Can the Japanese Agri-food Sectors Survive by Promoting their Exports?: A General Equilibrium Analysis with Farm Heterogeneity and Product Differentiation

Manufacturing industries have attracted research attention regarding roles of firm heterogeneity and product differentiation in the new new trade theory. Agricultural sectors also produce new goods by product differentiation through breeding, food processing, quality-upgrading, and branding. In reaction to the recent globalization, the Japanese government has sought strategies to promote its domestic agri-food sectors by means of product differentiation and export promotion. This computable general equilibrium study examines the relevance of these policies by simulating hypothetical trade liberalization in agriculture and/or food. We show that agricultural trade liberalization would not increase Japan s agricultural exports but would increase food exports; and that food trade liberalization would promote food exports. Both types of liberalization would increase domestic production in agri-food sectors through agri-food linkages and variety effects. This finding affords evidence of the relevance of product differentiation strategy through food processing and exportation, but not of agricultural export promotion strategy.This study is partly supported by JSPS KAKENHI grant (Nos. 16K03613, 16K07907, 16KT0036, 19K01622).http://www.grips.ac.jp/list/jp/facultyinfo/hosoe_nobuhiro

Development of healthy lifestyle consciousness index for gynecological cancer patients

PURPOSE: Healthy lifestyle is related to quality of life (QOL) after cancer diagnosis and prognosis. However, there are few reports on patients conscious of healthy lifestyle and patients requiring medical providers' attention regarding healthy lifestyle. We aimed to develop a healthy lifestyle consciousness index (HLCI) for cancer patients and evaluated its validity in gynecological cancer patients. METHODS: The HLCI was designed to assess degree of healthy lifestyle consciousness, including items regarding "diet, " "exercise, " "body weight, " and "sleep." Exploratory factor analysis was performed for dimensionality of the scale; Cronbach's alpha was calculated to assess internal-consistency reliability. For criterion-based validity, we calculated proportions of stage III/IV gynecological malignancies in those with categorized HLCI scores based on tertiles. Concurrent validity was evaluated between HLCI and other quality of life (QOL) scales including European Organization for Research and Treatment of Cancer QLQ-C30 in limited patients. RESULTS: HLCI comprised five 10-point items (0-45); higher values implied improved healthy lifestyle consciousness. Data from 108 gynecological malignancy patients at Kyoto University Hospital were analyzed. The mean age of subjects was 55.8 years; 36.1% of them had uterine corpus cancer; 34.3% were at stage III/IV of gynecological malignancy. The factor analysis revealed HLCI was unidimensional; the reliability based on Cronbach's alpha was satisfactory (0.88). The proportions of stage III/IV gynecological malignancies were 25.7%, 33.3%, and 44.4% in those with first (7-24 points), second (25-30 points), and third (31-46 points) tertiles of HLCI score, respectively. For patients with other QOL scales (n = 25), the mean scores of global health status of QLQ-C30 were 33.3, 50.0, and 83.3 for first, second, and third tertiles of HLCI score, respectively. CONCLUSION: HLCI was successfully validated; thus, patients with advanced stages or higher QOL might have strong consciousness regarding healthy lifestyle. HLCI may be useful in precision care for improved lifestyles and QOL

Tertiary lymphoid structures are associated with favorable survival outcomes in patients with endometrial cancer

Immunotherapy has experienced remarkable growth recently. Tertiary lymphoid structures (TLSs) and B cells may play a key role in the immune response and have a survival benefit in some solid tumors, but there have been no reports about their role in endometrial cancer (EC). We investigated the clinicopathological and pathobiological characteristics of the tumor microenvironment (TME) in EC. Patients with EC at Kyoto University Hospital during 2006–2011 were retrospectively included. In 104 patients with EC who met study inclusion criteria, 81 (77.9%) had TLSs, which consisted of areas rich in CD20⁺ B cells, CD8⁺ T cells, CD4⁺ T cells, and CD38⁺ plasma cells. The absence of TLS was independently associated with tumor progression (HR, 0.154; 95% CI, 0.044–0.536; P = 0.003). Patients with TLSs that included CD23⁺ germinal centers had better PFS. All tumor infiltrating lymphocytes were counted in the intratumor site. The number of CD20⁺ B cells was significantly larger in patients with TLSs than in those without TLS (P < 0.001). CD20⁺ B cells numbers were positively correlated with other TLSs. The larger number of CD20⁺ B cell was associated with better PFS (P = 0.015). TLSs and B cell infiltration into tumors are associated with favorable survival outcomes in patients with EC. They may represent an active immune reaction of the TME in endometrial cancer

B7-H3 Suppresses Antitumor Immunity via the CCL2–CCR2–M2 Macrophage Axis and Contributes to Ovarian Cancer Progression

New approaches beyond PD-1/PD-L1 inhibition are required to target the immunologically diverse tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC). In this study, we explored the immunosuppressive effect of B7-H3 (CD276) via the CCL2–CCR2–M2 macrophage axis and its potential as a therapeutic target. Transcriptome analysis revealed that B7-H3 is highly expressed in PD-L1–low, nonimmunoreactive HGSOC tumors, and its expression negatively correlated with an IFNγ signature, which reflects the tumor immune reactivity. In syngeneic mouse models, B7-H3 (Cd276) knockout (KO) in tumor cells, but not in stromal cells, suppressed tumor progression, with a reduced number of M2 macrophages and an increased number of IFNγ⁺CD8⁺ T cells. CCL2 expression was downregulated in the B7-H3 KO tumor cell lines. Inhibition of the CCL2–CCR2 axis partly negated the effects of B7-H3 suppression on M2 macrophage migration and differentiation, and tumor progression. In patients with HGSOC, B7-H3 expression positively correlated with CCL2 expression and M2 macrophage abundance, and patients with B7-H3–high tumors had fewer tumoral IFNγ⁺CD8⁺ T cells and poorer prognosis than patients with B7-H3–low tumors. Thus, B7-H3 expression in tumor cells contributes to CCL2–CCR2–M2 macrophage axis–mediated immunosuppression and tumor progression. These findings provide new insights into the immunologic TME and could aid the development of new therapeutic approaches against the unfavorable HGSOC phenotype

CXCL13-producing CD4⁺ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer

卵巣がんにおける新たな免疫の仕組みを発見 --三次リンパ様構造の形成メカニズムと予後への影響を解明--. 京都大学プレスリリース. 2022-08-05.Tertiary lymphoid structures (TLSs) are transient ectopic lymphoid aggregates whose formation might be caused by chronic inflammation states, such as cancer. However, how TLSs are induced in the tumor microenvironment (TME) and how they affect patient survival are not well understood. We investigated TLS distribution in relation to tumor infiltrating lymphocytes (TILs) and related gene expression in high grade serous ovarian cancer (HGSC) specimens. CXCL13 gene expression correlated with TLS presence and the infiltration of T cells and B cells, and was a favorable prognostic factor for HGSC patients. Coexistence of CD8⁺ T cells and B-cell lineages in the TME significantly improved the prognosis of HGSC and was correlated with the presence of TLSs. CXCL13 expression was predominantly coincident with CD4⁺ T cells in TLSs and CD8⁺ T cells in TILs, and shifted from CD4⁺ T cells to CD21⁺ follicular dendritic cells as TLS matured. In a mouse ovarian cancer model, recombinant CXCL13 induced TLSs and enhanced survival by the infiltration of CD8⁺ T cells. These results suggest that TLS formation was associated with CXCL13-producing CD4⁺ T cells and that TLSs facilitated the coordinated antitumor response of cellular and humoral immunity in ovarian cancer

Impact of Trade Liberalization on the Japanese Agri-food Sectors: A General Equilibrium Analysis with Farm Heterogeneity and Product Differentiation

Manufacturing industries have attracted considerable research attention in state-of-the-art trade studies with findings of firm heterogeneity and product differentiation, à la Melitz. In contrast, it is widely assumed that agricultural sectors produce homogeneous goods. However, they do in fact produce new goods by product differentiation through breeding, food processing, quality-upgrading, and branding. In reaction to the recent globalization and increasing penetration of imported agricultural goods, the Japanese government has sought strategies to promote its domestic agri-food sectors by means of product differentiation and export promotion. In this computable general equilibrium study, we seek to identify means by which Japan’s agricultural sectors can survive in the globalized economy and increase their exports; we focus on strategies that incorporate product differentiation and farm/firm heterogeneity. Our simulation experiments show that agricultural trade liberalization would not increase Japan’s agricultural exports but would increase food exports; and that food trade liberalization would promote food exports and some agricultural exports. In both liberalization scenarios, trade liberalization would increase domestic agri-food production. This finding affords evidence of the relevance of product differentiation strategy (especially as applied to food processing and exportation) but not of agricultural export promotion strategy

Impact of Trade Liberalization on the Japanese Agri-food Sectors: A General Equilibrium Analysis with Farm Heterogeneity and Product Differentiation

Manufacturing industries have attracted considerable research attention in state-of-the-art trade studies with findings of firm heterogeneity and product differentiation, à la Melitz. In contrast, it is widely assumed that agricultural sectors produce homogeneous goods. However, they do in fact produce new goods by product differentiation through breeding, food processing, quality-upgrading, and branding. In reaction to the recent globalization and increasing penetration of imported agricultural goods, the Japanese government has sought strategies to promote its domestic agri-food sectors by means of product differentiation and export promotion. In this computable general equilibrium study, we seek to identify means by which Japan’s agricultural sectors can survive in the globalized economy and increase their exports; we focus on strategies that incorporate product differentiation and farm/firm heterogeneity. Our simulation experiments show that agricultural trade liberalization would not increase Japan’s agricultural exports but would increase food exports; and that food trade liberalization would promote food exports and some agricultural exports. In both liberalization scenarios, trade liberalization would increase domestic agri-food production. This finding affords evidence of the relevance of product differentiation strategy (especially as applied to food processing and exportation) but not of agricultural export promotion strategy

Characteristic changes in plasma glutamate levels and free amino acid profiles in Japanese patients with type 1 diabetes mellitus

ABSTRACT Aims/Introduction In addition to absolute insulin deficiency, dysregulated glucagon in type 1 diabetes is considered pathophysiologically important. Previously, we confirmed the presence of dysregulated glucagon in Japanese patients with type 1 diabetes, and found a significant correlation between plasma glucagon and blood urea nitrogen levels, suggesting an association between glucagon and amino acid metabolism. In this study, we evaluated plasma amino acid levels in Japanese patients with type 1 diabetes in the context of their functional relationship with glucagon. Materials and Methods We assessed plasma free amino acid levels using liquid chromatography–mass spectrometry in 77 Japanese patients with type 1 diabetes, and statistically analyzed their characteristics and relationships with clinical parameters, including glucagon. Results Participants with type 1 diabetes showed a large decrease in glutamate levels together with a characteristic change in plasma free amino acid profiles. The network structural prediction analyses showed correlations between each amino acid and glucagon in type 1 diabetes. Conclusions Participants with type 1 diabetes showed characteristic changes in plasma glutamate levels and free amino acid profiles compared with controls and type 2 diabetes patients. Glucagon showed a closer correlation with amino acids than with parameters of glucose metabolism, suggesting that type 1 diabetes includes dysregulation in amino acids through dysregulated glucagon from remaining pancreatic α‐cells, together with that in glucose by insulin deficiency

Acquisition of a side population fraction augments malignant phenotype in ovarian cancer

Side population (SP) cells harbor malignant phenotypes in cancer. The aim of this study was to identify genes that modulate the proportion of ovarian cancer SP cells. Using a shRNA library targeting 15, 000 genes, a functional genomics screen was performed to identify genes whose suppression increased the SP percentage. The biological effects caused by alteration of those identified genes were investigated in vitro and in vivo. We found that suppression of MSL3, ZNF691, VPS45, ITGB3BP, TLE2, and ZNF498 increased the proportion of SP cells. Newly generated SP cells exhibit greater capacity for sphere formation, single cell clonogenicity, and in vivo tumorigenicity. On the contrary, overexpression of MSL3, VPS45, ITGB3BP, TLE2, and ZNF498 decreased the proportion of SP cells, sphere formation capacity and single cell clonogenicity. In ovarian cancer cases, low expression of MSL3, ZNF691 and VPS45 was related to poor prognosis. Suppression of these six genes enhanced activity of the hedgehog pathway. Cyclopamine, a hedgehog pathway inhibitor, significantly decreased the number of SP cells and their sphere forming ability. Our results provide new information regarding molecular mechanisms favoring SP cells and suggest that Hedgehog signaling may provide a viable target for ovarian cancer