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Chuan-Yuan Li

Adjunct Professor in the Department of Dermatology
Dermatology
Box 3135 Med Ctr, Durham, NC 27710
Box 3135, DUMC, C303A/LSRC, Durham, NC 27710

Selected Publications


Targeting Catechol-O-Methyltransferase Induces Mitochondrial Dysfunction and Enhances the Efficacy of Radiotherapy in Glioma.

Journal Article Cancer Res · November 4, 2024 Radiotherapy (RT) is commonly used to try to eliminate any remaining tumor cells following surgical resection of glioma. However, tumor recurrence is prevalent, highlighting the unmet medical need to develop therapeutic strategies to enhance the efficacy o ... Full text Link to item Cite

Data from Targeting Catechol-O-Methyltransferase Induces Mitochondrial Dysfunction and Enhances the Efficacy of Radiotherapy in Glioma

Other · November 4, 2024 <div>Abstract<p>Radiotherapy (RT) is commonly used to try to eliminate any remaining tumor cells following surgical resection of glioma. However, tumor recurrence is prevalent, highlighting the unmet medical need to develop therapeutic ... Full text Cite

VHL loss enhances antitumor immunity by activating the anti-viral DNA-sensing pathway.

Journal Article iScience · July 19, 2024 von Hippel-Lindau (VHL), known as a tumor suppressor gene, is frequently mutated in clear cell renal cell carcinoma (ccRCC). However, VHL mutation is not sufficient to promote tumor formation. In most cases other than ccRCC, VHL loss alters cellular homeos ... Full text Link to item Cite

Caspase-3 promotes oncogene-induced malignant transformation via EndoG-dependent Src-STAT3 phosphorylation.

Journal Article Cell Death Dis · July 9, 2024 Accumulating evidence suggests that caspase-3 plays critical roles beyond apoptosis, serving pro-survival functions in malignant transformation and tumorigenesis. However, the mechanism of non-apoptotic action of caspase-3 in oncogenic transformation remai ... Full text Link to item Cite

VHL loss enables immune checkpoint blockade therapy by boosting type I interferon response.

Journal Article bioRxiv · November 30, 2023 Despite a moderate mutation burden, clear cell renal cell carcinoma (ccRCC) responds well to immune checkpoint blockade (ICB) therapy. Here we report that loss-of-function mutations in the von Hippel-Lindau (VHL) gene, the most frequent in ccRCC, underlies ... Full text Link to item Cite

Near-Death Cells Cause Chemotherapy-Induced Metastasis via ATF4-Mediated NF-ĪŗB Signaling Activation.

Journal Article Adv Sci (Weinh) · April 2023 Cytotoxic chemotherapy is a primary treatment modality for many patients with advanced cancer. Increasing preclinical and clinical observations indicate that chemotherapy can exacerbate tumor metastasis. However, the underlying mechanism remains unclear. H ... Full text Link to item Cite

Cancer Cells Enter an Adaptive Persistence to Survive Radiotherapy and Repopulate Tumor.

Journal Article Adv Sci (Weinh) · March 2023 Repopulation of residual tumor cells impedes curative radiotherapy, yet the mechanism is not fully understood. It is recently appreciated that cancer cells adopt a transient persistence to survive the stress of chemo- or targeted therapy and facilitate eve ... Full text Link to item Cite

Non-canonical roles of apoptotic and DNA double-strand break repair factors in mediating cellular response to ionizing radiation.

Journal Article Int J Radiat Biol · 2023 PURPOSE: To provide an updated summary of recent advances in our understanding of the non-canonical roles of apoptotic and DNA double-strand break repair factors in various biological processes, especially in the cellular response to radiotherapy. CONCLUSI ... Full text Link to item Cite

SETDB1 Restrains Endogenous Retrovirus Expression and Antitumor Immunity during Radiotherapy.

Journal Article Cancer Res · August 3, 2022 UNLABELLED: The type I interferon response plays a pivotal role in promoting antitumor immune activity in response to radiotherapy. The identification of approaches to boost the radiation-induced type I interferon response could help improve the efficacy o ... Full text Link to item Cite

Inhibition of ALG3 stimulates cancer cell immunogenic ferroptosis to potentiate immunotherapy.

Journal Article Cell Mol Life Sci · June 8, 2022 Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. However, low response rates and immune-related adverse events remain important limitations. Here, we report that inhibiting ALG3, an a-1,3-mannosyl ... Full text Link to item Cite

SET8 Inhibition Potentiates Radiotherapy by Suppressing DNA Damage Repair in Carcinomas.

Journal Article Biomed Environ Sci · March 20, 2022 OBJECTIVE: SET8 is a member of the SET domain-containing family and the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20me1). SET8 has been implicated in many essential cellular processes, including cell cycle re ... Full text Link to item Cite

A pleiotropic ATM variant (rs1800057 C>G) is associated with risk of multiple cancers.

Journal Article Carcinogenesis · February 11, 2022 ATM (ataxia-telangiectasia mutated) is an important cell-cycle checkpoint kinase required for cellular response to DNA damage. Activated by DNA double strand breaks, ATM regulates the activities of many downstream proteins involved in various carcinogenic ... Full text Open Access Link to item Cite

Targeting Glycolysis in Alloreactive T Cells to Prevent Acute Graft-Versus-Host Disease While Preserving Graft-Versus-Leukemia Effect.

Journal Article Front Immunol · 2022 Alloreactive donor T cells undergo extensive metabolic reprogramming to become activated and induce graft-versus-host disease (GVHD) upon alloantigen encounter. It is generally thought that glycolysis, which promotes T cell growth and clonal expansion, is ... Full text Link to item Cite

A Gene Mutation Signature Predicting Immunotherapy Benefits in Patients With NSCLC.

Journal Article J Thorac Oncol · March 2021 INTRODUCTION: Identification of patients who can benefit from immune checkpoint blockade (ICB) therapy is key for improved clinical outcome. Recently, U.S. Food and Drug Administration approved tumor mutational burden (TMB) high (TMB-H or TMB ≄ 10) as a bi ... Full text Link to item Cite

ATM inhibition enhances cancer immunotherapy by promoting mtDNA leakage and cGAS/STING activation.

Journal Article J Clin Invest · February 1, 2021 Novel approaches are needed to boost the efficacy of immune checkpoint blockade (ICB) therapy. Ataxia telangiectasia mutated (ATM) protein plays a central role in sensing DNA double-stranded breaks (DSBs) and coordinating their repair. Recent data indicate ... Full text Link to item Cite

miR-29b-3p Increases Radiosensitivity in Stemness Cancer Cells via Modulating Oncogenes Axis.

Journal Article Front Cell Dev Biol · 2021 Radioresistance conferred by cancer stem cells (CSCs) is the principal cause of the failure of cancer radiotherapy. Eradication of CSCs is a prime therapeutic target and a requirement for effective radiotherapy. Three dimensional (3D) cell-cultured model c ... Full text Link to item Cite

Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer.

Journal Article Nature · December 2020 Despite its success in achieving the long-term survival of 10-30% of treated individuals, immune therapy is still ineffective for most patients with cancer1,2. Many efforts are therefore underway to identify new approaches that enhance such immune 'checkpo ... Full text Link to item Cite

JMJD5 couples with CDK9 to release the paused RNA polymerase II.

Journal Article Proc Natl Acad Sci U S A · August 18, 2020 More than 30% of genes in higher eukaryotes are regulated by RNA polymerase II (Pol II) promoter proximal pausing. Pausing is released by the positive transcription elongation factor complex (P-TEFb). However, the exact mechanism by which this occurs and w ... Full text Link to item Cite

ATM Paradoxically Promotes Oncogenic Transformation via Transcriptional Reprogramming.

Journal Article Cancer Res · April 15, 2020 The role of the ataxia-telangiectasia-mutated (ATM) gene in human malignancies, especially in solid tumors, remains poorly understood. In the present study, we explored the involvement of ATM in transforming primary human cells into cancer stem cells. We s ... Full text Link to item Cite

Endogenous Retrovirus Activation as a Key Mechanism of Anti-Tumor Immune Response in Radiotherapy.

Journal Article Radiat Res · April 2020 The generation of DNA double-strand breaks has historically been taught as the mechanism through which radiotherapy kills cancer cells. Recently, radiation-induced cytosolic DNA release and activation of the cGAS/STING pathway, with ensuing induction of in ... Full text Link to item Cite

JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes.

Journal Article Elife · February 12, 2020 More than 30% of genes in higher eukaryotes are regulated by promoter-proximal pausing of RNA polymerase II (Pol II). Phosphorylation of Pol II CTD by positive transcription elongation factor b (P-TEFb) is a necessary precursor event that enables productiv ... Full text Link to item Cite

Limited MOMP, ATM, and their roles in carcinogenesis and cancer treatment.

Journal Article Cell Biosci · 2020 Limited mitochondria outer membrane permeability (MOMP) is a novel biological process where mammalian cells initiate the intrinsic apoptosis pathway with increased mitochondrial permeability but survive. One of the major consequences of limited MOMP is apo ... Full text Link to item Cite

Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway.

Journal Article J Exp Clin Cancer Res · November 9, 2019 BACKGROUND: Tumor cell repopulation after radiotherapy is a major cause for the tumor radioresistance and recurrence. This study aims to investigate the underlying mechanism of tumor repopulation after radiotherapy, with focus on whether and how necroptosi ... Full text Link to item Cite

The Caspase-3/PKCĪ“/Akt/VEGF-A Signaling Pathway Mediates Tumor Repopulation during Radiotherapy.

Journal Article Clin Cancer Res · June 15, 2019 PURPOSE: Tumor repopulation is known as a major cause of treatment failure and/or tumor recurrence after radiotherapy. The underlying mechanism remains unclear. Our previous study demonstrated that irradiated apoptotic cells mediated tumor repopulation, in ... Full text Link to item Cite

Non-apoptotic Roles of Caspases in Stem Cell Biology, Carcinogenesis, and Radiotherapy

Journal Article Current Stem Cell Reports · March 15, 2019 Purpose of Review: To summarize recent findings on novel roles of caspases in stem cell biology, tumor repopulation, and tissue regeneration. Contrary to the long-held notion that apoptotic caspases are exclusively executioners of programmed cell death, an ... Full text Cite

CRISPR/Cas9-Mediated BRCA1 Knockdown Adipose Stem Cells Promote Breast Cancer Progression.

Journal Article Plast Reconstr Surg · March 2019 BACKGROUND: The tumor microenvironment within the breast is rich in adipose elements. The interaction between adipose cells and breast cancer is poorly understood, particularly as it pertains to patients with genetic susceptibility to breast cancer. This s ... Full text Link to item Cite

UBE2N Promotes Melanoma Growth via MEK/FRA1/SOX10 Signaling.

Journal Article Cancer Res · November 15, 2018 UBE2N is a K63-specific ubiquitin conjugase linked to various immune disorders and cancer. Here, we demonstrate that UBE2N and its partners UBE2V1 and UBE2V2 are highly expressed in malignant melanoma. Silencing of UBE2N and its partners significantly decr ... Full text Link to item Cite

Novel roles of apoptotic caspases in tumor repopulation, epigenetic reprogramming, carcinogenesis, and beyond.

Journal Article Cancer Metastasis Rev · September 2018 Apoptotic caspases have long been studied for their roles in programmed cell death and tumor suppression. With recent discoveries, however, it is becoming apparent these cell death executioners are involved in additional biological pathways beyond killing ... Full text Link to item Cite

Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells.

Journal Article Int J Cancer · August 15, 2018 Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 has also n ... Full text Link to item Cite

HMGB1 released by irradiated tumor cells promotes living tumor cell proliferation via paracrine effect.

Journal Article Cell Death Dis · May 29, 2018 Tumor repopulation during therapy is an important cause of treatment failure. Strategies to overcome repopulation are arising in parallel with advances in the comprehension of underlying biological mechanisms. Here, we reveal a new mechanism by which high ... Full text Link to item Cite

189 Genetic variants in the autophagy pathway genes predict melanoma survival

Conference Journal of Investigative Dermatology · May 2018 Full text Cite

UBE2N promotes melanoma growth by maintaining MEK and FRA1 signaling

Conference JOURNAL OF INVESTIGATIVE DERMATOLOGY · May 1, 2018 Link to item Cite

1213 Exosome-mediated RNAi delivery for melanoma therapy

Conference Journal of Investigative Dermatology · May 2018 Full text Cite

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7.

Journal Article Proc Natl Acad Sci U S A · September 12, 2017 Two of the unsolved, important questions about epigenetics are: do histone arginine demethylases exist, and is the removal of histone tails by proteolysis a major epigenetic modification process? Here, we report that two orphan Jumonji C domain (JmjC)-cont ... Full text Link to item Cite

Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis.

Journal Article Elife · July 10, 2017 The mechanism for Myc-induced genetic instability is not well understood. Here we show that sublethal activation of Caspase-3 plays an essential, facilitative role in Myc-induced genomic instability and oncogenic transformation. Overexpression of Myc resul ... Full text Link to item Cite

Self-inflicted DNA double-strand breaks sustain tumorigenicity and stemness of cancer cells.

Journal Article Cell Res · June 2017 DNA double-strand breaks (DSBs) are traditionally associated with cancer through their abilities to cause chromosomal instabilities or gene mutations. Here we report a new class of self-inflicted DNA DSBs that can drive tumor growth irrespective of their e ... Full text Link to item Cite

Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism.

Journal Article Cancer Lett · January 28, 2017 Vascular recovery or re-angiogenesis after radiotherapy plays a significant role in tumor recurrence, whereas molecular mechanisms of this process remain elusive. In this work, we found that dying glioma cells promoted post-irradiation angiogenesis through ... Full text Link to item Cite

Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.

Journal Article Cancer Res · September 1, 2016 Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genet ... Full text Link to item Cite

eIF4E-phosphorylation-mediated Sox2 upregulation promotes pancreatic tumor cell repopulation after irradiation.

Journal Article Cancer Lett · May 28, 2016 Pancreatic cancer is a devastating disease characterized by treatment resistance and high recurrence rate. Repopulation of surviving tumor cells undergoing radiotherapy is one of the most common reasons for recurrence. Our previous studies have discovered ... Full text Link to item Cite

Redefining the roles of apoptotic factors in carcinogenesis.

Journal Article Mol Cell Oncol · May 2016 In a recent study we reported that mammalian cells exposed to stress such as ionizing radiation can survive with activation of caspase-3 or caspase-7. We found that sublethal activation of the executioner caspases promotes chemical- and radiation-induced g ... Full text Link to item Cite

116 Roles of caspases in melanoma response to cytotoxic treatment

Conference Journal of Investigative Dermatology · May 2016 Full text Cite

Key roles of necroptotic factors in promoting tumor growth.

Journal Article Oncotarget · April 19, 2016 Necroptotic factors are generally assumed to play a positive role in tumor therapy by eliminating damaged tumor cells. Here we show that, contrary to expectation, necroptotic factors RIPK1, RIPK3, and MLKL promote tumor growth. We demonstrate that genetic ... Full text Link to item Cite

Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis.

Journal Article Oncotarget · October 20, 2015 Cytotoxic radiotherapy unfavorably induces tumor cells to generate various proangiogenic substances, promoting post-irradiation angiogenesis (PIA), which is one of major causes of radiotherapy failure. Though several studies have reported some mechanisms b ... Full text Link to item Cite

Abstract LB-087: A facilitative role for caspase 3 in promoting genetic instability and carcinogenesis

Conference Cancer Research · August 1, 2015 AbstractApoptosis and apoptotic caspases are generally considered tumor-suppressive since there are involved in the elimination of unwanted or damaged cells. However, the relationship between caspases and ca ... Full text Cite

Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells and are correlated with the poor prognosis in colorectal cancer.

Journal Article J Exp Clin Cancer Res · May 20, 2015 BACKGROUND: Dying tumor cells after irradiation could promote the proliferation of living tumor cells might cause tumor relapse and treatment failure. Our previous study showed that activated caspase-3 after irradiation probably participates in tumor repop ... Full text Link to item Cite

Caspase-3 promotes genetic instability and carcinogenesis.

Journal Article Mol Cell · April 16, 2015 Apoptosis is typically considered an anti-oncogenic process since caspase activation can promote the elimination of genetically unstable or damaged cells. We report that a central effector of apoptosis, caspase-3, facilitates rather than suppresses chemica ... Full text Link to item Cite

Dying tumor cells stimulate proliferation of living tumor cells via caspase-dependent protein kinase CĪ“ activation in pancreatic ductal adenocarcinoma.

Journal Article Mol Oncol · January 2015 Pancreatic cancer is one of the most lethal human cancers, and radiotherapy is often implemented for locally advanced pancreatic ductal adenocarcinoma. Tumor cell repopulation is a major challenge in treating cancers after radiotherapy. In order to address ... Full text Link to item Cite

Dissecting the roles of E1A and E1B in adenoviral replication and RCAd-enhanced RDAd transduction efficacy on tumor cells.

Journal Article Cancer Biol Ther · October 2014 Oncolytic viruses have recently received widespread attention for their potential in innovative cancer therapy. Many telomerase promoter-regulated oncolytic adenoviral vectors retain E1A and E1B. However, the functions of E1A and E1B proteins in the oncoly ... Full text Link to item Cite

Enhancing the efficiency of direct reprogramming of human primary fibroblasts into dopaminergic neuron-like cells through p53 suppression.

Journal Article Sci China Life Sci · September 2014 Dopaminergic (DA) neuron-like cells obtained through direct reprogramming of primary human fibroblasts offer exciting opportunities for treatment of Parkinson's disease. A significant obstacle is the low efficiency of conversion during the reprogramming pr ... Full text Link to item Cite

Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy.

Journal Article J Invest Dermatol · June 2014 Metastatic melanoma often relapses despite cytotoxic treatment, and hence the understanding of melanoma tumor repopulation is crucial for improving our current therapies. In this study, we aim to define the role of caspase 3 in melanoma tumor growth after ... Full text Link to item Cite

Mathematical modeling of the Phoenix Rising pathway.

Journal Article PLoS Comput Biol · February 2014 Apoptosis is a tightly controlled process in mammalian cells. It is important for embryogenesis, tissue homoeostasis, and cancer treatment. Apoptosis not only induces cell death, but also leads to the release of signals that promote rapid proliferation of ... Full text Link to item Cite

Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy

Journal Article Journal of Investigative Dermatology · January 1, 2014 Metastatic melanoma often relapses despite cytotoxic treatment, and hence the understanding of melanoma tumor repopulation is crucial for improving our current therapies. In this study, we aim to define the role of caspase 3 in melanoma tumor growth after ... Full text Cite

A novel EGFR isoform confers increased invasiveness to cancer cells.

Journal Article Cancer Res · December 1, 2013 As a validated therapeutic target in several human cancers, the EGF receptor (EGFR) provides a focus to gain deeper insights into cancer pathophysiology. In this study, we report the identification of a naturally occurring and widely expressed EGFR isoform ... Full text Link to item Cite

Preface

Journal Article Translational Cancer Research · October 1, 2013 Full text Cite

Novel prognostic markers for patients with triple-negative breast cancer.

Journal Article Hum Pathol · October 2013 Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by poor prognosis. Currently, no reliable markers have been identified as having a predictive role for the prognosis of TNBC patients. In this study, 119 breast cancer samples ... Full text Link to item Cite

Cell death-stimulated cell proliferation: a tissue regeneration mechanism usurped by tumors during radiotherapy.

Journal Article Semin Radiat Oncol · October 2013 The death of all the cancer cells in a tumor is the ultimate goal of cancer therapy. Therefore, much of the current effort in cancer research is focused on activating cellular machinery that facilitates cell death such as factors involved in causing apopto ... Full text Link to item Cite

Molecular markers of therapeutic resistance in breast cancer.

Journal Article Hum Pathol · July 2013 Resistance to chemotherapy and endocrine therapy is a serious obstacle in the treatment of breast cancer. Highly specific biomarkers for predicting therapeutic resistance have not yet been identified. In this study, the amounts of aldehyde dehydrogenase 1, ... Full text Link to item Cite

Relationship of oral glycine with radiation-induced HIF1-alpha and tumor growth delay in a prostate cancer xenograft.

Journal Article J Clin Oncol · February 20, 2013 81 Background: Preclinical studies have shown that nitric oxide (NO) is produced by upregulation of inducible nitric oxide synthase (iNOS) in activated macrophages recruited to the site of cytotoxic injury from radiation or chemotherapy. NO stabilizes hypo ... Full text Link to item Cite

Pharmacokinetics of combined gene therapy expressing constitutive human GM-CSF and hyperthermia-regulated human IL-12.

Journal Article J Exp Clin Cancer Res · January 26, 2013 BACKGROUND: An adenovirus that expresses both interleukin (IL)-12 and granulocyte-macrophage colony-stimulating-factor (GM-CSF) has been proven to be very effective in treating several tumors, but causes serious normal tissue toxicities. METHODS: In this s ... Full text Link to item Cite

Identification of novel predictive markers for the prognosis of pancreatic ductal adenocarcinoma.

Journal Article Hum Pathol · January 2013 Pancreatic cancer is a disease with poor prognosis and high mortality. To identify novel molecular markers that could predict the prognosis of pancreatic ductal adenocarcinoma, a total of 114 pancreatic ductal adenocarcinomas and 99 peritumoral tissues wer ... Full text Link to item Cite

Diphtheria toxin-epidermal growth factor fusion protein DAB389EGF for the treatment of bladder cancer.

Journal Article Clin Cancer Res · January 1, 2013 PURPOSE: The novel fusion protein, DAB(389)EGF, is composed of both the catalytic and the translocation domains of diphtheria toxin that are fused to the human EGF, providing a targeting and a toxicity component. We tested DAB(389)EGF for antitumor activit ... Full text Link to item Cite

Sonic hedgehog signaling pathway supports cancer cell growth during cancer radiotherapy.

Journal Article PLoS One · 2013 Tumor growth after radiotherapy is a commonly recognized cause of therapeutic failure. In this way, we examined tumor cell growth after radiotherapy by establishing a cancer cell growth model in vitro. We accomplished this model by seeding non-irradiated f ... Full text Link to item Cite

Heat induces gene amplification in cancer cells.

Journal Article Biochem Biophys Res Commun · October 26, 2012 BACKGROUND: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential ... Full text Link to item Cite

A novel immunocompetent murine tumor model for the evaluation of RCAd-enhanced RDAd transduction efficacy.

Journal Article Tumour Biol · August 2012 Low gene transfer rate in tumors, high dose-induced acute inflammatory response, and lack of an immunocompetent preclinical animal model to accurately reflect the therapeutic efficacy are prominent reasons for the lack of clinical success of adenoviral (Ad ... Full text Link to item Cite

Inhibitors of DNA repair for cancer therapy, ready for prime time?

Journal Article Translational Cancer Research · June 1, 2012 Genomic DNA is the central storage place for cellular information in DNA-based life forms. However, its integrity is under constant threat from errors in the replication process and damage from environmental insults. To neutralize these threats, our cells ... Full text Cite

Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA.

Journal Article Transl Cancer Res · June 2012 One of the key issues in cancer radiotherapy research is to sensitize tumor cells to the cell killing effects of ionizing radiation while leaving normal tissues intact. One potential approach to achieve this is through tumor-specific targeting of DNA repai ... Full text Link to item Cite

Enhancement of rAAV2-mediated transgene expression in retina cells in vitro and in vivo by coadministration of low-dose chemotherapeutic drugs.

Journal Article Invest Ophthalmol Vis Sci · May 4, 2012 PURPOSE: Recombinant adeno-associated viral vector serotype 2 (rAAV2) has been used with success to deliver retina-targeted gene therapeutics in retinal degeneration. However, one of the major limitations of this approach is the vector's low transduction e ... Full text Link to item Cite

Direct reprogramming of human fibroblasts int dopaminergic neurons

Conference JOURNAL OF INVESTIGATIVE DERMATOLOGY · May 1, 2012 Link to item Cite

Imaging molecular pathways: reporter genes.

Journal Article Radiat Res · April 2012 Molecular imaging is a rapidly advancing field that allows cancer biologists to look deeper into the complex inner workings of tumor cells, or whole tumors, in a non-invasive manner. In this review, we will summarize some recent advances that enable invest ... Full text Link to item Cite

Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells.

Journal Article Cell Res · February 2012 Featured Publication Transplantation of exogenous dopaminergic neuron (DA neurons) is a promising approach for treating Parkinson's disease (PD). However, a major stumbling block has been the lack of a reliable source of donor DA neurons. Here we show that a combination of fiv ... Full text Link to item Cite

Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy.

Journal Article Nat Med · July 3, 2011 Featured Publication In cancer treatment, apoptosis is a well-recognized cell death mechanism through which cytotoxic agents kill tumor cells. Here we report that dying tumor cells use the apoptotic process to generate potent growth-stimulating signals to stimulate the repopul ... Full text Link to item Cite

Quantitative, noninvasive imaging of radiation-induced DNA double-strand breaks in vivo.

Journal Article Cancer Res · June 15, 2011 Featured Publication DNA double-strand breaks (DSB) are a major form of DNA damage and a key mechanism through which radiotherapy and some chemotherapeutic agents kill cancer cells. Despite its importance, measuring DNA DSBs is still a tedious task that is normally carried out ... Full text Link to item Cite

A novel conditionally replicating "armed" adenovirus selectively targeting gastrointestinal tumors with aberrant wnt signaling.

Journal Article Hum Gene Ther · April 2011 Using conditionally replicating adenoviral vectors (CRAds) is a promising strategy in the treatment of solid tumors. The prospective of this study was to design a novel CRAd for the treatment of gastrointestinal cancer and show its efficacy in vitro, as we ... Full text Link to item Cite

Non-invasive, quantitative monitoring of hyperthermia-induced EGFR activation in xenograft tumours.

Journal Article Int J Hyperthermia · 2011 PURPOSE: To examine the molecular mechanism of cellular EGFR activation during hyperthermia treatment. MATERIALS AND METHODS: EGR activities in tumour cells were quantified through the use of a recently developed split-luciferase-based EGFR reporter system ... Full text Link to item Cite

Novel luciferase-based reporter system to monitor activation of ErbB2/Her2/neu pathway noninvasively during radiotherapy.

Journal Article Int J Radiat Oncol Biol Phys · January 1, 2011 PURPOSE: To develop a split-luciferase-based reporter system that allows for noninvasive monitoring of activation of the Her2/neu pathway in vivo in a quantitative and sensitive manner. METHODS AND MATERIALS: Fusion proteins of the ErbB2/Her2/neu receptor ... Full text Link to item Cite

Apoptotic caspases regulate induction of iPSCs from human fibroblasts.

Journal Article Cell Stem Cell · October 8, 2010 Featured Publication The molecular mechanisms involved in the derivation of induced pluripotent stem cells (iPSCs) from differentiated cells are poorly understood. Here we report that caspases 3 and 8, two proteases associated with apoptotic cell death, play critical roles in ... Full text Link to item Cite

Science signaling podcast: 23 February 2010

Journal Article Science Signaling · February 23, 2010 Full text Cite

Apoptotic cells activate the "phoenix rising" pathway to promote wound healing and tissue regeneration.

Journal Article Sci Signal · February 23, 2010 Featured Publication The ability to regenerate damaged tissues is a common characteristic of multicellular organisms. We report a role for apoptotic cell death in promoting wound healing and tissue regeneration in mice. Apoptotic cells released growth signals that stimulated t ... Full text Link to item Cite

Enhanced pancreatic cancer gene therapy by combination of adenoviral vector expressing c-erb-B2 (Her-2/neu)-targeted immunotoxin with a replication-competent adenovirus or etoposide.

Journal Article Hum Gene Ther · February 2010 Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, and even under optimal therapy these patients face a poor prognosis. Here we report a novel gene therapy-based strategy to battle this disease. We show that the maj ... Full text Link to item Cite

Construction and characterization of oncolytic adenovirus controlled under heat shock protein70 gene promoter

Journal Article Progress in Biochemistry and Biophysics · December 1, 2009 As an innovative class of promising cancer therapeutic, oncolytic adenovirus has been commonly used recently due to its ability to infect and lyse cancer cells specifically, while ideally leaving normal cells unharmed. A potential advantage of oncolytic ad ... Full text Cite

Noninvasive visualization of retinoblastoma growth and metastasis via bioluminescence imaging.

Journal Article Invest Ophthalmol Vis Sci · December 2009 PURPOSE: To establish human retinoblastoma (RB) animal models that allow sensitive, noninvasive and continuous monitoring of tumor growth and metastasis in vivo. METHODS: The human RB tumor cell lines HXO-Rb44 and Y79 were engineered to express a fusion re ... Full text Link to item Cite

Novel strategies to augment genetically delivered immunotoxin molecular therapy for cancer therapy.

Journal Article Cancer Gene Ther · November 2009 Immunotoxin therapy is a promising molecular cancer treatment strategy. Its main advantage is seletive cytotoxicity towards tumor cells and minimal toxicity in normal tissues. However, a short half-life and rapid clearance severely hampers its clinical app ... Full text Link to item Cite

Increased skin carcinogenesis in caspase-activated DNase knockout mice.

Journal Article Carcinogenesis · October 2009 Caspase-activated DNase (CAD), also called DNA fragmentation factor (DFF), is the enzyme responsible for DNA fragmentation during apoptosis, a hallmark of programmed cell death. CAD/DFF has been shown to suppress radiation-induced carcinogenesis by prevent ... Full text Link to item Cite

Oncolytic adenovirus delivering herpes simplex virus thymidine kinase suicide gene reduces the growth of human retinoblastoma in an in vivo mouse model.

Journal Article Exp Eye Res · August 2009 Oncolytic conditionally replicating adenoviruses (CRAd) can exclusively replicate in and lyse tumor cells and are therefore promising tools in cancer therapy. In this study, we combined the oncolytic potential of a CRAd with its ability to deliver a suicid ... Full text Link to item Cite

The effect of cobalt chloride on adenovirus gene expression

Journal Article Tumor · July 1, 2009 Objective: To investigate the effect of cobalt chloride (CoCl2) on transgene expression and viral particle titers in tumor cells infected by conditionally replicating adenovirus expression vector with hypoxia response elements (HRE)-regulated E1 ... Full text Cite

Molecular analysis of genetic instability caused by chronic inflammation.

Journal Article Methods Mol Biol · 2009 Genetic instability is a hallmark of human cancers. It is the driving force for tumor development as it facilitates the accumulation of mutations in genes that regulate cell death and proliferation and therefore promotes malignant transformation. Chronic i ... Full text Link to item Cite

In vivo bioluminescence imaging monitoring of hypoxia-inducible factor 1alpha, a promoter that protects cells, in response to chemotherapy.

Journal Article AJR Am J Roentgenol · December 2008 OBJECTIVE: Bioluminescence imaging is a powerful technique that has shown that hypoxia-inducible factor 1 (HIF-1), a transcription factor that protects tumor cells from hypoxia, is up-regulated in tumors after radiation therapy. We tested the hypothesis th ... Full text Link to item Cite

Induction of the human heat shock promoter HSP70B by nutritional stress: implications for cancer gene therapy.

Journal Article Cancer Invest · July 2008 BACKGROUND: We designed and tested, in vitro, an adenoviral construct containing the feline interleukin-12 (IL-12) gene under control of the heat-inducible promoter HSP70B. This construct, AdhspfIL12, was used in a phase I trial in feline soft tissue sarco ... Full text Link to item Cite

Noninvasive imaging and quantification of epidermal growth factor receptor kinase activation in vivo.

Journal Article Cancer Res · July 1, 2008 Featured Publication Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) critical in tumor growth and a major target for anticancer drug development. However, thus far, there is no effective system to monitor its activities in vivo. Here, we report a no ... Full text Link to item Cite

Enhanced transduction and improved photoreceptor survival of retinal degeneration by the combinatorial use of rAAV2 with a lower dose of adenovirus.

Journal Article Vision Res · July 2008 Recombinant adeno-associated virus (rAAV) is widely used in retinal gene therapy. Enhanced rAAV transduction may be important for better therapeutic effects in some retinal gene therapies. In this study, we examined the effects of adenovirus 5 (Ad5) on ret ... Full text Link to item Cite

Response of hypoxia-response element in human liver cancer cells to different microenvironments

Journal Article Tumor · May 25, 2008 Objective: Bel-7402 cells were stably transfected with a vector constructed with multiple copies of the hypoxia response- element (HRE) sequence of the human vascular endothelial growth factor (VEGF) gene and with the enhanced green fluorescent protein (EG ... Full text Cite

Distinctive gene transduction efficiencies of commonly used viral vectors in the retina.

Journal Article Curr Eye Res · January 2008 The transduction efficiency and cell tropism of viral vectors rAAV2/1, rAAV2, Ad5, Ad5/F35, and Lentivirus were evaluated in retina. All viral vectors achieved efficient transduction in living rat retina. However, each vector showed distinctive efficiency ... Full text Link to item Cite

Exploring the role of HIF-1 in early angiogenesis and response to radiotherapy.

Journal Article Radiother Oncol · June 2007 The objective of this review is to examine the role that HIF-1 plays in the initiation of angiogenesis and in radiotherapy response. Although these two phenomena may at first seem unrelated, there are parallelisms to be drawn associated with the importance ... Full text Link to item Cite

Systemic overexpression of angiopoietin-2 promotes tumor microvessel regression and inhibits angiogenesis and tumor growth.

Journal Article Cancer Res · April 15, 2007 Angiopoietin-2 (Ang-2) is a conditional antagonist and agonist for the endothelium-specific Tie-2 receptor. Although endogenous Ang-2 cooperates with vascular endothelial growth factor (VEGF) to protect tumor endothelial cells, the effect on tumor vasculat ... Full text Link to item Cite

Regulation of HIF-1alpha stability through S-nitrosylation.

Journal Article Mol Cell · April 13, 2007 Featured Publication Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional factor. Under normal oxygen tension, HIF-1 activity is usually suppressed due to the rapid, oxygen-dependent degradation of one of its two subunits, HIF-1alpha. Here we report that normoxic HIF ... Full text Link to item Cite

A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas.

Journal Article Mol Cancer Ther · January 2007 Interleukin-12 (IL-12), a proinflammatory cytokine, shows anticancer properties. Systemically administered IL-12 causes dose-dependent toxicity. To achieve localized intratumoral gene expression, an adenoviral gene therapy vector with IL-12 controlled by a ... Full text Link to item Cite

Regulation of mammalian horizontal gene transfer by apoptotic DNA fragmentation.

Journal Article Br J Cancer · December 18, 2006 Previously it was shown that horizontal DNA transfer between mammalian cells can occur through the uptake of apoptotic bodies, where genes from the apoptotic cells were transferred to neighbouring cells phagocytosing the apoptotic bodies. The regulation of ... Full text Link to item Cite

Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular transformation.

Journal Article Cancer Res · December 15, 2006 Featured Publication Tumor necrosis factor-alpha (TNF-alpha) is an important inflammation cytokine without known direct effect on DNA. In this study, we found that TNF-alpha can cause DNA damages through reactive oxygen species. The mutagenic effect of TNF-alpha is comparable ... Full text Link to item Cite

Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct.

Journal Article Int J Hyperthermia · November 2006 PURPOSE: Interleukin-12 (IL-12) is a pro-inflammatory cytokine possessing anti-cancer and anti-angiogenic properties. This study quantitatively assessed the anti-angiogenic effect of IL-12 delivered using an adenoviral vector with murine IL-12 placed under ... Full text Link to item Cite

Apoptotic DNA fragmentation factor maintains chromosome stability in a P53-independent manner.

Journal Article Oncogene · August 31, 2006 DNA fragmentation factor (DFF)/caspase-activated DNase (CAD) is responsible for DNA fragmentation, a hallmark event during apoptosis. Although DNA fragmentation is an evolutionarily conserved process across species, its biological function is not clearly u ... Full text Link to item Cite

High intensity focused ultrasound-induced gene activation in solid tumors.

Journal Article J Acoust Soc Am · July 2006 In this work, the activation of heat-sensitive trans-gene by high-intensity focused ultrasound (HIFU) in a tumor model was investigated. 4T1 cancer cells (2 x 10(6)) were inoculated subcutaneously in the hind limbs of Balb/C mice. The tumors were subsequen ... Full text Link to item Cite

A novel role of DNA fragmentation factor as a tumor suppressor through maintaining genomic stability.

Journal Article J Clin Oncol · June 20, 2006 10023 Background: DNA fragmentation is a hallmark of apoptosis. However, the biological function of apoptotic DNA fragmentation remains unclear. Genes encoding the nuclease responsible for DNA fragmentation, DFF40/CAD and DFF45/ICAD, are deleted, mutated, ... Link to item Cite

High intensity focused ultrasound induced gene activation in solid tumors

Journal Article Aip Conference Proceedings · May 8, 2006 In this work, the feasibility of using high intensity focused ultrasound (HIFU) to activate trans-gene expression in a mouse tumor model was investigated. 4T1 cancer cells were implanted subcutaneously in the hind limbs of Balb/C mice and adenovirus lucife ... Full text Cite

Abnormal gene expression profiles in unaffected parents of patients with hereditary-type retinoblastoma.

Journal Article Cancer Res · April 1, 2006 The hereditary form of retinoblastoma (Rb) is associated with a germ line mutation in one RB allele and is characterized by the occurrence of multiple, bilateral Rb tumors and a predisposition to the development of second cancers. In an earlier study, we o ... Full text Link to item Cite

Characterization of a recombinant adenovirus vector encoding heat-inducible feline interleukin-12 for use in hyperthermia-induced gene-therapy.

Journal Article Int J Hyperthermia · March 2006 Interleukin-12 (IL-12) is a pro-inflammatory cytokine that has shown great promise as a therapeutic agent in experimental models of infectious disease and cancer. However, it is also a highly toxic molecule and for that reason has not been accepted readily ... Full text Link to item Cite

A comparison of antiangiogenic therapies for the prevention of liver metastases.

Journal Article J Surg Res · March 2006 Angiogenesis is essential for solid tumor growth. Although successful antiangiogenic therapies have been demonstrated in animal models, a systematic comparison of the efficacy of different antiangiogenic factors has not been described in the hepatic enviro ... Full text Link to item Cite

Effects of rate, volume, and dose of intratumoral infusion on virus dissemination in local gene delivery.

Journal Article Mol Cancer Ther · February 2006 Recent studies have shown that up to 90% of viral vectors could disseminate to normal organs following intratumoral infusion. The amount of dissemination might be dependent on the infusion conditions. Therefore, we investigated the effects of infusion rate ... Full text Link to item Cite

Pim-1 kinase inhibits the activation of reporter gene expression in Elk-1 and c-Fos reporting systems but not the endogenous gene expression: an artifact of the reporter gene assay by transient co-transfection.

Journal Article Braz J Med Biol Res · February 2006 We have studied the molecular mechanism and signal transduction of pim-1, an oncogene encoding a serine-threonine kinase. This is a true oncogene which prolongs survival and inhibits apoptosis of hematopoietic cells. In order to determine whether the effec ... Full text Link to item Cite

A unique role of the DNA fragmentation factor in maintaining genomic stability.

Journal Article Proc Natl Acad Sci U S A · January 31, 2006 Featured Publication DNA fragmentation is a hallmark of apoptosis (programmed cell death). However, the biological function of apoptotic DNA fragmentation remains unclear. Here, we show that DNA fragmentation factor plays an important role for maintaining genomic stability. In ... Full text Link to item Cite

High intensity focused ultrasound-induced gene activation in sublethally injured tumor cells in vitro.

Journal Article J Acoust Soc Am · November 2005 Cultured human cervical cancer (HeLa) and rat mammary carcinoma (R3230Ac) cells were transfected with vectors encoding green fluorescent protein (GFP) under the control of hsp70B promoter. Aliquots of 10-microl transfected cells (5 x 10(7) cells/ml) were p ... Full text Link to item Cite

Focal gene induction in the liver of rats by a heat-inducible promoter using focused ultrasound hyperthermia: preliminary results.

Journal Article Invest Radiol · November 2005 OBJECTIVE: We sought to examine high-intensity focused ultrasound (HIFU)-induced hyperthermia in the liver of a rat model to focally induce green-fluorescent protein (GFP). MATERIALS AND METHODS: A total of 25 Copenhagen rats were included in this study. R ... Full text Link to item Cite

Enhancement of cancer radiation therapy by use of adenovirus-mediated secretable glucose-regulated protein 94/gp96 expression.

Journal Article Cancer Res · October 15, 2005 Tumor-derived glucose-regulated protein 94 (GRP94/gp96) has shown great promise as a tumor vaccine. However, current protein-based approaches require the availability of large quantities of tumor tissue, which are often not possible. In addition, the effic ... Full text Link to item Cite

A novel method for viral gene delivery in solid tumors.

Journal Article Cancer Res · September 1, 2005 Intratumoral infusion is the most commonly used method for viral gene delivery in clinical trials for cancer treatment. However, a potential problem in this approach is that viral vectors may disseminate from tumor to normal tissues during and after the in ... Full text Link to item Cite

Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity.

Journal Article Cancer Cell · August 2005 Featured Publication We have previously shown that radiation increases HIF-1 activity in tumors, causing significant radioprotection of the tumor vasculature. The impact that HIF-1 activation has on overall tumor radiosensitivity, however, is unknown. We reveal here that HIF-1 ... Full text Link to item Cite

Observation of incipient tumor angiogenesis that is independent of hypoxia and hypoxia inducible factor-1 activation.

Journal Article Cancer Res · July 1, 2005 It is well established that hypoxia potently stimulates tumor angiogenesis by activating hypoxia inducible factor-1 (HIF-1)-induced proangiogenic factors, such as vascular endothelial growth factor. However, very little is known about the role of hypoxia i ... Full text Link to item Cite

Expression of dominant negative Rho-binding domain of Rho-kinase in organ cultured human eye anterior segments increases aqueous humor outflow.

Journal Article Mol Vis · April 27, 2005 PURPOSE: Based on pharmacological inhibition of activity, a role has been proposed for Rho-kinase in the modulation of aqueous outflow and intraocular pressure (IOP). This study employed a molecular approach to specifically address the role of Rho-kinase i ... Link to item Cite

Characterisation of systemic dissemination of nonreplicating adenoviral vectors from tumours in local gene delivery.

Journal Article Br J Cancer · April 25, 2005 Systemic virus dissemination is a potential problem during local gene delivery in solid tumours. However, the kinetics and pathways of the dissemination have not been well characterised during the first 24 h after the infusion is started. To this end, we i ... Full text Link to item Cite

Cytokine and immuno-gene therapy for solid tumors.

Journal Article Cell Mol Immunol · April 2005 Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possib ... Link to item Cite

Enhancement of hypoxia-induced tumor cell death in vitro and radiation therapy in vivo by use of small interfering RNA targeted to hypoxia-inducible factor-1alpha.

Journal Article Cancer Res · November 15, 2004 Hypoxia-inducible factor-1alpha (HIF-1alpha) is an important transcriptional factor that is activated when mammalian cells experience hypoxia, a tumor microenvironmental condition that plays pivotal roles in tumor progression and treatment. In this study, ... Full text Link to item Cite

The relationship between hypoxia and angiogenesis.

Journal Article Semin Radiat Oncol · July 2004 Recent studies have generated a large amount of data supporting the hypothesis that hypoxia drives tumor angiogenesis. The relationship between the two is often considered a matter of supply and demand: ineffectively-vascularized tumor tissue becomes hypox ... Full text Link to item Cite

[Antitumoral action of interferons and interleukins in combination with radiotherapy. Part II: radiobiological and immunologic strategies].

Journal Article Strahlenther Onkol · June 2004 BACKGROUND: Combined tumor treatment with cytokines, e. g., interferons (IFN), and radiotherapy was initially of phenomenological nature but has increasingly been based on a radiobiological rationale. However, an improved understanding of the complex inter ... Full text Link to item Cite

Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules.

Journal Article Cancer Cell · May 2004 Featured Publication Through a poorly understood mechanism, tumors respond to radiation by secreting cytokines capable of inhibiting apoptosis in endothelial cells, thereby diminishing treatment response by minimizing vascular damage. We reveal here that this pathway is govern ... Full text Link to item Cite

GW112, a novel antiapoptotic protein that promotes tumor growth.

Journal Article Cancer Res · April 1, 2004 GW112 is a novel gene that has little homology to other known genes. It is overexpressed in a number of human tumor types, especially in those of the digestive system. We show here that GW112 is associated with GRIM-19, a protein known to be involved in re ... Full text Link to item Cite

[Antitumoral action of interferons and interleukins in combination with radiotherapy. Part I: immunologic basis].

Journal Article Strahlenther Onkol · April 2004 BACKGROUND: During the last 2 decades, cytokines such as interferons (IFN) have been used to modulate tumor response in radiotherapy. Initially, the focus was on antiviral and radiosensitizing effects of interferons but increasingly, the function of interf ... Full text Link to item Cite

A novel conditionally replicative adenovirus vector targeting telomerase-positive tumor cells.

Journal Article Clin Cancer Res · February 15, 2004 Featured Publication PURPOSE: To develop a novel conditionally replicative adenovirus vector that targets telomerase-positive cancer cells. EXPERIMENTAL DESIGN: A telomerase gene-derived promoter was used to control the expression of the E1a gene so that the E1a gene is only e ... Full text Link to item Cite

Responses of vascular endothelial cells to angiogenic signaling are important for tumor cell survival.

Journal Article FASEB J · February 2004 Neoplastic cells overexpress several angiogenic cytokines, which stimulate neovascularization. Whether the responses of the host endothelial cells to these signaling molecules affect tumor cells during early tumorigenesis has not been investigated. We inve ... Full text Link to item Cite

Systemic virus dissemination during local gene delivery in solid tumors and its control with an alginate solution.

Journal Article Conf Proc IEEE Eng Med Biol Soc · 2004 Intratumoral infusion, a routine method for local gene delivery in solid tumors, may cause a systemic dissemination of gene vectors. This is because tumor vessels are intrinsically leaky and intratumoral injection can also result in damage of tumor vessels ... Full text Link to item Cite

Role of VEGF in the growth and metastasis of a murine bladder carcinoma

Journal Article Chinese Science Bulletin · December 1, 2003 Bladder transitional cell carcinoma is the most common form of carcinoma in the urinary system. Although overexpression of VEGF has been identified in tissue, serum, and urine of patients with bladder cancer, the role of VEGF in transitional cell carcinoma ... Full text Cite

Systemic dissemination of viral vectors during intratumoral injection.

Journal Article Mol Cancer Ther · November 2003 Intratumoral injection is a routine method for local viral gene delivery that may improve interstitial transport of viral vectors in tumor tissues and reduce systemic toxicity. However, the concentration of transgene products in normal organs, such as in t ... Link to item Cite

Soluble TGFbeta type II receptor gene therapy ameliorates acute radiation-induced pulmonary injury in rats.

Journal Article Int J Radiat Oncol Biol Phys · October 1, 2003 PURPOSE: To assess whether administration of recombinant human adenoviral vector, which carries soluble TGFbeta1 Type II receptor (TbetaRII) gene, might reduce the availability of active TGFbeta1 and thereby protect the lung from radiation-induced injury. ... Full text Link to item Cite

Adenovirus dissemination in convention-enhanced delivery and its control with a polymeric vehicle.

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · September 1, 2003 Link to item Cite

Increased resistance of tumor cells to hyperthermia mediated by integrin-linked kinase.

Journal Article Clin Cancer Res · March 2003 PURPOSE: Integrin-linked kinase (ILK) is a serine-threonine kinase associated with anchorage-independent growth and tumorigenic transformation. Previous studies indicate that overexpression of ILK is common among several types of tumors, and it is involved ... Link to item Cite

GRP94 (gp96) and GRP94 N-terminal geldanamycin binding domain elicit tissue nonrestricted tumor suppression.

Journal Article J Exp Med · December 2, 2002 In chemical carcinogenesis models, GRP94 (gp96) elicits tumor-specific protective immunity. The tumor specificity of this response is thought to reflect immune responses to GRP94-bound peptide antigens, the cohort of which uniquely identifies the GRP94 tis ... Full text Link to item Cite

Cell cycle deregulation and xeroderma pigmentosum group C cell transformation.

Journal Article J Invest Dermatol · December 2002 We previously described a genetically unstable human fibroblast cell strain (GM2995), isolated from normal appearing skin of a xeroderma pigmentosum group C patient that repeatedly underwent changes characteristic of the transformed phenotype upon serial c ... Full text Link to item Cite

Reducing systemic toxicity in local tumor gene therapy using an alginate solution

Journal Article Annual International Conference of the IEEE Engineering in Medicine and Biology Proceedings · December 1, 2002 To reduce dissemination of viral vectors and their gene products during and after local gene therapy, we mixed adenoviral vectors with an alginate solution and subsequently injected the mixture into mouse tumors. We found that the alginate solution signifi ... Cite

Electromobility of plasmid DNA in tumor tissues during electric field-mediated gene delivery.

Journal Article Gene Ther · October 2002 Interstitial transport is a crucial step in plasmid DNA-based gene therapy. However, interstitial diffusion of large nucleic acids is prohibitively slow. Therefore, we proposed to facilitate interstitial transport of DNA via pulsed electric fields. To test ... Full text Link to item Cite

Target gene transfer mediated by electroporation for cancer therapy in vivo

Journal Article Progress in Biochemistry and Biophysics · October 1, 2002 A plasmid encoding green florescent protein (GFP) was first used to test efficiency of electroporation and optimize parameters for electroporation in vivo. GFP plasmid was efficiently delivered into muscle by electroporation and robust GFP expression in mu ... Cite

[Inhibitation of tumor angiogenesis, growth and metastasis by blocking VEGF paracrine pathway].

Journal Article Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) · March 2002 Solid tumors require an adequate vascular supply to grow beyond a certain dimension. It is known that formation of new blood vessels in tumor is mediated by unbalanced expression of angiogenic factors and their inhibitors. Among the former, the vascular en ... Link to item Cite

Intravital fluorescence facilitates measurement of multiple physiologic functions and gene expression in tumors of live animals.

Journal Article Dis Markers · 2002 The purpose of this report is to present an overview of the use of fluorescence imaging in vivo, with particular emphasis on oncology. It is important to note, however, that many of the methods described herein have been applied to the study of non-maligna ... Full text Link to item Cite

Hyperthermia-regulated immunogene therapy.

Journal Article Int J Hyperthermia · 2002 One of the key milestones that must be reached before gene therapy becomes feasible for clinical cancer treatment is to be able to regulate therapeutic gene expression. This is true for most current cancer gene therapy approaches, since the majority of the ... Full text Link to item Cite

[A novel model for visualization of tumor cell-induced angiogenesis in vivo].

Journal Article Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) · January 2002 The bladder transitional cell carcinoma cell line, BTT739 from the T739 mouse, was transfected with a plasmid that encoded an enhanced green fluorescence protein (GFP) and the cells stably expressing GFP were selected and subcloned. 1 x 10(3)-1 x 10(4) GFP ... Link to item Cite

Protection against oxidized low-density lipoprotein-induced vascular endothelial cell death by integrin-linked kinase.

Journal Article Circulation · December 4, 2001 BACKGROUND: Integrin-linked kinase (ILK) is a protein that plays important roles in extracellular matrix-mediated signaling. It has been shown that ILK is expressed preferentially in cardiac and skeletal muscles. Evidence points to its role as an upstream ... Full text Link to item Cite

Systemic vector leakage and transgene expression by intratumorally injected recombinant adenovirus vectors.

Journal Article Clin Cancer Res · November 2001 Interleukin 12 is a heterodimeric cytokine that exhibits potent immunostimulatory effects. It has shown some promise in preclinical and clinical studies but was accompanied by serious systemic toxicity such as flu-like syndromes, a rapid transient leukopen ... Link to item Cite

[Preparation of green fluorescent protein retrovirus and its application in mediating gene transfer into retinal pigment epithelial cells].

Journal Article Zhonghua Yan Ke Za Zhi · July 2001 OBJECTIVE: To determine whether human retinal pigment epithelial (RPE) cells can be infected by retrovirus and modified by retrovirus-mediated gene transfer. METHODS: Recombination retroviral vector pLNCX-GFP (green fluorescent protein, GFP) was generated ... Link to item Cite

[Using Hsp70 promoter to regulate target gene expression in tumor].

Journal Article Zhonghua Bing Li Xue Za Zhi · June 2001 OBJECTIVE: To regulate gene expression in the desired tumor cells both in vitro and in vivo. METHODS: Heat inducible green fluorescent protein (GFP) expression plasmid and adenovirus were built by using different sizes of 5' end regulating sequence from hu ... Link to item Cite

Generation of recombinant adeno-associated virus vectors by a complete adenovirus-mediated approach.

Journal Article Mol Ther · May 2001 An efficient approach to the large-scale production of rAAV will significantly facilitate the application of this promising gene delivery vector in human gene therapy applications. In this study, we report a novel approach to rAAV production that is based ... Full text Link to item Cite

Effective tumor therapy with plasmid-encoded cytokines combined with in vivo electroporation.

Journal Article Cancer Res · April 15, 2001 Plasmids may have unique advantages as a gene delivery system. However, a major obstacle is the low in vivo transduction efficiency. In this study, an electroporation-based gene transduction approach was taken to study the effect of interleukin (IL)-2 or I ... Link to item Cite

Persistent genetic instability in cancer cells induced by non-DNA-damaging stress exposures.

Journal Article Cancer Res · January 15, 2001 Featured Publication A hallmark of cancer cells is their pronounced genetic instability, which has been implicated in both tumor development and negative treatment outcomes. Recently, it has been reported that ionizing radiation may induce a persistent state of hypermutability ... Link to item Cite

Control of gene therapy by the heat shock promoter

Conference PROGRESS IN RADIO-ONCOLOGY VII, PROCEEDINGS · January 1, 2001 Link to item Cite

Enhancement of radiotherapy by hyperthermia-regulated gene therapy.

Journal Article Int J Radiat Oncol Biol Phys · December 1, 2000 PURPOSE: Interleukin 12 (IL-12) has shown strong antitumoral effects in numerous pre-clinical studies and appears to act synergistically with radiation in murine tumors. The major impediment to its clinical use has been its systemic toxicity. While using i ... Full text Link to item Cite

Mobility of plasmid DNA subject to pulsed electric fields

Journal Article Annals of Biomedical Engineering · December 1, 2000 The mobility of plasmid DNA in high amplitude/low duration electric fields was assessed. The influences of pulse amplitude, pulse duration and agarose gel concentration on mobility were compared. Movement of plasmid DNA in an electroporation setting was in ... Cite

Delivery of plasmid DNA through intratumoral infusion and electroporation

Journal Article American Society of Mechanical Engineers Bioengineering Division Publication BED · December 1, 2000 We investigated DNA transport in the interstitial space and across cell membrane facilitated by intratumoral infusion and in vivo electroporation, respectively. In the study, a rat fibrosarcoma was perfused ex vivo, and apparent hydraulic conductivity (K Cite

Combination treatment of murine tumors by adenovirus-mediated local B7/IL12 immunotherapy and radiotherapy.

Journal Article Mol Ther · September 2000 Failure of local tumor control still poses a problem for radiotherapy and translates into reduced survival. Combining radiation with chemotherapy or other newer modalities has shown promising results. Immunological approaches to tumor therapy have found re ... Full text Link to item Cite

Heat-induced gene expression as a novel targeted cancer gene therapy strategy.

Journal Article Cancer Res · July 1, 2000 One of the main advantages of gene therapy over traditional therapy is the potential to target the expression of therapeutic genes in desired cells or tissues. To achieve targeted gene expression, we experimented with a new approach based on the long-estab ... Link to item Cite

Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models.

Journal Article J Natl Cancer Inst · January 19, 2000 Featured Publication BACKGROUND: There is a paucity of information about events that follow immediately after tumor cells are triggered to initiate the process of angiogenesis (the formation of new blood vessels). Such information is relevant to the issue of when micrometastas ... Full text Link to item Cite

Delivery of plasmid DNA through intratumoral infusion and electroporation

Conference ASME International Mechanical Engineering Congress and Exposition, Proceedings (IMECE) · January 1, 2000 We investigated DNA transport in the interstitial spaceand across cell membrane facilitated by intratumoral infusionand in vivo electroporation, respectively. In the study, a ratfibrosarcoma was perfused ex vivo, and apparent hydraulicconductivity (Kaap) w ... Full text Cite

Role of incipient angiogenesis in cancer metastasis.

Journal Article Cancer Metastasis Rev · 2000 Metastasis is the primary cause of mortality in cancer patients. Angiogenesis is intimately involved in metastasis at the site of entry of tumor cells into the vasculature and at the site of eventual metastasis growth. In this commentary, we review current ... Full text Link to item Cite

Deletions and point mutations of p16,p15 gene in primary tumors and tumor cell lines.

Journal Article Chin Med Sci J · December 1999 Aberrations of chromosome 9 p21-22 are involved in the genesis of many forms of cancer. The gene p16 and p15 have been assigned to this region. Both p16 and p15 are an inhibitor of cyclin D-cdk4,cyclin D-cdk6 complex and have been implicated in a wide vari ... Link to item Cite

Noninvasive visualization of tumors in rodent dorsal skin window chambers.

Journal Article Nat Biotechnol · October 1999 Featured Publication Full text Link to item Cite

Influence of p53 expression on radiosensitivity of human normal and tumor cells

Journal Article Journal De Chimie Physique Et De Physico Chimie Biologique · January 1, 1998 The radiosensitivity of normal human fibroblasts is p53 dependent and associated with the loss of cells from the cycling population as the result of an irreversible G1 arrest; cells lacking normal p53 function show no arrest and are more radiore ... Full text Cite

Abrogation of p53 function by HPV16 E6 gene delays apoptosis and enhances mutagenesis but does not alter radiosensitivity in TK6 human lymphoblast cells.

Journal Article Oncogene · April 10, 1997 In order to gain a better understanding of the role of p53 in radiation-induced mitotic failure, apoptosis and mutagenesis, we introduced the HPV16 E6 gene via a retroviral vector into the TK6 human lymphoblast cell line which expresses wild type p53. Abro ... Full text Link to item Cite

Radio-induced modulation of transforming growth factor beta1 sensitivity in a p53 wild-type human colorectal-cancer cell line.

Journal Article Int J Cancer · September 27, 1996 Unlike normal intestinal cells, colorectal-carcinoma cell lines are usually not responsive to transforming growth factor beta1. The cyclin-dependent kinase inhibitor p21 that is induced by X irradiation in cells expressing normal p53 can also be induced by ... Full text Link to item Cite

Abrogation of P53 function by transfection of HPV16 E6 gene does not enhance resistance of human tumour cells to ionizing radiation.

Journal Article Int J Radiat Biol · August 1996 Suppression of wild-type p53 expression has been shown to enhance the radiation resistance of human diploid fibroblasts, but results concerning the role of p53 expression in the sensitivity of human tumour cells have been conflicting. In order to address t ... Full text Link to item Cite

Genomic instability and radiation mutagenesis

Journal Article Journal De Chimie Physique Et De Physico Chimie Biologique · January 1, 1996 An increase in the frequency of spontaneous mutations occurs in some cell populations arising from single cells surviving radiation exposure. This mutator phenotype may persist over many cell divisions. The spectrum of DNA structural changes at the hprt lo ... Full text Cite

Diminished capacity for p53 in mediating a radiation-induced G1 arrest in established human tumor cell lines.

Journal Article Oncogene · November 2, 1995 It has been reported that the p53 gene mediates an ionizing radiation-induced G1 arrest in mammalian cells. To further characterize this important phenomenon, a panel of seven human diploid fibroblast cell strains and 14 human tumor cell lines from a varie ... Link to item Cite

Abrogation of p53 function by transfection of HPV16 E6 gene enhances the resistance of human diploid fibroblasts to ionizing radiation.

Journal Article Oncogene · June 15, 1995 In order to examine the role of p53 expression on the sensitivity of cells to radiation-induced reproductive failure, we examined the radiosensitivity of a human diploid fibroblast cell strain (AG1521) before and after transfection with the E6 or E6/E7 gen ... Link to item Cite

Absence of radiation-induced G1 arrest in two closely related human lymphoblast cell lines that differ in p53 status.

Journal Article J Biol Chem · May 12, 1995 In order to examine more precisely the role of p53 in the activation of the G1/S checkpoint by ionizing radiation, we examined two human lymphoblast cell lines derived from the same donor. The TK6 line had a doubling time of 12.2 h and expressed wild type ... Full text Link to item Cite

Relationship between radiation-induced G1 phase arrest and p53 function in human tumor cells.

Journal Article Cancer Res · May 1, 1995 Three widely studied cell lines were used to examine the nature of the G1 arrest induced in human tumor cells by ionizing radiation and its relation to p53 status. Cell lines MCF-7 and RKO express wild-type p53, whereas HT29 expresses mutant p53. Exponenti ... Link to item Cite

Potential role of WAF1/Cip1/p21 as a mediator of TGF-beta cytoinhibitory effect.

Journal Article J Biol Chem · March 10, 1995 Transforming growth factor-beta (TGF-beta) inhibits cell cycle progression of many types of human cells by arresting them in the G1 phase of the cell cycle. The arrest is mediated through interactions of various cyclin-dependent protein kinases (CDKs) and ... Full text Link to item Cite

Radiation-induced irreversible G(0)/G(1) block is abolished in human diploid fibroblasts transfected with the human papilloma virus E6 gene: Implication of the p53-Cip1/WAF1 pathway

Journal Article International Journal of Oncology · January 1, 1995 It has been shown previously with human diploid fibroblasts that a fraction of cells remains irreversibly blocked in the G(0)/G(1) phase of the cell cycle when the cells are irradiated in confluent, density-inhibited cultures and released by subculture to ... Full text Cite

Elevated frequency of microsatellite mutations in TK6 human lymphoblast clones selected for mutations at the thymidine kinase locus.

Journal Article Mol Cell Biol · July 1994 A major question in carcinogenesis is, How can a normal cell accumulate multiple mutations in different genes on different chromosomes, when the mutation rate of each gene is in the range of 10(-8) to 10(-5) per cell division? We hypothesize that many muta ... Full text Link to item Cite

Immature teratomas of different origin carried by a pregnant mother and her fetus

Journal Article Diagnostic Molecular Pathology · 1993 We describe the case of a pregnant mother and her fetus who both carried teratomas during the pregnancy. The fetus was diagnosed at 38 weeks' gestation to have an intracranial mass, which was later determined to be an immature teratoma. During a cesarean s ... Cite

Evidence for coincident mutations in human lymphoblast clones selected for functional loss of a thymidine kinase gene.

Journal Article Mol Carcinog · 1992 A mitotic "recombination-competent state" inducible by x-irradiation is thought to exist in yeast. We sought evidence for such a process in mammalian cells by examining the occurrence of mutations at unlinked loci in clones derived from a human lymphoblast ... Full text Link to item Cite

Molecular mechanisms of spontaneous and induced loss of heterozygosity in human cells in vitro.

Journal Article Somat Cell Mol Genet · January 1992 The human TK6 lymphoblast cell line is heteroallelic at the thymidine kinase (TK) locus, with one functional and one nonfunctional allele. Cells that have undergone loss of heterozygosity (LOH) at TK can be selected and cloned in an in vitro assay. In orde ... Full text Link to item Cite