Effectiveness of HSV-tk Suicide Gene Therapy Driven by the Grp78 Stress-Inducible Promoter in Esophagogastric Junction and Gastric Adenocarcinomas

Azatian, Armen; Yu, Hong; Dai, Wande; Schneiders, F; Botelho, Natalia K.; Lord, Reginald V.

doi:10.1007/s11605-009-0839-1

Cited by 24 publications

(14 citation statements)

References 30 publications

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“…Gene expression in 16 SAT samples and 16 VAT samples was measured by a two‐step multiplexed tandem PCR method (23). Primers for the genes of interest and NONO (non‐POU domain containing, octamer binding; NM_007363) as reference gene were designed using modified Primer 3 software (primer sequences available on request), as done previously (24,25). Given our a priori hypothesis that circulating inflammatory molecules that predict or are implicated in the pathogenesis of T2D are differentially expressed in adipose tissue, we selected the following genes of interest: adiponectin, TNFα, complement C3, retinol‐binding protein‐4 (RBP4), IL‐1α, IL‐1β, IL‐6, IL‐8, IL‐8 receptor, macrophage inflammatory protein (MIP), serum amyloid A, nuclear factor‐κB, cAMP response element–binding protein‐3.…”

Section: Methods and Proceduresmentioning

confidence: 99%

Subcutaneous and Visceral Adipose Tissue Gene Expression of Serum Adipokines That Predict Type 2 Diabetes

Samaras

Botelho

Chisholm

et al. 2010

Obesity

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237

168

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Type 2 diabetes mellitus (T2D) is predicted by central obesity and circulating adipokines regulating inflammation. We hypothesized that visceral adipose tissue (VAT) in T2D expresses greater levels of proinflammatory molecules. Paired samples of subcutaneous (SAT) and VAT were excised at elective surgery (n = 16, 6 with T2D, n = 8 age‐ and gender‐ matched controls). Metabolic parameters were measured in the fasted state: body composition by dual‐energy X‐ray absorptiometry and insulin action by hyperinsulinemic–euglycemic clamp. Adipose tissue mRNA gene expression was measured by quantitative reverse transcriptase‐PCR. Subjects with T2D had higher VAT expression of molecules regulating inflammation (tumor necrosis factor‐α (TNFα), macrophage inflammatory protein (MIP), interleukin‐8 (IL‐8)). Fasting glucose related to VAT expression of TNFα, MIP, serum amyloid A (SAA), IL‐1α, IL‐1β, IL‐8, and IL‐8 receptor. Abdominal fat mass was related to VAT expression of MIP, SAA, cAMP response element–binding protein (CREBP), IL‐1β, and IL‐8. Insulin action related inversely to VAT complement C3 expression only. There were depot‐specific differences in expression of serum T2D predictors: VAT expressed higher levels of complement C3; SAT expressed higher levels of retinol‐binding protein‐4 (RBP4), adiponectin, and leptin. In summary, VAT in T2D expresses higher levels of adipokines involved in inflammation. VAT expression of these molecules is related to fasting glucose and insulin action. Increased production of these proinflammatory molecules by VAT may explain the links observed between visceral obesity, insulin resistance, and diabetes risk.

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Section: Methods and Proceduresmentioning

confidence: 99%

Subcutaneous and Visceral Adipose Tissue Gene Expression of Serum Adipokines That Predict Type 2 Diabetes

Samaras

Botelho

Chisholm

et al. 2010

Obesity

Self Cite

237

168

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“…As proof-of-principle, the Grp78 promoter driving the expression of the herpes simplex kinase suicide gene in a retroviral system results in eradication of sizable tumours 122,123 . Recently, systemic administration of a dual tumour-targeted phage containing the RGD tumour homing ligand and the Grp78 promoter, showed persistent transgene expression in vitro and significant killing of therapy resistant tumours in vivo 124 .…”

Section: Targeting Grpsmentioning

confidence: 99%

Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential

2014

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Preface The glucose regulated proteins (GRPs) are stress inducible chaperones majorly residing in the endoplasmic reticulum (ER) and the mitochondria. Recent advances reveal that the GRPs serve distinct functions from the related heat shock proteins (HSPs), and they can be actively translocated to other cellular locations and assume novel functions controlling signaling, proliferation, invasion, apoptosis, inflammation and immunity. Mouse models further identified their specific roles in development, tumorigenesis, metastasis and angiogenesis. This Review describes their discovery, regulation and their biological functions in cancer. Promising agents using or targeting the GRPs are being developed, and their efficacy as anti-cancer therapeutics is also discussed.

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“…This constitutes an ideal gene therapy system to selectively kill tumor cells without affecting normal tissues. Azatian et al (77) have demonstrated that, compared with LTR-tk/GCV, GRP78-tk/GCV treatment resulted in complete tumor elimination in GC cells with no p53 mutations in vitro and in vivo (Table I).…”

Section: Grp78 Variants and Promoter Polymorphisms In Gcmentioning

confidence: 99%

Endoplasmic reticulum chaperone glucose-regulated proteinï¿½78 in gastric cancer: An emerging biomarker (Review)

Wang

Zhang

et al. 2018

Oncol Lett

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The endoplasmic reticulum (ER) is the principal organelle responsible for the synthesis, initial post-translational modification, folding, export and secretion of proteins. It is also responsible for the maintenance of cellular homeostasis. In response to cellular stress conditions including glucose deprivation, hypoxia and changes in calcium homeostasis, ER stress machinery is activated and triggers the unfolded protein response, resulting in the restoration of homeostasis or activation of cell death. Glucose-regulated protein 78 (GRP78), a molecular chaperone, may be induced by ER stress at the transcriptional and translational level. A number of studies have demonstrated that GRP78 serves an important role in tumor cell proliferation, metastasis, angiogenesis and drug-resistance. The present review systematically describes the association between GRP78 expression and gastric cancer pathogenesis, and emphasizes that GRP78 is a novel diagnostic and therapeutic biomarker of gastric cancer.

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Effectiveness of HSV-tk Suicide Gene Therapy Driven by the Grp78 Stress-Inducible Promoter in Esophagogastric Junction and Gastric Adenocarcinomas

Cited by 24 publications

References 30 publications

Subcutaneous and Visceral Adipose Tissue Gene Expression of Serum Adipokines That Predict Type 2 Diabetes

Subcutaneous and Visceral Adipose Tissue Gene Expression of Serum Adipokines That Predict Type 2 Diabetes

Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential

Endoplasmic reticulum chaperone glucose-regulated proteinï¿½78 in gastric cancer: An emerging biomarker (Review)

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