AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C:...AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C: METAVIR = F4 or clinical cirrhosis) in chronic hepatitis C(CHC) patients. Additionally, to compare the accuracy of the MMs with the aspartate aminotransferase to platelet ratio index(APRI) and fibrosis index based on four factors(FIB-4). METHODS Sixty-nine patients who had undergone biopsy in the previous 12 mo or had clinical cirrhosis were included. The presence of any other liver disease was a criterion for exclusion. The MMs, constructed using partial least squares discriminant analysis and linear discriminant analysis formalisms, were tested by cross-validation, considering SF, AF and C. RESULTS Results showed that forty-two patients(61%) presented SF, 28(40%) AF and 18(26%) C. The MMs showed sensitivity and specificity of 97.6% and 92.6% to predict SF; 96.4% and 95.1% to predict AF; and 100% and 98.0% to predict C. Besides that, the MMs correctly classified all 27(39.7%) and 25(38.8%) patients with intermediate values of APRI and FIB-4, respectively. CONCLUSION The metabonomic strategy performed excellently in predicting significant and advanced liver fibrosis in CHC patients, including those in the gray zone of APRI and FIB-4, which may contribute to reducing the need for these patients to undergo liver biopsy.展开更多
The effect of treatment on patient’s outcome can easily be determined through the impact of the treatment on biological events. Observing the treatment for patients for a certain period of time can help in determinin...The effect of treatment on patient’s outcome can easily be determined through the impact of the treatment on biological events. Observing the treatment for patients for a certain period of time can help in determining whether there is any change in the biomarker of the patient. It is important to study how the biomarker changes due to treatment and whether for different individuals located in separate centers can be clustered together since they might have different distributions. The study is motivated by a Bayesian non-parametric mixture model, which is more flexible when compared to the Bayesian Parametric models and is capable of borrowing information across different centers allowing them to be grouped together. To this end, this research modeled Biological markers taking into consideration the Surrogate markers. The study employed the nested Dirichlet process prior, which is easily peaceable on different distributions for several centers, with centers from the same Dirichlet process component clustered automatically together. The study sampled from the posterior by use of Markov chain Monte carol algorithm. The model is illustrated using a simulation study to see how it performs on simulated data. Clearly, from the simulation study it was clear that, the model was capable of clustering data into different clusters.展开更多
AIM:To study the relationship between adverse events(AEs),efficacy,and nursing intervention for sorafenibtherapy in patients with hepatocellular carcinoma(HCC).METHODS:We enrolled 37 consecutive patients withadvanced ...AIM:To study the relationship between adverse events(AEs),efficacy,and nursing intervention for sorafenibtherapy in patients with hepatocellular carcinoma(HCC).METHODS:We enrolled 37 consecutive patients withadvanced HCC who received sorafenib therapy.Relationships among baseline characteristics as well as AEoccurrence and tumor response,overall survival(OS),and treatment duration were analyzed.The nursingintervention program consisted of education regardingself-monitoring and AEs management,and telephoneRESULTS:A total of 37 patients were enrolled in the study,comprising 30 males(81%) with a median age of 71 years.The disease control rate at 3 mo was 41%,and the median OS and treatment duration were 259 and 108 d,respectively.Nursing intervention was given to 24 patients(65%).Every patient exhibited some kinds of AEs,but no patients experienced G4 AEs.Frequently observed AEs > G2 included anorexia(57%),skin toxicity(57%),and fatigue(54%).Factors significantly associated with longer OS in multivariate analysis demonstrated that age ≤ 70 years,presence of > G2 skin toxicity,and absence of > G2 hypoalbuminemia.The disease control rate in patients with > G2 skin toxicity was 13/20(65%),which was significantly higher compared with that in patients with no or G1 skin toxicity.Multivariate analysis revealed that nursing intervention and > G2 skin toxicity were independent significant predictors for longer treatment duration.CONCLUSION:Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC.Nursing intervention contributed to better adher-ence,which may improve the efficacy of sorafenib.展开更多
AIM To investigate the relationship between the onsets of multikinase inhibitor(MKI)-associated hand-foot skin reaction(HFSR) and prognosis under intervention by pharmacists after the introduction of sorafenib.METHODS...AIM To investigate the relationship between the onsets of multikinase inhibitor(MKI)-associated hand-foot skin reaction(HFSR) and prognosis under intervention by pharmacists after the introduction of sorafenib.METHODS We conducted a retrospective study involving 40 patients treated with sorafenib. Intervention by pharmacists began at the time of treatment introduction and continued until the appearance of symptomatic exacerbation or non-permissible adverse reactions. We examined the relationship between MKI-associated HFSR and overall survival(OS) after the initiation of treatment.RESULTS The median OS was 10.9 mo in the MKI-associated HFSR group and 3.4 mo in the no HFSR group, showing a significant difference in multivariate analysis. A multivariate analysis of the time to treatment failure indicated that the intervention by pharmacists and MKI-associated HFSR were significant factors. The median cumulative dose and the mean medication possession ratio were significantly higher in the intervention group than in the non-intervention group. A borderline significant difference was observed in terms of OS in this group.CONCLUSION Intervention by pharmacists increased drug adherence. Under increased adherence, MKI-associated HFSR was an advantageous surrogate marker. Intervention by healthcare providers needs to be performed for adequate sorafenib treatment.展开更多
Thyroglobulin antibody (TgAb) has been used as a surrogate tumor marker of differentiated thyroid carcinoma (DTC) patients. Preoperative TgAb (PreopTgAb) is thought to affect the prevalence, disease severity, and outc...Thyroglobulin antibody (TgAb) has been used as a surrogate tumor marker of differentiated thyroid carcinoma (DTC) patients. Preoperative TgAb (PreopTgAb) is thought to affect the prevalence, disease severity, and outcome of DTC. The objective of the present study was to retrospectively analyze the prevalence of PreopTgAb in patients diagnosed with DTC and its relation to thyroid cancer characteristics, staging, and disease outcome. A retrospective analysis of 109 DTC patients with reports of PreopTgAb was carried out. Clinicopathological parameters, including patient demographics (age and gender), TNM staging, histopathologic characteristics (type of pathology, vascular invasion, extrathyroid extension, carcinoma variant, multifocality), treatment (surgery, radioactive iodine), and outcome were recorded. The association of PreopTgAb was compared with the study variables and outcome of the disease using the Chi-square test and Mann-Whitney tests. The prevalence of PreopTgAb was 59.6%. Among the 54 PreopTgAb positive patients, 34 patients had an excellent response and 15 patients had an indeterminate response, while biochemically and structurally incomplete response was observed in 3 and 2 patients, respectively. PreopTgAb was not significantly associated with age (p = 0.919), sex (p = 0.650), pathology (p = 0.079), stage at diagnosis (p = 0.513), vascular invasion (p = 0.211), extra thyroid extension (p = 0.734), histologic variant (p = 0.877), multifocality (p = 0.361), and outcome (p = 0.360). Although we did not find a significant association between positive PreopTgAb and clinical characteristics and outcome of DTC, it can still be considered as a surrogate marker of DTC during follow-up.展开更多
OBJECTIVE To evaluate if RNA helicase DDX20,highly expressed in triple negative breast cancer(TNBC)cells,could serve as a surrogate marker for simvastatin treatment response.METHODS We first assessed correlation betwe...OBJECTIVE To evaluate if RNA helicase DDX20,highly expressed in triple negative breast cancer(TNBC)cells,could serve as a surrogate marker for simvastatin treatment response.METHODS We first assessed correlation between 17 mevalonate pathway-related genes and expression of DDX20 in a cohort of 1325 breast cancer tumors.TNBC cells,MDA-MB-231,were then treated with simvastatin and mevalonate pathway intermediates to assess the alteration in DDX20 expression.In the mouse model,MDA-MB-231 cells were injected to tail veins of mice,groups of 8mice each were injected intraperioneally with vehicle or simvastatin 25mg·kg-1 3times a week for 6weeks.The number of metastatic colonies formed was quantified and immunohistochemical(IHC)staining of DDX20 was carried out in the lung tissues.RESULTS Among the 17 genes evaluated,positive correlation with DDX20 expression was observed in eight of them,with HMGCR having the highest correlation.Our in vitro experiments show exposure of breast cancer cells to simvastatin lead to a Rho-dependent decrease in gene expression of DDX20,leading to decreased tumor proliferation in a mevalonate pathway-dependent manner.Conversely,ectopic overexpression of DDX20 significantly abrogated the anti-metastatic activity of simvastatin.A similar observation is seen in the mouse model,where simvastatin-injected mice show significantly fewer visible lung metastases compared to placebo-fed mice.IHC staining on these lung tissues showed decreased DDX20 expression in simvastatin-injected group,corroborating our observations in vitro.CONCLUSION DDX20 is a potential surrogate marker for simvastatin treatment response in breast cancer and a long term implication of our findings is the possibility of an effective combinatorial therapeutic intervention using statins(to suppress DDX20 gene expression)and a suitable firstline agent″for the kill″of invasive breast cancer.展开更多
文摘AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C: METAVIR = F4 or clinical cirrhosis) in chronic hepatitis C(CHC) patients. Additionally, to compare the accuracy of the MMs with the aspartate aminotransferase to platelet ratio index(APRI) and fibrosis index based on four factors(FIB-4). METHODS Sixty-nine patients who had undergone biopsy in the previous 12 mo or had clinical cirrhosis were included. The presence of any other liver disease was a criterion for exclusion. The MMs, constructed using partial least squares discriminant analysis and linear discriminant analysis formalisms, were tested by cross-validation, considering SF, AF and C. RESULTS Results showed that forty-two patients(61%) presented SF, 28(40%) AF and 18(26%) C. The MMs showed sensitivity and specificity of 97.6% and 92.6% to predict SF; 96.4% and 95.1% to predict AF; and 100% and 98.0% to predict C. Besides that, the MMs correctly classified all 27(39.7%) and 25(38.8%) patients with intermediate values of APRI and FIB-4, respectively. CONCLUSION The metabonomic strategy performed excellently in predicting significant and advanced liver fibrosis in CHC patients, including those in the gray zone of APRI and FIB-4, which may contribute to reducing the need for these patients to undergo liver biopsy.
文摘The effect of treatment on patient’s outcome can easily be determined through the impact of the treatment on biological events. Observing the treatment for patients for a certain period of time can help in determining whether there is any change in the biomarker of the patient. It is important to study how the biomarker changes due to treatment and whether for different individuals located in separate centers can be clustered together since they might have different distributions. The study is motivated by a Bayesian non-parametric mixture model, which is more flexible when compared to the Bayesian Parametric models and is capable of borrowing information across different centers allowing them to be grouped together. To this end, this research modeled Biological markers taking into consideration the Surrogate markers. The study employed the nested Dirichlet process prior, which is easily peaceable on different distributions for several centers, with centers from the same Dirichlet process component clustered automatically together. The study sampled from the posterior by use of Markov chain Monte carol algorithm. The model is illustrated using a simulation study to see how it performs on simulated data. Clearly, from the simulation study it was clear that, the model was capable of clustering data into different clusters.
基金Supported by Japan Society for the Promotion of Science(JSPS)KAKENHI Grant-in-Aid for Young Scientists(B)21792240
文摘AIM:To study the relationship between adverse events(AEs),efficacy,and nursing intervention for sorafenibtherapy in patients with hepatocellular carcinoma(HCC).METHODS:We enrolled 37 consecutive patients withadvanced HCC who received sorafenib therapy.Relationships among baseline characteristics as well as AEoccurrence and tumor response,overall survival(OS),and treatment duration were analyzed.The nursingintervention program consisted of education regardingself-monitoring and AEs management,and telephoneRESULTS:A total of 37 patients were enrolled in the study,comprising 30 males(81%) with a median age of 71 years.The disease control rate at 3 mo was 41%,and the median OS and treatment duration were 259 and 108 d,respectively.Nursing intervention was given to 24 patients(65%).Every patient exhibited some kinds of AEs,but no patients experienced G4 AEs.Frequently observed AEs > G2 included anorexia(57%),skin toxicity(57%),and fatigue(54%).Factors significantly associated with longer OS in multivariate analysis demonstrated that age ≤ 70 years,presence of > G2 skin toxicity,and absence of > G2 hypoalbuminemia.The disease control rate in patients with > G2 skin toxicity was 13/20(65%),which was significantly higher compared with that in patients with no or G1 skin toxicity.Multivariate analysis revealed that nursing intervention and > G2 skin toxicity were independent significant predictors for longer treatment duration.CONCLUSION:Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC.Nursing intervention contributed to better adher-ence,which may improve the efficacy of sorafenib.
文摘AIM To investigate the relationship between the onsets of multikinase inhibitor(MKI)-associated hand-foot skin reaction(HFSR) and prognosis under intervention by pharmacists after the introduction of sorafenib.METHODS We conducted a retrospective study involving 40 patients treated with sorafenib. Intervention by pharmacists began at the time of treatment introduction and continued until the appearance of symptomatic exacerbation or non-permissible adverse reactions. We examined the relationship between MKI-associated HFSR and overall survival(OS) after the initiation of treatment.RESULTS The median OS was 10.9 mo in the MKI-associated HFSR group and 3.4 mo in the no HFSR group, showing a significant difference in multivariate analysis. A multivariate analysis of the time to treatment failure indicated that the intervention by pharmacists and MKI-associated HFSR were significant factors. The median cumulative dose and the mean medication possession ratio were significantly higher in the intervention group than in the non-intervention group. A borderline significant difference was observed in terms of OS in this group.CONCLUSION Intervention by pharmacists increased drug adherence. Under increased adherence, MKI-associated HFSR was an advantageous surrogate marker. Intervention by healthcare providers needs to be performed for adequate sorafenib treatment.
文摘Thyroglobulin antibody (TgAb) has been used as a surrogate tumor marker of differentiated thyroid carcinoma (DTC) patients. Preoperative TgAb (PreopTgAb) is thought to affect the prevalence, disease severity, and outcome of DTC. The objective of the present study was to retrospectively analyze the prevalence of PreopTgAb in patients diagnosed with DTC and its relation to thyroid cancer characteristics, staging, and disease outcome. A retrospective analysis of 109 DTC patients with reports of PreopTgAb was carried out. Clinicopathological parameters, including patient demographics (age and gender), TNM staging, histopathologic characteristics (type of pathology, vascular invasion, extrathyroid extension, carcinoma variant, multifocality), treatment (surgery, radioactive iodine), and outcome were recorded. The association of PreopTgAb was compared with the study variables and outcome of the disease using the Chi-square test and Mann-Whitney tests. The prevalence of PreopTgAb was 59.6%. Among the 54 PreopTgAb positive patients, 34 patients had an excellent response and 15 patients had an indeterminate response, while biochemically and structurally incomplete response was observed in 3 and 2 patients, respectively. PreopTgAb was not significantly associated with age (p = 0.919), sex (p = 0.650), pathology (p = 0.079), stage at diagnosis (p = 0.513), vascular invasion (p = 0.211), extra thyroid extension (p = 0.734), histologic variant (p = 0.877), multifocality (p = 0.361), and outcome (p = 0.360). Although we did not find a significant association between positive PreopTgAb and clinical characteristics and outcome of DTC, it can still be considered as a surrogate marker of DTC during follow-up.
基金The project supported by grants from the Academic Research Fund Tier 1(R-184-000-228-112)the Cancer Science Institute of Singapore,Experimental Therapeutics I Program(grant R-713-001-011-271)
文摘OBJECTIVE To evaluate if RNA helicase DDX20,highly expressed in triple negative breast cancer(TNBC)cells,could serve as a surrogate marker for simvastatin treatment response.METHODS We first assessed correlation between 17 mevalonate pathway-related genes and expression of DDX20 in a cohort of 1325 breast cancer tumors.TNBC cells,MDA-MB-231,were then treated with simvastatin and mevalonate pathway intermediates to assess the alteration in DDX20 expression.In the mouse model,MDA-MB-231 cells were injected to tail veins of mice,groups of 8mice each were injected intraperioneally with vehicle or simvastatin 25mg·kg-1 3times a week for 6weeks.The number of metastatic colonies formed was quantified and immunohistochemical(IHC)staining of DDX20 was carried out in the lung tissues.RESULTS Among the 17 genes evaluated,positive correlation with DDX20 expression was observed in eight of them,with HMGCR having the highest correlation.Our in vitro experiments show exposure of breast cancer cells to simvastatin lead to a Rho-dependent decrease in gene expression of DDX20,leading to decreased tumor proliferation in a mevalonate pathway-dependent manner.Conversely,ectopic overexpression of DDX20 significantly abrogated the anti-metastatic activity of simvastatin.A similar observation is seen in the mouse model,where simvastatin-injected mice show significantly fewer visible lung metastases compared to placebo-fed mice.IHC staining on these lung tissues showed decreased DDX20 expression in simvastatin-injected group,corroborating our observations in vitro.CONCLUSION DDX20 is a potential surrogate marker for simvastatin treatment response in breast cancer and a long term implication of our findings is the possibility of an effective combinatorial therapeutic intervention using statins(to suppress DDX20 gene expression)and a suitable firstline agent″for the kill″of invasive breast cancer.
