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Your search keyword '"Jennifer B Gordetsky"' showing total 16 results
Start Over Author "Jennifer B Gordetsky" Publisher american association for cancer research (aacr)
16 results on '"Jennifer B Gordetsky"'

1. Data from High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling

Author

Norio Nonomura, George J. Netto, Kazutake Tsujikawa, Eiichi Morii, Jennifer B. Gordetsky, Maria Del Carmen Rodriguez Pena, Motohide Uemura, Takeshi Ujike, Akira Nagahara, Atsunari Kawashima, Taigo Kato, Kentaro Jingushi, Kyosuke Matsuzaki, Toshiro Kinouchi, Yoshiyuki Yamamoto, Cong Wang, Yu Ishizuya, Kosuke Nakano, Yujiro Hayashi, Satoshi Nojima, Kazutoshi Fujita, and Takuji Hayashi

Abstract

Purpose: High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation.Experimental Design: We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre+;Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age. Cytokines which correlated with tumor growth were identified, and the changes of tumor growth and local immune cells after inhibition of the cytokine signals were evaluated in the mice. IHC analyses using prostatectomy specimens of obese patients were performed.Results: HFD accelerated tumor growth and increased the myeloid-derived suppressor cells (MDSCs) fraction and M2/M1 macrophage ratio in the model mice. Celecoxib-suppressed tumor growth, and decreased both local MDSCs and M2/M1 macrophage ratio in HFD-fed mice. HFD-induced tumor growth was associated with IL6 secreted by prostatic macrophages, as were phosphorylated STAT3 (pSTAT3)-positive tumor cells. Anti-IL6 receptor antibody administration suppressed tumor growth, and decreased local MDSCs and pSTAT3-positive cell fractions in HFD-fed mice. The tumor-infiltrating CD11b-positive cell count was significantly higher in prostatectomy specimens of obese than those of nonobese patients with prostate cancer.Conclusions: HFD increased MDSCs and accelerated prostate cancer tumor growth via IL6/pSTAT3 signaling in the mice. This mechanism could exist in obese patients with prostate cancer. IL6-mediated inflammation could be a therapeutic target for prostate cancer. Clin Cancer Res; 24(17); 4309–18. ©2018 AACR.

Published
2023
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2. Supplementary Figure S4 from High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling

Author

Norio Nonomura, George J. Netto, Kazutake Tsujikawa, Eiichi Morii, Jennifer B. Gordetsky, Maria Del Carmen Rodriguez Pena, Motohide Uemura, Takeshi Ujike, Akira Nagahara, Atsunari Kawashima, Taigo Kato, Kentaro Jingushi, Kyosuke Matsuzaki, Toshiro Kinouchi, Yoshiyuki Yamamoto, Cong Wang, Yu Ishizuya, Kosuke Nakano, Yujiro Hayashi, Satoshi Nojima, Kazutoshi Fujita, and Takuji Hayashi

Abstract

Positive controls of anti-mouse and anti-human antibodies for immunohistochemistry

Published
2023
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3. Figure S3 from Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Norio Nonomura, Kiyoshi Takeda, Shota Nakamura, Kazutake Tsujikawa, George J. Netto, Jennifer B. Gordetsky, Maria D.C. Rodriguez Pena, Ryoichi Imamura, Motohide Uemura, Takeshi Ujike, Atsunari Kawashima, Koji Hatano, Taigo Kato, Yu Ishizuya, Cong Wang, Kosuke Nakano, Yujiro Hayashi, Yoko Koh, Eisuke Tomiyama, Satoru Yumiba, Gaku Yamamichi, Kentaro Jingushi, Hiroaki Hase, Daisuke Motooka, Hisako Kayama, Takuji Hayashi, Kazutoshi Fujita, and Makoto Matsushita

Abstract

Alterations in systemic and local prostate expression of IGF-1 due to Abx administration.

Published
2023
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4. Supplementary Data, Methods, Table and Figure legends from High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling

Author

Norio Nonomura, George J. Netto, Kazutake Tsujikawa, Eiichi Morii, Jennifer B. Gordetsky, Maria Del Carmen Rodriguez Pena, Motohide Uemura, Takeshi Ujike, Akira Nagahara, Atsunari Kawashima, Taigo Kato, Kentaro Jingushi, Kyosuke Matsuzaki, Toshiro Kinouchi, Yoshiyuki Yamamoto, Cong Wang, Yu Ishizuya, Kosuke Nakano, Yujiro Hayashi, Satoshi Nojima, Kazutoshi Fujita, and Takuji Hayashi

Abstract

Detailed data were described.

Published
2023
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5. Supplementary Figure S3 from High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling

Author

Norio Nonomura, George J. Netto, Kazutake Tsujikawa, Eiichi Morii, Jennifer B. Gordetsky, Maria Del Carmen Rodriguez Pena, Motohide Uemura, Takeshi Ujike, Akira Nagahara, Atsunari Kawashima, Taigo Kato, Kentaro Jingushi, Kyosuke Matsuzaki, Toshiro Kinouchi, Yoshiyuki Yamamoto, Cong Wang, Yu Ishizuya, Kosuke Nakano, Yujiro Hayashi, Satoshi Nojima, Kazutoshi Fujita, and Takuji Hayashi

Abstract

Relative mRNA expressions and COX2 staining of CD-fed and HFD-fed mice with or without celecoxib / Immune cells of HFD-fed mice with control IgG and anti-IL6 receptor antibody

Published
2023
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6. Table S3 from Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Norio Nonomura, Kiyoshi Takeda, Shota Nakamura, Kazutake Tsujikawa, George J. Netto, Jennifer B. Gordetsky, Maria D.C. Rodriguez Pena, Ryoichi Imamura, Motohide Uemura, Takeshi Ujike, Atsunari Kawashima, Koji Hatano, Taigo Kato, Yu Ishizuya, Cong Wang, Kosuke Nakano, Yujiro Hayashi, Yoko Koh, Eisuke Tomiyama, Satoru Yumiba, Gaku Yamamichi, Kentaro Jingushi, Hiroaki Hase, Daisuke Motooka, Hisako Kayama, Takuji Hayashi, Kazutoshi Fujita, and Makoto Matsushita

Abstract

A list of 64 cording RNAs that were up-regulated in prostate of HFD PCa mice compared to HFD+Abx PCa mice on cDNA microarrays

Published
2023
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7. Figure S1 from Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Norio Nonomura, Kiyoshi Takeda, Shota Nakamura, Kazutake Tsujikawa, George J. Netto, Jennifer B. Gordetsky, Maria D.C. Rodriguez Pena, Ryoichi Imamura, Motohide Uemura, Takeshi Ujike, Atsunari Kawashima, Koji Hatano, Taigo Kato, Yu Ishizuya, Cong Wang, Kosuke Nakano, Yujiro Hayashi, Yoko Koh, Eisuke Tomiyama, Satoru Yumiba, Gaku Yamamichi, Kentaro Jingushi, Hiroaki Hase, Daisuke Motooka, Hisako Kayama, Takuji Hayashi, Kazutoshi Fujita, and Makoto Matsushita

Abstract

The effects of Abx administration on cancer-free prostates and serum testosterone levels, and the effects of gentamicin administration on HFD PCa mice.

Published
2023
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8. Data from Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Norio Nonomura, Kiyoshi Takeda, Shota Nakamura, Kazutake Tsujikawa, George J. Netto, Jennifer B. Gordetsky, Maria D.C. Rodriguez Pena, Ryoichi Imamura, Motohide Uemura, Takeshi Ujike, Atsunari Kawashima, Koji Hatano, Taigo Kato, Yu Ishizuya, Cong Wang, Kosuke Nakano, Yujiro Hayashi, Yoko Koh, Eisuke Tomiyama, Satoru Yumiba, Gaku Yamamichi, Kentaro Jingushi, Hiroaki Hase, Daisuke Motooka, Hisako Kayama, Takuji Hayashi, Kazutoshi Fujita, and Makoto Matsushita

Abstract

Excessive intake of animal fat and resultant obesity are major risk factors for prostate cancer. Because the composition of the gut microbiota is known to change with dietary composition and body type, we used prostate-specific Pten knockout mice as a prostate cancer model to investigate whether there is a gut microbiota–mediated connection between animal fat intake and prostate cancer. Oral administration of an antibiotic mixture (Abx) in prostate cancer–bearing mice fed a high-fat diet containing a large proportion of lard drastically altered the composition of the gut microbiota including Rikenellaceae and Clostridiales, inhibited prostate cancer cell proliferation, and reduced prostate Igf1 expression and circulating insulin-like growth factor-1 (IGF1) levels. In prostate cancer tissue, MAPK and PI3K activities, both downstream of the IGF1 receptor, were suppressed by Abx administration. IGF1 directly promoted the proliferation of prostate cancer cell lines DU145 and 22Rv1 in vitro. Abx administration also reduced fecal levels of short-chain fatty acids (SCFA) produced by intestinal bacteria. Supplementation with SCFAs promoted tumor growth by increasing IGF1 levels. In humans, IGF1 was found to be highly expressed in prostate cancer tissue from obese patients. In conclusion, IGF1 production stimulated by SCFAs from gut microbes influences the growth of prostate cancer via activating local prostate MAPK and PI3K signaling, indicating the existence of a gut microbiota-IGF1-prostate axis. Disrupting this axis by modulating the gut microbiota may aid in prostate cancer prevention and treatment.Significance:These results suggest that intestinal bacteria, acting through short-chain fatty acids, regulate systemic and local prostate IGF1 in the host, which can promote proliferation of prostate cancer cells.

Published
2023
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9. Figure S2 from Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Norio Nonomura, Kiyoshi Takeda, Shota Nakamura, Kazutake Tsujikawa, George J. Netto, Jennifer B. Gordetsky, Maria D.C. Rodriguez Pena, Ryoichi Imamura, Motohide Uemura, Takeshi Ujike, Atsunari Kawashima, Koji Hatano, Taigo Kato, Yu Ishizuya, Cong Wang, Kosuke Nakano, Yujiro Hayashi, Yoko Koh, Eisuke Tomiyama, Satoru Yumiba, Gaku Yamamichi, Kentaro Jingushi, Hiroaki Hase, Daisuke Motooka, Hisako Kayama, Takuji Hayashi, Kazutoshi Fujita, and Makoto Matsushita

Abstract

Variation in the composition of gut and prostate tissue microbiota.

Published
2023
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10. Supplementary Figure S2 from High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling

Author

Norio Nonomura, George J. Netto, Kazutake Tsujikawa, Eiichi Morii, Jennifer B. Gordetsky, Maria Del Carmen Rodriguez Pena, Motohide Uemura, Takeshi Ujike, Akira Nagahara, Atsunari Kawashima, Taigo Kato, Kentaro Jingushi, Kyosuke Matsuzaki, Toshiro Kinouchi, Yoshiyuki Yamamoto, Cong Wang, Yu Ishizuya, Kosuke Nakano, Yujiro Hayashi, Satoshi Nojima, Kazutoshi Fujita, and Takuji Hayashi

Abstract

Body weights, prostate weights, H&E staining and immune cells of CD-fed and HFD-fed mice with or without celecoxib

Published
2023
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11. Table S2 from Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Norio Nonomura, Kiyoshi Takeda, Shota Nakamura, Kazutake Tsujikawa, George J. Netto, Jennifer B. Gordetsky, Maria D.C. Rodriguez Pena, Ryoichi Imamura, Motohide Uemura, Takeshi Ujike, Atsunari Kawashima, Koji Hatano, Taigo Kato, Yu Ishizuya, Cong Wang, Kosuke Nakano, Yujiro Hayashi, Yoko Koh, Eisuke Tomiyama, Satoru Yumiba, Gaku Yamamichi, Kentaro Jingushi, Hiroaki Hase, Daisuke Motooka, Hisako Kayama, Takuji Hayashi, Kazutoshi Fujita, and Makoto Matsushita

Abstract

The primers used in quantitative real-time PCR

Published
2023
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12. Table S1 from Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Norio Nonomura, Kiyoshi Takeda, Shota Nakamura, Kazutake Tsujikawa, George J. Netto, Jennifer B. Gordetsky, Maria D.C. Rodriguez Pena, Ryoichi Imamura, Motohide Uemura, Takeshi Ujike, Atsunari Kawashima, Koji Hatano, Taigo Kato, Yu Ishizuya, Cong Wang, Kosuke Nakano, Yujiro Hayashi, Yoko Koh, Eisuke Tomiyama, Satoru Yumiba, Gaku Yamamichi, Kentaro Jingushi, Hiroaki Hase, Daisuke Motooka, Hisako Kayama, Takuji Hayashi, Kazutoshi Fujita, and Makoto Matsushita

Abstract

Composition and energy values of control diet and high-fat diet

Published
2023
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13. Figure S4 from Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Norio Nonomura, Kiyoshi Takeda, Shota Nakamura, Kazutake Tsujikawa, George J. Netto, Jennifer B. Gordetsky, Maria D.C. Rodriguez Pena, Ryoichi Imamura, Motohide Uemura, Takeshi Ujike, Atsunari Kawashima, Koji Hatano, Taigo Kato, Yu Ishizuya, Cong Wang, Kosuke Nakano, Yujiro Hayashi, Yoko Koh, Eisuke Tomiyama, Satoru Yumiba, Gaku Yamamichi, Kentaro Jingushi, Hiroaki Hase, Daisuke Motooka, Hisako Kayama, Takuji Hayashi, Kazutoshi Fujita, and Makoto Matsushita

Abstract

Abx-induced changes in phosphorylation MEK and S6RP in cancer cells of CD and HFD mice.

Published
2023
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14. Supplementary Figure S1 from High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling

Author

Norio Nonomura, George J. Netto, Kazutake Tsujikawa, Eiichi Morii, Jennifer B. Gordetsky, Maria Del Carmen Rodriguez Pena, Motohide Uemura, Takeshi Ujike, Akira Nagahara, Atsunari Kawashima, Taigo Kato, Kentaro Jingushi, Kyosuke Matsuzaki, Toshiro Kinouchi, Yoshiyuki Yamamoto, Cong Wang, Yu Ishizuya, Kosuke Nakano, Yujiro Hayashi, Satoshi Nojima, Kazutoshi Fujita, and Takuji Hayashi

Abstract

Prostate weights, H&E staining and local immune cells of normal and Pten-deficient model mice

Published
2023
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15. Supplementary Methods from Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Norio Nonomura, Kiyoshi Takeda, Shota Nakamura, Kazutake Tsujikawa, George J. Netto, Jennifer B. Gordetsky, Maria D.C. Rodriguez Pena, Ryoichi Imamura, Motohide Uemura, Takeshi Ujike, Atsunari Kawashima, Koji Hatano, Taigo Kato, Yu Ishizuya, Cong Wang, Kosuke Nakano, Yujiro Hayashi, Yoko Koh, Eisuke Tomiyama, Satoru Yumiba, Gaku Yamamichi, Kentaro Jingushi, Hiroaki Hase, Daisuke Motooka, Hisako Kayama, Takuji Hayashi, Kazutoshi Fujita, and Makoto Matsushita

Abstract

Method details

Published
2023
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16. Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling

Author

Makoto Matsushita, Maria Del Carmen Rodriguez Pena, Hiroaki Hase, Hisako Kayama, Yoko Koh, Daisuke Motooka, Cong Wang, Kentaro Jingushi, Taigo Kato, Motohide Uemura, Yujiro Hayashi, Eisuke Tomiyama, Gaku Yamamichi, Jennifer B. Gordetsky, Yu Ishizuya, Takeshi Ujike, Koji Hatano, Satoru Yumiba, Atsunari Kawashima, Kazutake Tsujikawa, Norio Nonomura, Kazutoshi Fujita, George J. Netto, Takuji Hayashi, Ryoichi Imamura, Kiyoshi Takeda, Shota Nakamura, and Kosuke Nakano

Subjects
Male, MAPK/ERK pathway, Cancer Research, Gut flora, Mice, Prostate cancer, DU145, Prostate, medicine, Animals, Humans, PTEN, Insulin-Like Growth Factor I, PI3K/AKT/mTOR pathway, Mice, Knockout, biology, Prostatic Neoplasms, Fatty Acids, Volatile, biology.organism_classification, medicine.disease, Gastrointestinal Microbiome, Disease Models, Animal, medicine.anatomical_structure, Oncology, Knockout mouse, Cancer research, biology.protein, Signal Transduction
Abstract

Excessive intake of animal fat and resultant obesity are major risk factors for prostate cancer. Because the composition of the gut microbiota is known to change with dietary composition and body type, we used prostate-specific Pten knockout mice as a prostate cancer model to investigate whether there is a gut microbiota–mediated connection between animal fat intake and prostate cancer. Oral administration of an antibiotic mixture (Abx) in prostate cancer–bearing mice fed a high-fat diet containing a large proportion of lard drastically altered the composition of the gut microbiota including Rikenellaceae and Clostridiales, inhibited prostate cancer cell proliferation, and reduced prostate Igf1 expression and circulating insulin-like growth factor-1 (IGF1) levels. In prostate cancer tissue, MAPK and PI3K activities, both downstream of the IGF1 receptor, were suppressed by Abx administration. IGF1 directly promoted the proliferation of prostate cancer cell lines DU145 and 22Rv1 in vitro. Abx administration also reduced fecal levels of short-chain fatty acids (SCFA) produced by intestinal bacteria. Supplementation with SCFAs promoted tumor growth by increasing IGF1 levels. In humans, IGF1 was found to be highly expressed in prostate cancer tissue from obese patients. In conclusion, IGF1 production stimulated by SCFAs from gut microbes influences the growth of prostate cancer via activating local prostate MAPK and PI3K signaling, indicating the existence of a gut microbiota-IGF1-prostate axis. Disrupting this axis by modulating the gut microbiota may aid in prostate cancer prevention and treatment. Significance: These results suggest that intestinal bacteria, acting through short-chain fatty acids, regulate systemic and local prostate IGF1 in the host, which can promote proliferation of prostate cancer cells.

Published
2021
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