Objective： To determine the clinicopathological characteristics, and evaluate the appropriate extent of lymph node dissection in distal gastric cancer patients with comparable T category. Methods： A retrospective st...Objective： To determine the clinicopathological characteristics, and evaluate the appropriate extent of lymph node dissection in distal gastric cancer patients with comparable T category. Methods： A retrospective study was conducted on 570 distal gastric cancer patients, who underwent gastric resection with D2 nodal dissection, which was performed by the same surgical team from January 1997 to January 2011. We compared the differences in lymph node metastasis rates and metastatic lymph node ratios between different T categories. Additionally, we investigated the impact of lymph node metastasis in the 7th station on survival rate of distal gastric cancer patients with the same TNM staging. Results： Among the 570 patients, the overall lymph node metastasis rate of advanced distal gastric cancer was 78.1%, and the metastatic lymph node ratio was 27%. The lymph node metastasis rate in the 7th station was similar to that of perigastric lymph nodes. There was no statistical significance in patients with the same TNM stage （stage Ⅱ and Ⅲ）, irrespective of the metastatic status in the 7th station. Conclusions： Our results suggest that to a certain extent, it is reasonable to include lymph nodes in the 7th station in the D 1 lymph node dissection.展开更多
Organ-specific metastasis is the primary cause of cancer patient death.The distant metastasis of tumor cells to specific organs depends on both the intrinsic characteristics of the tumor cells and extrinsic factors in...Organ-specific metastasis is the primary cause of cancer patient death.The distant metastasis of tumor cells to specific organs depends on both the intrinsic characteristics of the tumor cells and extrinsic factors in their microenvironment.During an intermediate stage of metastasis,circulating tumor cells(CTCs)are released into the bloodstream from primary and metastatic tumors.CTCs harboring aggressive or metastatic features can extravasate to remote sites for continuous colonizing growth,leading to further lesions.In the past decade,numerous studies demonstrated that CTCs exhibited huge clinical value including predicting distant metastasis,assessing prognosis and monitoring treatment response et al.Furthermore,increasingly numerous experiments are dedicated to identifying the key molecules on or inside CTCs and exploring how they mediate CTC-related organ-specific metastasis.Based on the above molecules,more and more inhibitors are being developed to target CTCs and being utilized to completely clean CTCs,which should provide promising prospects to administer advanced tumor.Recently,the application of various nanomaterials and microfluidic technologies in CTCs enrichment technology has assisted to improve our deep insights into the phenotypic characteristics and biological functions of CTCs as a potential therapy target,which may pave the way for us to make practical clinical strategies.In the present review,we mainly focus on the role of CTCs being involved in targeted organ metastasis,especially the latest molecular mechanism research and clinical intervention strategies related to CTCs.展开更多
KRAS-TP53 co-mutation is strongly associated with poor prognosis and high malignancy in gastrointestinal cancers.Therefore,a novel approach to oncotherapy may lie in combination therapy targeting both KRAS and TP53.He...KRAS-TP53 co-mutation is strongly associated with poor prognosis and high malignancy in gastrointestinal cancers.Therefore,a novel approach to oncotherapy may lie in combination therapy targeting both KRAS and TP53.Herein,we present a novel self-assembled nanoparticle(HA-TPP/A)that are functionalized nano-carrier hyaluronic acid(HA)-TPP conjugate(HA-TPP)to degrade mutant p53 proteins(mutp53)and co-deliver AMG510 for treating KRAS-TP53 co-alteration of gastrointestinal cancers by inhibiting the mutant KRAS and mutp53 signaling pathways.The HA-TPP/A nanoparticles led to ubiquitination-dependent proteasomal degradation of mutp53 by targeting damage to mitochondria.Furthermore,these nanoparticles abrogated the gain-of-function(GOF)phenotypes of mutp53 and increased sensitivity to AMG510-induced cell killing,thereby reducing cell proliferation and migration in gastrointestinal cancer with KRAS-TP53 co-mutation.The co-loaded HA-TPP/A nanoparticles demonstrated remarkable therapeutic efficacy in a tumor-bearing mouse model,particularly in KRAS-TP53 double mutant expressing cancer cells,compared with single drug and combined free drug groups.Notably,HA-TPP/A is the first reported nanoparticle with an ability to co-target KRAS-TP53,providing a promising approach for therapy in highly malignant gastrointestinal tumors and potentially expanding clinical indications for AMG510 targeted therapies in gastrointestinal tumors.展开更多
文摘Objective： To determine the clinicopathological characteristics, and evaluate the appropriate extent of lymph node dissection in distal gastric cancer patients with comparable T category. Methods： A retrospective study was conducted on 570 distal gastric cancer patients, who underwent gastric resection with D2 nodal dissection, which was performed by the same surgical team from January 1997 to January 2011. We compared the differences in lymph node metastasis rates and metastatic lymph node ratios between different T categories. Additionally, we investigated the impact of lymph node metastasis in the 7th station on survival rate of distal gastric cancer patients with the same TNM staging. Results： Among the 570 patients, the overall lymph node metastasis rate of advanced distal gastric cancer was 78.1%, and the metastatic lymph node ratio was 27%. The lymph node metastasis rate in the 7th station was similar to that of perigastric lymph nodes. There was no statistical significance in patients with the same TNM stage （stage Ⅱ and Ⅲ）, irrespective of the metastatic status in the 7th station. Conclusions： Our results suggest that to a certain extent, it is reasonable to include lymph nodes in the 7th station in the D 1 lymph node dissection.
基金supported by grants from the National Natural Science Foundation of China(82330065,30900650,81372501,81572260,81172232,and 31430030)the Guangzhou or Guangdong Science and Technology Planning Program(2023B1111020005,2023B03J0106,2021B1212040017,20170402094,2018A050506036 and 2020B1515120032).
文摘Organ-specific metastasis is the primary cause of cancer patient death.The distant metastasis of tumor cells to specific organs depends on both the intrinsic characteristics of the tumor cells and extrinsic factors in their microenvironment.During an intermediate stage of metastasis,circulating tumor cells(CTCs)are released into the bloodstream from primary and metastatic tumors.CTCs harboring aggressive or metastatic features can extravasate to remote sites for continuous colonizing growth,leading to further lesions.In the past decade,numerous studies demonstrated that CTCs exhibited huge clinical value including predicting distant metastasis,assessing prognosis and monitoring treatment response et al.Furthermore,increasingly numerous experiments are dedicated to identifying the key molecules on or inside CTCs and exploring how they mediate CTC-related organ-specific metastasis.Based on the above molecules,more and more inhibitors are being developed to target CTCs and being utilized to completely clean CTCs,which should provide promising prospects to administer advanced tumor.Recently,the application of various nanomaterials and microfluidic technologies in CTCs enrichment technology has assisted to improve our deep insights into the phenotypic characteristics and biological functions of CTCs as a potential therapy target,which may pave the way for us to make practical clinical strategies.In the present review,we mainly focus on the role of CTCs being involved in targeted organ metastasis,especially the latest molecular mechanism research and clinical intervention strategies related to CTCs.
基金supported by the National Key Research and Development Plan(2022YFC3401000)National Natural Science Foundation of China(81871994,82022037,T2222014 and 32071398)+2 种基金Guangdong Provincial Natural Science Foundation(2019B151502063)Guangdong Basic and Applied Basic Research Foundation(2021B1515230009)Key Research and Development Plan of Guangdong Province(2020B0101030006,2020B1515120096 and 2022B0202010002).
文摘KRAS-TP53 co-mutation is strongly associated with poor prognosis and high malignancy in gastrointestinal cancers.Therefore,a novel approach to oncotherapy may lie in combination therapy targeting both KRAS and TP53.Herein,we present a novel self-assembled nanoparticle(HA-TPP/A)that are functionalized nano-carrier hyaluronic acid(HA)-TPP conjugate(HA-TPP)to degrade mutant p53 proteins(mutp53)and co-deliver AMG510 for treating KRAS-TP53 co-alteration of gastrointestinal cancers by inhibiting the mutant KRAS and mutp53 signaling pathways.The HA-TPP/A nanoparticles led to ubiquitination-dependent proteasomal degradation of mutp53 by targeting damage to mitochondria.Furthermore,these nanoparticles abrogated the gain-of-function(GOF)phenotypes of mutp53 and increased sensitivity to AMG510-induced cell killing,thereby reducing cell proliferation and migration in gastrointestinal cancer with KRAS-TP53 co-mutation.The co-loaded HA-TPP/A nanoparticles demonstrated remarkable therapeutic efficacy in a tumor-bearing mouse model,particularly in KRAS-TP53 double mutant expressing cancer cells,compared with single drug and combined free drug groups.Notably,HA-TPP/A is the first reported nanoparticle with an ability to co-target KRAS-TP53,providing a promising approach for therapy in highly malignant gastrointestinal tumors and potentially expanding clinical indications for AMG510 targeted therapies in gastrointestinal tumors.
