Serum transforming growth factor-β1 levels and pancreatic cancer risk: a nested case–control study (Japan)

Lin, Yingsong; Kikuchi, Shogo; Tamakoshi, Akiko; Obata, Yuki; Yagyu, Kiyoko; Inaba, Yutaka; Kurosawa, Michiko; Kawamura, Takashi; Motohashi, Yutaka; Ishibashi, Teruo

doi:10.1007/s10552-006-0048-0

Cited by 17 publications

(22 citation statements)

References 20 publications

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“…Although both our study and the only other study to examine this association, a Japanese cohort including 85 cases [4], found some evidence of a positive association between serum TGF-β1 and pancreatic cancer, the timing of the associations differed. We did not observe any association during the first 10 years of follow-up, whereas the Japanese study observed an association despite having a maximum of approximately 12 years of follow-up.…”

Section: Discussioncontrasting

confidence: 58%

“…One biomarker, serum transforming growth factor-β1 (TGF-β1) concentration, was associated with increased risk in a small case-control study nested within a Japanese cohort which included 85 cases of pancreatic cancer (OR=2.5, 95% CI 0.9-6.9 for highest vs. lowest quartile, p trend = 0.04) [4]. TGF-β1 is a protein that plays an important role in many biological processes including cell proliferation and immune regulation [5].…”

Section: Introductionmentioning

confidence: 99%

“…TGF-β1 signaling is important in pancreatic carcinogenesis and can have either tumor suppressive or tumor promoting effects depending on the setting [6,7]. However, it is unclear what mechanism explains the association between serum TGF-β1 concentration and increased risk of pancreatic cancer observed in the Japanese cohort study [4]. …”

Section: Introductionmentioning

confidence: 99%

“…Combining these studies provided a large study size for replicating the association observed in the Japanese cohort study [4] and for examining results stratified by smoking and time since blood draw.…”

Section: Introductionmentioning

confidence: 99%

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Serum transforming growth factor-β1 and risk of pancreatic cancer in three prospective cohort studies

Jacobs

Newton

Silverman

et al. 2014

Cancer Causes Control

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Purpose Clinically evident chronic pancreatitis is a strong risk factor for pancreatic cancer. A small Japanese cohort study previously reported that pre-diagnostic serum transforming growth factor-β1 (TGF-β1) concentration, a potential marker of subclinical pancreatic inflammation, was associated with higher risk of pancreatic cancer. We further explored this association in a larger prospective study. Methods Serum TGF-β1 concentrations were measured in pre-diagnostic samples from 729 pancreatic cancer cases and 907 matched controls from a cohort of Finnish male smokers (the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study) and two cohorts of U.S. men and women, the Cancer Prevention Study-II (CPS-II) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Multivariable-adjusted odds ratios (ORs) were estimated using conditional logistic regression. Results Overall, serum TGF-β1 concentration was not associated with a clear increase in pancreatic cancer risk (OR=1.36, 95% confidence interval (CI), 0.98-1.88 for highest vs. lowest quintile, p trend = 0.20). However, this association differed significantly by follow-up time (p=0.02). Serum TGF-β1 concentration was not associated with risk during the first 10 years of follow-up, but was associated with higher risk during follow-up after 10 years (OR=2.13, 95% CI 1.23-3.68 for highest vs. lowest quintile, p trend=0.001). During follow-up after 10 years, serum TGF-β1 was associated with higher risk only in the ATBC cohort, although most subjects were from ATBC during this time period and statistical evidence for heterogeneity across cohorts was limited (p=0.14). Conclusions These results suggest that high serum TGF-β1 may be associated with increased risk of pancreatic cancer although a long follow-up period may be needed to observe this association.

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Section: Discussioncontrasting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum transforming growth factor-β1 and risk of pancreatic cancer in three prospective cohort studies

Jacobs

Newton

Silverman

et al. 2014

Cancer Causes Control

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“…Both tumor cells and immune cells, such as regulatory T cells and myeloid-derived suppressor cells (MDSC), contribute to enhanced TGF-b production in patients with cancer. Elevated TGF-b levels in serum and tumors correlate with poor prognosis in patients with tumor (5,6). Thus, TGF-b has generated interest as a target for novel anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Efficacy of Bifunctional siRNA Combining TGF-β1 Silencing with RIG-I Activation in Pancreatic Cancer

et al. 2013

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Deregulated TGF-b signaling in pancreatic cancer promotes tumor growth, invasion, metastasis, and a potent immunosuppressive network. A strategy for disrupting this tumor-promoting pathway is silencing TGF-b by siRNA. By introducing a triphosphate group at the 5 0 end of siRNA (ppp-siRNA), gene silencing can be combined with immune activation via the cytosolic helicase retinoic acid-inducible gene I (RIG-I), a ubiquitously expressed receptor recognizing viral RNA. We validated RIG-I as a therapeutic target by showing that activation of RIG-I in pancreatic carcinoma cells induced IRF-3 phosphorylation, production of type I IFN, the chemokine CXCL10, as well as caspase-9-mediated tumor cell apoptosis. Next, we generated a bifunctional ppp-siRNA that combines RIG-

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An ISCOM vaccine combined with a TLR9 agonist breaks immune evasion mediated by regulatory T cells in an orthotopic model of pancreatic carcinoma

Jacobs

Duewell

Heckelsmiller³

et al. 2010

Intl Journal of Cancer

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Vaccines based on immune stimulatory complexes (ISCOM) induce T-cell responses against tumor antigen (Ag). However, immune responses are impaired in pancreatic cancer patients. We investigated the efficacy of an ISCOM vaccine in a murine pancreatic carcinoma model. Panc02 cells expressing OVA as a model Ag were induced subcutaneously or orthotopically in the pancreas of C57BL/6 mice. Treatment consisted of an OVA containing ISCOM vaccine, either used alone or in combination with the TLR9 agonist CpG Pancreatic cancer is one of the most fatal malignancies in the Western world. It is the fourth leading cause of cancer death in the United States. 1 The 5-year survival rate is less than 5% with a median overall survival time of 3-6 months. Despite advancements made over the past two decades in elucidating molecular pathways involved in pancreatic carcinogenesis and in the field of targeted therapy, the clinical outcome has not yet significantly improved. At the time of diagnosis the majority of patients present with locally advanced, unresectable tumors or metastatic disease. Even in the small number of patients who undergo surgery in a curative intention most patients succumb to recurrent and metastatic disease. Therefore, new treatments are urgently needed.Immunotherapy may offer a new treatment option. Pancreatic carcinoma cells can be recognized by T cells, which are found in the blood of pancreatic carcinoma patients.2 Tumor infiltration with T cells represents a positive prognostic factor.3 However, pancreatic carcinomas promote systemic and locally active immunosuppressive mechanisms.4 These include inhibition of T-cell activation, secretion of immunosuppressive cytokines, defects in Ag presentation and recruitment of regulatory T cells (Treg), a subgroup of CD4 þ T cells with suppressor function. 5,6 In patients with pancreatic carcinoma, increased numbers of Treg are found in the

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Serum transforming growth factor-β1 levels and pancreatic cancer risk: a nested case–control study (Japan)

Abstract: Our prospective data indicate that high serum TGF-beta1 levels may be associated with an increased risk of death from pancreatic cancer.

Cited by 17 publications

References 20 publications

Serum transforming growth factor-β1 and risk of pancreatic cancer in three prospective cohort studies

Serum transforming growth factor-β1 and risk of pancreatic cancer in three prospective cohort studies

Therapeutic Efficacy of Bifunctional siRNA Combining TGF-β1 Silencing with RIG-I Activation in Pancreatic Cancer

An ISCOM vaccine combined with a TLR9 agonist breaks immune evasion mediated by regulatory T cells in an orthotopic model of pancreatic carcinoma

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