The capture of circulating tumor cells(CTCs)is of great significance in reducing cancer mortality and complications.However,the nonspecific binding of proteins and white blood cells(WBCs)weakens the targeting capabili...The capture of circulating tumor cells(CTCs)is of great significance in reducing cancer mortality and complications.However,the nonspecific binding of proteins and white blood cells(WBCs)weakens the targeting capabilities of the capture surfaces,which critically hampers the efficiency and purity of the captured CTCs.Herein,we propose a liquid-like interface design strategy that consists of liquid-like polymer chains and anti-EpCAM modification processes for high-purity and high-efficiency capture of CTCs.The dynamic flexible feature of the liquid-like chains endows the modified surfaces with excellent antiadhesion property for proteins and blood cells.The liquid-like surfaces can capture the target CTCs and show high cell viability due to the environmentfriendly surface modification processes.When liquid-like surface designs were introduced in the deterministic lateral displacement(DLD)-patterned microfluidic chip,the nonspecific adhesion rate of WBCs was reduced by more than fivefold compared to that in the DLD chip without liquid-like interface design,while maintaining comparable capture efficiency.Overall,this strategy provides a novel perspective on surface design for achieving high purity and efficient capture of CTCs.展开更多
Objective： To evaluate the feasibility of dynamic contrast-enhanced magnetic resonance imaging（DCEMRI） for predicting tumor response to radiotherapy in patients with suspected primary central nervous system（CNS） ...Objective： To evaluate the feasibility of dynamic contrast-enhanced magnetic resonance imaging（DCEMRI） for predicting tumor response to radiotherapy in patients with suspected primary central nervous system（CNS） germ cell tumors（GCTs）.Methods： DCE-MRI parameters of 35 patients with suspected primary CNS GCTs were obtained prior to diagnostic radiation, using the Tofts and Kermode model. Radiosensitivity was determined in tumors diagnosed 2 weeks after radiation by observing changes in tumor size and markers as a response to MRI. Taking radiosensitivity as the gold standard, the cut-off value of DCE-MRI parameters was measured by receiver operating characteristic（ROC） curve. Diagnostic accuracy of DCE-MRI parameters for predicting radiosensitivity was evaluated by ROC curve.Results： A significant elevation in transfer constant（K^trans） and extravascular extracellular space（Ve）（P=0.000）, as well as a significant reduction in rate constant（Kep）（P=0.000） was observed in tumors. K^trans, relative K^trans, and relative Kep of the responsive group were significantly higher than non-responsive groups. No significant difference was found in Kep, Ve, and relative Ve between the two groups. Relative K^trans showed the best diagnostic value in predicting radiosensitivity with a sensitivity of 100%, specificity of 91.7%, positive predictive value（PPV） of 95.8%, and negative predictive value（NPV） of 100%.Conclusions： Relative K^trans appeared promising in predicting tumor response to radiation therapy（RT）. It is implied that DCE-MRI pre-treatment is a requisite step in diagnostic procedures and a novel and reliable approach to guide clinical choice of RT.展开更多
Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be stra...Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be straightforward but computing performance often counterbalances simplicity. Computationally convenient simulation times can be achieved by choosing appropriate data structures, memory and cell handling as well as domain setup. We propose a cellular automaton model of tumor growth with a domain that expands dynamically as the tumor population increases. We discuss memory access, data structures and implementation techniques that yield high-performance multi-scale Monte Carlo simulations of tumor growth. We discuss tumor properties that favor the proposed high-performance design and present simulation results of the tumor growth model. We estimate to which parameters the model is the most sensitive, and show that tumor volume depends on a number of parameters in a non-monotonic manner.展开更多
BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always problematic.To use liquid biopsies clinical...BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always problematic.To use liquid biopsies clinically,it will be very important to address these questions.AIM To assess the origin of ctDNA,clarify the dynamics of ctDNA levels,assess ctDNA levels by using a xenograft mouse after treatment,and to determine whether tumor volume and invasion are related to ctDNA levels.METHODS Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell line.Groups of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA analysis.Analysis of ctDNA was performed by droplet digital PCR,using the human telomerase reverse transcriptase(hTERT)gene.RESULTS Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week 8.No hTERT was detected at week 4,but it was detected at week 8.However,in four-site xenograft mice,hTERT was detected both at week 4 and week 6.These experiments revealed that both tumor invasion and tumor volume were asso ciated with the detection of ctDNA.In resection experiments,hTERT was detected at resection,but had decreased by 6 h,and was no longer detected 1 and 3 d after resection.CONCLUSION We clarified the origin and dynamics of ctDNA,showing that tumor volume is an important factor.We also found that when the tumor was completely resected,ctDNA was absent after one or more days.展开更多
AIM: To investigate the merits of texture analysis on parametric maps derived from pharmacokinetic modeling with dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) as imaging biomarkers for the prediction o...AIM: To investigate the merits of texture analysis on parametric maps derived from pharmacokinetic modeling with dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) as imaging biomarkers for the prediction of treatment response in patients with head and neck squamous cell carcinoma(HNSCC). METHODS: In this retrospective study,19 HNSCC patients underwent pre- and intra-treatment DCEMRI scans at a 1.5T MRI scanner. All patients had chemo-radiation treatment. Pharmacokinetic modeling was performed on the acquired DCE-MRI images,generating maps of volume transfer rate(Ktrans) and volume fraction of the extravascular extracellular space(ve). Image texture analysis was then employed on maps of Ktrans and ve,generating two texture measures: Energy(E) and homogeneity.RESULTS: No significant changes were found for the mean and standard deviation for Ktrans and ve between pre- and intra-treatment(P > 0.09). Texture analysis revealed that the imaging biomarker E of ve was significantly higher in intra-treatment scans,relative to pretreatment scans(P < 0.04). CONCLUSION: Chemo-radiation treatment in HNSCC significantly reduces the heterogeneity of tumors.展开更多
Poromechanics plays a key role in modelling hard and soft tissue behaviours,by providing a thermodynamic framework in which chemo-mechanical mutual interactions among fluid and solid constituents can be consistently r...Poromechanics plays a key role in modelling hard and soft tissue behaviours,by providing a thermodynamic framework in which chemo-mechanical mutual interactions among fluid and solid constituents can be consistently rooted,at different scale levels.In this context,how different biological species(including cells,extra-cellular components and chemical metabolites)interplay within complex environments is studied for characterizing the mechanobiology of tumor growth,governed by intra-tumoral residual stresses that initiate mechanotransductive processes deregulating normal tissue homeostasis and leading to tissue remodelling.Despite the coupling between tumor poroelasticity and interspecific competitive dynamics has recently highlighted how microscopic cells and environment interactions influence growth-associated stresses and tumor pathophysiology,the nonlinear interlacing among biochemical factors and mechanics somehow hindered the possibility of gaining qualitative insights into cells dynamics.Motivated by this,in the present work we recover the linear poroelasticity in order to benefit of a reduced complexity,so first deriving the well-known Lyapunov stability criterion from the thermodynamic dissipation principle and then analysing the stability of the mechanical competition among cells fighting for common space and resources during cancer growth and invasion.At the end,the linear poroelastic model enriched by interspecific dynamics is also exploited to show how growth anisotropy can alter the stress field in spherical tumor masses,by thus indirectly affecting cell mechano-sensing.展开更多
The understanding of the macroscopic phenomenological models of the population growth at a microscopic level is important to predict the population behaviors emerged from the interactions between the individuals. In t...The understanding of the macroscopic phenomenological models of the population growth at a microscopic level is important to predict the population behaviors emerged from the interactions between the individuals. In this work, we consider the influence of the population growth rate R on the cell-cell interaction in a tumor system and show that, in most cases especially small proliferative probabilities, the regulative role of the interaction will be strengthened with the decline of the intrinsic proliferative probabilities. For the high replication rates of an individual and the cooperative interactions, the proliferative probability almost has no effect. We compute the dependences of R on the interactions between the cells under the approximation of the nearest neighbor in the rim of an avascular tumor. Our results are helpful to qualitatively understand the influence of the interactions between the individuals on the growth rate in population systems.展开更多
BACKGROUND： Metastasis is the primary cause of mortality in cancer patients. Therefore, elucidating the genetics and epigenetics of metastatic tumor cells and the mechanisms by which tumor cells acquire metastatic pr...BACKGROUND： Metastasis is the primary cause of mortality in cancer patients. Therefore, elucidating the genetics and epigenetics of metastatic tumor cells and the mechanisms by which tumor cells acquire metastatic properties constitute significant challenges in cancer research. OBJECTIVE： To summarize the current understandings of the specific genotype and phenotype of the metastatic tumor cells. METHOD and RESULT： In-depth genetic analysis of tumor cells, especially with advances in the next-generation sequencing, have revealed insights of the genotypes of metastatic tumor cells. Also, studies have shown that the cancer stem cell （CSC） and epithelial to mesenchymal transition （EMT） phenotypes are associated with the metastatic cascade. CONCLUSION： In this review, we will discuss recent advances in the field by focusing on the genomic instability and phenotypic dynamics of metastatic tumor cells.展开更多
基金supported by the National Natural Science Foundation of China(grant nos.52025132,21975209,22275156,21621091,22021001,22005255,and T2241022)the National Science Foundation of Fujian Province of China(grant no.2022J02059)+4 种基金the Fundamental Research Funds for the Central Universities of China(grant nos.20720220019 and 20720220085)the 111 Project(grant nos.B17027 and B16029)the Science and Technology Projects of Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(grant no.RD2022070601)the State Key Laboratory of Bio-Fibers and Eco-Textiles(Qingdao University)(grant no.KFKT202221)the Tencent Foundation(The XPLORER PRIZE).
文摘The capture of circulating tumor cells(CTCs)is of great significance in reducing cancer mortality and complications.However,the nonspecific binding of proteins and white blood cells(WBCs)weakens the targeting capabilities of the capture surfaces,which critically hampers the efficiency and purity of the captured CTCs.Herein,we propose a liquid-like interface design strategy that consists of liquid-like polymer chains and anti-EpCAM modification processes for high-purity and high-efficiency capture of CTCs.The dynamic flexible feature of the liquid-like chains endows the modified surfaces with excellent antiadhesion property for proteins and blood cells.The liquid-like surfaces can capture the target CTCs and show high cell viability due to the environmentfriendly surface modification processes.When liquid-like surface designs were introduced in the deterministic lateral displacement(DLD)-patterned microfluidic chip,the nonspecific adhesion rate of WBCs was reduced by more than fivefold compared to that in the DLD chip without liquid-like interface design,while maintaining comparable capture efficiency.Overall,this strategy provides a novel perspective on surface design for achieving high purity and efficient capture of CTCs.
基金supported by Beijing Natural Science Foundation(No.7122029)
文摘Objective： To evaluate the feasibility of dynamic contrast-enhanced magnetic resonance imaging（DCEMRI） for predicting tumor response to radiotherapy in patients with suspected primary central nervous system（CNS） germ cell tumors（GCTs）.Methods： DCE-MRI parameters of 35 patients with suspected primary CNS GCTs were obtained prior to diagnostic radiation, using the Tofts and Kermode model. Radiosensitivity was determined in tumors diagnosed 2 weeks after radiation by observing changes in tumor size and markers as a response to MRI. Taking radiosensitivity as the gold standard, the cut-off value of DCE-MRI parameters was measured by receiver operating characteristic（ROC） curve. Diagnostic accuracy of DCE-MRI parameters for predicting radiosensitivity was evaluated by ROC curve.Results： A significant elevation in transfer constant（K^trans） and extravascular extracellular space（Ve）（P=0.000）, as well as a significant reduction in rate constant（Kep）（P=0.000） was observed in tumors. K^trans, relative K^trans, and relative Kep of the responsive group were significantly higher than non-responsive groups. No significant difference was found in Kep, Ve, and relative Ve between the two groups. Relative K^trans showed the best diagnostic value in predicting radiosensitivity with a sensitivity of 100%, specificity of 91.7%, positive predictive value（PPV） of 95.8%, and negative predictive value（NPV） of 100%.Conclusions： Relative K^trans appeared promising in predicting tumor response to radiation therapy（RT）. It is implied that DCE-MRI pre-treatment is a requisite step in diagnostic procedures and a novel and reliable approach to guide clinical choice of RT.
文摘Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be straightforward but computing performance often counterbalances simplicity. Computationally convenient simulation times can be achieved by choosing appropriate data structures, memory and cell handling as well as domain setup. We propose a cellular automaton model of tumor growth with a domain that expands dynamically as the tumor population increases. We discuss memory access, data structures and implementation techniques that yield high-performance multi-scale Monte Carlo simulations of tumor growth. We discuss tumor properties that favor the proposed high-performance design and present simulation results of the tumor growth model. We estimate to which parameters the model is the most sensitive, and show that tumor volume depends on a number of parameters in a non-monotonic manner.
文摘BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always problematic.To use liquid biopsies clinically,it will be very important to address these questions.AIM To assess the origin of ctDNA,clarify the dynamics of ctDNA levels,assess ctDNA levels by using a xenograft mouse after treatment,and to determine whether tumor volume and invasion are related to ctDNA levels.METHODS Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell line.Groups of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA analysis.Analysis of ctDNA was performed by droplet digital PCR,using the human telomerase reverse transcriptase(hTERT)gene.RESULTS Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week 8.No hTERT was detected at week 4,but it was detected at week 8.However,in four-site xenograft mice,hTERT was detected both at week 4 and week 6.These experiments revealed that both tumor invasion and tumor volume were asso ciated with the detection of ctDNA.In resection experiments,hTERT was detected at resection,but had decreased by 6 h,and was no longer detected 1 and 3 d after resection.CONCLUSION We clarified the origin and dynamics of ctDNA,showing that tumor volume is an important factor.We also found that when the tumor was completely resected,ctDNA was absent after one or more days.
基金Supported by The National Cancer Institute/National Institutes of HealthNo.1 R01 CA115895
文摘AIM: To investigate the merits of texture analysis on parametric maps derived from pharmacokinetic modeling with dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) as imaging biomarkers for the prediction of treatment response in patients with head and neck squamous cell carcinoma(HNSCC). METHODS: In this retrospective study,19 HNSCC patients underwent pre- and intra-treatment DCEMRI scans at a 1.5T MRI scanner. All patients had chemo-radiation treatment. Pharmacokinetic modeling was performed on the acquired DCE-MRI images,generating maps of volume transfer rate(Ktrans) and volume fraction of the extravascular extracellular space(ve). Image texture analysis was then employed on maps of Ktrans and ve,generating two texture measures: Energy(E) and homogeneity.RESULTS: No significant changes were found for the mean and standard deviation for Ktrans and ve between pre- and intra-treatment(P > 0.09). Texture analysis revealed that the imaging biomarker E of ve was significantly higher in intra-treatment scans,relative to pretreatment scans(P < 0.04). CONCLUSION: Chemo-radiation treatment in HNSCC significantly reduces the heterogeneity of tumors.
基金M.F.,A.C.and S.P.acknowledge the Italian Ministry of Education,University and Research(MIUR)(Grants ARS01-01384-PROSCAN and PRIN 201720177TTP3S).A.R.C.acknowledges the support from PON-AIM 1849854-1.
文摘Poromechanics plays a key role in modelling hard and soft tissue behaviours,by providing a thermodynamic framework in which chemo-mechanical mutual interactions among fluid and solid constituents can be consistently rooted,at different scale levels.In this context,how different biological species(including cells,extra-cellular components and chemical metabolites)interplay within complex environments is studied for characterizing the mechanobiology of tumor growth,governed by intra-tumoral residual stresses that initiate mechanotransductive processes deregulating normal tissue homeostasis and leading to tissue remodelling.Despite the coupling between tumor poroelasticity and interspecific competitive dynamics has recently highlighted how microscopic cells and environment interactions influence growth-associated stresses and tumor pathophysiology,the nonlinear interlacing among biochemical factors and mechanics somehow hindered the possibility of gaining qualitative insights into cells dynamics.Motivated by this,in the present work we recover the linear poroelasticity in order to benefit of a reduced complexity,so first deriving the well-known Lyapunov stability criterion from the thermodynamic dissipation principle and then analysing the stability of the mechanical competition among cells fighting for common space and resources during cancer growth and invasion.At the end,the linear poroelastic model enriched by interspecific dynamics is also exploited to show how growth anisotropy can alter the stress field in spherical tumor masses,by thus indirectly affecting cell mechano-sensing.
基金Supported by the National Natural Science Foundation of China under Grant Nos.11675008 and 21434001
文摘The understanding of the macroscopic phenomenological models of the population growth at a microscopic level is important to predict the population behaviors emerged from the interactions between the individuals. In this work, we consider the influence of the population growth rate R on the cell-cell interaction in a tumor system and show that, in most cases especially small proliferative probabilities, the regulative role of the interaction will be strengthened with the decline of the intrinsic proliferative probabilities. For the high replication rates of an individual and the cooperative interactions, the proliferative probability almost has no effect. We compute the dependences of R on the interactions between the cells under the approximation of the nearest neighbor in the rim of an avascular tumor. Our results are helpful to qualitatively understand the influence of the interactions between the individuals on the growth rate in population systems.
文摘BACKGROUND： Metastasis is the primary cause of mortality in cancer patients. Therefore, elucidating the genetics and epigenetics of metastatic tumor cells and the mechanisms by which tumor cells acquire metastatic properties constitute significant challenges in cancer research. OBJECTIVE： To summarize the current understandings of the specific genotype and phenotype of the metastatic tumor cells. METHOD and RESULT： In-depth genetic analysis of tumor cells, especially with advances in the next-generation sequencing, have revealed insights of the genotypes of metastatic tumor cells. Also, studies have shown that the cancer stem cell （CSC） and epithelial to mesenchymal transition （EMT） phenotypes are associated with the metastatic cascade. CONCLUSION： In this review, we will discuss recent advances in the field by focusing on the genomic instability and phenotypic dynamics of metastatic tumor cells.
