Objective: To investigate the severity of xerostomia and its impact on the quality of life in patients with nasopharyngeal carcinoma after conventional radiation therapy. Methods: One hundred and thirty-six patients w...Objective: To investigate the severity of xerostomia and its impact on the quality of life in patients with nasopharyngeal carcinoma after conventional radiation therapy. Methods: One hundred and thirty-six patients with nasopharyngeal carcinoma, treated by conventional radiation therapy in Cancer Center, Sun Yat-sen University, were surveyed by interview at the outpatient department. A questionnaire and a visual analog scale (VAS) were used to analyze xerostomia and xerostomia-related problems. Results: Of 136 patints, 73.5% experienced a moderate to severe degree of xerostomia; 82.4% had to sip water to facilitate speech; 92.6% had to sip water to facilitate chewing and swallowing; 91.2% changed their feeding pattern (eating only mashed food); 61.3% had to wake up to drink water because of dry mouth; 75.0% had dental lesions to varying degrees. Conclusion: 73.5% of the patients with nasopharyngeal carcinoma after conventional radiation therapy experienced a moderate to severe degree of xerostomia. Xerostomia has a significant impact on the patient's speech, deglutition, and sleep, and can increase the morbidity of the dental diseases.展开更多
AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still...AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.展开更多
Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, trans...Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, translation, and differential cellular localization of various isoforms. Recent advances in our understanding of post-transcriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi) technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.展开更多
Bleeding from esophageal varices (EVs) is a catastrophic complication of chronic liver disease. Many years ago, surgical procedures such as esophageal transection or distal splenorenal shunting were the only treatment...Bleeding from esophageal varices (EVs) is a catastrophic complication of chronic liver disease. Many years ago, surgical procedures such as esophageal transection or distal splenorenal shunting were the only treatments for EVs. In the 1970s, interventional radiology procedures such as transportal obliteration, left gastric artery embolization, and partial splenic artery embolization were introduced, improving the survival of patients with bleeding EVs. In the 1980s, endoscopic treatment, endoscopic injection sclerotherapy (EIS), and endoscopic variceal ligation (EVL), further contributed to improved survival. We combined IVR with endoscopic treatment or EIS with EVL. Most patients with EVs treated endoscopically required follow- up treatment for recurrent varices. Proper management of recurrent EVs can significantly improve patients’ quality of life. Recently, we have performed EVL at 2-mo (bimonthly) intervals for the management of EVs. Longer intervals between treatment sessions resulted in a higher rate of total eradication and lower rates of recurrence and additional treatment.展开更多
AIM:To conduct a multicentre retrospective review of virological response rates in Asians infected with genotype 1 chronic hepatitis C(CHC) treated with combination interferon and ribavirin and then to compare thei...AIM:To conduct a multicentre retrospective review of virological response rates in Asians infected with genotype 1 chronic hepatitis C(CHC) treated with combination interferon and ribavirin and then to compare their responses to that among Caucasians.METHODS:Asian patients infected with genotype 1 CHC treated at 4 Australian centres between 2001 to 2005 were identified through hospital databases.Baseline demographic characteristics,biochemical,virological and histological data and details of treatment were collected.Sustained virological responses(SVR) in this cohort were then compared to that in Caucasian subjects,matched by genotype,age,gender and the stage of hepatic fibrosis.RESULTS:A total of 108 Asians with genotype 1 CHC were identified.The end of treatment response(ETR) for the cohort was 79% while the SVR was 67%.Due to the relatively advanced age of the Asian cohort,only sixty-four subjects could be matched with Caucasians.The ETR among matched Asians and Caucasians was 81% and 56% respectively(P=0.003),while the SVR rates were 73% and 36%(P 〈0.001) respectively.This difference remained significant after adjusting for other predictive variables. CONCLUSION: Genotype 1 CHC in Asian subjects is associated with higher rates of virological response compared to that in Caucasians.展开更多
Objective: To evaluate the effect of topical corticosteroid for treatment of moderate or severe dry eye. Methods: Sixty eyes of 30 patients with moderate or severe dry eye, who were not sensitive to artificial tears, ...Objective: To evaluate the effect of topical corticosteroid for treatment of moderate or severe dry eye. Methods: Sixty eyes of 30 patients with moderate or severe dry eye, who were not sensitive to artificial tears, were treated with 0.1% fluoro- metholone eye drops. Subjective symptom and objective tests were used to evaluate the efficacy of treatment before and after application of 0.1% fluorometholone eye drops for 1 week and 1 month. Side effects were also evaluated. Results: After 1 week of treatment, subjective symptoms were improved in all dry eye patients; objective tests were improved in all dry eye patients 1 month after treatment, and the difference was significant. Conclusion: Topical corticosteroid drops can rapidly and effectively relieve the symptoms and signs of moderate or severe dry eye.展开更多
AIM: To evaluate the efficacy and safety of pegylated- interferon alpha-2a in hemodialysis patients with chronic hepatitis C. METHODS: Thirty-six hemodialysis patients with chronic hepatitis C were enrolled in a con...AIM: To evaluate the efficacy and safety of pegylated- interferon alpha-2a in hemodialysis patients with chronic hepatitis C. METHODS: Thirty-six hemodialysis patients with chronic hepatitis C were enrolled in a controlled and prospective study. All patients were treatment naive, positive tested for anti-HCV antibodies, and positive tested for serum HCV-RNA. Twenty-two patients received 135 μg peglyated-interferon α-2a weekly for 48 wk (group A). The remaining patients were left untreated, eleven refused therapy, and three were not candidates for kidney transplantation and were allocated to the control group (group B). At the end of the treatment biochemical and virological response was evaluated, and 24 wk after completetion of therapy sustained virological response (SVR) was assessed. Side effects were monitored. RESULTS: Of 22 hemodialysis patients, 12 were male and 10 female, with a mean age of 35.2 ± 12.1 years. Virological end-of-treatment response was observed in 14 patients (82.4%) in group A and in one patient (7.1%) in group B (P = 0.001). Sustained virological response was observed in 11 patients (64.7%) in group A and in one patient in group B (7.1%). Biochemical response parameters normalized in 10/14 patients (71.4%) at the end of the treatment. ALT levels in group B were initially high in six patients and normalized in one of them (25%) at the end of the 48 wk. In five patients (22.7%) therapy had to be stopped at mo 4 due to complications of weakness, anemia, and bleeding. CONCLUSION: SVR could be achieved in 64.7% of patients on hemodialysis with chronic hepatitis C by a treatment with peglyated-interferon α-2a. Group A had a significantly better efficacy compared to the control group B, but the side effects need to be concerned.展开更多
RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human ...RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human cells.RNAi-based gene therapies, especially in viral diseases have become more and more interesting and promising. Recently,small interfering RNA (siRNA) can be used to protect host from viral infection, inhibit the expression of viral antigen and accessory genes, control the transcription and replication of viral genome, hinder the assembly of viral particles, and display influences in virus-host interactions. In this review, we attempt to present recent progresses of this breakthrough technology in the above fields and summarize the possibilities of siRNA-based drugs.展开更多
Chronic hepatitis C is a leading cause of hepatocellular carcinoma (HCC) worldwide.Interferon (IFN) ther-apy decreases the incidence of HCC in patients with chronic hepatitis C.Prevention of chronic-hepatitis-C-relate...Chronic hepatitis C is a leading cause of hepatocellular carcinoma (HCC) worldwide.Interferon (IFN) ther-apy decreases the incidence of HCC in patients with chronic hepatitis C.Prevention of chronic-hepatitis-C-related HCC is one of the most important issues in current hepatology.We have previously reported that male gender and high titer of hepatitis C virus (HCV) RNA are predictive factors for the development of HCC in HCV-related cirrhosis.Clinical efforts at eradicat-ing or reducing the viral load may reduce the risk for HCC.Furthermore,because HCC often recurs after ablation therapy,we performed a trial of IFN in pa-tients with chronic liver disease caused by HCV to see whether IFN therapy decreases recurrence after abla-tion therapy of HCV-related HCC.By using IFN therapy as a secondary prevention,patients with HCC who had received complete tumor ablation showed better sur-vival,primarily as a result of the preservation of liver function and also probably prevention of recurrence.Postoperative IFN therapy appears to decrease recur-rence after ablation therapy such as radiofrequency ablation (RFA) therapy of HCV-related HCC.We believe that there is a survival benefit in secondary prevention using IFN therapy.However,a controlled study is es-sential to obtain conclusive evidence of the efficacy of this strategy.展开更多
OBJECTIVE To investigate the significance of angiogenesis of lung cancer, in order to provide a scientific basis for interventional therapy. METHODS Double-phase enhancementscanning spiral CT and DSA were performed in...OBJECTIVE To investigate the significance of angiogenesis of lung cancer, in order to provide a scientific basis for interventional therapy. METHODS Double-phase enhancementscanning spiral CT and DSA were performed in 56 pathologically confi rmed lung cancer cases, in order to evaluate angiogenesis of the tumors. The patients included 36 males and 20 females, with ages ranging from 33 to 76 years (average of 53). Assessments and indexes for SCT and DSA examinations were as follows: a) Peak value (PV) of the cancerous focus was the difference between the maximum CT value after enhancement and the CT value of a plain scan; b) The abnormally distorted and expanded new vessels of the cancerous focus which could be macroscopically discriminated; c) DSA staining of the focus of cancer was sparse, grid-like and dense. Chemotherapy and embolotherapy via the bronchial artery (interventional therapy) were conducted. Radiotherapy was added for some of the solid tumors with a diameter exceeding 4 cm. RESULTS a) There were 25 cases with a central-type lesion, among which 4 were small cell lung cancers (SCLC) and 21 non-small cell lung cancers (NSCLC). The cases with a peripheral location accounted for 31 of the total, with a maximum diameter of 1.5 to 13.5 cm and a median of 4.2 cm, including 5 small cell lung cancers and 26 NSCLC cases. b) The reinforced PVs of the cancerous foci were as follows: The PV ranged from 45 to 70 Hu in 34 cases, 25 to 45 Hu in 19, and 10 to 25 Hu in 3. Sparse DSA staining occurred in 3 cases, there was uneven grid-like staining in 22 and dense staining in 31; c) The interventional therapy via the bronchial artery was con-ducted twice in 5 cases with the SCLC, and three times in 4 SCLC cases. For 3 of the latter cases, a dose of 5,000 to 7,000 cGy radiation therapy was added during the interventional treatment. Complete remissions (CR) were seen in 88.9% of the cases (8/9) and partial remission (PR) in 11.1% (1/9). Interventional therapy was conducted twice in 8 cases with NSCLC and three times in 30 with NSCLC and four times in 9 cases. Among the total cases, 13 received radiotherapy during interventional therapy, with a radiation dose of 5,000-7,000 cGy; The CR rate was 78.7% (37/47), PR was 14.9% (7/47) and the rate of non-remission was 6.4% (3/47). CONCLUSION Using imaging technology, analysis of angiogenesis of lung cancers was employed to accurately detect and quantify angiogenesis. This analysis was combined for interventional therapy, using embolizing agents and large doses of the anti-tumor drugs and angiogenesis inhibitors. The agents were selectively delivered into the tumor vessels to eliminate the primary tumor, in order to depress distant metastases and thus enhance the curative effect of the therapy.展开更多
Background There are limited data on long-term (〉 5 years) outcomes of drug-eluting stent (DES) implantation compared with coro- nary artery bypass grafting (CABG) for ostial/rnidshaft left main coronary artery...Background There are limited data on long-term (〉 5 years) outcomes of drug-eluting stent (DES) implantation compared with coro- nary artery bypass grafting (CABG) for ostial/rnidshaft left main coronary artery (LMCA) lesions. Methods Of the 259 consecutive pa- tients in Beijing Anzhen Hospital with ostial/midshaff LMCA lesions, 149 were treated with percutaneous coronary intervention (PCI) with DES and 110 were with CABG. The endpoints of the study were death, repeat revascularization, myocardial infarction (MI), stroke, the composite of cardiac death, and major adverse cardiac and cerebrovascular events (MACCE, the composite of cardiac death, MI, stroke or repeat revascularization).The duration of follow-up is 7.1 years (interquartile range 5.3 to 8.2 years). Results There is no significant differ- ence between the PCI and CABG group during the median follow-up of 7.1 years (interquartile range: 5.3-8.2 years) in the occurrence of death (HR: 0.727, 95% CI: 0.335-1.578; P = 0.421), the composite endpoint of cardiac death, MI or stroke (HR: 0.730, 95% CI: 0.375-1.421; P = 0.354), MACCE (HR: 1.066, 95% CI: 0.648-1.753; P = 0.801), MI (HR: 1.112, 95% CI: 0.414-2.987; P = 0.833), stroke (HR: 1.875, 95% CI: 0.528-6.659; P = 0.331), and repeat revascularization (HR: 1.590, 95% CI: 0.800-3.161; P = 0.186). These results remained after multivariable adjusting. Conclusion During a follow-up up to 8.2 years, we found that DES implantation had similar endpoint outcomes compared with CABG.展开更多
Proteins like Raf kinase inhibitory protein (RKIP) that serve as modulators of signaling pathways, either by promoting or inhibiting the formation of productive signaling complexes through protein-protein interactions...Proteins like Raf kinase inhibitory protein (RKIP) that serve as modulators of signaling pathways, either by promoting or inhibiting the formation of productive signaling complexes through protein-protein interactions, have been demon- strated to play an increasingly important role in a number of cell types and organisms. These proteins have been implicated in development as well as the progression of cancer. RKIP is a particularly interesting regulator, as it is a highly conserved, ubiquitously expressed protein that has been shown to play a role in growth and differentiation in a number of organisms and can regulate multiple signaling pathways. RKIP is also the first MAP kinase signaling modulator to be identified as playing a role in cancer metastasis, and identification of the mechanism by which it regulates Raf-1 activation provides new targets for therapeutic intervention.展开更多
AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS: ...AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS: WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein (EGFP). An animal model of HCC in Wistar rats was established by implanting HCC cells (CBRH7919) combined with an immunosuppressive drug. EGFP labeled liver stern cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stern cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stern cells within the tumor tissue were observed and analyzed.RESULTS: Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue.CONCLUSION: Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.展开更多
RNA interference (RNAi) is an evolutionally conserved gene silencing mechanism present in a variety of eukaryotic species. RNAi uses short double-stranded RNA (dsRNA) to trigger degradation or translation repression o...RNA interference (RNAi) is an evolutionally conserved gene silencing mechanism present in a variety of eukaryotic species. RNAi uses short double-stranded RNA (dsRNA) to trigger degradation or translation repression of homologous RNA targets in a sequence-specific manner. This system can be induced effectively in vitro and in vivo by direct application of small interfering RNAs (siRNAs), or by expression of short hairpin RNA (shRNA) with non-viral and viral vectors. To date, RNAi has been extensively used as a novel and effective tool for functional genomic studies, and has displayed great potential in treating human diseases, including human genetic and acquired disorders such as cancer and viral infections. In the present review, we focus on the recent development in the use of RNAi in the prevention and treatment of viral infections. The mechanisms, strategies, hurdles and prospects of employing RNAi in the pharmaceutical industry are also discussed.展开更多
AIM: To investigate the serum positive percentage of TT virus (TTV) in patients with chronic hepatitis B or C and the response of the coinfected TTV to interferon (IFN) during IFN therapy for chronic hepatitis B and C...AIM: To investigate the serum positive percentage of TT virus (TTV) in patients with chronic hepatitis B or C and the response of the coinfected TTV to interferon (IFN) during IFN therapy for chronic hepatitis B and C. METHODS: We retrospectively studied the serum samples of 70 patients with chronic hepatitis who had received IFN-alpha therapy from January 1997 to June 2000, which included 40 cases of hepatitis B and 30 hepatitis C. All the patients had been followed up for at least 6 months after the end of IFN therapy. The serum TTV DNA was detected using the polymerase chain reaction (PCR) before and every month during the course of IFN treatment. RESULTS: TTV infection was detected in 15% (6/40) of the chronic hepatitis B group and 30% (9/30) of the chronic hepatitis C group. Loss of serum TTV DNA during IFN therapy occurred in 3 of 6 patients (50%) and 6 of 9 (67%) of hepatitis B and C groups, respectively. Seronegativity of TTV was found all during the first month of IFN therapy in the 9 patients. There was no correlation between the seroconversion of TTV and the biochemical changes of the patients. CONCLUSION: TTV is not infrequently coinfected in patients with chronic hepatitis B and C in Taiwan, and more than half of the TTV infections are IFN-sensitive. However, the loss of serum TTV DNA does not affect the clinical course of the patients with chronic hepatitis B or C.展开更多
文摘Objective: To investigate the severity of xerostomia and its impact on the quality of life in patients with nasopharyngeal carcinoma after conventional radiation therapy. Methods: One hundred and thirty-six patients with nasopharyngeal carcinoma, treated by conventional radiation therapy in Cancer Center, Sun Yat-sen University, were surveyed by interview at the outpatient department. A questionnaire and a visual analog scale (VAS) were used to analyze xerostomia and xerostomia-related problems. Results: Of 136 patints, 73.5% experienced a moderate to severe degree of xerostomia; 82.4% had to sip water to facilitate speech; 92.6% had to sip water to facilitate chewing and swallowing; 91.2% changed their feeding pattern (eating only mashed food); 61.3% had to wake up to drink water because of dry mouth; 75.0% had dental lesions to varying degrees. Conclusion: 73.5% of the patients with nasopharyngeal carcinoma after conventional radiation therapy experienced a moderate to severe degree of xerostomia. Xerostomia has a significant impact on the patient's speech, deglutition, and sleep, and can increase the morbidity of the dental diseases.
文摘AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.
文摘Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, translation, and differential cellular localization of various isoforms. Recent advances in our understanding of post-transcriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi) technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.
文摘Bleeding from esophageal varices (EVs) is a catastrophic complication of chronic liver disease. Many years ago, surgical procedures such as esophageal transection or distal splenorenal shunting were the only treatments for EVs. In the 1970s, interventional radiology procedures such as transportal obliteration, left gastric artery embolization, and partial splenic artery embolization were introduced, improving the survival of patients with bleeding EVs. In the 1980s, endoscopic treatment, endoscopic injection sclerotherapy (EIS), and endoscopic variceal ligation (EVL), further contributed to improved survival. We combined IVR with endoscopic treatment or EIS with EVL. Most patients with EVs treated endoscopically required follow- up treatment for recurrent varices. Proper management of recurrent EVs can significantly improve patients’ quality of life. Recently, we have performed EVL at 2-mo (bimonthly) intervals for the management of EVs. Longer intervals between treatment sessions resulted in a higher rate of total eradication and lower rates of recurrence and additional treatment.
文摘AIM:To conduct a multicentre retrospective review of virological response rates in Asians infected with genotype 1 chronic hepatitis C(CHC) treated with combination interferon and ribavirin and then to compare their responses to that among Caucasians.METHODS:Asian patients infected with genotype 1 CHC treated at 4 Australian centres between 2001 to 2005 were identified through hospital databases.Baseline demographic characteristics,biochemical,virological and histological data and details of treatment were collected.Sustained virological responses(SVR) in this cohort were then compared to that in Caucasian subjects,matched by genotype,age,gender and the stage of hepatic fibrosis.RESULTS:A total of 108 Asians with genotype 1 CHC were identified.The end of treatment response(ETR) for the cohort was 79% while the SVR was 67%.Due to the relatively advanced age of the Asian cohort,only sixty-four subjects could be matched with Caucasians.The ETR among matched Asians and Caucasians was 81% and 56% respectively(P=0.003),while the SVR rates were 73% and 36%(P 〈0.001) respectively.This difference remained significant after adjusting for other predictive variables. CONCLUSION: Genotype 1 CHC in Asian subjects is associated with higher rates of virological response compared to that in Caucasians.
文摘Objective: To evaluate the effect of topical corticosteroid for treatment of moderate or severe dry eye. Methods: Sixty eyes of 30 patients with moderate or severe dry eye, who were not sensitive to artificial tears, were treated with 0.1% fluoro- metholone eye drops. Subjective symptom and objective tests were used to evaluate the efficacy of treatment before and after application of 0.1% fluorometholone eye drops for 1 week and 1 month. Side effects were also evaluated. Results: After 1 week of treatment, subjective symptoms were improved in all dry eye patients; objective tests were improved in all dry eye patients 1 month after treatment, and the difference was significant. Conclusion: Topical corticosteroid drops can rapidly and effectively relieve the symptoms and signs of moderate or severe dry eye.
文摘AIM: To evaluate the efficacy and safety of pegylated- interferon alpha-2a in hemodialysis patients with chronic hepatitis C. METHODS: Thirty-six hemodialysis patients with chronic hepatitis C were enrolled in a controlled and prospective study. All patients were treatment naive, positive tested for anti-HCV antibodies, and positive tested for serum HCV-RNA. Twenty-two patients received 135 μg peglyated-interferon α-2a weekly for 48 wk (group A). The remaining patients were left untreated, eleven refused therapy, and three were not candidates for kidney transplantation and were allocated to the control group (group B). At the end of the treatment biochemical and virological response was evaluated, and 24 wk after completetion of therapy sustained virological response (SVR) was assessed. Side effects were monitored. RESULTS: Of 22 hemodialysis patients, 12 were male and 10 female, with a mean age of 35.2 ± 12.1 years. Virological end-of-treatment response was observed in 14 patients (82.4%) in group A and in one patient (7.1%) in group B (P = 0.001). Sustained virological response was observed in 11 patients (64.7%) in group A and in one patient in group B (7.1%). Biochemical response parameters normalized in 10/14 patients (71.4%) at the end of the treatment. ALT levels in group B were initially high in six patients and normalized in one of them (25%) at the end of the 48 wk. In five patients (22.7%) therapy had to be stopped at mo 4 due to complications of weakness, anemia, and bleeding. CONCLUSION: SVR could be achieved in 64.7% of patients on hemodialysis with chronic hepatitis C by a treatment with peglyated-interferon α-2a. Group A had a significantly better efficacy compared to the control group B, but the side effects need to be concerned.
文摘RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human cells.RNAi-based gene therapies, especially in viral diseases have become more and more interesting and promising. Recently,small interfering RNA (siRNA) can be used to protect host from viral infection, inhibit the expression of viral antigen and accessory genes, control the transcription and replication of viral genome, hinder the assembly of viral particles, and display influences in virus-host interactions. In this review, we attempt to present recent progresses of this breakthrough technology in the above fields and summarize the possibilities of siRNA-based drugs.
文摘Chronic hepatitis C is a leading cause of hepatocellular carcinoma (HCC) worldwide.Interferon (IFN) ther-apy decreases the incidence of HCC in patients with chronic hepatitis C.Prevention of chronic-hepatitis-C-related HCC is one of the most important issues in current hepatology.We have previously reported that male gender and high titer of hepatitis C virus (HCV) RNA are predictive factors for the development of HCC in HCV-related cirrhosis.Clinical efforts at eradicat-ing or reducing the viral load may reduce the risk for HCC.Furthermore,because HCC often recurs after ablation therapy,we performed a trial of IFN in pa-tients with chronic liver disease caused by HCV to see whether IFN therapy decreases recurrence after abla-tion therapy of HCV-related HCC.By using IFN therapy as a secondary prevention,patients with HCC who had received complete tumor ablation showed better sur-vival,primarily as a result of the preservation of liver function and also probably prevention of recurrence.Postoperative IFN therapy appears to decrease recur-rence after ablation therapy such as radiofrequency ablation (RFA) therapy of HCV-related HCC.We believe that there is a survival benefit in secondary prevention using IFN therapy.However,a controlled study is es-sential to obtain conclusive evidence of the efficacy of this strategy.
文摘OBJECTIVE To investigate the significance of angiogenesis of lung cancer, in order to provide a scientific basis for interventional therapy. METHODS Double-phase enhancementscanning spiral CT and DSA were performed in 56 pathologically confi rmed lung cancer cases, in order to evaluate angiogenesis of the tumors. The patients included 36 males and 20 females, with ages ranging from 33 to 76 years (average of 53). Assessments and indexes for SCT and DSA examinations were as follows: a) Peak value (PV) of the cancerous focus was the difference between the maximum CT value after enhancement and the CT value of a plain scan; b) The abnormally distorted and expanded new vessels of the cancerous focus which could be macroscopically discriminated; c) DSA staining of the focus of cancer was sparse, grid-like and dense. Chemotherapy and embolotherapy via the bronchial artery (interventional therapy) were conducted. Radiotherapy was added for some of the solid tumors with a diameter exceeding 4 cm. RESULTS a) There were 25 cases with a central-type lesion, among which 4 were small cell lung cancers (SCLC) and 21 non-small cell lung cancers (NSCLC). The cases with a peripheral location accounted for 31 of the total, with a maximum diameter of 1.5 to 13.5 cm and a median of 4.2 cm, including 5 small cell lung cancers and 26 NSCLC cases. b) The reinforced PVs of the cancerous foci were as follows: The PV ranged from 45 to 70 Hu in 34 cases, 25 to 45 Hu in 19, and 10 to 25 Hu in 3. Sparse DSA staining occurred in 3 cases, there was uneven grid-like staining in 22 and dense staining in 31; c) The interventional therapy via the bronchial artery was con-ducted twice in 5 cases with the SCLC, and three times in 4 SCLC cases. For 3 of the latter cases, a dose of 5,000 to 7,000 cGy radiation therapy was added during the interventional treatment. Complete remissions (CR) were seen in 88.9% of the cases (8/9) and partial remission (PR) in 11.1% (1/9). Interventional therapy was conducted twice in 8 cases with NSCLC and three times in 30 with NSCLC and four times in 9 cases. Among the total cases, 13 received radiotherapy during interventional therapy, with a radiation dose of 5,000-7,000 cGy; The CR rate was 78.7% (37/47), PR was 14.9% (7/47) and the rate of non-remission was 6.4% (3/47). CONCLUSION Using imaging technology, analysis of angiogenesis of lung cancers was employed to accurately detect and quantify angiogenesis. This analysis was combined for interventional therapy, using embolizing agents and large doses of the anti-tumor drugs and angiogenesis inhibitors. The agents were selectively delivered into the tumor vessels to eliminate the primary tumor, in order to depress distant metastases and thus enhance the curative effect of the therapy.
文摘Background There are limited data on long-term (〉 5 years) outcomes of drug-eluting stent (DES) implantation compared with coro- nary artery bypass grafting (CABG) for ostial/rnidshaft left main coronary artery (LMCA) lesions. Methods Of the 259 consecutive pa- tients in Beijing Anzhen Hospital with ostial/midshaff LMCA lesions, 149 were treated with percutaneous coronary intervention (PCI) with DES and 110 were with CABG. The endpoints of the study were death, repeat revascularization, myocardial infarction (MI), stroke, the composite of cardiac death, and major adverse cardiac and cerebrovascular events (MACCE, the composite of cardiac death, MI, stroke or repeat revascularization).The duration of follow-up is 7.1 years (interquartile range 5.3 to 8.2 years). Results There is no significant differ- ence between the PCI and CABG group during the median follow-up of 7.1 years (interquartile range: 5.3-8.2 years) in the occurrence of death (HR: 0.727, 95% CI: 0.335-1.578; P = 0.421), the composite endpoint of cardiac death, MI or stroke (HR: 0.730, 95% CI: 0.375-1.421; P = 0.354), MACCE (HR: 1.066, 95% CI: 0.648-1.753; P = 0.801), MI (HR: 1.112, 95% CI: 0.414-2.987; P = 0.833), stroke (HR: 1.875, 95% CI: 0.528-6.659; P = 0.331), and repeat revascularization (HR: 1.590, 95% CI: 0.800-3.161; P = 0.186). These results remained after multivariable adjusting. Conclusion During a follow-up up to 8.2 years, we found that DES implantation had similar endpoint outcomes compared with CABG.
文摘Proteins like Raf kinase inhibitory protein (RKIP) that serve as modulators of signaling pathways, either by promoting or inhibiting the formation of productive signaling complexes through protein-protein interactions, have been demon- strated to play an increasingly important role in a number of cell types and organisms. These proteins have been implicated in development as well as the progression of cancer. RKIP is a particularly interesting regulator, as it is a highly conserved, ubiquitously expressed protein that has been shown to play a role in growth and differentiation in a number of organisms and can regulate multiple signaling pathways. RKIP is also the first MAP kinase signaling modulator to be identified as playing a role in cancer metastasis, and identification of the mechanism by which it regulates Raf-1 activation provides new targets for therapeutic intervention.
文摘AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS: WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein (EGFP). An animal model of HCC in Wistar rats was established by implanting HCC cells (CBRH7919) combined with an immunosuppressive drug. EGFP labeled liver stern cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stern cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stern cells within the tumor tissue were observed and analyzed.RESULTS: Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue.CONCLUSION: Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.
基金RFCID, No 01030152, RGC, CUHK4428/06M, ITF ITS091/03 of Hong Kong Government, and Faculty Direct Fund of the Chinese University of Hong Kong
文摘RNA interference (RNAi) is an evolutionally conserved gene silencing mechanism present in a variety of eukaryotic species. RNAi uses short double-stranded RNA (dsRNA) to trigger degradation or translation repression of homologous RNA targets in a sequence-specific manner. This system can be induced effectively in vitro and in vivo by direct application of small interfering RNAs (siRNAs), or by expression of short hairpin RNA (shRNA) with non-viral and viral vectors. To date, RNAi has been extensively used as a novel and effective tool for functional genomic studies, and has displayed great potential in treating human diseases, including human genetic and acquired disorders such as cancer and viral infections. In the present review, we focus on the recent development in the use of RNAi in the prevention and treatment of viral infections. The mechanisms, strategies, hurdles and prospects of employing RNAi in the pharmaceutical industry are also discussed.
文摘AIM: To investigate the serum positive percentage of TT virus (TTV) in patients with chronic hepatitis B or C and the response of the coinfected TTV to interferon (IFN) during IFN therapy for chronic hepatitis B and C. METHODS: We retrospectively studied the serum samples of 70 patients with chronic hepatitis who had received IFN-alpha therapy from January 1997 to June 2000, which included 40 cases of hepatitis B and 30 hepatitis C. All the patients had been followed up for at least 6 months after the end of IFN therapy. The serum TTV DNA was detected using the polymerase chain reaction (PCR) before and every month during the course of IFN treatment. RESULTS: TTV infection was detected in 15% (6/40) of the chronic hepatitis B group and 30% (9/30) of the chronic hepatitis C group. Loss of serum TTV DNA during IFN therapy occurred in 3 of 6 patients (50%) and 6 of 9 (67%) of hepatitis B and C groups, respectively. Seronegativity of TTV was found all during the first month of IFN therapy in the 9 patients. There was no correlation between the seroconversion of TTV and the biochemical changes of the patients. CONCLUSION: TTV is not infrequently coinfected in patients with chronic hepatitis B and C in Taiwan, and more than half of the TTV infections are IFN-sensitive. However, the loss of serum TTV DNA does not affect the clinical course of the patients with chronic hepatitis B or C.