Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the ...Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine（PORCN） that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159（ETC-159） had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors.Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.展开更多
Objective: To evaluate the clinical effects of concurrent and sequential therapy for middle and advanced stage non-small cell lung cancer (NSCLC) useing IMRT combined with NP regimen chemotherapy. Methods: Eighty pati...Objective: To evaluate the clinical effects of concurrent and sequential therapy for middle and advanced stage non-small cell lung cancer (NSCLC) useing IMRT combined with NP regimen chemotherapy. Methods: Eighty patients with middle and advanced stage NSCLC were randomized into two groups. Forty patients were underwent sequential therapy and other 40 patients were underwent concurrent therapy. IMRT was used in radiotherapy and NP regimen of vinorelbine+cispatin (NP) was used in chemotherapy. Results: (1) The overall response (CR+PR) rate was 75% in concurrent group and 45% in sequential group (P<0.05); (2) The treatment courses were 84 days and 140 days for concurrent group and sequential group respectively (P<0.05); (3) One-year survival rate in concurrent group was 72.4% and 52.3% in sequential group respectively; (4) The toxic effects can be tolerable by all of patients. Conclusion: The concurrent chemo-radiotherapy has better overall re- sponse, one-year survival rate and shorter treatment course than the sequential chemo-radiotherapy, so it is a better method for the treatment of middle and advanced stage NSCLC, but the long term survival rate will be studied.展开更多
There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the m...There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. There is a subset of patients thatare likely to recur after locoregional treatment that is thought of as a "high-risk" population. This more aggressive subset includes patients with clinical stage greater than T2 b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/d L. The rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5-fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. These trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. This review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer.展开更多
Objective: To observe the effect of acupuncture on the contents of stress hormones of the hypothalamus pituitary adrenal axis (HPA) in treatment of type II diabetes with concurrent acute cerebral infarction patients. ...Objective: To observe the effect of acupuncture on the contents of stress hormones of the hypothalamus pituitary adrenal axis (HPA) in treatment of type II diabetes with concurrent acute cerebral infarction patients. Methods: 60 cases of inpatients were randomly and evenly divided into treatment group (conventional medication plus acupuncture) and control (conventional mediation) group. Plasma corticotropin releasing hormone (CRH), adrenocorticotropin hormone (ACTH) and corticosteroid (CS) contents before and after treatment were measured using radioimmunoassay (RIA) and compared with those of healthy subject group (n=30). Results: Plasma CRH, ACTH and CS levels in patients of both treatment group and control group at admission were significant higher than those of normal subject group (P<0.05). After treatment for 15～30 days, results showed that plasma CRH, ACTH and CS levels in both treatment and control groups lowered significantly in comparison with those of pre treatment (P<0.05 or 0.01); while those of treatment group were even more lower (being closer to the normal values) than those of control group (P<0.05 or 0.01). Conclusion: Acupuncture therapy can reduce the stress state of HPA in type II diabetes with concurrent acute cerebral infarction patients, i.e. regulate the neuroendocrine immunological net, which may be one of the mechanisms for acupuncture treatment of cerebral stroke.展开更多
Objective： To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy （3D-CRT） for locally advanced non-small cell lung cancer （NSCLC）. Methods： From April 2002 t...Objective： To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy （3D-CRT） for locally advanced non-small cell lung cancer （NSCLC）. Methods： From April 2002 to June 2005, 38 patients with inoperable stage Ⅲ NSCLC were treated with gemcitabine and 3D-CRT simultaneously. Chemotherapy consisted of intravenously gemcitabine 350 mg/m^2 on days 1, 8, 15, 22, 29, 36.3D-CRT was delivered up to a total dose of 60-64 Gy with a 2.0 Gy dose fraction per day, 5 days per week. Results： The overall response rates of primary tumor and mediastinum metastatic node were 86.8% （33/38） and 90.6% （29/32） respectively, and 91.7% （22/24） and 78.6% （11/14） for squamous cell carcinoma and adenocarcinoma respectively. The acute side effects of patients were mostly myelosuppression, nausea, vomiting, radiation-induced esophagitis and pneumonitis （RTOG 1/11）, however, all of them were cured. Conclusion： Concurrent application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.展开更多
目的探讨基于动态对比增强磁共振成像(dynamic contrast-enhanced magnetic resonance imaging,DCE-MRI)的肿瘤内及含肿瘤外缘5 mm移行带的瘤周影像组学标签对进展期宫颈鳞癌同步放化疗(concurrent chemotherapy and radiation therapy,...目的探讨基于动态对比增强磁共振成像(dynamic contrast-enhanced magnetic resonance imaging,DCE-MRI)的肿瘤内及含肿瘤外缘5 mm移行带的瘤周影像组学标签对进展期宫颈鳞癌同步放化疗(concurrent chemotherapy and radiation therapy,CCRT)反应的预测价值。方法回顾性收集126例经病理活检证实的宫颈鳞癌患者DCE-MRI图像及临床资料,按照7∶3的比例随机分为训练组(n=88)和验证组(n=38)。使用3D-Slicer软件在两个靶区(VOI、VOI+5mm)提取影像组学特征,采用最大相关最小冗余(mRMR)及最小绝对收缩与选择算子(LASSO)算法进行特征筛选并构建影像组学标签。利用ROC曲线及决策曲线(DCA)分析评估影像组学标签的预测效能及临床应用价值。结果VOI+5mm瘤周影像组学标签在训练组和验证组中的AUC(分别为0.855和0.819)均高于VOI瘤内影像组学标签(分别为0.770和0.750),瘤内标签和瘤周标签在训练组中预测CCRT反应的敏感度和特异度分别为74.5%和70.7%、76.6%和82.9%,而在验证组中分别为60.0%和83.3%、80.0%和77.8%。DCA显示当阈值概率分别为0.06~0.71和0.01~1.00时,瘤内标签和瘤周标签的临床净收益最大。结论基于DCE-MRI的影像组学标签在预测进展期宫颈鳞癌CCRT反应方面有一定临床应用价值,瘤周影像组学特征对于提升预测效能具有很大潜力,可为宫颈癌患者优化诊疗策略及改善预后提供参考。展开更多
基金supported by an NIH grant to BOW (R01AR053293)the Van Andel Research Institutesupported in part by the National Research Foundation Singapore
文摘Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine（PORCN） that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159（ETC-159） had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors.Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.
基金Supported by a grant from Health Bureau of Lianyungang City’s Fund Program (No. 05051).
文摘Objective: To evaluate the clinical effects of concurrent and sequential therapy for middle and advanced stage non-small cell lung cancer (NSCLC) useing IMRT combined with NP regimen chemotherapy. Methods: Eighty patients with middle and advanced stage NSCLC were randomized into two groups. Forty patients were underwent sequential therapy and other 40 patients were underwent concurrent therapy. IMRT was used in radiotherapy and NP regimen of vinorelbine+cispatin (NP) was used in chemotherapy. Results: (1) The overall response (CR+PR) rate was 75% in concurrent group and 45% in sequential group (P<0.05); (2) The treatment courses were 84 days and 140 days for concurrent group and sequential group respectively (P<0.05); (3) One-year survival rate in concurrent group was 72.4% and 52.3% in sequential group respectively; (4) The toxic effects can be tolerable by all of patients. Conclusion: The concurrent chemo-radiotherapy has better overall re- sponse, one-year survival rate and shorter treatment course than the sequential chemo-radiotherapy, so it is a better method for the treatment of middle and advanced stage NSCLC, but the long term survival rate will be studied.
文摘There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. There is a subset of patients thatare likely to recur after locoregional treatment that is thought of as a "high-risk" population. This more aggressive subset includes patients with clinical stage greater than T2 b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/d L. The rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5-fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. These trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. This review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer.
文摘Objective: To observe the effect of acupuncture on the contents of stress hormones of the hypothalamus pituitary adrenal axis (HPA) in treatment of type II diabetes with concurrent acute cerebral infarction patients. Methods: 60 cases of inpatients were randomly and evenly divided into treatment group (conventional medication plus acupuncture) and control (conventional mediation) group. Plasma corticotropin releasing hormone (CRH), adrenocorticotropin hormone (ACTH) and corticosteroid (CS) contents before and after treatment were measured using radioimmunoassay (RIA) and compared with those of healthy subject group (n=30). Results: Plasma CRH, ACTH and CS levels in patients of both treatment group and control group at admission were significant higher than those of normal subject group (P<0.05). After treatment for 15～30 days, results showed that plasma CRH, ACTH and CS levels in both treatment and control groups lowered significantly in comparison with those of pre treatment (P<0.05 or 0.01); while those of treatment group were even more lower (being closer to the normal values) than those of control group (P<0.05 or 0.01). Conclusion: Acupuncture therapy can reduce the stress state of HPA in type II diabetes with concurrent acute cerebral infarction patients, i.e. regulate the neuroendocrine immunological net, which may be one of the mechanisms for acupuncture treatment of cerebral stroke.
文摘Objective： To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy （3D-CRT） for locally advanced non-small cell lung cancer （NSCLC）. Methods： From April 2002 to June 2005, 38 patients with inoperable stage Ⅲ NSCLC were treated with gemcitabine and 3D-CRT simultaneously. Chemotherapy consisted of intravenously gemcitabine 350 mg/m^2 on days 1, 8, 15, 22, 29, 36.3D-CRT was delivered up to a total dose of 60-64 Gy with a 2.0 Gy dose fraction per day, 5 days per week. Results： The overall response rates of primary tumor and mediastinum metastatic node were 86.8% （33/38） and 90.6% （29/32） respectively, and 91.7% （22/24） and 78.6% （11/14） for squamous cell carcinoma and adenocarcinoma respectively. The acute side effects of patients were mostly myelosuppression, nausea, vomiting, radiation-induced esophagitis and pneumonitis （RTOG 1/11）, however, all of them were cured. Conclusion： Concurrent application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.
文摘目的探讨基于动态对比增强磁共振成像(dynamic contrast-enhanced magnetic resonance imaging,DCE-MRI)的肿瘤内及含肿瘤外缘5 mm移行带的瘤周影像组学标签对进展期宫颈鳞癌同步放化疗(concurrent chemotherapy and radiation therapy,CCRT)反应的预测价值。方法回顾性收集126例经病理活检证实的宫颈鳞癌患者DCE-MRI图像及临床资料,按照7∶3的比例随机分为训练组(n=88)和验证组(n=38)。使用3D-Slicer软件在两个靶区(VOI、VOI+5mm)提取影像组学特征,采用最大相关最小冗余(mRMR)及最小绝对收缩与选择算子(LASSO)算法进行特征筛选并构建影像组学标签。利用ROC曲线及决策曲线(DCA)分析评估影像组学标签的预测效能及临床应用价值。结果VOI+5mm瘤周影像组学标签在训练组和验证组中的AUC(分别为0.855和0.819)均高于VOI瘤内影像组学标签(分别为0.770和0.750),瘤内标签和瘤周标签在训练组中预测CCRT反应的敏感度和特异度分别为74.5%和70.7%、76.6%和82.9%,而在验证组中分别为60.0%和83.3%、80.0%和77.8%。DCA显示当阈值概率分别为0.06~0.71和0.01~1.00时,瘤内标签和瘤周标签的临床净收益最大。结论基于DCE-MRI的影像组学标签在预测进展期宫颈鳞癌CCRT反应方面有一定临床应用价值,瘤周影像组学特征对于提升预测效能具有很大潜力,可为宫颈癌患者优化诊疗策略及改善预后提供参考。
