Finding your CAR: The road ahead for engineered T-cells
Am J Pathol. 2024 Apr 30:S0002-9440(24)00162-7. doi: 10.1016/j.ajpath.2024.04.002. Online ahead of print.ABSTRACTAdoptive cellular therapy using chimeric antigen receptors (CAR) has transformed immunotherapy by engineering T cells to target specific antigens on tumor cells. As the field continues to advance, pathology laboratories will play increasingly essential roles in the complicated multi-step process of CAR-T therapy. These include the detection of targetable tumor antigens by flow cytometry or immunohistochemistry at the time of disease diagnosis and the isolation and infusion of CAR-T cells. Additional roles includ...
Source: The American Journal of Pathology - May 2, 2024 Category: Pathology Authors: Po-Han Chen Rianna Raghunandan Jon S Morrow Samuel G Katz Source Type: research

Modulating PCGF4 Stability Is an Efficient Metastasis-Regulatory Strategy Used by Distinct Subtypes of Cancer-Associated Fibroblasts in Intrahepatic Cholangiocarcinoma
Am J Pathol. 2024 Apr 24:S0002-9440(24)00160-3. doi: 10.1016/j.ajpath.2024.03.012. Online ahead of print.ABSTRACTIntrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and prone to metastasis. It is unclear if cancer-associated fibroblasts (CAFs) affect the metastasis of ICC. Here, we have established ICC patient-derived CAF lines and related cancerous cell lines and analyzed the effects of CAFs on the tumor progressive properties of the ICC cancerous cells. Results demonstrated that CAFs can be classified into cancer-restraining or cancer-promoting categories based on distinct tumorigenic effects. The RNA-se...
Source: The American Journal of Pathology - April 26, 2024 Category: Pathology Authors: Jinjing Hu Hao Xu Xiaojun Ma Mingzhen Bai Yongqiang Zhou Ruidong Miao Fanghong Wang Xun Li Bo Cheng Source Type: research

Modulating PCGF4 Stability Is an Efficient Metastasis-Regulatory Strategy Used by Distinct Subtypes of Cancer-Associated Fibroblasts in Intrahepatic Cholangiocarcinoma
Am J Pathol. 2024 Apr 24:S0002-9440(24)00160-3. doi: 10.1016/j.ajpath.2024.03.012. Online ahead of print.ABSTRACTIntrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and prone to metastasis. It is unclear if cancer-associated fibroblasts (CAFs) affect the metastasis of ICC. Here, we have established ICC patient-derived CAF lines and related cancerous cell lines and analyzed the effects of CAFs on the tumor progressive properties of the ICC cancerous cells. Results demonstrated that CAFs can be classified into cancer-restraining or cancer-promoting categories based on distinct tumorigenic effects. The RNA-se...
Source: The American Journal of Pathology - April 26, 2024 Category: Pathology Authors: Jinjing Hu Hao Xu Xiaojun Ma Mingzhen Bai Yongqiang Zhou Ruidong Miao Fanghong Wang Xun Li Bo Cheng Source Type: research

Modulating PCGF4 Stability Is an Efficient Metastasis-Regulatory Strategy Used by Distinct Subtypes of Cancer-Associated Fibroblasts in Intrahepatic Cholangiocarcinoma
Am J Pathol. 2024 Apr 24:S0002-9440(24)00160-3. doi: 10.1016/j.ajpath.2024.03.012. Online ahead of print.ABSTRACTIntrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and prone to metastasis. It is unclear if cancer-associated fibroblasts (CAFs) affect the metastasis of ICC. Here, we have established ICC patient-derived CAF lines and related cancerous cell lines and analyzed the effects of CAFs on the tumor progressive properties of the ICC cancerous cells. Results demonstrated that CAFs can be classified into cancer-restraining or cancer-promoting categories based on distinct tumorigenic effects. The RNA-se...
Source: The American Journal of Pathology - April 26, 2024 Category: Pathology Authors: Jinjing Hu Hao Xu Xiaojun Ma Mingzhen Bai Yongqiang Zhou Ruidong Miao Fanghong Wang Xun Li Bo Cheng Source Type: research

Modulating PCGF4 stability is an efficient metastasis-regulatory strategy utilized by distinct subtypes of Cancer-Associated Fibroblasts in intrahepatic cholangiocarcinoma
Am J Pathol. 2024 Apr 24:S0002-9440(24)00160-3. doi: 10.1016/j.ajpath.2024.03.012. Online ahead of print.ABSTRACTIntrahepatic Cholangiocarcinoma (ICC) is highly malignant neoplasm and prone to metastasis. It is unclear if cancer-associated fibroblasts (CAFs) affect the metastasis of ICC. Here, we have established ICC patient-derived CAF lines and related cancerous cell lines and analyzed the effects of CAFs on the tumor progressive properties of the ICC cancerous cells. Results demonstrated that CAFs can be classified into cancer-restraining or promoting categories (rCAFs or pCAFs) based on distinct tumorigenic effects. Th...
Source: The American Journal of Pathology - April 26, 2024 Category: Pathology Authors: Jinjing Hu Hao Xu Xiaojun Ma Mingzhen Bai Yongqiang Zhou Ruidong Miao Fanghong Wang Xun Li Bo Cheng Source Type: research

Modulating PCGF4 stability is an efficient metastasis-regulatory strategy utilized by distinct subtypes of Cancer-Associated Fibroblasts in intrahepatic cholangiocarcinoma
Am J Pathol. 2024 Apr 24:S0002-9440(24)00160-3. doi: 10.1016/j.ajpath.2024.03.012. Online ahead of print.ABSTRACTIntrahepatic Cholangiocarcinoma (ICC) is highly malignant neoplasm and prone to metastasis. It is unclear if cancer-associated fibroblasts (CAFs) affect the metastasis of ICC. Here, we have established ICC patient-derived CAF lines and related cancerous cell lines and analyzed the effects of CAFs on the tumor progressive properties of the ICC cancerous cells. Results demonstrated that CAFs can be classified into cancer-restraining or promoting categories (rCAFs or pCAFs) based on distinct tumorigenic effects. Th...
Source: The American Journal of Pathology - April 26, 2024 Category: Pathology Authors: Jinjing Hu Hao Xu Xiaojun Ma Mingzhen Bai Yongqiang Zhou Ruidong Miao Fanghong Wang Xun Li Bo Cheng Source Type: research

Integrated bioinformatics and machine learning analysis identify ACADL as a potent biomarker of reactive mesothelial cells
This study aimed to identify and validate potential biomarkers that distinguish mesothelial cells from mesothelioma cells through machine learning combined with immunohistochemistry (IHC) experiments. We integrated the gene expression matrix from three GEO datasets (GSE2549, GSE12345, GSE51024) to analyze the differently expressed gene (DEGs) between normal and mesothelioma tissues. Then three machine learning algorithms, least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF) were used to screen and obtain four shared candidate markers...
Source: The American Journal of Pathology - April 24, 2024 Category: Pathology Authors: Yige Yin Qianwen Cui Jiarong Zhao Qiang Wu Qiuyan Sun Hong-Qiang Wang Wulin Yang Source Type: research

Integrated bioinformatics and machine learning analysis identify ACADL as a potent biomarker of reactive mesothelial cells
This study aimed to identify and validate potential biomarkers that distinguish mesothelial cells from mesothelioma cells through machine learning combined with immunohistochemistry (IHC) experiments. We integrated the gene expression matrix from three GEO datasets (GSE2549, GSE12345, GSE51024) to analyze the differently expressed gene (DEGs) between normal and mesothelioma tissues. Then three machine learning algorithms, least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF) were used to screen and obtain four shared candidate markers...
Source: The American Journal of Pathology - April 24, 2024 Category: Pathology Authors: Yige Yin Qianwen Cui Jiarong Zhao Qiang Wu Qiuyan Sun Hong-Qiang Wang Wulin Yang Source Type: research

Integrated bioinformatics and machine learning analysis identify ACADL as a potent biomarker of reactive mesothelial cells
This study aimed to identify and validate potential biomarkers that distinguish mesothelial cells from mesothelioma cells through machine learning combined with immunohistochemistry (IHC) experiments. We integrated the gene expression matrix from three GEO datasets (GSE2549, GSE12345, GSE51024) to analyze the differently expressed gene (DEGs) between normal and mesothelioma tissues. Then three machine learning algorithms, least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF) were used to screen and obtain four shared candidate markers...
Source: The American Journal of Pathology - April 24, 2024 Category: Pathology Authors: Yige Yin Qianwen Cui Jiarong Zhao Qiang Wu Qiuyan Sun Hong-Qiang Wang Wulin Yang Source Type: research

Uremia Impedes Skeletal Myocyte Myomixer Expression and Fusogenic Activity: Implication for Uremic Sarcopenia
Am J Pathol. 2024 May;194(5):759-771. doi: 10.1016/j.ajpath.2024.01.005.ABSTRACTIn patients with chronic kidney disease (CKD), skeletal muscle mass and function are known to occasionally decline. However, the muscle regeneration and differentiation process in uremia has not been extensively studied. In mice with CKD induced by adenine-containing diet, the tibialis anterior muscle injured using a barium chloride injection method recovered poorly as compared to control mice. In the cultured murine skeletal myocytes, stimulation with indoxyl sulfate (IS), a representative uremic toxin, morphologically jeopardized the differen...
Source: The American Journal of Pathology - April 18, 2024 Category: Pathology Authors: Takaaki Higashihara Motoki Odawara Hiroshi Nishi Takehito Sugasawa Yumika Suzuki Satoshi Kametaka Reiko Inagi Masaomi Nangaku Source Type: research

Uremia Impedes Skeletal Myocyte Myomixer Expression and Fusogenic Activity: Implication for Uremic Sarcopenia
Am J Pathol. 2024 May;194(5):759-771. doi: 10.1016/j.ajpath.2024.01.005.ABSTRACTIn patients with chronic kidney disease (CKD), skeletal muscle mass and function are known to occasionally decline. However, the muscle regeneration and differentiation process in uremia has not been extensively studied. In mice with CKD induced by adenine-containing diet, the tibialis anterior muscle injured using a barium chloride injection method recovered poorly as compared to control mice. In the cultured murine skeletal myocytes, stimulation with indoxyl sulfate (IS), a representative uremic toxin, morphologically jeopardized the differen...
Source: The American Journal of Pathology - April 18, 2024 Category: Pathology Authors: Takaaki Higashihara Motoki Odawara Hiroshi Nishi Takehito Sugasawa Yumika Suzuki Satoshi Kametaka Reiko Inagi Masaomi Nangaku Source Type: research

Stromal rigidity stress accelerates pancreatic intraepithelial neoplasia progression and chromosomal instability via nuclear PTK2 localization
Am J Pathol. 2024 Apr 15:S0002-9440(24)00132-9. doi: 10.1016/j.ajpath.2024.02.023. Online ahead of print.ABSTRACTSince the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and γH2AX foci links to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+;Trp53flox/flox;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3μm micropores. To search for pan...
Source: The American Journal of Pathology - April 17, 2024 Category: Pathology Authors: Li-Yun Ding Chia-Jung Chang Szu-Ying Chen Kuan-Lin Chen Yueh-Shan Li Yun-Chieh Wu Ting-Yi Hsu Hsin-Yu Ying Hsin-Yi Wu Michael W Hughes Chia-Yih Wang Chih-Han Chang Ming-Jer Tang Woei-Jer Chuang Yan-Shen Shan Chia-Jung Chang Po-Hsien Huang Source Type: research

Stromal rigidity stress accelerates pancreatic intraepithelial neoplasia progression and chromosomal instability via nuclear PTK2 localization
Am J Pathol. 2024 Apr 15:S0002-9440(24)00132-9. doi: 10.1016/j.ajpath.2024.02.023. Online ahead of print.ABSTRACTSince the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and γH2AX foci links to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+;Trp53flox/flox;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3μm micropores. To search for pan...
Source: The American Journal of Pathology - April 17, 2024 Category: Pathology Authors: Li-Yun Ding Chia-Jung Chang Szu-Ying Chen Kuan-Lin Chen Yueh-Shan Li Yun-Chieh Wu Ting-Yi Hsu Hsin-Yu Ying Hsin-Yi Wu Michael W Hughes Chia-Yih Wang Chih-Han Chang Ming-Jer Tang Woei-Jer Chuang Yan-Shen Shan Chia-Jung Chang Po-Hsien Huang Source Type: research

This Month in AJP
Am J Pathol. 2024 Apr 8:S0002-9440(24)00126-3. doi: 10.1016/j.ajpath.2024.04.001. Online ahead of print.NO ABSTRACTPMID:38599460 | DOI:10.1016/j.ajpath.2024.04.001 (Source: The American Journal of Pathology)
Source: The American Journal of Pathology - April 10, 2024 Category: Pathology Source Type: research

Differentiation of Type 17 Mucosal-Associated Invariant T Cells in Circulation Contributes to the Severity of Sepsis
This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RAR-related orphan receptor γt in patients with sepsis. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA-sequencing analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in patients with sepsis. Cell-culture experiments demonstrated that phosphoinositide 3-kinase-LDHA signaling was required for RAR-related orphan receptor γt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 cells in sepsis. In su...
Source: The American Journal of Pathology - April 10, 2024 Category: Pathology Authors: Xinying Li Sicheng Fu Hao Cheng Min Ma Zijian Song Jun Li Shuang Wu Chong Zhang Xiaoxia Wang Maoyu Tang Xuexue Pu Qiang Ji Jinquan Liang Zhibin Zhao Heinrich K örner Bin Li Min Shao Hua Wang Source Type: research