Diffuse large B cell lymphoma (DLBCL) is a clinical and genetically heterogeneous lymphoid malignancy. Although R-CHOP (rituximab plus cyclophosphamide, vincristine, doxorubicin, and prednisone) treatment can improve the survival rate of patients with DLBCL, more than 30% of patients exhibit treatment failure, relapse, or refractory disease. Therefore, novel drugs or targeted therapies are needed to improve the survival of patients with DLBCL. The compound DCZ0014 is a novel chemical similar to berberine. In this study, we found that DCZ0014 significantly inhibited the proliferation and activity of DLBCL cells, and induced cell apoptosis. Following treatment with DCZ0014, DLBCL cells accumulated in G0/G1-phase of the cell cycle and showed decreased mitochondrial membrane potential. Additionally, DCZ0014 inhibited DNA synthesis, enhanced DNA damage in DLBCL cells, as well as inhibited Lyn/Syk in B cell receptor signaling pathway. Further experiments demonstrated that DCZ0014 did not significantly affect peripheral blood mononuclear cells. Tumor xenograft model showed that DCZ0014 not only inhibited tumor growth but also extended the survival time of mice. Thus, DCZ0014 showed potential for clinical application in the treatment of patients with DLBCL.
{"title":"DCZ0014, a novel compound in the therapy of diffuse large B-cell lymphoma via the B cell receptor signaling pathway.","authors":"Shuaikang Chang, Bo Li, Yongsheng Xie, Yingcong Wang, Zhijian Xu, Shuhan Jin, D. Yu, Huaping Wang, Yumeng Lu, Yong Zhang, Ruye Ma, Cheng Huang, Weiming Lai, Xiaosong Wu, Weiliang Zhu, Jumei Shi","doi":"10.21203/rs.3.rs-48447/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-48447/v1","url":null,"abstract":"Diffuse large B cell lymphoma (DLBCL) is a clinical and genetically heterogeneous lymphoid malignancy. Although R-CHOP (rituximab plus cyclophosphamide, vincristine, doxorubicin, and prednisone) treatment can improve the survival rate of patients with DLBCL, more than 30% of patients exhibit treatment failure, relapse, or refractory disease. Therefore, novel drugs or targeted therapies are needed to improve the survival of patients with DLBCL. The compound DCZ0014 is a novel chemical similar to berberine. In this study, we found that DCZ0014 significantly inhibited the proliferation and activity of DLBCL cells, and induced cell apoptosis. Following treatment with DCZ0014, DLBCL cells accumulated in G0/G1-phase of the cell cycle and showed decreased mitochondrial membrane potential. Additionally, DCZ0014 inhibited DNA synthesis, enhanced DNA damage in DLBCL cells, as well as inhibited Lyn/Syk in B cell receptor signaling pathway. Further experiments demonstrated that DCZ0014 did not significantly affect peripheral blood mononuclear cells. Tumor xenograft model showed that DCZ0014 not only inhibited tumor growth but also extended the survival time of mice. Thus, DCZ0014 showed potential for clinical application in the treatment of patients with DLBCL.","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72436607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-28DOI: 10.1016/J.NEO.2017.11.008
J. Gibcus, L. Tan, G. Harms, R. Schakel, D. de Jong, T. Blokzijl, P. Möller, S. Poppema, B. Kroesen, A. van den Berg
{"title":"Corrigendum to \"Hodgkin Lymphoma Cell Lines Are Characterized by a Specific miRNA Expression Profile.\" Neoplasia 2009, Feb;11(2):167-176.","authors":"J. Gibcus, L. Tan, G. Harms, R. Schakel, D. de Jong, T. Blokzijl, P. Möller, S. Poppema, B. Kroesen, A. van den Berg","doi":"10.1016/J.NEO.2017.11.008","DOIUrl":"https://doi.org/10.1016/J.NEO.2017.11.008","url":null,"abstract":"","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2018-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74400869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-04-15DOI: 10.1158/1538-7445.AM2012-3745
B. Mukherjee, N. Tomimatsu, K. Amancherla, Cristel V. Camacho, N. Pichamoorthy, S. Burma
Inhibitors of PI3K/Akt signaling are being actively developed for tumor therapy owing to the frequent mutational activation of the PI3K-Akt-mTORC1 pathway in many cancers, including glioblastomas (GBMs). NVP-BEZ235 is a novel and potent dual PI3K/mTOR inhibitor that is currently in phase 1/2 clinical trials for advanced solid tumors. Here, we show that NVP-BEZ235 also potently inhibits ATM and DNA-PKcs, the two major kinases responding to ionizing radiation (IR)-induced DNA double-strand breaks (DSBs). Consequently, NVP-BEZ235 blocks both nonhomologous end joining and homologous recombination DNA repair pathways resulting in significant attenuation of DSB repair. In addition, phosphorylation of ATMtargets and implementation of the G(2)/M cell cycle checkpoint are also attenuated by this drug. As a result, NVP-BEZ235 confers an extreme degree of radiosensitization and impairs DSB repair in a panel of GBM cell lines irrespective of their Akt activation status. NVP-BEZ235 also significantly impairs DSB repair in a mouse tumor model thereby validating the efficacy of this drug as a DNA repair inhibitor in vivo. Our results, showing that NVP-BEZ235 is a potent and novel inhibitor of ATM and DNA-PKcs, have important implications for the informed and rational design of clinical trials involving this drug and also reveal the potential utility of NVP-BEZ235 as an effective radiosensitizer for GBMs in the clinic.
{"title":"The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKCs-mediated DNA damage responses.","authors":"B. Mukherjee, N. Tomimatsu, K. Amancherla, Cristel V. Camacho, N. Pichamoorthy, S. Burma","doi":"10.1158/1538-7445.AM2012-3745","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2012-3745","url":null,"abstract":"Inhibitors of PI3K/Akt signaling are being actively developed for tumor therapy owing to the frequent mutational activation of the PI3K-Akt-mTORC1 pathway in many cancers, including glioblastomas (GBMs). NVP-BEZ235 is a novel and potent dual PI3K/mTOR inhibitor that is currently in phase 1/2 clinical trials for advanced solid tumors. Here, we show that NVP-BEZ235 also potently inhibits ATM and DNA-PKcs, the two major kinases responding to ionizing radiation (IR)-induced DNA double-strand breaks (DSBs). Consequently, NVP-BEZ235 blocks both nonhomologous end joining and homologous recombination DNA repair pathways resulting in significant attenuation of DSB repair. In addition, phosphorylation of ATMtargets and implementation of the G(2)/M cell cycle checkpoint are also attenuated by this drug. As a result, NVP-BEZ235 confers an extreme degree of radiosensitization and impairs DSB repair in a panel of GBM cell lines irrespective of their Akt activation status. NVP-BEZ235 also significantly impairs DSB repair in a mouse tumor model thereby validating the efficacy of this drug as a DNA repair inhibitor in vivo. Our results, showing that NVP-BEZ235 is a potent and novel inhibitor of ATM and DNA-PKcs, have important implications for the informed and rational design of clinical trials involving this drug and also reveal the potential utility of NVP-BEZ235 as an effective radiosensitizer for GBMs in the clinic.","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2012-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88970982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-04-15DOI: 10.1158/1538-7445.AM2011-3919
V. A. Venkatesha, L. A. Parsels, J. Parsels, Lili Zhao, S. Zabludoff, D. Simeone, J. Maybaum, T. Lawrence, M. Morgan
Checkpoint kinase 1 (Chk1) inhibition sensitizes pancreatic cancer cells and tumors to gemcitabine. We hypothesized that Chk1 inhibition would sensitize pancreatic cancer stem cells to gemcitabine. We tested this hypothesis by using two patient-derived xenograft models (designated J and F) and the pancreatic cancer stem cell markers CD24, CD44, and ESA. We determined the percentage of marker-positive cells and their tumor-initiating capacity (by limiting dilution assays) after treatment with gemcitabine and the Chk1 inhibitor, AZD7762. We found that marker-positive cells were significantly reduced by the combination of gemcitabine and AZD7762. In addition, secondary tumor initiation was significantly delayed in response to primary tumor treatment with gemcitabine + AZD7762 compared with control, gemcitabine, or AZD7762 alone. Furthermore, for the same number of stem cells implanted from gemcitabine- versus gemcitabine + AZD7762-treated primary tumors, secondary tumor initiation at 10 weeks was 83% versus 43%, respectively. We also found that pS345 Chk1, which is a measure of DNA damage, was induced in marker-positive cells but not in the marker-negative cells. These data demonstrate that Chk1 inhibition in combination with gemcitabine reduces both the percentage and the tumor-initiating capacity of pancreatic cancer stem cells. Furthermore, the finding that the Chk1-mediated DNA damage response was greater in stem cells than in non-stem cells suggests that Chk1 inhibition may selectively sensitize pancreatic cancer stem cells to gemcitabine, thus making Chk1 a potential therapeutic target for improving pancreatic cancer therapy.
{"title":"Sensitization of pancreatic cancer stem cells to gemcitabine by Chk1 inhibition.","authors":"V. A. Venkatesha, L. A. Parsels, J. Parsels, Lili Zhao, S. Zabludoff, D. Simeone, J. Maybaum, T. Lawrence, M. Morgan","doi":"10.1158/1538-7445.AM2011-3919","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2011-3919","url":null,"abstract":"Checkpoint kinase 1 (Chk1) inhibition sensitizes pancreatic cancer cells and tumors to gemcitabine. We hypothesized that Chk1 inhibition would sensitize pancreatic cancer stem cells to gemcitabine. We tested this hypothesis by using two patient-derived xenograft models (designated J and F) and the pancreatic cancer stem cell markers CD24, CD44, and ESA. We determined the percentage of marker-positive cells and their tumor-initiating capacity (by limiting dilution assays) after treatment with gemcitabine and the Chk1 inhibitor, AZD7762. We found that marker-positive cells were significantly reduced by the combination of gemcitabine and AZD7762. In addition, secondary tumor initiation was significantly delayed in response to primary tumor treatment with gemcitabine + AZD7762 compared with control, gemcitabine, or AZD7762 alone. Furthermore, for the same number of stem cells implanted from gemcitabine- versus gemcitabine + AZD7762-treated primary tumors, secondary tumor initiation at 10 weeks was 83% versus 43%, respectively. We also found that pS345 Chk1, which is a measure of DNA damage, was induced in marker-positive cells but not in the marker-negative cells. These data demonstrate that Chk1 inhibition in combination with gemcitabine reduces both the percentage and the tumor-initiating capacity of pancreatic cancer stem cells. Furthermore, the finding that the Chk1-mediated DNA damage response was greater in stem cells than in non-stem cells suggests that Chk1 inhibition may selectively sensitize pancreatic cancer stem cells to gemcitabine, thus making Chk1 a potential therapeutic target for improving pancreatic cancer therapy.","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2011-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91335129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-15DOI: 10.1158/1538-7445.AM10-3428
Sun-jin Kim, Jang‐Seong Kim, E. Park, Ju-Seog Lee, Qingtang Lin, R. Langley, Marva Maya, Junqin He, S. Kim, Weihua Zhang, K. Balasubramanian, D. Fan, G. Mills, M. Hung, I. Fidler
In the United States, more than 40% of cancer patients develop brain metastasis. The median survival for untreated patients is 1 to 2 months, which may be extended to 6 months with conventional radiotherapy and chemotherapy. The growth and survival of metastasis depend on the interaction of tumor cells with host factors in the organ microenvironment. Brain metastases are surrounded and infiltrated by activated astrocytes and are highly resistant to chemotherapy. We report here that coculture of human breast cancer cells or lung cancer cells with murine astrocytes (but not murine fibroblasts) led to the up-regulation of survival genes, including GSTA5, BCL2L1, and TWIST1, in the tumor cells. The degree of up-regulation directly correlated with increased resistance to all tested chemotherapeutic agents. We further show that the up-regulation of the survival genes and consequent resistance are dependent on the direct contact between the astrocytes and tumor cells through gap junctions and are therefore transient. Knocking down these genes with specific small interfering RNA rendered the tumor cells sensitive to chemotherapeutic agents. These data clearly demonstrate that host cells in the microenvironment influence the biologic behavior of tumor cells and reinforce the contention that the organ microenvironment must be taken into consideration during the design of therapy.
{"title":"Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy.","authors":"Sun-jin Kim, Jang‐Seong Kim, E. Park, Ju-Seog Lee, Qingtang Lin, R. Langley, Marva Maya, Junqin He, S. Kim, Weihua Zhang, K. Balasubramanian, D. Fan, G. Mills, M. Hung, I. Fidler","doi":"10.1158/1538-7445.AM10-3428","DOIUrl":"https://doi.org/10.1158/1538-7445.AM10-3428","url":null,"abstract":"In the United States, more than 40% of cancer patients develop brain metastasis. The median survival for untreated patients is 1 to 2 months, which may be extended to 6 months with conventional radiotherapy and chemotherapy. The growth and survival of metastasis depend on the interaction of tumor cells with host factors in the organ microenvironment. Brain metastases are surrounded and infiltrated by activated astrocytes and are highly resistant to chemotherapy. We report here that coculture of human breast cancer cells or lung cancer cells with murine astrocytes (but not murine fibroblasts) led to the up-regulation of survival genes, including GSTA5, BCL2L1, and TWIST1, in the tumor cells. The degree of up-regulation directly correlated with increased resistance to all tested chemotherapeutic agents. We further show that the up-regulation of the survival genes and consequent resistance are dependent on the direct contact between the astrocytes and tumor cells through gap junctions and are therefore transient. Knocking down these genes with specific small interfering RNA rendered the tumor cells sensitive to chemotherapeutic agents. These data clearly demonstrate that host cells in the microenvironment influence the biologic behavior of tumor cells and reinforce the contention that the organ microenvironment must be taken into consideration during the design of therapy.","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2010-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74009150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-15DOI: 10.1158/1538-7445.AM10-LB-179
Huajun Zhao, F. Ou-Yang, I. Chen, M. Hou, S. Yuan, Hsueh-Ling Chang, Yi-Chen Lee, R. Plattner, S. Waltz, S. Ho, J. Sims, Shao-Chun Wang
Targeting the estrogen receptor is an important strategy in breast cancer therapy. However, although inhibiting estrogen receptor function with specific estrogen receptor modulators can achieve a primary response in cancer patients, intrinsic or subsequently acquired resistance to the therapy remains a major obstacle in the clinic. Thus, it is critical to gain a more thorough understanding of how estrogen receptor functions are regulated in breast cancer.Here, we demonstrate that the non-receptor tyrosine kinase c-ABL is a functional partner of the estrogen receptor, as expression of c-ABL sustained transcriptional activity of the estrogen receptor. More importantly, inhibition of c-ABL resulted in sensitization to treatment by tamoxifen (TAM) in estrogen receptor-positive breast cancer cells, as manifested by inhibition of cell survival and suppression of anchorage-independent growth. We found that c-ABL interacts with estrogen receptor in breast cancer cells and that expression of c-ABL is a frequent event in primary breast cancer tumor tissues. In estrogen receptor-positive tumors, the expression of c-ABL significantly correlated with disease progression and metastasis. This study shows that c-ABL regulates the cellular response to TAM through functional interaction with the estrogen receptor, which suggests c-ABL as a therapeutic target and a prognostic tumor marker for breast cancer.
{"title":"Enhanced resistance to tamoxifen by the c-ABL proto-oncogene in breast cancer.","authors":"Huajun Zhao, F. Ou-Yang, I. Chen, M. Hou, S. Yuan, Hsueh-Ling Chang, Yi-Chen Lee, R. Plattner, S. Waltz, S. Ho, J. Sims, Shao-Chun Wang","doi":"10.1158/1538-7445.AM10-LB-179","DOIUrl":"https://doi.org/10.1158/1538-7445.AM10-LB-179","url":null,"abstract":"Targeting the estrogen receptor is an important strategy in breast cancer therapy. However, although inhibiting estrogen receptor function with specific estrogen receptor modulators can achieve a primary response in cancer patients, intrinsic or subsequently acquired resistance to the therapy remains a major obstacle in the clinic. Thus, it is critical to gain a more thorough understanding of how estrogen receptor functions are regulated in breast cancer.Here, we demonstrate that the non-receptor tyrosine kinase c-ABL is a functional partner of the estrogen receptor, as expression of c-ABL sustained transcriptional activity of the estrogen receptor. More importantly, inhibition of c-ABL resulted in sensitization to treatment by tamoxifen (TAM) in estrogen receptor-positive breast cancer cells, as manifested by inhibition of cell survival and suppression of anchorage-independent growth. We found that c-ABL interacts with estrogen receptor in breast cancer cells and that expression of c-ABL is a frequent event in primary breast cancer tumor tissues. In estrogen receptor-positive tumors, the expression of c-ABL significantly correlated with disease progression and metastasis. This study shows that c-ABL regulates the cellular response to TAM through functional interaction with the estrogen receptor, which suggests c-ABL as a therapeutic target and a prognostic tumor marker for breast cancer.","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2010-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80715255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Grochola, T. Greither, H. Taubert, P. Möller, U. Knippschild, A. Udelnow, D. Henne-Bruns, P. Würl
Telomerase is thought to play an essential role in tumorigenesis and progression. Its activity is directly correlated with the expression of its catalytic subunit, human telomerase reverse transcriptase (hTERT). A correlation of transcript expression with a poor prognosis has been detected in different human malignancies. However, data on hTERT in pancreatic ductal adenocarcinoma (PDAC) are purely descriptive so far. Therefore, we evaluated the impact of hTERT expression on patients' prognosis. Human telomerase reverse transcriptase mRNA isolates from 56 human microdissected PDAC tissues were analyzed by quantitative reverse transcription-polymerase chain reaction and multivariate Cox regression hazard test. Elevated hTERT transcript levels were measured in 23 of 56 PDAC tissues, 33 patients showed no detectable transcripts. Unexpectedly, a low expression of hTERT mRNA levels was associated with a worse prognosis for overall survival (relative risk = 5.33; P = .013) when compared to high levels, whereas undetectable expression showed an intermediate risk of tumor-related death. These data challenge previous findings outlining hTERT's negative impact on overall survival. The risk pattern obtained in PDAC suggests a more complex regulation of hTERT.
{"title":"Prognostic relevance of hTERT mRNA expression in ductal adenocarcinoma of the pancreas.","authors":"L. Grochola, T. Greither, H. Taubert, P. Möller, U. Knippschild, A. Udelnow, D. Henne-Bruns, P. Würl","doi":"10.1055/S-0028-1089530","DOIUrl":"https://doi.org/10.1055/S-0028-1089530","url":null,"abstract":"Telomerase is thought to play an essential role in tumorigenesis and progression. Its activity is directly correlated with the expression of its catalytic subunit, human telomerase reverse transcriptase (hTERT). A correlation of transcript expression with a poor prognosis has been detected in different human malignancies. However, data on hTERT in pancreatic ductal adenocarcinoma (PDAC) are purely descriptive so far. Therefore, we evaluated the impact of hTERT expression on patients' prognosis. Human telomerase reverse transcriptase mRNA isolates from 56 human microdissected PDAC tissues were analyzed by quantitative reverse transcription-polymerase chain reaction and multivariate Cox regression hazard test. Elevated hTERT transcript levels were measured in 23 of 56 PDAC tissues, 33 patients showed no detectable transcripts. Unexpectedly, a low expression of hTERT mRNA levels was associated with a worse prognosis for overall survival (relative risk = 5.33; P = .013) when compared to high levels, whereas undetectable expression showed an intermediate risk of tumor-related death. These data challenge previous findings outlining hTERT's negative impact on overall survival. The risk pattern obtained in PDAC suggests a more complex regulation of hTERT.","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2008-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87333941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Z. Gil, K. Kelly, P. Brader, J. Shah, Y. Fong, R. Wong
Prostate, pancreatic, and head and neck carcinomas have a high propensity to invade nerves. Surgical resection is a treatment modality for these patients, but it may incur significant deficits. The development of an imaging method able to detect neural invasion (NI) by cancer cells may guide surgical resection and facilitate preservation of normal nerves. We describe an imaging method for the detection of NI using a herpes simplex virus, NV1066, carrying tyrosine kinase and enhanced green fluorescent protein (eGFP). Infection of pancreatic (MiaPaCa2), prostate (PC3 and DU145), and adenoid cystic carcinoma (ACC3) cell lines with NV1066 induced a high expression of eGFP in vitro. An in vivo murine model of NI was established by implanting tumors into the sciatic nerves of nude mice. Nerves were then injected with NV1066, and infection was confirmed by polymerase chain reaction. Positron emission tomography with [(18)F]-2'-fluoro-2'-deoxyarabinofuranosyl-5-ethyluracil performed showed significantly higher uptake in NI than in control animals. Intraoperative fluorescent stereoscopic imaging revealed eGFP signal in NI treated with NV1066. These findings show that NV1066 may be an imaging method to enhance the detection of nerves infiltrated by cancer cells. This method may improve the diagnosis and treatment of patients with neurotrophic cancers by reducing injury to normal nerves and facilitating identification of infiltrated nerves requiring resection.
{"title":"Utility of a herpes oncolytic virus for the detection of neural invasion by cancer.","authors":"Z. Gil, K. Kelly, P. Brader, J. Shah, Y. Fong, R. Wong","doi":"10.1055/s-2008-1093272","DOIUrl":"https://doi.org/10.1055/s-2008-1093272","url":null,"abstract":"Prostate, pancreatic, and head and neck carcinomas have a high propensity to invade nerves. Surgical resection is a treatment modality for these patients, but it may incur significant deficits. The development of an imaging method able to detect neural invasion (NI) by cancer cells may guide surgical resection and facilitate preservation of normal nerves. We describe an imaging method for the detection of NI using a herpes simplex virus, NV1066, carrying tyrosine kinase and enhanced green fluorescent protein (eGFP). Infection of pancreatic (MiaPaCa2), prostate (PC3 and DU145), and adenoid cystic carcinoma (ACC3) cell lines with NV1066 induced a high expression of eGFP in vitro. An in vivo murine model of NI was established by implanting tumors into the sciatic nerves of nude mice. Nerves were then injected with NV1066, and infection was confirmed by polymerase chain reaction. Positron emission tomography with [(18)F]-2'-fluoro-2'-deoxyarabinofuranosyl-5-ethyluracil performed showed significantly higher uptake in NI than in control animals. Intraoperative fluorescent stereoscopic imaging revealed eGFP signal in NI treated with NV1066. These findings show that NV1066 may be an imaging method to enhance the detection of nerves infiltrated by cancer cells. This method may improve the diagnosis and treatment of patients with neurotrophic cancers by reducing injury to normal nerves and facilitating identification of infiltrated nerves requiring resection.","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2008-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88833322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-03-01DOI: 10.1016/S1569-9056(08)60821-0
R. Kuefer, F. Genze, Waltraud Zugmaier, R. Hautmann, L. Rinnab, J. Gschwend, Marina Angelmeier, A. Estrada, B. Buechele
{"title":"Antagonistic effects of sodium butyrate and N-(4-hydroxyphenyl)-retinamide on prostate cancer.","authors":"R. Kuefer, F. Genze, Waltraud Zugmaier, R. Hautmann, L. Rinnab, J. Gschwend, Marina Angelmeier, A. Estrada, B. Buechele","doi":"10.1016/S1569-9056(08)60821-0","DOIUrl":"https://doi.org/10.1016/S1569-9056(08)60821-0","url":null,"abstract":"","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2007-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74578350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neoplasia was launched in 1999 with the mission of providing a high-quality publication venue for the rapid dissemination of novel and exciting advances in cancer research. The journal has grown, in a very rapid fashion, from a bimonthly publication to a monthly publication by publishing a broad-based range of articles ranging from apoptosis to angiogenesis, as shown in Table 1. This table categorizes articles published by Neoplasia by general topic for publication years 2004 to 2006. Cancer genetics, cell and tumor biology, experimental therapeutics, and cancer imaging continue to be significant components of article growth published over these years. The number of submissions and published articles has continually increased over the year, and, next year, Neoplasia will enter its ninth year of publication (Vol. 9). The success of Neoplasia has affirmed to the editorial staff and editorial board that there was and continues to be a significant need for a broad-based cancer journal. During the past year, Neoplasia has further adapted and taken the lead in online peer-reviewed publication of cancer research articles. Table 1 Major Research Topics Published in Neoplasia from 2004 to 2006. In 2006, Neoplasia adopted the open access (OA) model for all articles published. This allows for all articles to be made available free to the scientific and layman communities through online electronic access. All articles are linked through PubMed (www.PubMEd.gov) to a Web-based database, which hosts all Neoplasia articles published to date. Moreover, beginning in 2007, all Neoplasia articles published in Neoplasia will also be freely available through the Biomedcentral portal (http://www.biomedcentral.com/) beginning on the day of publication, rather than after 6 to 12 months like most journals. Of 8700 selected journals currently covered in Web of Science, only 160 are available through Biomedcentral. The effect of immediate OA on the impact of Neoplasia is anticipated to dramatically improve the citation impact factor in terms of the frequency with which an article is cited in the literature (http://dlib.org/dlib/june04/harnad/06harnad.html) [301]. Overall, OA will provide for dramatically increased readership due to access to articles, which would traditionally be unavailable due to costs associated with access tolls to the journal in which it was published because their affiliated institution could not afford the price of subscription. Overall, providing OA to all past, present, and future articles published in Neoplasia should significantly improve the quality and speed at which cancer research advances will be made due to more rapid dissemination of knowledge. Neoplasia is committed to meeting the challenges and emerging needs of the cancer research scientific community. This commitment has been met through the early establishment of a rapid online peer-review system, which has facilitated review of submitted articles. Moreover, the re
《肿瘤》杂志于1999年创办，其使命是提供一个高质量的出版场所，以便快速传播癌症研究方面令人兴奋的新进展。通过发表从细胞凋亡到血管生成的广泛的文章，该杂志以非常迅速的方式从双月刊发展到月刊，如表1所示。本表按2004至2006年出版年度Neoplasia发表的文章按一般题目分类。癌症遗传学，细胞和肿瘤生物学，实验治疗学和癌症成像继续是这些年来发表的文章增长的重要组成部分。投稿和发表的文章数量在过去的一年中不断增加，明年，Neoplasia将进入其出版的第九个年头(第9卷)。Neoplasia的成功向编辑人员和编辑委员会证实了对一本基础广泛的癌症期刊的巨大需求。在过去的一年里，Neoplasia进一步适应并在在线同行评审的癌症研究文章发表方面处于领先地位。表1 2004 - 2006年肿瘤学发表的主要研究课题。2006年，Neoplasia对所有发表的文章采用开放获取(OA)模式。这使得所有的文章都可以通过在线电子访问免费提供给科学界和非专业人士。所有文章都通过PubMed (www.PubMEd.gov)链接到一个基于web的数据库，该数据库包含迄今为止发表的所有Neoplasia文章。此外，从2007年开始，所有发表在Neoplasia上的文章也将从发表当天开始通过生物中心门户网站(http://www.biomedcentral.com/)免费提供，而不是像大多数期刊那样需要6到12个月。在Web Of Science目前收录的8700种精选期刊中，只有160种可以通过Biomedcentral找到。直接开放获取对Neoplasia影响的影响预计将显著提高文献中文章被引用的频率(http://dlib.org/dlib/june04/harnad/06harnad.html)[301]。总的来说，开放获取将极大地增加读者数量，因为他们可以访问文章，而这些文章在传统上是无法获得的，因为他们的附属机构无法负担订阅费用，而这些费用与发表文章的期刊的访问费用相关。总的来说，为Neoplasia杂志上发表的所有过去、现在和未来的文章提供OA应该会显著提高癌症研究的质量和速度，因为知识的传播更加迅速。肿瘤学致力于满足癌症研究科学界的挑战和新兴需求。通过早期建立快速在线同行评议系统实现了这一承诺，该系统促进了对提交文章的评议。此外，2006年的开放获取，以及2007年扩展到生物医学中心，将最大限度地提供Neoplasia发表的所有手稿的国际传播。这种前瞻性的方法允许所有已发表文章的即时OA可用性，应该为使用Neoplasia作为其发表场所的作者提供其令人兴奋的研究成果的最大影响。
{"title":"Neoplasia: Where We Have Been and Where We Are Going","authors":"A. Rehemtulla","doi":"10.1593/NEO.08EDI","DOIUrl":"https://doi.org/10.1593/NEO.08EDI","url":null,"abstract":"Neoplasia was launched in 1999 with the mission of providing a high-quality publication venue for the rapid dissemination of novel and exciting advances in cancer research. The journal has grown, in a very rapid fashion, from a bimonthly publication to a monthly publication by publishing a broad-based range of articles ranging from apoptosis to angiogenesis, as shown in Table 1. This table categorizes articles published by Neoplasia by general topic for publication years 2004 to 2006. Cancer genetics, cell and tumor biology, experimental therapeutics, and cancer imaging continue to be significant components of article growth published over these years. The number of submissions and published articles has continually increased over the year, and, next year, Neoplasia will enter its ninth year of publication (Vol. 9). The success of Neoplasia has affirmed to the editorial staff and editorial board that there was and continues to be a significant need for a broad-based cancer journal. During the past year, Neoplasia has further adapted and taken the lead in online peer-reviewed publication of cancer research articles. \u0000 \u0000 \u0000 \u0000Table 1 \u0000 \u0000Major Research Topics Published in Neoplasia from 2004 to 2006. \u0000 \u0000 \u0000 \u0000In 2006, Neoplasia adopted the open access (OA) model for all articles published. This allows for all articles to be made available free to the scientific and layman communities through online electronic access. All articles are linked through PubMed (www.PubMEd.gov) to a Web-based database, which hosts all Neoplasia articles published to date. Moreover, beginning in 2007, all Neoplasia articles published in Neoplasia will also be freely available through the Biomedcentral portal (http://www.biomedcentral.com/) beginning on the day of publication, rather than after 6 to 12 months like most journals. Of 8700 selected journals currently covered in Web of Science, only 160 are available through Biomedcentral. The effect of immediate OA on the impact of Neoplasia is anticipated to dramatically improve the citation impact factor in terms of the frequency with which an article is cited in the literature (http://dlib.org/dlib/june04/harnad/06harnad.html) [301]. Overall, OA will provide for dramatically increased readership due to access to articles, which would traditionally be unavailable due to costs associated with access tolls to the journal in which it was published because their affiliated institution could not afford the price of subscription. Overall, providing OA to all past, present, and future articles published in Neoplasia should significantly improve the quality and speed at which cancer research advances will be made due to more rapid dissemination of knowledge. \u0000 \u0000Neoplasia is committed to meeting the challenges and emerging needs of the cancer research scientific community. This commitment has been met through the early establishment of a rapid online peer-review system, which has facilitated review of submitted articles. Moreover, the re","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2006-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88166866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：