenesis is essential to the survival, growth, invasion, and metastasis of various human soli... more Angiogenesis is essential to the survival, growth, invasion, and metastasis of various human solid tumors. We compared the microvessel density (MVD) and clinicopathologic features of two different groups of hepatocellular carcinoma (HCC), namely HCC with cirrhosis (HCC-C) and without cirrhosis (HCC-NC). A tissue microarray composed of 20 normal livers, 20 cirrhotic livers, tumor and adjacent background non-neoplastic liver tissues from 20 HCC-C and 20 HCC-NC were constructed and stained immunohistochemically with antibodies against the antigen CD34. The MVD was determined by the measurement of the area and density of CD34 positive sinusoidal endothelial cells using the Image Pro Plus software. There was a trend of increased MVD in cirrhotic liver compared to normal liver and in cirrhotic background non-neoplastic liver adjacent to the tumor compared to the non-cirrhotic background non-neoplastic liver. Tumor tissue of HCC-C and HCC-NC both showed significantly higher MVD than their ...
Riccardin D, a liverwort-derived naturally occurring macrocyclic bisbibenzyl, has been found to e... more Riccardin D, a liverwort-derived naturally occurring macrocyclic bisbibenzyl, has been found to exert anticancer effects in multiple cancer cell types. In this study, we investigated the effect and mechanism of Riccardin D on human breast cancer. Experiments were performed on human breast cancer MCF-7 and MDA-MB-231 cells. The antitumour effects of Riccardin D were assessed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and human breast cancer xenografts mice model. TRAPeze(®) XL Telomerase Detection assay was used for the detection of telomerase activity. γ-H2 AX foci formation was tested for the induction of DNA damage response. Cell cycle distribution was analysed by flow cytometry, and cell apoptosis was determined by annexin V-FITC/PI staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay and Western blotting. Riccardin D effectively inhibited the growth of MCF-7 and MDA-MB-231 cells in vitro. And Riccardin D also effectively delayed the growth of MCF-7 and MDA-MB-231-luc-D3H2LN xenografts without significant loss of body-weight. Further analysis suggested that Riccardin D's effects may arise from its suppression of telomerase activity, which led to telomere dysfunction. Telomerase inhibition and telomere dysfunction could activate the canonical ataxia telangiectasia-mutated (ATM) kinase-mediated DNA damage response, as shown by elevated expression of γ-H2 AX, p-ATM and p-Chk2. This is finally followed by the induction of cell cycle arrest and apoptosis, as shown by the increase of TUNEL-stained cells, caspase activation, PARP cleavage and the increase of bax/bcl-2 ratio. Moreover, Riccardin D induced p53-proficient MCF-7 cells to arrest in G1 phase and p53-deficient MDA-MB-231 cells to arrest in G2/M phase. Overall, these results demonstrate that Riccardin D may inhibit human breast cancer growth through suppression of telomerase activity.
Pneumatosis cystoides intestinalis (PCI) is a condition with multiple gas-filled cysts within the... more Pneumatosis cystoides intestinalis (PCI) is a condition with multiple gas-filled cysts within the bowel wall, associated with diverse background diseases. Its pathogenesis is still a mystery. Some previous observations scattered in the literature have suggested an association of the cystic spaces in PCI with the lymphatics. To further investigate whether PCI results from the ballooning of gas-filled lymphatic channels. We did immunostaining of podoplanin, a mucoprotein preferentially expressed in lymphatic endothelial cells, in 13 cases (8 men, 5 women; age range, 18-80 years) of PCI. Ten cases were diagnosed in resected segments of bowel and 3 in biopsies. Pneumatosis was seen in the right side of the colon (9 cases), transverse colon (1 case), sigmoid colon (1 case), and small bowel (2 cases). In addition, immunostaining for CD31, calretinin, WT1, CD68, smooth muscle actin, desmin, vimentin, and cytokeratins was also performed for comparison and correlation. A strong immunopositiv...
Although glucocorticoids and cyclosporine are frequently used to treat patients with various type... more Although glucocorticoids and cyclosporine are frequently used to treat patients with various types of glomerulopathy, clinical responses to treatment vary considerably. Considerable interindividual heterogeneity in the suppressive effects of glucocorticoids on lymphocyte proliferation in vitro has been previously reported, suggesting that differences in the pharmacodynamic responsiveness of the immune system to these agents might be an important determinant of how well an individual patient responds to treatment. It also has been shown that methylprednisolone is significantly more suppressive than prednisolone. To identify cellular mechanisms by which these drugs act, a study of the suppressive effects of prednisolone, methylprednisolone, and cyclosporine on lymphocyte proliferation and the expression of the cell surface receptor for interleukin-2 (IL-2R) was conducted using phytohemagglutin-stimulated peripheral blood mononuclear cells (PBMCs) from 13 patients with glomerulopathy and 12 control subjects. Heterogeneity among individuals in both parameters of lymphocyte responsiveness to these drugs was again found, and the significantly greater suppressive effect of methylprednisolone was confirmed for both proliferation and IL-2R expression in patients and control subjects. Cyclosporine alone was moderately suppressive. For most individuals, the greatest degree of suppression occurred when cells were exposed to both cyclosporine and glucocorticoid. Further studies are being conducted to determine whether pretreatment assessment of in vitro lymphocyte responsiveness has any predictive value regarding therapeutic efficacy of each drug in individual patients and to identify of those patients likely to require a more intensive or multidrug immunosuppressive regimen.
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Papers by Zuhua Gao