Accumulation of lactate in tumor has been linked to poor prognosis of oral squamous cell carcinoma (OSCC), but the underlying mechanism remained largely uncertain. Previous studies have suggested that presence of canc...Accumulation of lactate in tumor has been linked to poor prognosis of oral squamous cell carcinoma (OSCC), but the underlying mechanism remained largely uncertain. Previous studies have suggested that presence of cancer stem cells (CSCs) closely correlated with cellular malignancy of OSCC. Here, using 3D organoid culture model, we investigated whether lactate promoted CSCs phenotype in primary OSCC cells. We generated organoids using fresh OSCC specimens and verified that organoids recapitulated histopathology and cellular heterogeneity of parental tumor;Organoids were then transfected with a Wnt reporter to visualize Wnt activity. The sphere forming assay demonstrated that high Wnt activity functionally designated CSCs population in OSCC cells. Further investigations indicated that lactate treatment promoted Wnt activity and increased the expression of CSCs (i.e. CD133^+ cells) in organoids. Moreover, silencing monocarboxylate transporter 1 (MCT1), the prominent path for lactate uptake in human tumor with siRNA significantly impaired organoid forming capacity of OSCC cells. Together, our study demonstrated that lactate can promote CSCs phenotype of OSCC,and MCT1 may be a therapeutic target against OSCC growth.展开更多
6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), an enzyme producing fructose 2, 6-bisphosphate (F-2, 6-BP), serves as a switch to activate phosphofructokinase-1, and is a critical enzyme for endotheli...6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), an enzyme producing fructose 2, 6-bisphosphate (F-2, 6-BP), serves as a switch to activate phosphofructokinase-1, and is a critical enzyme for endothelial glycolysis, mediating circadian control of carcinogenesis. Also, tumor-associated macrophages (TAMs) play an important role in the progression and prognosis of numerous cancers. However, the role and clinical significance of PFKFB3 and TAMs in oral squamous cell carcinoma (OSCC) have not been elucidated. The present study was designed to investigate the correlation between PFKFB3 expression, CD 163+ TAMs infiltration and tumor angiogenesis in OSCC by tissue microarray. Tissue microarrays containing 117 OSCC specimens and 56 matched paracarcinoma tissues were studied by immunohistochemistry. The expression levels of PFKFB3, CD163 and CD31 were significantly increased in OSCC specimens as compared with normal oral mucosa (P<0.05), and PFKFB was significantly correlated with tumor differentiation and tumor size (P<0.05), and CD 163 was significantly correlated with areca nut chewing habit among OSCC tissues (P<0.05). Furthermore, Pearson's correlation analysis revealed that PFKFB3 was significantly correlated with both CD 163 and CD31 (P<0.05), meanwhile CD 163 was significantly correlated with CD31 (P<0.001), suggesting PFKFB3 may promote angiogenesis in tumor progression and metastases by regulating CD 163+ TAMs infiltration in OSCC.展开更多
The study aimed to retrospectively evaluate surgical treatment outcomes after delayed parotid gland and duct injuries. Nine patients subjected to parotid gland and duct injuries with l- to 3-month treatment delay were...The study aimed to retrospectively evaluate surgical treatment outcomes after delayed parotid gland and duct injuries. Nine patients subjected to parotid gland and duct injuries with l- to 3-month treatment delay were retrospectively evaluated with special reference of etiology, past medical history, and injury location. Conservative treatment, microsurgical anastomosis, and diversion of salivary flow or ligation were chosen for delayed parotid gland and duct injuries concerning to their site of injury, time of repair and procedures. Assistant treatment as pressure dressing was adopted thereafter. All patients experienced an uneventful recovery at the time of finalizing the study. Two patients received Stensen's duct ligation, 5 received microsurgical anastomosis and 2 accepted salivary flow diversion for 5 patients with sialoceles and 4 patients with fistulas, and no re-occurrence was found. Facial paralysis occurred after surgery in 4 patients, and 3 of them recovered after the nerve nutrition treatment. Our study suggested that appropriate surgical treatment is efficient for the re-establishment of the tissue function and facial aesthetic for delayed injury of the parotid and its duct.展开更多
BACKGROUND Sclerosing polycystic adenosis(SPA)is a rare disease of salivary glands,similar to fibrocystic disease of the breast.It occurs over a wide age range and exhibits a slight female preference.Most SPA cases ha...BACKGROUND Sclerosing polycystic adenosis(SPA)is a rare disease of salivary glands,similar to fibrocystic disease of the breast.It occurs over a wide age range and exhibits a slight female preference.Most SPA cases have occurred in the parotid gland.The exact nature of SPA is unclear,but its tumor nature has recently been proposed.Although SPA has a good prognosis after adequate surgery,atypical lesions might occur,ranging from mild dysplasia to carcinoma in situ in some cases.To the best of our knowledge,only five cases of SPA in the submandibular gland have been reported to date.Here,we present two new cases of SPA involving the submandibular gland.CASE SUMMARY A 50-year-old woman and a 52-year-old woman were referred to Tongji Hospital in Wuhan,China,with complaints of moderate pain,recurrent swelling,and a mass in the submandibular area.After admission,the two cases of the submandibular mass were examined physically.The boundary of the submandibular tumor was clear,and the range of motion was good.After preoperative examinations,surgery was performed on a selective basis.Postoperative histopathological examination revealed a well-defined mass with acinar structures,ducts,or cystic dilated glands of various sizes scattered in a large number of proliferative sclerosing stroma.There were flat and cuboidal cells,and eosinophils in the duct epithelium.There was also a eosinophilic substance in the lumen of dilated cysts.No atypical epithelial hyperplasia,invasive growth,or carcinoma in situ was found.Based on the above findings,the mass was diagnosed as SPA.Both patients have remained asymptomatic and no recurrence or distant metastasis had occurred by the 7-mo and 5-year follow-up,respectively.CONCLUSIONSPA is a rare disease of the salivary gland. Even though it has a good prognosisafter adequate surgery, atypical lesions may occur from mild dysplasia tocarcinoma in situ. However, no recurrence, distant metastasis, or mortality hasbeen reported for submandibular gland SPA. Clinicians and pathologists shouldbe familiar with the characteristics of SPA in the submandibular gland to avoidmisdiagnosis and overtreatment.展开更多
目的放射性骨坏死是头颈癌放疗后的一种严重并发症,严重影响头颈癌幸存者的生活质量,增加患者经济负担。目前,在世界范围内有关放射性骨坏死的预防和管理缺乏专门的指南,本研究针对这一问题进行最佳证据汇总,以期为临床实践提供参考。...目的放射性骨坏死是头颈癌放疗后的一种严重并发症,严重影响头颈癌幸存者的生活质量,增加患者经济负担。目前,在世界范围内有关放射性骨坏死的预防和管理缺乏专门的指南,本研究针对这一问题进行最佳证据汇总,以期为临床实践提供参考。方法系统检索中国知网、维普、万方、中国生物医学文献数据库、PubMed、Web of Science、Cochrane Library、Cinahl数据库,国内外指南数据库以及相关专业学会组织官网以获取相关的证据,包括指南、专家共识及系统评价。检索时间为建库至2020年6月18日。采用相应的质量评价工具评价纳入的文献,汇总有关放射性骨坏死预防和管理的最佳证据。结果最终纳入11篇文献,包括6篇指南,3篇专家共识,2篇系统评价。纳入文献的方法学质量总体较高。研究者总结了放射性骨坏死(Osteoradionecrosis,ORN)的危险因素(包括患者因素、肿瘤因素和放疗相关因素),放疗前(外科预防、口腔卫生教育、牙科检查和处理)、放疗中(口腔和牙齿监测、放疗注意事项)、放疗后(口腔和牙齿随访监测、龋齿和牙周疾病的预防以及放疗后拔牙注意事项)ORN的预防以及ORN的管理(影像学检查、保守治疗、手术治疗以及下颌骨ORN的疗效评价)。针对尚存争议的高压氧治疗,现有证据不推荐单独或常规使用高压氧治疗。结论本研究总结了头颈癌患者预防和管理放射性骨坏死的最佳证据,强调了口腔卫生教育、口腔和牙齿监测、积极预防和治疗龋病及牙周病在ORN预防方面的重要性,在放疗方式的选择上推荐调强放疗以减少靶区辐射剂量,在ORN的治疗方面主要包括保守治疗和手术治疗。然而,本研究汇总的证据也存在一定的局限性,在实际临床应用中医务人员应结合具体情况综合考虑。展开更多
Background:Data on the incidence,mortality,and other burden of oral cancer as well as their secular trends are necessary to provide policy-makers with the information needed to allocate resources appropriately.The pur...Background:Data on the incidence,mortality,and other burden of oral cancer as well as their secular trends are necessary to provide policy-makers with the information needed to allocate resources appropriately.The purpose of this study was to use the Global Burden of Disease(GBD)2017 results to estimate the incidence,mortality,and disability-adjusted life years(DALYs)for oral cancer from 1990 to 2017.Methods:We collected detailed data on oral cancer from 1990 to 2017 from the GBD 2017.The global incidence,mortality,and DALYs attributable to oral cancer as well as the corresponding age-standardized rates(ASRs)were calculated.The estimated annual percentage changes in the ASRs of incidence(ASRI)and mortality(ASRM)and age-standardized DALYs of oral cancer were also calculated according to regions and countries to quantify the secular trends in these rates.Results:We tracked the incidence,mortality,and DALYs of oral cancer in 195 countries/territories over 28 years.Globally,the incidence,mortality,and DALYs of oral cancer increased by about 1.0-fold from 1990 to 2017.The ASRI of oral cancer showed a similar trend,increasing from 4.41 to 4.84 per 100,000 person-years during the study period.The ASRM remained approximately stable at about 2.4 per 100,000 from 1990 to 2017,as did the age-standardized DALYs,at about 64.0 per 100,000 person-years.ASRI was highest in Pakistan(27.03/100,000,95%CI=22.13-32.75/100,000),followed by Taiwan China,and lowest in Iraq(0.96/100,000,95%CI=0.86-1.06/100,000).ASRM was highest in Pakistan(16.85/100,000,95%CI=13.92-20.17/100,000)and lowest in Kuwait(0.51/100,000,95%CI=0.45-0.58/100,000).Conclusions:The ASRI of oral cancer has increased slightly worldwide,while the ASRM and age-standardized DALY have remained stable.However,these characteristics vary between countries,suggesting that current prevention strategies should be reoriented,and much more targeted and specific strategies should be established in some countries to forestall the increase in oral cancer.展开更多
基金This project was supported by the National Natural Science Foundation of China (No.81602742).
文摘Accumulation of lactate in tumor has been linked to poor prognosis of oral squamous cell carcinoma (OSCC), but the underlying mechanism remained largely uncertain. Previous studies have suggested that presence of cancer stem cells (CSCs) closely correlated with cellular malignancy of OSCC. Here, using 3D organoid culture model, we investigated whether lactate promoted CSCs phenotype in primary OSCC cells. We generated organoids using fresh OSCC specimens and verified that organoids recapitulated histopathology and cellular heterogeneity of parental tumor;Organoids were then transfected with a Wnt reporter to visualize Wnt activity. The sphere forming assay demonstrated that high Wnt activity functionally designated CSCs population in OSCC cells. Further investigations indicated that lactate treatment promoted Wnt activity and increased the expression of CSCs (i.e. CD133^+ cells) in organoids. Moreover, silencing monocarboxylate transporter 1 (MCT1), the prominent path for lactate uptake in human tumor with siRNA significantly impaired organoid forming capacity of OSCC cells. Together, our study demonstrated that lactate can promote CSCs phenotype of OSCC,and MCT1 may be a therapeutic target against OSCC growth.
基金This study was supported by the National Natural Science Foundation of China (No.81702708 and No.81873717).
文摘6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), an enzyme producing fructose 2, 6-bisphosphate (F-2, 6-BP), serves as a switch to activate phosphofructokinase-1, and is a critical enzyme for endothelial glycolysis, mediating circadian control of carcinogenesis. Also, tumor-associated macrophages (TAMs) play an important role in the progression and prognosis of numerous cancers. However, the role and clinical significance of PFKFB3 and TAMs in oral squamous cell carcinoma (OSCC) have not been elucidated. The present study was designed to investigate the correlation between PFKFB3 expression, CD 163+ TAMs infiltration and tumor angiogenesis in OSCC by tissue microarray. Tissue microarrays containing 117 OSCC specimens and 56 matched paracarcinoma tissues were studied by immunohistochemistry. The expression levels of PFKFB3, CD163 and CD31 were significantly increased in OSCC specimens as compared with normal oral mucosa (P<0.05), and PFKFB was significantly correlated with tumor differentiation and tumor size (P<0.05), and CD 163 was significantly correlated with areca nut chewing habit among OSCC tissues (P<0.05). Furthermore, Pearson's correlation analysis revealed that PFKFB3 was significantly correlated with both CD 163 and CD31 (P<0.05), meanwhile CD 163 was significantly correlated with CD31 (P<0.001), suggesting PFKFB3 may promote angiogenesis in tumor progression and metastases by regulating CD 163+ TAMs infiltration in OSCC.
基金This project was supported by the National Natural Science Foundation of China (No. 81372879, No. 81672666).
文摘The study aimed to retrospectively evaluate surgical treatment outcomes after delayed parotid gland and duct injuries. Nine patients subjected to parotid gland and duct injuries with l- to 3-month treatment delay were retrospectively evaluated with special reference of etiology, past medical history, and injury location. Conservative treatment, microsurgical anastomosis, and diversion of salivary flow or ligation were chosen for delayed parotid gland and duct injuries concerning to their site of injury, time of repair and procedures. Assistant treatment as pressure dressing was adopted thereafter. All patients experienced an uneventful recovery at the time of finalizing the study. Two patients received Stensen's duct ligation, 5 received microsurgical anastomosis and 2 accepted salivary flow diversion for 5 patients with sialoceles and 4 patients with fistulas, and no re-occurrence was found. Facial paralysis occurred after surgery in 4 patients, and 3 of them recovered after the nerve nutrition treatment. Our study suggested that appropriate surgical treatment is efficient for the re-establishment of the tissue function and facial aesthetic for delayed injury of the parotid and its duct.
基金National Natural Science Foundation of China,No.82002893.
文摘BACKGROUND Sclerosing polycystic adenosis(SPA)is a rare disease of salivary glands,similar to fibrocystic disease of the breast.It occurs over a wide age range and exhibits a slight female preference.Most SPA cases have occurred in the parotid gland.The exact nature of SPA is unclear,but its tumor nature has recently been proposed.Although SPA has a good prognosis after adequate surgery,atypical lesions might occur,ranging from mild dysplasia to carcinoma in situ in some cases.To the best of our knowledge,only five cases of SPA in the submandibular gland have been reported to date.Here,we present two new cases of SPA involving the submandibular gland.CASE SUMMARY A 50-year-old woman and a 52-year-old woman were referred to Tongji Hospital in Wuhan,China,with complaints of moderate pain,recurrent swelling,and a mass in the submandibular area.After admission,the two cases of the submandibular mass were examined physically.The boundary of the submandibular tumor was clear,and the range of motion was good.After preoperative examinations,surgery was performed on a selective basis.Postoperative histopathological examination revealed a well-defined mass with acinar structures,ducts,or cystic dilated glands of various sizes scattered in a large number of proliferative sclerosing stroma.There were flat and cuboidal cells,and eosinophils in the duct epithelium.There was also a eosinophilic substance in the lumen of dilated cysts.No atypical epithelial hyperplasia,invasive growth,or carcinoma in situ was found.Based on the above findings,the mass was diagnosed as SPA.Both patients have remained asymptomatic and no recurrence or distant metastasis had occurred by the 7-mo and 5-year follow-up,respectively.CONCLUSIONSPA is a rare disease of the salivary gland. Even though it has a good prognosisafter adequate surgery, atypical lesions may occur from mild dysplasia tocarcinoma in situ. However, no recurrence, distant metastasis, or mortality hasbeen reported for submandibular gland SPA. Clinicians and pathologists shouldbe familiar with the characteristics of SPA in the submandibular gland to avoidmisdiagnosis and overtreatment.
文摘目的放射性骨坏死是头颈癌放疗后的一种严重并发症,严重影响头颈癌幸存者的生活质量,增加患者经济负担。目前,在世界范围内有关放射性骨坏死的预防和管理缺乏专门的指南,本研究针对这一问题进行最佳证据汇总,以期为临床实践提供参考。方法系统检索中国知网、维普、万方、中国生物医学文献数据库、PubMed、Web of Science、Cochrane Library、Cinahl数据库,国内外指南数据库以及相关专业学会组织官网以获取相关的证据,包括指南、专家共识及系统评价。检索时间为建库至2020年6月18日。采用相应的质量评价工具评价纳入的文献,汇总有关放射性骨坏死预防和管理的最佳证据。结果最终纳入11篇文献,包括6篇指南,3篇专家共识,2篇系统评价。纳入文献的方法学质量总体较高。研究者总结了放射性骨坏死(Osteoradionecrosis,ORN)的危险因素(包括患者因素、肿瘤因素和放疗相关因素),放疗前(外科预防、口腔卫生教育、牙科检查和处理)、放疗中(口腔和牙齿监测、放疗注意事项)、放疗后(口腔和牙齿随访监测、龋齿和牙周疾病的预防以及放疗后拔牙注意事项)ORN的预防以及ORN的管理(影像学检查、保守治疗、手术治疗以及下颌骨ORN的疗效评价)。针对尚存争议的高压氧治疗,现有证据不推荐单独或常规使用高压氧治疗。结论本研究总结了头颈癌患者预防和管理放射性骨坏死的最佳证据,强调了口腔卫生教育、口腔和牙齿监测、积极预防和治疗龋病及牙周病在ORN预防方面的重要性,在放疗方式的选择上推荐调强放疗以减少靶区辐射剂量,在ORN的治疗方面主要包括保守治疗和手术治疗。然而,本研究汇总的证据也存在一定的局限性,在实际临床应用中医务人员应结合具体情况综合考虑。
基金This study was supported by The Interdisciplinary Program of Shanghai Jiao Tong University(ZH2018QNA08)(Zhang Zhiyuan)Academician Workstation Scientific Research Fund(2019)+2 种基金The SHIPM-mu fund No.JC201902 from the Shanghai Institute of Precision Medicine,Ninth People’s Hospital Shanghai Jiao Tong University School of MedicineThe Shanghai Anticancer Association Eyas Project(SACA-CY1B06)the National Social Science Foundation of China(No.16BGL183).
文摘Background:Data on the incidence,mortality,and other burden of oral cancer as well as their secular trends are necessary to provide policy-makers with the information needed to allocate resources appropriately.The purpose of this study was to use the Global Burden of Disease(GBD)2017 results to estimate the incidence,mortality,and disability-adjusted life years(DALYs)for oral cancer from 1990 to 2017.Methods:We collected detailed data on oral cancer from 1990 to 2017 from the GBD 2017.The global incidence,mortality,and DALYs attributable to oral cancer as well as the corresponding age-standardized rates(ASRs)were calculated.The estimated annual percentage changes in the ASRs of incidence(ASRI)and mortality(ASRM)and age-standardized DALYs of oral cancer were also calculated according to regions and countries to quantify the secular trends in these rates.Results:We tracked the incidence,mortality,and DALYs of oral cancer in 195 countries/territories over 28 years.Globally,the incidence,mortality,and DALYs of oral cancer increased by about 1.0-fold from 1990 to 2017.The ASRI of oral cancer showed a similar trend,increasing from 4.41 to 4.84 per 100,000 person-years during the study period.The ASRM remained approximately stable at about 2.4 per 100,000 from 1990 to 2017,as did the age-standardized DALYs,at about 64.0 per 100,000 person-years.ASRI was highest in Pakistan(27.03/100,000,95%CI=22.13-32.75/100,000),followed by Taiwan China,and lowest in Iraq(0.96/100,000,95%CI=0.86-1.06/100,000).ASRM was highest in Pakistan(16.85/100,000,95%CI=13.92-20.17/100,000)and lowest in Kuwait(0.51/100,000,95%CI=0.45-0.58/100,000).Conclusions:The ASRI of oral cancer has increased slightly worldwide,while the ASRM and age-standardized DALY have remained stable.However,these characteristics vary between countries,suggesting that current prevention strategies should be reoriented,and much more targeted and specific strategies should be established in some countries to forestall the increase in oral cancer.