Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of ...Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.展开更多
股骨头坏死(osteonecrosis of the femoral head,ONFH)是一种致残性骨科疾病,以进行性股骨头塌陷伴骨小梁、关节软骨结构破坏为病理特征,导致髋关节疼痛及进行性功能障碍。骨髓间充质干细胞来源细胞外囊泡(BMSC-derived exosomes,BMSC-E...股骨头坏死(osteonecrosis of the femoral head,ONFH)是一种致残性骨科疾病,以进行性股骨头塌陷伴骨小梁、关节软骨结构破坏为病理特征,导致髋关节疼痛及进行性功能障碍。骨髓间充质干细胞来源细胞外囊泡(BMSC-derived exosomes,BMSC-EVs)在组织修复和再生方面有良好的前景,免疫原性和致瘤性较低,影响成骨、成血管和免疫调节。本文综述了BMSC-EVs在ONFH中的治疗效果及其潜在机制,为ONFH的治疗提供理论依据。展开更多
背景:非创伤性股骨头坏死的发病机制尚不明确,其中血脂代谢紊乱是引起非创伤性股骨头坏死的重要假说,通过调节血脂代谢来抑制股骨头坏死的进展,已成为当前治疗非创伤性股骨头坏死的重要方法。目的:综述非创伤性股骨头坏死与脂质代谢紊...背景:非创伤性股骨头坏死的发病机制尚不明确,其中血脂代谢紊乱是引起非创伤性股骨头坏死的重要假说,通过调节血脂代谢来抑制股骨头坏死的进展,已成为当前治疗非创伤性股骨头坏死的重要方法。目的:综述非创伤性股骨头坏死与脂质代谢紊乱的关系及治疗研究进展。方法:以“股骨头坏死,非创伤性股骨头坏死,骨坏死,骨与脂质代谢,股骨头坏死与脂质,股骨头坏死机制,股骨头坏死通路,股骨头坏死治疗”为中文检索词,以“osteonecrosis of femoral head,Nontraumatic osteonecrosis of femoral head,femoral head necrosis,osteonecrosis and lipid,lipid metabolism osteonecrosis,polymorphisms osteonecrosis of femoral head,pathway osteonecrosis of femoral head,steroid-induced osteonecrosis of the femoral head,alcohol-induced osteonecrosis of femoral head”为英文检索词,检索中国知网、万方医学网、中华医学期刊数据库、PubMed数据库,最终纳入104篇文献进行归纳总结。结果与结论:①股骨头坏死患者常伴随血脂异常,研究发现总胆固醇、三酰甘油、低密度脂蛋白胆固醇、载脂蛋白B水平升高与载脂蛋白A1水平降低是引起股骨头坏死的危险因素,并且不同诱因的股骨头坏死患者血脂水平存在差异;②激素和酒精作为非创伤性股骨头坏死的两大诱因,可以诱导骨髓间充质干细胞的成脂分化,使骨髓腔内脂肪细胞增多、脂滴聚集,最终导致股骨头坏死;③许多与脂质代谢相关的分子和脂肪因子,如脂联素、瘦素、脂质运载蛋白2等都被证实与股骨头坏死有关;④过氧化物酶体增殖物激活受体γ、Wnt/β-catenin、腺苷酸环化蛋白激酶等信号通路可以改变骨髓间充质干细胞的成骨-成脂分化潜能,从而参与股骨头坏死的发生发展;磷脂酰肌醇3激酶/蛋白激酶B、骨形态发生蛋白2等脂代谢信号通路也与股骨头坏死有关,可能通过调节脂质代谢影响股骨头坏死的进展;⑤研究发现,虫草素、三七总皂苷、骨蚀灵胶囊等中药和他汀类药物可以通过改善脂质代谢紊乱达到治疗非创伤性股骨头坏死的效果。展开更多
It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1...It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1 evidence in the literature makes it difficult to identify optimal treatment protocols to manage patients with pre-collapse avascular necrosis of the femoral head, and early intervention prior to collapse is critical to successful outcomes in joint preserving procedures. There have been a variety of traumatic and atraumatic factors that have been identified as risk factors for osteonecrosis, but the etiology and pathogenesis still remains unclear. Current osteonecrosis diagnosis is dependent upon plain anteroposterior and frog-leg lateral radiographs of the hip, followed by magnetic resonance imaging(MRI). Generally, the first radiographic changes seen by radiograph will be cystic and sclerotic changes in the femoral head. Although the diagnosis may be made by radiograph, plain radiographs are generally insufficient for early diagnosis, therefore MRI is considered the most accurate benchmark. Treatment options include pharmacologic agents such as bisphosphonates and statins, biophysical treatments, as well as joint-preserving and joint-replacing surgeries. the surgical treatment of osteonecrosis of the femoral head can be divided into two major branches: femoral head sparing procedures(FHSP) and femoral head replacement procedures(FHRP). In general, FHSP are indicated at pre-collapse stages with minimal symptoms whereas FHRP are preferred at post-collapse symptomatic stages. It is difficult to know whether any treatment modality changes the natural history of core decompression since the true natural history of core decompression has not been delineated.展开更多
Cancer is one of the leading causes of death in America, and there is an urgent need for new therapeutic approaches. The progesterone receptor membrane component 1 (PGRMC1) is a cytochrome b5 related protein that bind...Cancer is one of the leading causes of death in America, and there is an urgent need for new therapeutic approaches. The progesterone receptor membrane component 1 (PGRMC1) is a cytochrome b5 related protein that binds heme and is associated with signaling, apoptotic suppression and autophagy. PGRMC1 is essential for tumor formation, invasion and metastasis, and is upregulated in breast, colon, lung and thyroid tumors. In the present study, we have analyzed PGRMC1 levels in over 600 tumor sections, including a larger cohort of lung tumors than in previous studies, and report the first clinical analysis of PGRMC1 levels in human oral cavity and ovarian tumors compared to corresponding nonmalignant tissues. PGRMC1 was highly expressed in lung and ovarian cancers and correlated with patient survival. PGRMC1 has been previously associated with drug resistance, a characteristic of cancer stem cells. The stem cell theory proposes that a subset of cancerous stem cells contribute to drug resistance and tumor maintenance, and PGRMC1 was detected in lung-tumor derived stem cells. Drug treatment with a PGRMC1 inhibitor, AG-205, triggered stem cell death whereas treatment with erlotinib and the ERK inhibitor, PD98059, did not, suggesting a specific role for PGRMC1 in cancer stem cell viability. Together, our data demonstrate PGRMC1 as a potential tumor biomarker across a variety of tumors, as well as a therapeutic target for cancer stem cells.展开更多
By co-culturing humm mesenchymal stem cells (hMSCs) and human umbilical rein endothelial cells (HUVECs) under hypoxia and creating a microenvironment similar to that of transplanted hMSCs for the treatment of avascula...By co-culturing humm mesenchymal stem cells (hMSCs) and human umbilical rein endothelial cells (HUVECs) under hypoxia and creating a microenvironment similar to that of transplanted hMSCs for the treatment of avascular ni ANFH, the effect of hMSCs on survival, apoptosis, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) under the hypoxic condition were investigated in vitro. hMSCs and HUVECs were cultured and identified in vitro. Three kinds of conditioned media, CdM-CdMNOR, CdM-CdMHYP and HUVEC-CdMHYP were prepared. HUVECs were cultured with these conditioned media under hypoxia. The survival rate, apoptosis rate, migration and angiogenesis of HUVECs were respectively detected by CCK-8, flow cytometry, Transwell and tube formation assay. The content of SDF-1α, VEGF and IL-6 in CdM was determined by ELISA. Our results showed that hMSCs and HUVECs were cultured and identified successfully. Compared with MSC-CdMNOR and HUVEC-CdMHYP groups, the survival rate, migra-tion and angiogenesis of HUVECs in MSC-CdMHYP group were significantly increased while the apoptosis rate was declined (P<0.05). Moreover, the expression of SDF-1α, VEGF and IL-6 in MSC-CdMHYP group was up-regulated. Under hypoxia, the apoptosis of HUVECs was inhibited while survival, migration and angiogenesis were improved by co-culture of hMSCs and HUVECs. The underlying mechanism may be that hMSCs could secrete a number of cytokines and improve niche, which might be helpful in the treatment of femoral head necrosis.展开更多
文摘Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.
文摘股骨头坏死(osteonecrosis of the femoral head,ONFH)是一种致残性骨科疾病,以进行性股骨头塌陷伴骨小梁、关节软骨结构破坏为病理特征,导致髋关节疼痛及进行性功能障碍。骨髓间充质干细胞来源细胞外囊泡(BMSC-derived exosomes,BMSC-EVs)在组织修复和再生方面有良好的前景,免疫原性和致瘤性较低,影响成骨、成血管和免疫调节。本文综述了BMSC-EVs在ONFH中的治疗效果及其潜在机制,为ONFH的治疗提供理论依据。
文摘背景:非创伤性股骨头坏死的发病机制尚不明确,其中血脂代谢紊乱是引起非创伤性股骨头坏死的重要假说,通过调节血脂代谢来抑制股骨头坏死的进展,已成为当前治疗非创伤性股骨头坏死的重要方法。目的:综述非创伤性股骨头坏死与脂质代谢紊乱的关系及治疗研究进展。方法:以“股骨头坏死,非创伤性股骨头坏死,骨坏死,骨与脂质代谢,股骨头坏死与脂质,股骨头坏死机制,股骨头坏死通路,股骨头坏死治疗”为中文检索词,以“osteonecrosis of femoral head,Nontraumatic osteonecrosis of femoral head,femoral head necrosis,osteonecrosis and lipid,lipid metabolism osteonecrosis,polymorphisms osteonecrosis of femoral head,pathway osteonecrosis of femoral head,steroid-induced osteonecrosis of the femoral head,alcohol-induced osteonecrosis of femoral head”为英文检索词,检索中国知网、万方医学网、中华医学期刊数据库、PubMed数据库,最终纳入104篇文献进行归纳总结。结果与结论:①股骨头坏死患者常伴随血脂异常,研究发现总胆固醇、三酰甘油、低密度脂蛋白胆固醇、载脂蛋白B水平升高与载脂蛋白A1水平降低是引起股骨头坏死的危险因素,并且不同诱因的股骨头坏死患者血脂水平存在差异;②激素和酒精作为非创伤性股骨头坏死的两大诱因,可以诱导骨髓间充质干细胞的成脂分化,使骨髓腔内脂肪细胞增多、脂滴聚集,最终导致股骨头坏死;③许多与脂质代谢相关的分子和脂肪因子,如脂联素、瘦素、脂质运载蛋白2等都被证实与股骨头坏死有关;④过氧化物酶体增殖物激活受体γ、Wnt/β-catenin、腺苷酸环化蛋白激酶等信号通路可以改变骨髓间充质干细胞的成骨-成脂分化潜能,从而参与股骨头坏死的发生发展;磷脂酰肌醇3激酶/蛋白激酶B、骨形态发生蛋白2等脂代谢信号通路也与股骨头坏死有关,可能通过调节脂质代谢影响股骨头坏死的进展;⑤研究发现,虫草素、三七总皂苷、骨蚀灵胶囊等中药和他汀类药物可以通过改善脂质代谢紊乱达到治疗非创伤性股骨头坏死的效果。
文摘It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1 evidence in the literature makes it difficult to identify optimal treatment protocols to manage patients with pre-collapse avascular necrosis of the femoral head, and early intervention prior to collapse is critical to successful outcomes in joint preserving procedures. There have been a variety of traumatic and atraumatic factors that have been identified as risk factors for osteonecrosis, but the etiology and pathogenesis still remains unclear. Current osteonecrosis diagnosis is dependent upon plain anteroposterior and frog-leg lateral radiographs of the hip, followed by magnetic resonance imaging(MRI). Generally, the first radiographic changes seen by radiograph will be cystic and sclerotic changes in the femoral head. Although the diagnosis may be made by radiograph, plain radiographs are generally insufficient for early diagnosis, therefore MRI is considered the most accurate benchmark. Treatment options include pharmacologic agents such as bisphosphonates and statins, biophysical treatments, as well as joint-preserving and joint-replacing surgeries. the surgical treatment of osteonecrosis of the femoral head can be divided into two major branches: femoral head sparing procedures(FHSP) and femoral head replacement procedures(FHRP). In general, FHSP are indicated at pre-collapse stages with minimal symptoms whereas FHRP are preferred at post-collapse symptomatic stages. It is difficult to know whether any treatment modality changes the natural history of core decompression since the true natural history of core decompression has not been delineated.
文摘Cancer is one of the leading causes of death in America, and there is an urgent need for new therapeutic approaches. The progesterone receptor membrane component 1 (PGRMC1) is a cytochrome b5 related protein that binds heme and is associated with signaling, apoptotic suppression and autophagy. PGRMC1 is essential for tumor formation, invasion and metastasis, and is upregulated in breast, colon, lung and thyroid tumors. In the present study, we have analyzed PGRMC1 levels in over 600 tumor sections, including a larger cohort of lung tumors than in previous studies, and report the first clinical analysis of PGRMC1 levels in human oral cavity and ovarian tumors compared to corresponding nonmalignant tissues. PGRMC1 was highly expressed in lung and ovarian cancers and correlated with patient survival. PGRMC1 has been previously associated with drug resistance, a characteristic of cancer stem cells. The stem cell theory proposes that a subset of cancerous stem cells contribute to drug resistance and tumor maintenance, and PGRMC1 was detected in lung-tumor derived stem cells. Drug treatment with a PGRMC1 inhibitor, AG-205, triggered stem cell death whereas treatment with erlotinib and the ERK inhibitor, PD98059, did not, suggesting a specific role for PGRMC1 in cancer stem cell viability. Together, our data demonstrate PGRMC1 as a potential tumor biomarker across a variety of tumors, as well as a therapeutic target for cancer stem cells.
基金supported by agrant from the National Natural Sciences Foundation of China(No.30750010)
文摘By co-culturing humm mesenchymal stem cells (hMSCs) and human umbilical rein endothelial cells (HUVECs) under hypoxia and creating a microenvironment similar to that of transplanted hMSCs for the treatment of avascular ni ANFH, the effect of hMSCs on survival, apoptosis, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) under the hypoxic condition were investigated in vitro. hMSCs and HUVECs were cultured and identified in vitro. Three kinds of conditioned media, CdM-CdMNOR, CdM-CdMHYP and HUVEC-CdMHYP were prepared. HUVECs were cultured with these conditioned media under hypoxia. The survival rate, apoptosis rate, migration and angiogenesis of HUVECs were respectively detected by CCK-8, flow cytometry, Transwell and tube formation assay. The content of SDF-1α, VEGF and IL-6 in CdM was determined by ELISA. Our results showed that hMSCs and HUVECs were cultured and identified successfully. Compared with MSC-CdMNOR and HUVEC-CdMHYP groups, the survival rate, migra-tion and angiogenesis of HUVECs in MSC-CdMHYP group were significantly increased while the apoptosis rate was declined (P<0.05). Moreover, the expression of SDF-1α, VEGF and IL-6 in MSC-CdMHYP group was up-regulated. Under hypoxia, the apoptosis of HUVECs was inhibited while survival, migration and angiogenesis were improved by co-culture of hMSCs and HUVECs. The underlying mechanism may be that hMSCs could secrete a number of cytokines and improve niche, which might be helpful in the treatment of femoral head necrosis.
