Objective: To evaluate the effectiveness of intraoperative radiotherapy (IORT) in combination with regional chemotherapy in the treatment of advanced pancreatic carcinoma.Methods: 17 patients with advanced pancreatic ...Objective: To evaluate the effectiveness of intraoperative radiotherapy (IORT) in combination with regional chemotherapy in the treatment of advanced pancreatic carcinoma.Methods: 17 patients with advanced pancreatic adenocarcinoma were treated with IORT and regional chemotherapy with 5-FU, Epirubucin and Mitomycin, and 6 cases accepted external radiotherapy postoperatively.Results: 35.29% (6/17) of the patients were clinical benefit responders and 23.53% (4/17) had a partial response. The median survival time was 11 months and the 1-year survival rate was 35.29% (6/17)Conclusion: IORT in combination with regional chemotherapy had a good impact on clinical benefit without severe side effects in locally advanced pancreatic carcinoma and led to a significant prolongation of the survival time. Key words pancreatic cancer - intraoperative radiotherapy - chemotherapy展开更多
Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small...Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Fifty patients with advanced NSCLC (stages III to IV), who had received therapies in our Center (Department of Biotherapy, Affiliated to Cancer Hospital of Shanxi Medical University, Taiyuan, China) from August 2008 to January 2010, were treated by DC-CIK + chemotherapy as the combined treatment group; fifty advanced NSCLC patients treated with chemotherapy at the same time served as controls. The immunologic function, short-term therapeutic effects, the 1-year survival rate, the life quality, the chemotherapy side effects were compared between the two groups, the safety and therapeutic effects of DC-CIK cells therapy were observed too. Results: There was no obvious change of subsets of T cells in peripheral blood before and after therapy in DC-CIK + chemotherapy group, and IFN-γ was improved after therapy in this group (P < 0.05); in chemotherapy alone group, the ratios of CD3+CD4+, CD3+CD8+, CD3-CD56+ cells and the secretion of IL-2, TNF-α decreased significantly after therapy (P < 0.05); the ratios of CD3+CD8+, CD3+CD56+ were improved after cell culture (P < 0.05). The disease control rate (DCR) of DC-CIK + chemotherapy group was higher than that in the chemotherapy alone group (78.0% vs 56.0%, P < 0.05); the 1-year survival rates of DC-CIK + chemotherapy group and chemotherapy alone group were 50% and 44% respectively, had no significant difference. Compared with chemotherapy alone group, the occurrence of chemotherapy side effects (including bone marrow suppression, nausea and vomiting, peripheral nerve toxicity) was less in the DC-CIK + chemotherapy group (P < 0.05). The physical and appetite were better in DC-CIK + chemotherapy group after therapy. Conclusion: To compare with simple chemotherapy, DC-CIK + chemotherapy for advanced NSCLC is safe and effective, and it can improve patients' life quality and remission rate, and prolong their survival time.展开更多
Oncological treatment is currently directed toward a tailored therapy concept.Squamous cell carcinoma of the anal canal could be considered a suitable platform to test new therapeutic strategies to minimize treatment ...Oncological treatment is currently directed toward a tailored therapy concept.Squamous cell carcinoma of the anal canal could be considered a suitable platform to test new therapeutic strategies to minimize treatment morbidity.Standard of care for patients with anal canal cancer consists of a combination of radiotherapy and chemotherapy.This treatment has led to a high rate of local control and a 60% cure rate with preservation of the anal sphincter,thus replacing surgical abdominoperineal resection.Lymph node metastases represent a critical independent prognostic factor for local recurrence and survival.Mesorectal and iliac lymph nodes are usually included in the radiation field,whereas the inclusion of inguinal regions still remains controversial because of the subsequent adverse side effects.Sentinel lymph node biopsies could clearly identify inguinal node-positive patients eligible for therapeutic groin irradiation.A sentinel lymph node navigation procedure is reported here to be a feasible and effective method for establishing the true inguinal node status in patients suffering from anal canal cancer.Based on the results of sentinel node biopsies,a selective approach could be proposed where node-positive patients could be selected for inguinal node irradiation while node-negative patients could take advantage of inguinal sparing irradiation,thus avoiding toxic side effects.展开更多
Dialysis patients have risk in Zoster virus because of low immune. Valacyclovir, used for Zoster virus, is digested in kidney and it has side effect of nerve virus on patients with malfimction kidneys. This article re...Dialysis patients have risk in Zoster virus because of low immune. Valacyclovir, used for Zoster virus, is digested in kidney and it has side effect of nerve virus on patients with malfimction kidneys. This article reviews 8 dialysis cases and discusses the proper Valacyclovir portion for peritoneal dialysis patients.展开更多
Cyproterone acetate (CPA) is a steroidal synthetic progestagen and anti-androgenic compound widely administered in prostate cancer which has been evidentially correlated with a severe hepatotoxic potency. Three male p...Cyproterone acetate (CPA) is a steroidal synthetic progestagen and anti-androgenic compound widely administered in prostate cancer which has been evidentially correlated with a severe hepatotoxic potency. Three male patients aged 78-83 years are presented, in whom severe hepatotoxic reactions emerged after CPA administration. Patients were treated with CPA at the doses of 200-300 mg/d for malignant prostate disease for 3-12 mo prior to the acute manifestation of the hepatic disease. Clinical features compatible with mixed hepatocellular and cholestatic liver disease including jaundice, white stools and dark urine, manifested in all three cases whereas encephalopathy and ascites were present in two of the patients. Other primary causes of hepatotoxicity (alcohol consumption and viral hepatitis) were also verified in two cases, and in those patients biopsy findings revealed the presence of cirrhotic lesions in liver parenchyma. Discontinuation of the therapeutic agent led to the amelioration of the clinical profile in all the patients whereas a patient died 40 d after hospital admission due to sepsis, despite acute liver disease improvement. The current article highlights the hepatotoxic potency of a widely administered therapeutic agent and illustrates the importance of clinical surveillance especially in patients with previous hepatic diseases. Three relevant cases are reported and a review of the published literature is made.展开更多
AIM: To investigate the safety of β-L-D4A on DNA polymerase α.METHODS: Ion exchange chromatography was used to separate DNA polymerase cc from crude extract of human Hela cells. Detailed kinetic parameters were de...AIM: To investigate the safety of β-L-D4A on DNA polymerase α.METHODS: Ion exchange chromatography was used to separate DNA polymerase cc from crude extract of human Hela cells. Detailed kinetic parameters were determined for β-L-D4A against DNA polymeraseα . RESULTS: DNA polymerase was purified with 4% yield and 31000 units/mg specific activity. The Michaelis constant (Km = 3.22 i^mol/L), 50% inhibition concentration (IC50 = 178.49 μmol/L) and inhibition constant (Ki = 126 mol/L) of β-L-D4A were determined by kinetic analysis. CONCLUSION: β-L-D4A is a more safe nucleoside for hepatitis B virus (HBV) infection with a lower host toxicity.展开更多
Thiazolidinediones(TZDs),such as rosiglitazone(RSG),which activates peroxisome proliferator activated receptor-y(PPARy),are a potent class of oral antidiabetic agents with good durability.However,the clinical use of T...Thiazolidinediones(TZDs),such as rosiglitazone(RSG),which activates peroxisome proliferator activated receptor-y(PPARy),are a potent class of oral antidiabetic agents with good durability.However,the clinical use of TZDs is challenging because of their side effects,including weight gain and hepatotoxicity.Here,we found that bavachinin(BVC),a lead natural product,additively activates PPARγ with lowdose RSG to preserve the maximum antidiabetic effects while reducing weight gain and hepatotoxicity in db/db mice caused by RSG monotherapy.Structural and biochemical assays demonstrated that an unexplored hotspot around Met329 and Ser332 in helix 5 is triggered by BVC cobinding to RSG-bound PPARy,thereby allosterically stabilizing the active state of the activation-function 2 motif responsible for additive activation with RSG.Based on this hotspot,we discovered a series of new classes of allosteric agonists inducing the activity of TZDs in the same manner as BVC.Together,our data illustrate that the hotspot of PPARγ is druggable for the discovery of new allosteric synergists,and the combination thera py of allosteric synergists and TZD drugs may provide a potential alternative approach to the treatment of type 2 diabetes mellitus.展开更多
Breast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to...Breast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to increase the cure rate or survival of patients. In recent years, liposomes have been regarded as a kind of new carrier for targeted drugs. Being effective for enhancing drug efficacy and reducing side effects, they have been widely used for devel- oping anticancer drugs. As a kind of anthracycline with high anticancer activity, doxorubicin can treat or alleviate a variety of malignant tumors effectively when it is used on its own or in combination with other anticancer drugs~ Alt- hough liposomal doxorubicin has been extensively used in the adjuvant chemotherapy of breast cancer, its exact therapeutic efficacy and side effects have not been definitely proven. Various clinical studies have adopted different combined regimes, dosages, and staging, so their findings differ to certain extent. This paper reviews the clinical application of liposomal doxorubicin in the adjuvant chemotherapy of breast cancer and illustrates therapeutic effects and side effects of pegylated liposomal doxorubicin (PLD) and non-PLD (NPLD) in clinical research, in order to discuss the strategies for applying these drugs in such adjuvant chemotherapy, looking forward to providing references for related research and clinical treatment in terms of dosage, staging, combined regimes, and analysis methods and so on.展开更多
Chemotherapy as an effective cancer treatment technique has been widely used in tumor therapy. However, it is still a challenge to overcome the serious side effects of chemotherapy, especially for its myelotoxicity. H...Chemotherapy as an effective cancer treatment technique has been widely used in tumor therapy. However, it is still a challenge to overcome the serious side effects of chemotherapy, especially for its myelotoxicity. Here we report a novel strategy using the water soluble gadofullerene nanocrystals(GFNCs) to protect against chemotherapy injury in hepatocarcinoma bearing mice, which was induced by the commonly chemotherapeutic agent cyclophosphamide(CTX).The GFNCs were revealed to specifically accumulate in the bone marrow after intravenously injecting to mice and they exhibited excellent radical scavenging function, resulting in a prominent increase of mice blood cells and pathological improvements of the primary organs in the GFNCs(15 mg kg-(-1))treated mice after the CTX(60 mg kg-(-1)) therapy. Moreover,the GFNCs maintained and even strengthened the antineoplastic activity of the CTX agent. Therefore, the GFNCs would be the promising chemoprotective agents in chemotherapy based on their high efficiency, low toxicity and metabolizable property.展开更多
Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections ...Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections has led to the evolution and spread of drug resistance.As a universal antimicrobial technique unapt to induce drug resistance,photothermal therapy(PTT)is attracting extensive attention in recent years.However,its unspecific killing capability and side effects towards adjacent mammalian cells severely impede the practical applications.Herein,we proposed a metabolic engineering strategy to selectively inactivate Gram-positive bacteria by PTT.A bioorthogonal photothermal agent was prepared by the conjugation of IR-780 iodide and dibenzocyclooctyne(IR780-DBCO).Upon pre-metabolizing with 3-azido-D-alanine,Gram-positive bacteria rather than Gramnegative ones,such as Staphylococcus aureus and vancomycinresistant Enterococcus faecalis(VRE),could be specifically tied up by the explosive IR780-DBCO via copper-free click chemistry.Thereafter,they spontaneously detonated under 15 min near-infrared light irradiation and inactivated nearly 100% Gram-positive bacteria in vitro.Moreover,superbug VRE-induced infection was significantly inhibited by this approach in a mouse skin wound model.This metabolic labelling-based photothermal ablation strategy specific to Gram-positive microbes would stimulate the development of precise antibacterial candidates for preclinical applications.展开更多
文摘Objective: To evaluate the effectiveness of intraoperative radiotherapy (IORT) in combination with regional chemotherapy in the treatment of advanced pancreatic carcinoma.Methods: 17 patients with advanced pancreatic adenocarcinoma were treated with IORT and regional chemotherapy with 5-FU, Epirubucin and Mitomycin, and 6 cases accepted external radiotherapy postoperatively.Results: 35.29% (6/17) of the patients were clinical benefit responders and 23.53% (4/17) had a partial response. The median survival time was 11 months and the 1-year survival rate was 35.29% (6/17)Conclusion: IORT in combination with regional chemotherapy had a good impact on clinical benefit without severe side effects in locally advanced pancreatic carcinoma and led to a significant prolongation of the survival time. Key words pancreatic cancer - intraoperative radiotherapy - chemotherapy
基金Supported by a grant from the key Scientific Foundation of Shanxi Province (No. 051096-2)
文摘Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Fifty patients with advanced NSCLC (stages III to IV), who had received therapies in our Center (Department of Biotherapy, Affiliated to Cancer Hospital of Shanxi Medical University, Taiyuan, China) from August 2008 to January 2010, were treated by DC-CIK + chemotherapy as the combined treatment group; fifty advanced NSCLC patients treated with chemotherapy at the same time served as controls. The immunologic function, short-term therapeutic effects, the 1-year survival rate, the life quality, the chemotherapy side effects were compared between the two groups, the safety and therapeutic effects of DC-CIK cells therapy were observed too. Results: There was no obvious change of subsets of T cells in peripheral blood before and after therapy in DC-CIK + chemotherapy group, and IFN-γ was improved after therapy in this group (P < 0.05); in chemotherapy alone group, the ratios of CD3+CD4+, CD3+CD8+, CD3-CD56+ cells and the secretion of IL-2, TNF-α decreased significantly after therapy (P < 0.05); the ratios of CD3+CD8+, CD3+CD56+ were improved after cell culture (P < 0.05). The disease control rate (DCR) of DC-CIK + chemotherapy group was higher than that in the chemotherapy alone group (78.0% vs 56.0%, P < 0.05); the 1-year survival rates of DC-CIK + chemotherapy group and chemotherapy alone group were 50% and 44% respectively, had no significant difference. Compared with chemotherapy alone group, the occurrence of chemotherapy side effects (including bone marrow suppression, nausea and vomiting, peripheral nerve toxicity) was less in the DC-CIK + chemotherapy group (P < 0.05). The physical and appetite were better in DC-CIK + chemotherapy group after therapy. Conclusion: To compare with simple chemotherapy, DC-CIK + chemotherapy for advanced NSCLC is safe and effective, and it can improve patients' life quality and remission rate, and prolong their survival time.
文摘Oncological treatment is currently directed toward a tailored therapy concept.Squamous cell carcinoma of the anal canal could be considered a suitable platform to test new therapeutic strategies to minimize treatment morbidity.Standard of care for patients with anal canal cancer consists of a combination of radiotherapy and chemotherapy.This treatment has led to a high rate of local control and a 60% cure rate with preservation of the anal sphincter,thus replacing surgical abdominoperineal resection.Lymph node metastases represent a critical independent prognostic factor for local recurrence and survival.Mesorectal and iliac lymph nodes are usually included in the radiation field,whereas the inclusion of inguinal regions still remains controversial because of the subsequent adverse side effects.Sentinel lymph node biopsies could clearly identify inguinal node-positive patients eligible for therapeutic groin irradiation.A sentinel lymph node navigation procedure is reported here to be a feasible and effective method for establishing the true inguinal node status in patients suffering from anal canal cancer.Based on the results of sentinel node biopsies,a selective approach could be proposed where node-positive patients could be selected for inguinal node irradiation while node-negative patients could take advantage of inguinal sparing irradiation,thus avoiding toxic side effects.
文摘Dialysis patients have risk in Zoster virus because of low immune. Valacyclovir, used for Zoster virus, is digested in kidney and it has side effect of nerve virus on patients with malfimction kidneys. This article reviews 8 dialysis cases and discusses the proper Valacyclovir portion for peritoneal dialysis patients.
文摘Cyproterone acetate (CPA) is a steroidal synthetic progestagen and anti-androgenic compound widely administered in prostate cancer which has been evidentially correlated with a severe hepatotoxic potency. Three male patients aged 78-83 years are presented, in whom severe hepatotoxic reactions emerged after CPA administration. Patients were treated with CPA at the doses of 200-300 mg/d for malignant prostate disease for 3-12 mo prior to the acute manifestation of the hepatic disease. Clinical features compatible with mixed hepatocellular and cholestatic liver disease including jaundice, white stools and dark urine, manifested in all three cases whereas encephalopathy and ascites were present in two of the patients. Other primary causes of hepatotoxicity (alcohol consumption and viral hepatitis) were also verified in two cases, and in those patients biopsy findings revealed the presence of cirrhotic lesions in liver parenchyma. Discontinuation of the therapeutic agent led to the amelioration of the clinical profile in all the patients whereas a patient died 40 d after hospital admission due to sepsis, despite acute liver disease improvement. The current article highlights the hepatotoxic potency of a widely administered therapeutic agent and illustrates the importance of clinical surveillance especially in patients with previous hepatic diseases. Three relevant cases are reported and a review of the published literature is made.
基金National Natural Science Foundation of China,No.30330680
文摘AIM: To investigate the safety of β-L-D4A on DNA polymerase α.METHODS: Ion exchange chromatography was used to separate DNA polymerase cc from crude extract of human Hela cells. Detailed kinetic parameters were determined for β-L-D4A against DNA polymeraseα . RESULTS: DNA polymerase was purified with 4% yield and 31000 units/mg specific activity. The Michaelis constant (Km = 3.22 i^mol/L), 50% inhibition concentration (IC50 = 178.49 μmol/L) and inhibition constant (Ki = 126 mol/L) of β-L-D4A were determined by kinetic analysis. CONCLUSION: β-L-D4A is a more safe nucleoside for hepatitis B virus (HBV) infection with a lower host toxicity.
基金the National Natural Science Foundation of China(21708025,81925034,91753117,and 81773793)the Open Fund of State Key Laboratory of Oncogenes and Related Genes,Shanghai Jiao Tong University School of Medicine+3 种基金the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-01-E00036)the Shanghai Science and Technology Innovation Foundation(19431901600)the China Postdoctoral Science Foundation(2016M601618 and 2017T100303)the National Science and Technology Major Project of China(2018ZX09711001-005-022)。
文摘Thiazolidinediones(TZDs),such as rosiglitazone(RSG),which activates peroxisome proliferator activated receptor-y(PPARy),are a potent class of oral antidiabetic agents with good durability.However,the clinical use of TZDs is challenging because of their side effects,including weight gain and hepatotoxicity.Here,we found that bavachinin(BVC),a lead natural product,additively activates PPARγ with lowdose RSG to preserve the maximum antidiabetic effects while reducing weight gain and hepatotoxicity in db/db mice caused by RSG monotherapy.Structural and biochemical assays demonstrated that an unexplored hotspot around Met329 and Ser332 in helix 5 is triggered by BVC cobinding to RSG-bound PPARy,thereby allosterically stabilizing the active state of the activation-function 2 motif responsible for additive activation with RSG.Based on this hotspot,we discovered a series of new classes of allosteric agonists inducing the activity of TZDs in the same manner as BVC.Together,our data illustrate that the hotspot of PPARγ is druggable for the discovery of new allosteric synergists,and the combination thera py of allosteric synergists and TZD drugs may provide a potential alternative approach to the treatment of type 2 diabetes mellitus.
基金Project supported by the"151"Excellent Middle-Aged and Talented Young Persons of Zhejiang Province,China(No.2010382)the Key Platform Technological Project of Zhejiang Medical Science and Hygiene(No.2016ZDB003),China
文摘Breast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to increase the cure rate or survival of patients. In recent years, liposomes have been regarded as a kind of new carrier for targeted drugs. Being effective for enhancing drug efficacy and reducing side effects, they have been widely used for devel- oping anticancer drugs. As a kind of anthracycline with high anticancer activity, doxorubicin can treat or alleviate a variety of malignant tumors effectively when it is used on its own or in combination with other anticancer drugs~ Alt- hough liposomal doxorubicin has been extensively used in the adjuvant chemotherapy of breast cancer, its exact therapeutic efficacy and side effects have not been definitely proven. Various clinical studies have adopted different combined regimes, dosages, and staging, so their findings differ to certain extent. This paper reviews the clinical application of liposomal doxorubicin in the adjuvant chemotherapy of breast cancer and illustrates therapeutic effects and side effects of pegylated liposomal doxorubicin (PLD) and non-PLD (NPLD) in clinical research, in order to discuss the strategies for applying these drugs in such adjuvant chemotherapy, looking forward to providing references for related research and clinical treatment in terms of dosage, staging, combined regimes, and analysis methods and so on.
基金financially supported by the National Natural Science Foundation of China(51472248,51372251 and 51502301)the National Major Scientific Instruments and Equipments Development Project(ZDYZ2015-2)the Key Research Program of the Chinese Academy of Sciences(QYZDJ-SSW-SLH025,KGZD-EWT02 and XDA09030302)
文摘Chemotherapy as an effective cancer treatment technique has been widely used in tumor therapy. However, it is still a challenge to overcome the serious side effects of chemotherapy, especially for its myelotoxicity. Here we report a novel strategy using the water soluble gadofullerene nanocrystals(GFNCs) to protect against chemotherapy injury in hepatocarcinoma bearing mice, which was induced by the commonly chemotherapeutic agent cyclophosphamide(CTX).The GFNCs were revealed to specifically accumulate in the bone marrow after intravenously injecting to mice and they exhibited excellent radical scavenging function, resulting in a prominent increase of mice blood cells and pathological improvements of the primary organs in the GFNCs(15 mg kg-(-1))treated mice after the CTX(60 mg kg-(-1)) therapy. Moreover,the GFNCs maintained and even strengthened the antineoplastic activity of the CTX agent. Therefore, the GFNCs would be the promising chemoprotective agents in chemotherapy based on their high efficiency, low toxicity and metabolizable property.
基金supported by the National Natural Science Foundation of China(52003222 and 21875189)Ningbo Natural Science Foundation(202003N4064)+2 种基金the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0752)the Joint Research Funds of Department of Science&Technology of Shaanxi Province and Northwestern Polytechnical University(2020GXLH-Z-013)the Fundamental Research Funds for the Central Universities.
文摘Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections has led to the evolution and spread of drug resistance.As a universal antimicrobial technique unapt to induce drug resistance,photothermal therapy(PTT)is attracting extensive attention in recent years.However,its unspecific killing capability and side effects towards adjacent mammalian cells severely impede the practical applications.Herein,we proposed a metabolic engineering strategy to selectively inactivate Gram-positive bacteria by PTT.A bioorthogonal photothermal agent was prepared by the conjugation of IR-780 iodide and dibenzocyclooctyne(IR780-DBCO).Upon pre-metabolizing with 3-azido-D-alanine,Gram-positive bacteria rather than Gramnegative ones,such as Staphylococcus aureus and vancomycinresistant Enterococcus faecalis(VRE),could be specifically tied up by the explosive IR780-DBCO via copper-free click chemistry.Thereafter,they spontaneously detonated under 15 min near-infrared light irradiation and inactivated nearly 100% Gram-positive bacteria in vitro.Moreover,superbug VRE-induced infection was significantly inhibited by this approach in a mouse skin wound model.This metabolic labelling-based photothermal ablation strategy specific to Gram-positive microbes would stimulate the development of precise antibacterial candidates for preclinical applications.