Objective To explore the expression of novel protein kinase C ε ( PKCε) in normal prostate ( NP) tissue, benign prostate hyperplasia ( BPH) ,pericancerous ( PC) tissue and prostate cancer ( Pca) ,and study its corre...Objective To explore the expression of novel protein kinase C ε ( PKCε) in normal prostate ( NP) tissue, benign prostate hyperplasia ( BPH) ,pericancerous ( PC) tissue and prostate cancer ( Pca) ,and study its correlation with the grade and stage of Pca. Methods Ten NP slides,ten BPH slides,ten PC slides and 43 Pca展开更多
Prostate cancer is the most common malignancy in men lack of efficient early diagnosis and therapeutics,calling for effective molecular probes.Herein,we performed cell-based systematic evolution of ligands by exponent...Prostate cancer is the most common malignancy in men lack of efficient early diagnosis and therapeutics,calling for effective molecular probes.Herein,we performed cell-based systematic evolution of ligands by exponential enrichment（cell-SELEX） to obtain specific recognition of human prostate cancer cells PC-3M.Four aptamers were successfully obtained that can bind to target cells with high affinity and specificity.A 51-nt truncated sequence named Xq-2-C1 was identified after further elaborative analysis on the secondary structure.More importantly,the achieved aptamer Xq-2-C1 not only demonstrated excellent specific to target cells,but also revealed specific recognition to clinical prostate cancer tissue.The tissue imaging results showed that Xq-2-C1 had better recognition ratio for clinical prostate cancer tissue samples（85%） compared to the random sequence（9%）.These results demonstrate that these newly generated aptamers would furnish potential applications in the early diagnosis and clinical treatment of prostate cancer.展开更多
Deep-tissue solid cancer treatment has a poor prognosis,resulting in a very low 5-year patient survival rate.The primary challenges facing solid tumor therapies are accessibility,incomplete surgical removal of tumor t...Deep-tissue solid cancer treatment has a poor prognosis,resulting in a very low 5-year patient survival rate.The primary challenges facing solid tumor therapies are accessibility,incomplete surgical removal of tumor tissue,the resistance of the hypoxic and heterogeneous tumor microenvironment to chemotherapy and radiation,and suffering caused by off-target toxicities.Here,sonodynamic therapy(SDT)is an evolving therapeutic approach that uses low-intensity ultrasound to target deep-tissue solid tumors.The ability of ultrasound to deliver energy safely and precisely into small deep-tissue(>10 cm)volumes makes SDT more effective than conventional photodynamic therapy.While SDT is currently in phase 1/2 clinical trials for glioblastoma multiforme,its use for other solid cancer treatments,such as breast,pancreatic,liver,and prostate cancer,is still in the preclinical stage,with further investigation required to improve its therapeutic efficacy.This review,therefore,focuses on recent advances in SDT cancer treatments.We describe the interaction between ultrasound and sonosensitizer molecules and the associated energy transfer mechanism to malignant cells,which plays a central role in SDT-mediated cell death.Different sensitizers used in clinical and preclinical trials of various cancer treatments are listed,and the critical ultrasound parameters for SDT are reviewed.We also discuss approaches to improve the efficacies of these sonosensitizers,the role of the 3-dimensional spheroid in vitro investigations,ultrasound-controlled CAR-T cell and SDT-based multimodal therapy,and machine learning for sonosensitizer optimization,which could facilitate clinical translation of SDT.展开更多
MicroRNAs(mi RNAs)are endogenous,noncoding,single-stranded small RNAs that regulate expression of tumor suppressor genes and oncogenes and are involved in almost all tumor-related processes.Mi RNA dysregulation plays ...MicroRNAs(mi RNAs)are endogenous,noncoding,single-stranded small RNAs that regulate expression of tumor suppressor genes and oncogenes and are involved in almost all tumor-related processes.Mi RNA dysregulation plays an important role in the occurrence and development of esophageal cancer through specific signal pathways,including the Wnt/β-catenin signaling pathway,and is closely related to the malignant characteristics of esophageal cancer.The interaction between mi RNAs and the Wnt/β-catenin signaling pathway,which is specifically expressed in esophageal cancer tissues,shows potential as a new biomarker and therapeutic target.This article reviews the role of mi RNAs related to the Wnt pathway in the carcinogenesis of esophageal carcinoma and its role in Wnt signal transduction.The content of this review can be used as the basis for formulating or improving the treatment strategy of esophageal cancer.展开更多
BACKGROUND： Recent studies have shown the clinical significance of epidermal growth factor-like domain 7（EGFL7）in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer...BACKGROUND： Recent studies have shown the clinical significance of epidermal growth factor-like domain 7（EGFL7）in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer（PC） remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC.METHODS： The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally,correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated.RESULTS： EGFL7 was widely expressed in all PC cell lines tested.EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues（P0.040）. In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival,accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for longterm outcome of PC.CONCLUSION： Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.展开更多
AIM To investigate genotype variation among induced pluripotent stem cell(iPSC) lines that were clonally generated from heterogeneous colon cancer tissues using next-generation sequencing. METHODS Human iPSC lines wer...AIM To investigate genotype variation among induced pluripotent stem cell(iPSC) lines that were clonally generated from heterogeneous colon cancer tissues using next-generation sequencing. METHODS Human iPSC lines were clonally established by selecting independent single colonies expanded from heterogeneous primary cells of S-shaped colon cancer tissues by retroviral gene transfer(OCT3/4, SOX2, and KLF4). The ten iPSC lines, their starting cancer tissues, and the matched adjacent non-cancerous tissues were analyzed using nextgeneration sequencing and bioinformatics analysis using the human reference genome hg19. Non-synonymous single-nucleotide variants(SNVs)(missense, nonsense,and read-through) were identified within the target region of 612 genes related to cancer and the human kinome. All SNVs were annotated using dbS NP135, CCDS, RefSeq, GENCODE, and 1000 Genomes. The SNVs of the iPSC lines were compared with the genotypes of the cancerous and non-cancerous tissues. The putative genotypes were validated using allelic depth and genotype quality. For final confirmation, mutated genotypes were manually curated using the Integrative Genomics Viewer. RESULTS In eight of the ten iPSC lines, one or two non-synonymous SNVs in EIF2AK2, TTN, ULK4, TSSK1 B, FLT4, STK19, STK31, TRRAP, WNK1, PLK1 or PIK3R5 were identified as novel SNVs and were not identical to the genotypes found in the cancer and non-cancerous tissues. This result suggests that the SNVs were de novo or pre-existing mutations that originated from minor populations, such as multifocal pre-cancer(stem) cells or pre-metastatic cancer cells from multiple, different clonal evolutions, present within the heterogeneous cancer tissue. The genotypes of all ten iPSC lines were different from the mutated ERBB2 and MKNK2 genotypes of the cancer tissues and were identical to those of the noncancerous tissues and that found in the human reference genome hg19. Furthermore, two of the ten iPSC lines did not have any confirmed mutated genotypes, despite being derived from cancerous tissue. These results suggest that the traceability and preference of the starting single cells being derived from pre-cancer(stem) cells, stroma cells such as cancer-associated fibroblasts, and immune cells that co-existed in the tissues along with the mature cancer cells.CONCLUSION The genotypes of iPSC lines derived from heterogeneous cancer tissues can provide information on the type of starting cell that the iPSC line was generated from.展开更多
Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy regimens.Identifying the m...Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy regimens.Identifying the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic targets.Defects in mesenchymal stem cell differentiation,abnormal expression of oncogenes and tumor suppressors,and dysregulation within various important signaling pathways have all been implicated in development of various disease phenotypes.As such,a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific aberrancies.Born out of these and similar investigations,a variety of emerging therapies are now undergoing various phases of OS clinical testing.They broadly include angiogenesis inhibitors,drugs that act on the bone microenvironment,receptor tyrosine kinase inhibitors,immune system modulators,and other radio-or chemo-sensitizing agents.As new forms of drug delivery are being developed simultaneously,the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than ever.In this review,we not only summarize our current understanding of OS disease processes,but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.展开更多
Early diagnosis of brain tumors is often hindered by non-specific symptoms,particularly in eloquent brain regions where open surgery for tissue sampling is unfeasible.This limitation increases the risk of misdiagnosis...Early diagnosis of brain tumors is often hindered by non-specific symptoms,particularly in eloquent brain regions where open surgery for tissue sampling is unfeasible.This limitation increases the risk of misdiagnosis due to tumor heterogeneity in stereotactic biopsies.Label-free diagnostic methods,including intraoperative probes and cellular origin analysis techniques,hold promise for improving diagnostic accuracy.Polarimetry offers valuable information on the polarization properties of biomedical samples,yet it may not fully reveal specific structural characteristics.The interpretative scope of polarimetric data is sometimes constrained by the limitations of existing decomposition methods.On the other hand,dynamic laser speckle analysis(DLSA),a burgeoning technique,not only does not account for the polarimetric attributes but also is known for tracking only the temporal activity of the dynamic samples.This study bridges these gaps by synergizing conventional polarimetric imaging with DLSA for an indepth examination of sample polarization properties.The effectiveness of our system is shown by analyzing the collection of polarimetric images of various tissue samples,utilizing a variety of adapted numerical and graphical statistical post-processing methods.展开更多
文摘Objective To explore the expression of novel protein kinase C ε ( PKCε) in normal prostate ( NP) tissue, benign prostate hyperplasia ( BPH) ,pericancerous ( PC) tissue and prostate cancer ( Pca) ,and study its correlation with the grade and stage of Pca. Methods Ten NP slides,ten BPH slides,ten PC slides and 43 Pca
基金supported by the National Natural Science Foundation of China(Nos.21175035,21275043,21190040)the National Basic Research Program(No.2011CB911002)the Hunan Province Science and Technology Project of China(No.2013FJ4042)
文摘Prostate cancer is the most common malignancy in men lack of efficient early diagnosis and therapeutics,calling for effective molecular probes.Herein,we performed cell-based systematic evolution of ligands by exponential enrichment（cell-SELEX） to obtain specific recognition of human prostate cancer cells PC-3M.Four aptamers were successfully obtained that can bind to target cells with high affinity and specificity.A 51-nt truncated sequence named Xq-2-C1 was identified after further elaborative analysis on the secondary structure.More importantly,the achieved aptamer Xq-2-C1 not only demonstrated excellent specific to target cells,but also revealed specific recognition to clinical prostate cancer tissue.The tissue imaging results showed that Xq-2-C1 had better recognition ratio for clinical prostate cancer tissue samples（85%） compared to the random sequence（9%）.These results demonstrate that these newly generated aptamers would furnish potential applications in the early diagnosis and clinical treatment of prostate cancer.
文摘Deep-tissue solid cancer treatment has a poor prognosis,resulting in a very low 5-year patient survival rate.The primary challenges facing solid tumor therapies are accessibility,incomplete surgical removal of tumor tissue,the resistance of the hypoxic and heterogeneous tumor microenvironment to chemotherapy and radiation,and suffering caused by off-target toxicities.Here,sonodynamic therapy(SDT)is an evolving therapeutic approach that uses low-intensity ultrasound to target deep-tissue solid tumors.The ability of ultrasound to deliver energy safely and precisely into small deep-tissue(>10 cm)volumes makes SDT more effective than conventional photodynamic therapy.While SDT is currently in phase 1/2 clinical trials for glioblastoma multiforme,its use for other solid cancer treatments,such as breast,pancreatic,liver,and prostate cancer,is still in the preclinical stage,with further investigation required to improve its therapeutic efficacy.This review,therefore,focuses on recent advances in SDT cancer treatments.We describe the interaction between ultrasound and sonosensitizer molecules and the associated energy transfer mechanism to malignant cells,which plays a central role in SDT-mediated cell death.Different sensitizers used in clinical and preclinical trials of various cancer treatments are listed,and the critical ultrasound parameters for SDT are reviewed.We also discuss approaches to improve the efficacies of these sonosensitizers,the role of the 3-dimensional spheroid in vitro investigations,ultrasound-controlled CAR-T cell and SDT-based multimodal therapy,and machine learning for sonosensitizer optimization,which could facilitate clinical translation of SDT.
文摘MicroRNAs(mi RNAs)are endogenous,noncoding,single-stranded small RNAs that regulate expression of tumor suppressor genes and oncogenes and are involved in almost all tumor-related processes.Mi RNA dysregulation plays an important role in the occurrence and development of esophageal cancer through specific signal pathways,including the Wnt/β-catenin signaling pathway,and is closely related to the malignant characteristics of esophageal cancer.The interaction between mi RNAs and the Wnt/β-catenin signaling pathway,which is specifically expressed in esophageal cancer tissues,shows potential as a new biomarker and therapeutic target.This article reviews the role of mi RNAs related to the Wnt pathway in the carcinogenesis of esophageal carcinoma and its role in Wnt signal transduction.The content of this review can be used as the basis for formulating or improving the treatment strategy of esophageal cancer.
基金supported by a grant from the Research Special Fund for Public Welfare Industry of Health(201202007)
文摘BACKGROUND： Recent studies have shown the clinical significance of epidermal growth factor-like domain 7（EGFL7）in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer（PC） remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC.METHODS： The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally,correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated.RESULTS： EGFL7 was widely expressed in all PC cell lines tested.EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues（P0.040）. In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival,accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for longterm outcome of PC.CONCLUSION： Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.
文摘AIM To investigate genotype variation among induced pluripotent stem cell(iPSC) lines that were clonally generated from heterogeneous colon cancer tissues using next-generation sequencing. METHODS Human iPSC lines were clonally established by selecting independent single colonies expanded from heterogeneous primary cells of S-shaped colon cancer tissues by retroviral gene transfer(OCT3/4, SOX2, and KLF4). The ten iPSC lines, their starting cancer tissues, and the matched adjacent non-cancerous tissues were analyzed using nextgeneration sequencing and bioinformatics analysis using the human reference genome hg19. Non-synonymous single-nucleotide variants(SNVs)(missense, nonsense,and read-through) were identified within the target region of 612 genes related to cancer and the human kinome. All SNVs were annotated using dbS NP135, CCDS, RefSeq, GENCODE, and 1000 Genomes. The SNVs of the iPSC lines were compared with the genotypes of the cancerous and non-cancerous tissues. The putative genotypes were validated using allelic depth and genotype quality. For final confirmation, mutated genotypes were manually curated using the Integrative Genomics Viewer. RESULTS In eight of the ten iPSC lines, one or two non-synonymous SNVs in EIF2AK2, TTN, ULK4, TSSK1 B, FLT4, STK19, STK31, TRRAP, WNK1, PLK1 or PIK3R5 were identified as novel SNVs and were not identical to the genotypes found in the cancer and non-cancerous tissues. This result suggests that the SNVs were de novo or pre-existing mutations that originated from minor populations, such as multifocal pre-cancer(stem) cells or pre-metastatic cancer cells from multiple, different clonal evolutions, present within the heterogeneous cancer tissue. The genotypes of all ten iPSC lines were different from the mutated ERBB2 and MKNK2 genotypes of the cancer tissues and were identical to those of the noncancerous tissues and that found in the human reference genome hg19. Furthermore, two of the ten iPSC lines did not have any confirmed mutated genotypes, despite being derived from cancerous tissue. These results suggest that the traceability and preference of the starting single cells being derived from pre-cancer(stem) cells, stroma cells such as cancer-associated fibroblasts, and immune cells that co-existed in the tissues along with the mature cancer cells.CONCLUSION The genotypes of iPSC lines derived from heterogeneous cancer tissues can provide information on the type of starting cell that the iPSC line was generated from.
基金supported in part by research grants from the National Institutes of Health(AT004418,AR50142,AR054381 to TCH,RCH and HHL)the 973 Program of Ministry of Science and Technology(MOST)of China(#2011CB707900 to TCH)
文摘Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy regimens.Identifying the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic targets.Defects in mesenchymal stem cell differentiation,abnormal expression of oncogenes and tumor suppressors,and dysregulation within various important signaling pathways have all been implicated in development of various disease phenotypes.As such,a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific aberrancies.Born out of these and similar investigations,a variety of emerging therapies are now undergoing various phases of OS clinical testing.They broadly include angiogenesis inhibitors,drugs that act on the bone microenvironment,receptor tyrosine kinase inhibitors,immune system modulators,and other radio-or chemo-sensitizing agents.As new forms of drug delivery are being developed simultaneously,the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than ever.In this review,we not only summarize our current understanding of OS disease processes,but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.
文摘Early diagnosis of brain tumors is often hindered by non-specific symptoms,particularly in eloquent brain regions where open surgery for tissue sampling is unfeasible.This limitation increases the risk of misdiagnosis due to tumor heterogeneity in stereotactic biopsies.Label-free diagnostic methods,including intraoperative probes and cellular origin analysis techniques,hold promise for improving diagnostic accuracy.Polarimetry offers valuable information on the polarization properties of biomedical samples,yet it may not fully reveal specific structural characteristics.The interpretative scope of polarimetric data is sometimes constrained by the limitations of existing decomposition methods.On the other hand,dynamic laser speckle analysis(DLSA),a burgeoning technique,not only does not account for the polarimetric attributes but also is known for tracking only the temporal activity of the dynamic samples.This study bridges these gaps by synergizing conventional polarimetric imaging with DLSA for an indepth examination of sample polarization properties.The effectiveness of our system is shown by analyzing the collection of polarimetric images of various tissue samples,utilizing a variety of adapted numerical and graphical statistical post-processing methods.
