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Table S1 shows the raw result with adjustment for gender, age, education, income and BMI. provided by SPSS software. The joint effects by cumulative amount of smoking and alcohol drinking are assessed here, but no significant interaction is observed (p=0.088).

Table S2 shows the significant dietary results of univariate logistic regression analysis without adjustment for confounders. As mentioned in the article, each food or food type listed in Fig. 2 was analyzed to be statistically significant when conducting univariate logistic regression analysis, and some of them remained significant associations after performing adjusted logistic regression model (Fig. 2).

Table S3 shows the insignificant dietary results of univariate logistic regression analysis without adjustment for confounders. These insignificant data are not further analysed in the adjusted logistic regression model.

Supplementary Figures 1-6 from Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity

Tumor-associated immunosuppressive strategies, such as lack of tumor antigen recognition and failure of lymphocyte activation and homing, resist the development of tumor-specific immunity and hamper the immune response–mediated elimination of cancerous cells. In this report, we show that reovirus virotherapy overrides such a tumor immune evasion and establishes clinically meaningful antitumor immunity capable of protecting against subsequent tumor challenge. Reovirus-mediated destruction of tumor cells facilitates the recognition of tumor antigens by promoting the display of otherwise inaccessible tumor-specific immunogenic peptides on the surface of dendritic cells (DC). Furthermore, on exposure to reovirus, DCs produce IL-1α, IL-1β, IL-6, IL-12p40/70, IL-17, CD30L, eotaxin, GM-CSF, KC, MCP-1, MCP-5, M-CSF, MIG, MIP-1α, RANTES, TNF-α, VCAM-1, VSGF, CXCL-16, AXL, and MCP-2; undergo maturation; and migrate into the tumor microenvironment along with CD8 T cells. These reovirus-activated DCs also acquire the capacity to prime tumor antigen–specific transgenic T cells in vitro and intrinsic antitumor T-cell response in vivo. Further, reovirus virotherapy augments the efficacy of DC- or T cell–based anticancer immunotherapies and synergistically enhances the survival in tumor-bearing mice. Most importantly, antitumor cellular immune responses initiated during reovirus oncotherapy protect the host against subsequent tumor challenge in a reovirus-independent but antigen-dependent manner. These reovirus oncotherapy–initiated antitumor immune responses represent an anticancer therapeutic entity that can maintain a long-term cancer-free health even after discontinuation of therapy. Mol Cancer Ther; 9(11); 2924–33. ©2010 AACR.

Supplementary Figure 5 from Oncogenic Ras Promotes Reovirus Spread by Suppressing IFN-β Production through Negative Regulation of RIG-I Signaling

Supplementary Figure 1 from Oncogenic Ras Promotes Reovirus Spread by Suppressing IFN-β Production through Negative Regulation of RIG-I Signaling

Supplementary Figure 2 from Oncogenic Ras Promotes Reovirus Spread by Suppressing IFN-β Production through Negative Regulation of RIG-I Signaling

Supplementary Figure Legends 1-6 from Oncogenic Ras Promotes Reovirus Spread by Suppressing IFN-β Production through Negative Regulation of RIG-I Signaling

Supplementary Figure 4 from Oncogenic Ras Promotes Reovirus Spread by Suppressing IFN-β Production through Negative Regulation of RIG-I Signaling

Supplementary Figure 6 from Oncogenic Ras Promotes Reovirus Spread by Suppressing IFN-β Production through Negative Regulation of RIG-I Signaling

Supplementary Figure 3 from Oncogenic Ras Promotes Reovirus Spread by Suppressing IFN-β Production through Negative Regulation of RIG-I Signaling

Reovirus is the first naturally occurring human virus reported to exploit activated Ras signaling in the host cell for infection, and is currently undergoing clinical trials as a cancer therapeutic. Recent evidence suggests that Ras transformation promotes three reoviral replication steps during the first round of infection: uncoating of the incoming virion, generation of progeny viruses with enhanced infectivity, and virus release through enhanced apoptosis. Whether oncogenic Ras also enhances reovirus spread in subsequent rounds of infection through other mechanisms has not been examined. Here, we show that compared with nontransformed cells, Ras-transformed cells are severely compromised not only in their response to IFN-β, but also in the induction of IFN-β mRNA following reovirus infection. Defects in both IFN-β production and response allow for efficient virus spread in Ras-transformed cells. We show that the MEK/ERK pathway downstream of Ras is responsible for inhibiting IFN-β expression by blocking signaling from the retinoic acid–inducible gene I (RIG-I) which recognizes viral RNAs. Overexpression of wild-type RIG-I restores INF-β expression in reovirus-infected Ras-transformed cells. In vitro–synthesized viral mRNAs also invoke robust RIG-I–mediated IFN-β production in transfected nontransformed cells, but not in Ras-transformed cells. Collectively, our data suggest that oncogenic Ras promotes virus spread by suppressing viral RNA–induced IFN-β production through negative regulation of RIG-I signaling. Cancer Res; 70(12); 4912–21. ©2010 AACR.

Better understanding of esophageal precancerous lesions (EPL) can inform prevention strategies for esophageal squamous cell carcinoma (ESCC). Here, a cross-sectional epidemiologic study based on the Early Diagnosis and Early Treatment Project of Esophageal Cancer database from 2011 to 2017 was performed to fully investigate and characterize the epidemiology of EPL in rural Huai'an District. Data of 11,518 participants ages 35–75 years were collected through face-to-face interviews by questionnaire. Participants underwent a routine endoscopy examination, tissues were biopsied, and diagnosed according to the histologic criteria of dysplasia. Unconditional univariate and multivariate logistic regression analyses were performed to obtain crude and adjusted odds ratios and corresponding 95% confidence intervals, respectively. A total of 667 subjects were diagnosed with EPL. Factors associated with an increased risk of EPL included: drinking shallow well water and surface water, irregular diet, excessive smoking, exposure to secondhand smoke, consumption of corn, corn flour, pickled food, fried food, and hot food, and having a history of digestive system diseases. In addition, liquor use, but not other alcohol types, contributed to risk of EPL. Consumption of deep well water and vegetables, fruits, and animal livers were associated with lower EPL risk. This study suggested a completely distinct pattern that alcohol use plays only a minor role in EPL and excessive tobacco use shows a significant association in rural Huai'an District, while eating habits and environmental exposure may be the dominant factors. This work may be promising to provide scientific evidence to support primary prevention of ESCC in this region.

Reovirus is the first naturally occurring human virus reported to exploit activated Ras signaling in the host cell for infection, and is currently undergoing clinical trials as a cancer therapeutic. Recent evidence suggests that Ras transformation promotes three reoviral replication steps during the first round of infection: uncoating of the incoming virion, generation of progeny viruses with enhanced infectivity, and virus release through enhanced apoptosis. Whether oncogenic Ras also enhances reovirus spread in subsequent rounds of infection through other mechanisms has not been examined. Here, we show that compared with nontransformed cells, Ras-transformed cells are severely compromised not only in their response to IFN-β, but also in the induction of IFN-β mRNA following reovirus infection. Defects in both IFN-β production and response allow for efficient virus spread in Ras-transformed cells. We show that the MEK/ERK pathway downstream of Ras is responsible for inhibiting IFN-β expression by blocking signaling from the retinoic acid–inducible gene I (RIG-I) which recognizes viral RNAs. Overexpression of wild-type RIG-I restores INF-β expression in reovirus-infected Ras-transformed cells. In vitro–synthesized viral mRNAs also invoke robust RIG-I–mediated IFN-β production in transfected nontransformed cells, but not in Ras-transformed cells. Collectively, our data suggest that oncogenic Ras promotes virus spread by suppressing viral RNA–induced IFN-β production through negative regulation of RIG-I signaling. Cancer Res; 70(12); 4912–21. ©2010 AACR.