Epithelial-mesenchymal transition(EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells(CSCs) but also direct them across the ...Epithelial-mesenchymal transition(EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells(CSCs) but also direct them across the multiple organ systems to promote tumor recurrence and metastasis. CSCs are reported to express stem cell genes as well as specific cell surfacemarkers and allow aberrant differentiation of progenies.It facilitates cancer cells to leave primary tumor, acquire migratory characteristics, grow into new environment and develop radio-chemo-resistance. Based on the current information, present review discusses and summarizes the recent advancements on the molecular mechanisms that derive epithelial plasticity and its major role in generating a subset of tumor cells with stemness properties and pathophysiological spread of tumor. This paper further highlights the critical need to examine the regulation of EMT and CSC pathways in identifying the novel probable therapeutic targets.These improved therapeutic strategies based on the co-administration of inhibitors of EMT, CSCs as well as differentiated tumor cells may provide improved antineoplastic response with no tumor relapse.展开更多
Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumo...Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumor relapse is thought to be caused by the presence of these cells.CSC-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional therapies.Additionally,the metabolic properties of cancer cells differ markedly from those of normal cells.The efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer cells.Metabolic targeting of breast CSCs(BCSCs)may be a very effective strategy for anti-cancer treatment of breast cancer cells.Thus,in this review,we focus on discussing the studies involving metabolism and targeted therapy in BCSCs.展开更多
BACKGROUND The clinical presentation of acute lymphoblastic lymphoma is highly varied.While prognosis is good, recurrence of disease can occur. Gastrointestinal relapse, including intussusception, is well-described bu...BACKGROUND The clinical presentation of acute lymphoblastic lymphoma is highly varied.While prognosis is good, recurrence of disease can occur. Gastrointestinal relapse, including intussusception, is well-described but the absence of abdominal pain in this setting is rare.CASE SUMMARY We report a 13-year-old male with B-cell precursor acute lymphoblastic leukemia in remission presenting with anemia and weight loss. Examination was significant for absence of abdominal pain, but a stool sample was positive for occult blood. Pan-endoscopy was performed with colonoscopy revealing a mass filling the colonic lumen. Biopsy of the mass confirmed recurrence of recurrent Bcell lymphoma. Computed tomography scan revealed ileocolic intussusception resulting from the tumor. This case is unusual in that the patient had no abdominal pain despite the presence of intussusception.CONCLUSION While intestinal involvement with lymphoma has been well described in the literature, presentation as painless intussusception has not been reported. This case report highlights the wide spectrum of clinical manifestations of recurrent Bcell lymphoma involving the gastrointestinal tract, in particular the near absence of symptoms despite the finding of intussusception.展开更多
Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia(ALL),yet the underlying mechanisms are still elusive.Here,we demonstrate that phosphoribosyl pyrophosphate synthetase 2(P...Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia(ALL),yet the underlying mechanisms are still elusive.Here,we demonstrate that phosphoribosyl pyrophosphate synthetase 2(PRPS2)mutations drive ALL relapse through influencing PRPS1/2 hexamer stability.Ultra-deep sequencing was performed to identify PRPS2 mutations in ALL samples.The effects of PRPS2 mutations on cell survival,cell apoptosis,and drug resistance were evaluated.In vitro PRPS2 enzyme activity and ADP/GDP feedback inhibition of PRPS enzyme activity were assessed.Purine metabolites were analyzed by ultra-performance liquid-chromatography tandem mass spectrometry(UPLC–MS/MS).Integrating sequencing data with clinical information,we identified PRPS2 mutations only in relapsed childhood ALL with thiopurine therapy.Functional PRPS2 mutations mediated purine metabolism specifically on thiopurine treatment by influencing PRPS1/2 hexamer stability,leading to reduced nucleotide feedback inhibition of PRPS activity and enhanced thiopurine resistance.The 3-amino acid V103-G104-E105,the key difference between PRPS1 and PRPS2,insertion in PRPS2 caused severe steric clash to the interface of PRPS hexamer,leading to its low enzyme activity.In addition,we demonstrated that PRPS2 P173R increased thiopurine resistance in xenograft models.Our work describes a novel mechanism by which PRPS2 mutants drive childhood ALL relapse and highlights PRPS2 mutations as biomarkers for relapsed childhood ALL.展开更多
BACKGROUND Late relapses of early-stage germ cell tumors are rare.Most patients(-85%)with stage I seminoma are cured by radical orchiectomy.The detection of late relapse is challenging given the relative rarity of thi...BACKGROUND Late relapses of early-stage germ cell tumors are rare.Most patients(-85%)with stage I seminoma are cured by radical orchiectomy.The detection of late relapse is challenging given the relative rarity of this phenomenon,and the fact that patients who have completed surveillance are usually not undergoing regular oncologic workup nor imaging.While many treatment options do exist for a patient with late relapse of seminoma,surgery is typically the mainstay as these tumors are generally thought to be more chemo-resistant.CASE SUMMARY In this article,we describe the management of a patient with an early-stage pure seminoma who was subsequently identified to have a recurrence two decades later.We provide a review of the literature not only focused on clinical factors and biology,but also the management of late recurrences specifically in pure seminoma and in prostate gland.CONCLUSION There is a paucity of data and treatment recommendations for this clinical entity,and a multidisciplinary approach emphasizing subspecialty expert consultation and patient education is imperative.展开更多
The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor ...The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy.We developed a highly efficient delivery system HA/PEI-KT(HKT)to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide(CpG).On the one hand,CpG induced the expression of OX40 on T cells within tumors.On the other hand,OX40L plasmids achieved the OX40L anchoring on the tumor cell membrane to next promote T cells responses via OX40/OX40L axis.Such synergistic tumor“self-killing”strategy finally turned“cold”tumors to“hot”,to sensitize tumors to programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)blockade therapy,and promoted an immune-mediated tumor regression in both B16F10 and 4T1 tumor models,with prevention of tumor recurrence and metastasis.To avoid the side effects,the gene-guided OX40L anchoring and PD-L1 silencing was proposed to replace the existing antibody therapy,which showed negligible toxicity in vivo.Our work provided a new possibility for tumor“self-killing”immunotherapy to treated various solid tumors.展开更多
文摘Epithelial-mesenchymal transition(EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells(CSCs) but also direct them across the multiple organ systems to promote tumor recurrence and metastasis. CSCs are reported to express stem cell genes as well as specific cell surfacemarkers and allow aberrant differentiation of progenies.It facilitates cancer cells to leave primary tumor, acquire migratory characteristics, grow into new environment and develop radio-chemo-resistance. Based on the current information, present review discusses and summarizes the recent advancements on the molecular mechanisms that derive epithelial plasticity and its major role in generating a subset of tumor cells with stemness properties and pathophysiological spread of tumor. This paper further highlights the critical need to examine the regulation of EMT and CSC pathways in identifying the novel probable therapeutic targets.These improved therapeutic strategies based on the co-administration of inhibitors of EMT, CSCs as well as differentiated tumor cells may provide improved antineoplastic response with no tumor relapse.
文摘Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumor relapse is thought to be caused by the presence of these cells.CSC-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional therapies.Additionally,the metabolic properties of cancer cells differ markedly from those of normal cells.The efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer cells.Metabolic targeting of breast CSCs(BCSCs)may be a very effective strategy for anti-cancer treatment of breast cancer cells.Thus,in this review,we focus on discussing the studies involving metabolism and targeted therapy in BCSCs.
文摘BACKGROUND The clinical presentation of acute lymphoblastic lymphoma is highly varied.While prognosis is good, recurrence of disease can occur. Gastrointestinal relapse, including intussusception, is well-described but the absence of abdominal pain in this setting is rare.CASE SUMMARY We report a 13-year-old male with B-cell precursor acute lymphoblastic leukemia in remission presenting with anemia and weight loss. Examination was significant for absence of abdominal pain, but a stool sample was positive for occult blood. Pan-endoscopy was performed with colonoscopy revealing a mass filling the colonic lumen. Biopsy of the mass confirmed recurrence of recurrent Bcell lymphoma. Computed tomography scan revealed ileocolic intussusception resulting from the tumor. This case is unusual in that the patient had no abdominal pain despite the presence of intussusception.CONCLUSION While intestinal involvement with lymphoma has been well described in the literature, presentation as painless intussusception has not been reported. This case report highlights the wide spectrum of clinical manifestations of recurrent Bcell lymphoma involving the gastrointestinal tract, in particular the near absence of symptoms despite the finding of intussusception.
基金National Natural Science Foundation of China(81972341,81900158,81772663,81874078,82072896)Shanghai Municipal Science and Technology Commission(201409002700,19JC1413500,21XD1403100)+1 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20161310)Pudong New Area Science&Technology Development Fund(PKJ2018-Y47).
文摘Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia(ALL),yet the underlying mechanisms are still elusive.Here,we demonstrate that phosphoribosyl pyrophosphate synthetase 2(PRPS2)mutations drive ALL relapse through influencing PRPS1/2 hexamer stability.Ultra-deep sequencing was performed to identify PRPS2 mutations in ALL samples.The effects of PRPS2 mutations on cell survival,cell apoptosis,and drug resistance were evaluated.In vitro PRPS2 enzyme activity and ADP/GDP feedback inhibition of PRPS enzyme activity were assessed.Purine metabolites were analyzed by ultra-performance liquid-chromatography tandem mass spectrometry(UPLC–MS/MS).Integrating sequencing data with clinical information,we identified PRPS2 mutations only in relapsed childhood ALL with thiopurine therapy.Functional PRPS2 mutations mediated purine metabolism specifically on thiopurine treatment by influencing PRPS1/2 hexamer stability,leading to reduced nucleotide feedback inhibition of PRPS activity and enhanced thiopurine resistance.The 3-amino acid V103-G104-E105,the key difference between PRPS1 and PRPS2,insertion in PRPS2 caused severe steric clash to the interface of PRPS hexamer,leading to its low enzyme activity.In addition,we demonstrated that PRPS2 P173R increased thiopurine resistance in xenograft models.Our work describes a novel mechanism by which PRPS2 mutants drive childhood ALL relapse and highlights PRPS2 mutations as biomarkers for relapsed childhood ALL.
文摘BACKGROUND Late relapses of early-stage germ cell tumors are rare.Most patients(-85%)with stage I seminoma are cured by radical orchiectomy.The detection of late relapse is challenging given the relative rarity of this phenomenon,and the fact that patients who have completed surveillance are usually not undergoing regular oncologic workup nor imaging.While many treatment options do exist for a patient with late relapse of seminoma,surgery is typically the mainstay as these tumors are generally thought to be more chemo-resistant.CASE SUMMARY In this article,we describe the management of a patient with an early-stage pure seminoma who was subsequently identified to have a recurrence two decades later.We provide a review of the literature not only focused on clinical factors and biology,but also the management of late recurrences specifically in pure seminoma and in prostate gland.CONCLUSION There is a paucity of data and treatment recommendations for this clinical entity,and a multidisciplinary approach emphasizing subspecialty expert consultation and patient education is imperative.
基金This work was financially supported by the National Key R&D Program of China(2021YFB3800900)National Natural Science Foundation of China(51925305,51873208,51833010,51803210,51973217)Jilin province science and technology development program(20200201075JC).
文摘The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy.We developed a highly efficient delivery system HA/PEI-KT(HKT)to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide(CpG).On the one hand,CpG induced the expression of OX40 on T cells within tumors.On the other hand,OX40L plasmids achieved the OX40L anchoring on the tumor cell membrane to next promote T cells responses via OX40/OX40L axis.Such synergistic tumor“self-killing”strategy finally turned“cold”tumors to“hot”,to sensitize tumors to programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)blockade therapy,and promoted an immune-mediated tumor regression in both B16F10 and 4T1 tumor models,with prevention of tumor recurrence and metastasis.To avoid the side effects,the gene-guided OX40L anchoring and PD-L1 silencing was proposed to replace the existing antibody therapy,which showed negligible toxicity in vivo.Our work provided a new possibility for tumor“self-killing”immunotherapy to treated various solid tumors.
