Androgen receptor interacting proteins in prostate cancer development and therapy resistance
Am J Pathol. 2023 Dec 15:S0002-9440(23)00461-3. doi: 10.1016/j.ajpath.2023.12.003. Online ahead of print.ABSTRACTEndocrine therapy for prostate cancer is based on the use of drugs that diminish androgen concentration and androgen receptor (AR) signaling inhibitors and is limited by the functional consequences of AR point mutations and increased expression of constitutively active receptors. Many coactivators (> 280) interact with different AR regions. Most studies have determined the expression of coactivators and their effects in the presence of increasing concentrations of androgen or the anti-androgen enzalutamide. T...
Source: Am J Pathol - December 17, 2023 Category: Pathology Authors: Zoran Culig Martin Puhr Source Type: research
Vitamin D receptor activation reduces hepatic inflammation via enhancing macrophage autophagy in cholestatic mice
Am J Pathol. 2023 Dec 15:S0002-9440(23)00462-5. doi: 10.1016/j.ajpath.2023.11.016. Online ahead of print.ABSTRACTMacrophage autophagy dysfunction aggravates liver injury by activating inflammasomes, which can cleave pro-IL-1β to its active, secreted form. Here, to determine whether the vitamin D (VD)/ VD receptor (VDR) axis could upregulate macrophage autophagy function to inhibit the activation of inflammasome-dependent IL-1β during cholestasis. Paricalcitol (PAL, VDR agonist) was intraperitoneally injected into bile duct ligated (BDL) mice for 5 days. Research found that upregulation of VDR expression by PAL reduced li...
Source: Am J Pathol - December 17, 2023 Category: Pathology Authors: Tianfu Wen Jing Xie Liman Ma Zhiqing Hao Weiwei Zhang Tingyao Wu Lihua Li Source Type: research
Androgen receptor interacting proteins in prostate cancer development and therapy resistance
Am J Pathol. 2023 Dec 15:S0002-9440(23)00461-3. doi: 10.1016/j.ajpath.2023.12.003. Online ahead of print.ABSTRACTEndocrine therapy for prostate cancer is based on the use of drugs that diminish androgen concentration and androgen receptor (AR) signaling inhibitors and is limited by the functional consequences of AR point mutations and increased expression of constitutively active receptors. Many coactivators (> 280) interact with different AR regions. Most studies have determined the expression of coactivators and their effects in the presence of increasing concentrations of androgen or the anti-androgen enzalutamide. T...
Source: Am J Pathol - December 17, 2023 Category: Pathology Authors: Zoran Culig Martin Puhr Source Type: research
Vitamin D receptor activation reduces hepatic inflammation via enhancing macrophage autophagy in cholestatic mice
Am J Pathol. 2023 Dec 15:S0002-9440(23)00462-5. doi: 10.1016/j.ajpath.2023.11.016. Online ahead of print.ABSTRACTMacrophage autophagy dysfunction aggravates liver injury by activating inflammasomes, which can cleave pro-IL-1β to its active, secreted form. Here, to determine whether the vitamin D (VD)/ VD receptor (VDR) axis could upregulate macrophage autophagy function to inhibit the activation of inflammasome-dependent IL-1β during cholestasis. Paricalcitol (PAL, VDR agonist) was intraperitoneally injected into bile duct ligated (BDL) mice for 5 days. Research found that upregulation of VDR expression by PAL reduced li...
Source: Am J Pathol - December 17, 2023 Category: Pathology Authors: Tianfu Wen Jing Xie Liman Ma Zhiqing Hao Weiwei Zhang Tingyao Wu Lihua Li Source Type: research
Androgen receptor interacting proteins in prostate cancer development and therapy resistance
Am J Pathol. 2023 Dec 15:S0002-9440(23)00461-3. doi: 10.1016/j.ajpath.2023.12.003. Online ahead of print.ABSTRACTEndocrine therapy for prostate cancer is based on the use of drugs that diminish androgen concentration and androgen receptor (AR) signaling inhibitors and is limited by the functional consequences of AR point mutations and increased expression of constitutively active receptors. Many coactivators (> 280) interact with different AR regions. Most studies have determined the expression of coactivators and their effects in the presence of increasing concentrations of androgen or the anti-androgen enzalutamide. T...
Source: Am J Pathol - December 17, 2023 Category: Pathology Authors: Zoran Culig Martin Puhr Source Type: research
Vitamin D receptor activation reduces hepatic inflammation via enhancing macrophage autophagy in cholestatic mice
Am J Pathol. 2023 Dec 15:S0002-9440(23)00462-5. doi: 10.1016/j.ajpath.2023.11.016. Online ahead of print.ABSTRACTMacrophage autophagy dysfunction aggravates liver injury by activating inflammasomes, which can cleave pro-IL-1β to its active, secreted form. Here, to determine whether the vitamin D (VD)/ VD receptor (VDR) axis could upregulate macrophage autophagy function to inhibit the activation of inflammasome-dependent IL-1β during cholestasis. Paricalcitol (PAL, VDR agonist) was intraperitoneally injected into bile duct ligated (BDL) mice for 5 days. Research found that upregulation of VDR expression by PAL reduced li...
Source: Am J Pathol - December 17, 2023 Category: Pathology Authors: Tianfu Wen Jing Xie Liman Ma Zhiqing Hao Weiwei Zhang Tingyao Wu Lihua Li Source Type: research
Clonal origin and lineage ambiguity in mixed neuroendocrine carcinoma of the uterine cervix
In this study, a panel of organoid lines from patients with SCNEC/cervix was established and focused on one line, which retained a mixed tumor phenotype, both in vitro and in vivo. Histologically, both organoids and xenograft tumors showed distinct differentiation into either SCNEC or adenocarcinoma in some regions and ambiguous differentiation in others. By tracking single cells, the existence of cells with bipotential differentiation towards SCNEC and adenocarcinomas was revealed. Single-cell transcriptional analysis identified three distinct clusters: SCNEC-like, adenocarcinoma-like, and a cluster lacking specific diffe...
Source: Am J Pathol - December 16, 2023 Category: Pathology Authors: Masamune Masuda Keita Iida Sadahiro Iwabuchi Mie Tanaka Satoshi Kubota Hiroyuki Uematsu Kunishige Onuma Yoji Kukita Kikuya Kato Shoji Kamiura Aya Nakajima Roberto Coppo Mizuki Kanda Kiyoshi Yoshino Yutaka Ueda Eiichi Morii Tadashi Kimura Jumpei Kondo Mari Source Type: research
Clonal origin and lineage ambiguity in mixed neuroendocrine carcinoma of the uterine cervix
In this study, a panel of organoid lines from patients with SCNEC/cervix was established and focused on one line, which retained a mixed tumor phenotype, both in vitro and in vivo. Histologically, both organoids and xenograft tumors showed distinct differentiation into either SCNEC or adenocarcinoma in some regions and ambiguous differentiation in others. By tracking single cells, the existence of cells with bipotential differentiation towards SCNEC and adenocarcinomas was revealed. Single-cell transcriptional analysis identified three distinct clusters: SCNEC-like, adenocarcinoma-like, and a cluster lacking specific diffe...
Source: Am J Pathol - December 16, 2023 Category: Pathology Authors: Masamune Masuda Keita Iida Sadahiro Iwabuchi Mie Tanaka Satoshi Kubota Hiroyuki Uematsu Kunishige Onuma Yoji Kukita Kikuya Kato Shoji Kamiura Aya Nakajima Roberto Coppo Mizuki Kanda Kiyoshi Yoshino Yutaka Ueda Eiichi Morii Tadashi Kimura Jumpei Kondo Mari Source Type: research
Suppression of overactive IGF-1 attenuates trauma-induced heterotopic ossification in mice
In conclusion, our results indicated that IGF-1 mediated the progression of traumatic HO through PI3K/Akt/mTOR signaling, and suppressing IGF-1 signaling cascades attenuated HO formation, providing a promising therapeutic strategy targeting HO.PMID:38101566 | DOI:10.1016/j.ajpath.2023.11.012 (Source: Am J Pathol)
Source: Am J Pathol - December 15, 2023 Category: Pathology Authors: Dong Mao Kai Wang Hong Jiang Jingyi Mi Xiaoyun Pan Gang Zhao Yongjun Rui Source Type: research
IL-22 binding protein controls IL-22 driven bleomycin-induced lung injury
Am J Pathol. 2023 Dec 13:S0002-9440(23)00456-X. doi: 10.1016/j.ajpath.2023.11.011. Online ahead of print.ABSTRACTThe high mortality rates of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) challenge the field to identify biomarkers and factors that can be exploited for therapeutic approaches. IL-22 is a cytokine that has antibacterial and reparative properties in the lung. However, it can also exacerbate inflammation and requires tight control by the extracellular inhibitory protein known as IL-22 binding protein (IL-22BP) (Il22ra2). Here we demonstrate the necessity of IL-22BP in controlling and pre...
Source: Am J Pathol - December 15, 2023 Category: Pathology Authors: Zhe Zhang Mazvita B Chakawa Joshua A Frydman Michaela J Allen Michelle Galeas Pena MaryJane Jones Derek Pociask Source Type: research
Suppression of overactive IGF-1 attenuates trauma-induced heterotopic ossification in mice
In conclusion, our results indicated that IGF-1 mediated the progression of traumatic HO through PI3K/Akt/mTOR signaling, and suppressing IGF-1 signaling cascades attenuated HO formation, providing a promising therapeutic strategy targeting HO.PMID:38101566 | DOI:10.1016/j.ajpath.2023.11.012 (Source: Am J Pathol)
Source: Am J Pathol - December 15, 2023 Category: Pathology Authors: Dong Mao Kai Wang Hong Jiang Jingyi Mi Xiaoyun Pan Gang Zhao Yongjun Rui Source Type: research
IL-22 binding protein controls IL-22 driven bleomycin-induced lung injury
Am J Pathol. 2023 Dec 13:S0002-9440(23)00456-X. doi: 10.1016/j.ajpath.2023.11.011. Online ahead of print.ABSTRACTThe high mortality rates of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) challenge the field to identify biomarkers and factors that can be exploited for therapeutic approaches. IL-22 is a cytokine that has antibacterial and reparative properties in the lung. However, it can also exacerbate inflammation and requires tight control by the extracellular inhibitory protein known as IL-22 binding protein (IL-22BP) (Il22ra2). Here we demonstrate the necessity of IL-22BP in controlling and pre...
Source: Am J Pathol - December 15, 2023 Category: Pathology Authors: Zhe Zhang Mazvita B Chakawa Joshua A Frydman Michaela J Allen Michelle Galeas Pena MaryJane Jones Derek Pociask Source Type: research
A complex interplay between Notch effectors and β-catenin signaling in morular differentiation of endometrial carcinoma cells
Am J Pathol. 2023 Dec 12:S0002-9440(23)00459-5. doi: 10.1016/j.ajpath.2023.11.014. Online ahead of print.ABSTRACTNotch signaling contributes to tissue development and homeostasis, but little is known about its roles in morular differentiation of endometrial carcinoma (Em Ca) cells. The current study focused on crosstalk between Notch and β-catenin signaling in Em Ca with morules. Promoters of hairy and enhancer of split 1 (Hes1) and mastermind-like 2 (MAML2) were activated by Notch intracellular domain 1 (NICD1) but not β-catenin; we also observed a positive feedback loop between Hes1 and MAML2. Immunoreactivities for nu...
Source: Am J Pathol - December 14, 2023 Category: Pathology Authors: Ako Yokoi Akari Murayama Miki Hashimura Yasuko Oguri Yohei Harada Naomi Fukagawa Misato Hayashi Mototsugu Ono Kensuke Ohhigata Makoto Saegusa Source Type: research
Vision transformers for breast cancer human epidermal growth factor receptor 2 (HER2) expression staging without immunohistochemical (IHC) staining
This article argues for the effectiveness of customized vision transformers in staging HER2 expression in breast cancer using only H&E-stained images. This work introduces a spatial transformer network (STN) for weakly localizing critical image features before utilizing a vision transformer-based deep learning architecture. An ordinal loss function is employed to precisely characterize HER2 expression stages. The proposed algorithm comprises three modules: a localization module for weak feature identification using spatial transformers, an attention module for global learning via vision transformers, and a loss module ...
Source: Am J Pathol - December 14, 2023 Category: Pathology Authors: Gelan Ayana Eonjin Lee Se-Woon Choe Source Type: research
A complex interplay between Notch effectors and β-catenin signaling in morular differentiation of endometrial carcinoma cells
Am J Pathol. 2023 Dec 12:S0002-9440(23)00459-5. doi: 10.1016/j.ajpath.2023.11.014. Online ahead of print.ABSTRACTNotch signaling contributes to tissue development and homeostasis, but little is known about its roles in morular differentiation of endometrial carcinoma (Em Ca) cells. The current study focused on crosstalk between Notch and β-catenin signaling in Em Ca with morules. Promoters of hairy and enhancer of split 1 (Hes1) and mastermind-like 2 (MAML2) were activated by Notch intracellular domain 1 (NICD1) but not β-catenin; we also observed a positive feedback loop between Hes1 and MAML2. Immunoreactivities for nu...
Source: Am J Pathol - December 14, 2023 Category: Pathology Authors: Ako Yokoi Akari Murayama Miki Hashimura Yasuko Oguri Yohei Harada Naomi Fukagawa Misato Hayashi Mototsugu Ono Kensuke Ohhigata Makoto Saegusa Source Type: research
