Pathogenesis of follicular thymic hyperplasia associated with rheumatoid arthritis

Ohe, Rintaro; Yang, Suran; Yamashita, Daisuke; Ichikawa, Chihiro; Saito, Akihisa; Kabasawa, Takanobu; Utsunomiya, Aya; Aung, Naing Ye; Urano, Y; Kitaoka, Takumi; Suzuki, Kazushi; Takahara, Daiichiro; Sasaki, Akira; Takakubo, Yuya; Takagi, Michiaki; Yamakawa, Mitsunori; Futakuchi, Mitsuru

doi:10.1111/pin.13212

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…We previously demonstrated the semiquantitative analysis of stromal cells in immunohistochemistry (IHC) specimens by ImageJ and HALO software (Indica Labs, Albuquerque, NM, USA) using arti cial intelligence [14,15]. These studies demonstrated that the number of stromal cells in the TME is involved in the malignancy or pathogenesis of diseases [14,15]. Hence, histological spatial analysis by HALO software in this study may help in examining tumor-stromal interactions between CRC cells and Mφs.…”

Section: Introductionmentioning

confidence: 80%

“…Additionally, the use of arti cial intelligence for predicting lymph node metastasis by whole-slide imaging of CRC specimens has been reported [13]. We previously demonstrated the semiquantitative analysis of stromal cells in immunohistochemistry (IHC) specimens by ImageJ and HALO software (Indica Labs, Albuquerque, NM, USA) using arti cial intelligence [14,15]. These studies demonstrated that the number of stromal cells in the TME is involved in the malignancy or pathogenesis of diseases [14,15].…”

Section: Introductionmentioning

confidence: 99%

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Neighboring macrophage-induced alteration in the phenotype of colorectal cancer cells in the tumor budding area

Kawamura

Ohe

Suzuki

et al. 2023

Preprint

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Background A higher number of tumor buds in the invasive front of colorectal cancer (CRC) specimens has been shown to contribute to a poor prognosis in CRC patients. Because macrophages (Mφs) have been demonstrated to alter the phenotype of cancer cells, we hypothesized that the phenotype of CRC cells in the tumor budding (TB) area might be changed by the interaction between CRC cells and Mφs. Methods We assessed the expression of topoisomerase 1 in CRC cells to estimate the acquisition of chemoresistance in CRC. To demonstrate the tumor-stromal interaction between CRC cells and Mφs, we assessed two histological findings, the number of Mφs per single CRC cell and the proximity between CRC cells and Mφs by histological spatial analysis using HALO software. Results The expression levels of topoisomerase 1 in CRC cells were decreased in deeper areas, especially in the TB area, compared to the surface area. Our histological spatial analysis revealed that approximately 2.6 Mφs located within 50 µm of a single CRC cell were required to alter the phenotype of the CRC cell. Double-immunofluorescence staining revealed that many CD68+ Mφs were positive for interleukin-6 (IL-6) in the TB area and that AE1/AE3-positive CRC cells in the TB area were positive for phospho-STAT3 (pSTAT3); thus, the IL-6 receptor (IL-6R)/STAT3 signaling pathway in CRC cells was upregulated by IL-6 derived from neighboring Mφs. Conclusions The phenotype of CRC cells in the TB area is altered by neighboring Mφs via the IL-6R/STAT3 signaling pathway.

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Section: Introductionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Neighboring macrophage-induced alteration in the phenotype of colorectal cancer cells in the tumor budding area

Kawamura

Ohe

Suzuki

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, the use of artificial intelligence for predicting lymph node metastasis by whole-slide imaging of CRC specimens has been reported [ 13 ]. We previously demonstrated the semiquantitative analysis of stromal cells in immunohistochemistry (IHC) specimens by ImageJ and HALO software (Indica Labs, Albuquerque, NM, USA) using artificial intelligence [ 14 , 15 ]. These studies demonstrated that the number of stromal cells in the TME would be involved in the malignancy or pathogenesis of diseases [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…We previously demonstrated the semiquantitative analysis of stromal cells in immunohistochemistry (IHC) specimens by ImageJ and HALO software (Indica Labs, Albuquerque, NM, USA) using artificial intelligence [ 14 , 15 ]. These studies demonstrated that the number of stromal cells in the TME would be involved in the malignancy or pathogenesis of diseases [ 14 , 15 ]. Hence, histological spatial analysis by HALO software may help in examining tumor–stromal interactions between CRC cells and Mφs.…”

Section: Introductionmentioning

confidence: 99%

Neighboring macrophage-induced alteration in the phenotype of colorectal cancer cells in the tumor budding area

Kawamura,

Ohe,

Suzuki

et al. 2024

Cancer Cell Int

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Background A higher number of tumor buds in the invasive front of colorectal cancer (CRC) specimens has been shown to contribute to a poor prognosis in CRC patients. Because macrophages (Mφs) have been demonstrated to alter the phenotype of cancer cells, we hypothesized that the phenotype of CRC cells in the tumor budding (TB) area might be changed by the interaction between CRC cells and Mφs. Methods We assessed the expression of topoisomerase 1 in CRC cells to estimate the acquisition of chemoresistance in CRC. To demonstrate the tumor–stromal interaction between CRC cells and Mφs, we assessed two histological findings, the number of Mφs per single CRC cell and the proximity between CRC cells and Mφs by histological spatial analysis using HALO software. Results The expression levels of topoisomerase 1 in CRC cells were decreased in deeper areas, especially in the TB area, compared to the surface area. Our histological spatial analysis revealed that 2.6 Mφs located within 60 μm of a single CRC cell were required to alter the phenotype of the CRC cell. Double-immunofluorescence staining revealed that higher Mφs were positive for interleukin-6 (IL-6) in the TB area and that AE1/AE3-positive CRC cells were also positive for phospho-STAT3 (pSTAT3) in the TB area; thus, the IL-6 receptor (IL-6R)/STAT3 signaling pathway in CRC cells was upregulated by IL-6 derived from neighboring Mφs. Conclusion IL-6 secreted from the neighboring Mφs would alter the phenotype of CRC cells via IL-6R/STAT3 signaling pathway.

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A case of methotrexate-related lymphoproliferative disease showing multiple liver lesions in a patient with rheumatoid arthritis

Nagata,

Akiba,

Horiuchi

et al. 2024

Clin J Gastroenterol

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A 66-year-old woman with rheumatoid arthritis (RA) who had been receiving methotrexate (MTX) for 2 years presented with tarry stools. Contrast-enhanced computed tomography (CT) of the abdomen revealed irregular wall thickening in the ileocecal region and multiple low-contrast masses in both lobes of the liver. Lower gastrointestinal endoscopy revealed a type 2 tumor in the ileocecal region with a semi-peripheral ulcer. Histological examination of liver and colon biopsies showed other iatrogenic immunodeficiency-associated lymphoproliferative disorder (Oi-LPD), diffuse large B-cell lymphoma type, with positivity for Epstein-Barr virus DNA. After withdrawal of MTX, the LPD lesions disappeared and the patient achieved remission. We considered this to be a sporadic case of Oi-LPD, diffuse large B-cell lymphoma type, in the liver and colon due to treatment with MTX. There has been no previous report of this condition with simultaneous hepatic and colonic lesions, and the present case is thought to be highly informative in relation to the pathogenesis.

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Pathogenesis of follicular thymic hyperplasia associated with rheumatoid arthritis

Cited by 6 publications

References 26 publications

Neighboring macrophage-induced alteration in the phenotype of colorectal cancer cells in the tumor budding area

Neighboring macrophage-induced alteration in the phenotype of colorectal cancer cells in the tumor budding area

Neighboring macrophage-induced alteration in the phenotype of colorectal cancer cells in the tumor budding area

A case of methotrexate-related lymphoproliferative disease showing multiple liver lesions in a patient with rheumatoid arthritis

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