Journal of Pathology and Translational Medicine

Reviews

Diagnosis of interstitial lung diseases: from Averill A. Liebow to artificial intelligence: Eunhee S. Yi, Paul Wawryko, Jay H. Ryu; J Pathol Transl Med. 2024;58(1):1-11. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.17

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Abstract PDF: Histopathologic criteria of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) were defined over the years and endorsed by leading organizations decades after Dr. Averill A. Liebow first coined the term UIP in the 1960s as a distinct pathologic pattern of fibrotic interstitial lung disease. Novel technology and recent research on interstitial lung diseases with genetic component shed light on molecular pathogenesis of UIP/IPF. Two antifibrotic agents introduced in the mid-2010s opened a new era of therapeutic approaches to UIP/IPF, albeit contentious issues regarding their efficacy, side effects, and costs. Recently, the concept of progressive pulmonary fibrosis was introduced to acknowledge additional types of progressive fibrosing interstitial lung diseases with the clinical and pathologic phenotypes comparable to those of UIP/IPF. Likewise, some authors have proposed a paradigm shift by considering UIP as a stand-alone diagnostic entity to encompass other fibrosing interstitial lung diseases that manifest a relentless progression as in IPF. These trends signal a pendulum moving toward the tendency of lumping diagnoses, which poses a risk of obscuring potentially important information crucial to both clinical and research purposes. Recent advances in whole slide imaging for digital pathology and artificial intelligence technology could offer an unprecedented opportunity to enhance histopathologic evaluation of interstitial lung diseases. However, current clinical practice trends of moving away from surgical lung biopsies in interstitial lung disease patients may become a limiting factor in this endeavor as it would be difficult to build a large histopathologic database with correlative clinical data required for artificial intelligence models.

A review of liver fibrosis and cirrhosis regression: Michael J. Lee; J Pathol Transl Med. 2023;57(4):189-195. Published online June 20, 2023; DOI: https://doi.org/10.4132/jptm.2023.05.24

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Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic liver disease, there is regression of fibrosis and cirrhosis, improvement in clinical parameters (i.e. liver function and hemodynamic markers, hepatic venous pressure gradient), and survival rates, demonstrating that fibrosis and fibrolysis are a dynamic process moving in two directions. Microscopically, hepatocytes push into thinning fibrous septa with eventual perforation leaving behind delicate periportal spikes in the portal tracts and loss of portal veins. Obliterated portal veins during progressive fibrosis and cirrhosis due to parenchymal extinction, vascular remodeling and thrombosis often leave behind a bile duct and hepatic artery within the portal tract. Traditional staging classification systems focused on a linear, progressive process; however, the Beijing classification system incorporates both the bidirectional nature for the progression and regression of fibrosis. However, even with regression, vascular lesions/remodeling, parenchymal extinction and a cumulative mutational burden place patients at an increased risk for developing hepatocellular carcinoma and should continue to undergo active clinical surveillance. It is more appropriate to consider cirrhosis as another stage in the evolution of chronic liver disease as a bidirectional process rather than an end-stage, irreversible state.

Citations

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Emerging advanced approaches for diagnosis and inhibition of liver fibrogenesis
Tamer A. Addissouky, Majeed M. A. Ali, Ibrahim El Tantawy El Sayed, Yuliang Wang
The Egyptian Journal of Internal Medicine.2024;[Epub] CrossRef
AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis
Jesús García-Bañuelos, Edén Oceguera-Contreras, Ana Sandoval-Rodríguez, Blanca Estela Bastidas-Ramírez, Silvia Lucano-Landeros, Daniela Gordillo-Bastidas, Belinda C. Gómez-Meda, Arturo Santos, Eira Cerda-Reyes, Juan Armendariz-Borunda
Cells.2023; 12(17): 2127. CrossRef

Inflammatory bowel disease–associated intestinal fibrosis: Ji Min Park, Jeongseok Kim, Yoo Jin Lee, Sung Uk Bae, Hye Won Lee; J Pathol Transl Med. 2023;57(1):60-66. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.11.02

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Abstract PDF

Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.

Citations

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Resistance to apoptosis in complicated Crohn's disease: Relevance in ileal fibrosis
M. Seco-Cervera, D. Ortiz-Masiá, D.C. Macias-Ceja, S. Coll, L. Gisbert-Ferrándiz, J. Cosín-Roger, C. Bauset, M. Ortega, B. Heras-Morán, F. Navarro-Vicente, M. Millán, J.V. Esplugues, S. Calatayud, M.D. Barrachina
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2024; 1870(2): 166966. CrossRef
Food additives impair gut microbiota from healthy individuals and IBD patients in a colonic in vitro fermentation model
Irma Gonza, Elizabeth Goya-Jorge, Caroline Douny, Samiha Boutaleb, Bernard Taminiau, Georges Daube, Marie–Louise Scippo, Edouard Louis, Véronique Delcenserie
Food Research International.2024; 182: 114157. CrossRef
Epigenetic Regulation of EMP/EMT-Dependent Fibrosis
Margherita Sisto, Sabrina Lisi
International Journal of Molecular Sciences.2024; 25(5): 2775. CrossRef
Disease clearance in ulcerative colitis: A new therapeutic target for the future
Syed Adeel Hassan, Neeraj Kapur, Fahad Sheikh, Anam Fahad, Somia Jamal
World Journal of Gastroenterology.2024; 30(13): 1801. CrossRef
Pathways Affected by Falcarinol-Type Polyacetylenes and Implications for Their Anti-Inflammatory Function and Potential in Cancer Chemoprevention
Ruyuf Alfurayhi, Lei Huang, Kirsten Brandt
Foods.2023; 12(6): 1192. CrossRef
Time to eRAASe chronic inflammation: current advances and future perspectives on renin-angiotensin-aldosterone-system and chronic intestinal inflammation in dogs and humans
Romy M. Heilmann, Georg Csukovich, Iwan A. Burgener, Franziska Dengler
Frontiers in Veterinary Science.2023;[Epub] CrossRef
Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition
Dulce C. Macias-Ceja, M. Teresa Mendoza-Ballesteros, María Ortega-Albiach, M. Dolores Barrachina, Dolores Ortiz-Masià
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef

Original Articles

Inflammation and tissue remodeling contribute to fibrogenesis in stricturing Crohn’s disease: image processing and analysis study: Mustafa Erdem Arslan, Rupinder Brar, Lianna Goetz, Dipti Karamchandani, Michael W. Mikula, Kyle Hodge, Hua Li, Sangtae Ahn, Hwajeong Lee; J Pathol Transl Med. 2022;56(5):239-248. Published online July 4, 2022; DOI: https://doi.org/10.4132/jptm.2022.05.18

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Abstract PDF Supplementary Material: Background
Inflammation and structural remodeling may contribute to fibrogenesis in Crohn’s disease (CD). We quantified the immunoexpression of calretinin, CD34, and calprotectin as a surrogate for mucosal innervation, telocytes (interstitial cells playing a role in networking), and inflammation, respectively, and correlated them with bowel alterations in stricturing CD.
Methods
Primary resection specimens for ileal CD (n = 44, 31 stricturing CD, 13 inflammatory CD) were identified. Left-sided ulcerative colitis and trauma cases were used as controls. Proximal and distal margin and middle (diseased) sections were stained for calretinin, CD34, and calprotectin. Microscopic images were captured from the mucosa (calretinin), submucosa (calprotectin), and myenteric plexus (CD34), and the immunostaining was quantified using image processing and analysis. Bowel thickness at the corresponding sections were measured and correlated with the amount of immunoexpression.
Results
A total of 2,037 images were analyzed. In stricturing CD, submucosal alteration/thickening at the stricture site correlated with calprotectin staining and inversely correlated with calretinin staining at the proximal margin. Muscularis propria alteration/thickening at the stricture site correlated with mucosal calretinin staining at the proximal margin. Submucosal alteration/thickening at the proximal margin correlated with calretinin and CD34 staining at the proximal margin and inversely correlated with CD34 staining at the stricture site. Calretinin immunostaining at the distal margin was significantly higher in stricturing CD than the controls.
Conclusions
Inflammation and tissue remodeling appear to contribute to fibrogenesis in stricturing CD. Increased mucosal calretinin immunostaining distal to the diseased segment could be helpful in diagnosing CD in the right clinical context.

Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury: Badr Alzahrani, Mohamed M. S. Gaballa, Ahmed A. Tantawy, Maha A. Moussa, Salma A. Shoulah, Said M. Elshafae; J Pathol Transl Med. 2022;56(2):81-91. Published online March 2, 2022; DOI: https://doi.org/10.4132/jptm.2021.12.27

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Abstract PDF

Background
Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI.
Methods
In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice.
Results
Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment.
Conclusions
All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis.

Citations

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Mechanisms underlying dose-limiting toxicities of conventional chemotherapeutic agents
Mohammad Amin Manavi, Mohammad Hosein Fathian Nasab, Razieh Mohammad Jafari, Ahmad Reza Dehpour
Journal of Chemotherapy.2024; : 1. CrossRef
Innate Immune Response-Mediated Inflammation in Viral Pneumonia
Weiwei Ni, Xin Wei, Rui Wu
Journal of Pediatric Infectious Diseases.2024;[Epub] CrossRef
TLR9: A friend or a foe
Mona M. Saber, Nada Monir, Azza S. Awad, Marwa E. Elsherbiny, Hala F. Zaki
Life Sciences.2022; 307: 120874. CrossRef

Significance of Intratumoral Fibrosis in Clear Cell Renal Cell Carcinoma: Jae Won Joung, Hoon Kyu Oh, Sun Jae Lee, Young Ah Kim, Hyun Jin Jung; J Pathol Transl Med. 2018;52(5):323-330. Published online August 19, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.21

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Abstract PDF

Background
Intratumoral fibrosis (ITF) is a frequent histologic finding in solid organ tumors. Renal cell carcinoma (RCC) is a highly vascularized tumor with different shapes and degrees of ITF and inflammation. ITF is a poor prognostic factor, especially in breast cancer, and is related to intratumoral necrosis (ITN) and intratumoral inflammation (ITI). However, the significance of ITF in RCC has not been fully studied. In this study, we evaluate the relationships between ITF and other clinicopathologic parameters associated with RCC prognosis.
Methods
ITF was evaluated in 204 clear cell renal cell carcinoma (CCRCC) specimens according to presence and grade of fibrosis, degree of ITI, and presence of ITN. Lysyl oxidase (LOX) expression in tumor cells was also evaluated with clinicopathologic parameters.
Results
Among 204 CCRCC cases, 167 (81.7%) showed ITF, 71 (34.8%) showed ITI, 35 (17.2%) showed ITN, and 111 (54.4%) showed LOX expression. ITF correlated with Fuhrman nuclear grade (p = .046), lymphovascular invasion (LVI) (p = .027), and ITN (p = .036). Patients with ITF had a poor five-year overall survival rate (p = .104).
Conclusions
ITF is related to other poor prognostic factors in CCRCC, such as Fuhrman nuclear grade, ITN, and LVI, but ITF itself had no significant correlation with prognosis of CCRCC.

Citations

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New insights into fibrotic signaling in renal cell carcinoma
Jiao-Yi Chen, Wai-Han Yiu, Patrick Ming-Kuen Tang, Sydney Chi-Wai Tang
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Tumor-associated fibrosis impairs the response to immunotherapy
Angha Naik, Andrew Leask
Matrix Biology.2023; 119: 125. CrossRef
Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model
P. A. Abramicheva, D. S. Semenovich, L. D. Zorova, I. B. Pevzner, I. A. Sokolov, V. A. Popkov, E. P. Kazakov, D. B. Zorov, E. Y. Plotnikov
Scientific Reports.2023;[Epub] CrossRef
Intratumoral fibrosis and patterns of immune infiltration in clear cell renal cell carcinoma
Songchen Han, Wenbo Yang, Caipeng Qin, Yiqing Du, Mengting Ding, Huaqi Yin, Tao Xu
BMC Cancer.2022;[Epub] CrossRef
Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis
Seungwon Ryu, Jae Woo Shin, Soie Kwon, Jiwon Lee, Yong Chul Kim, Yoe-Sik Bae, Yong-Soo Bae, Dong Ki Kim, Yon Su Kim, Seung Hee Yang, Hye Young Kim
Journal of Clinical Investigation.2022;[Epub] CrossRef
The atypical sphingosine 1‐phosphate variant, d16:1 S1P, mediates CTGF induction via S1P2 activation in renal cell carcinoma
Melanie Glueck, Alexander Koch, Robert Brunkhorst, Nerea Ferreiros Bouzas, Sandra Trautmann, Liliana Schaefer, Waltraud Pfeilschifter, Josef Pfeilschifter, Rajkumar Vutukuri
The FEBS Journal.2022; 289(18): 5670. CrossRef
The Synergistic Cooperation between TGF-β and Hypoxia in Cancer and Fibrosis
Pramod Mallikarjuna, Yang Zhou, Maréne Landström
Biomolecules.2022; 12(5): 635. CrossRef
In Vitro Characterization of Renal Drug Transporter Activity in Kidney Cancer
Pedro Caetano-Pinto, Nathanil Justian, Maria Dib, Jana Fischer, Maryna Somova, Martin Burchardt, Ingmar Wolff
International Journal of Molecular Sciences.2022; 23(17): 10177. CrossRef
PD-1 immunobiology in glomerulonephritis and renal cell carcinoma
Colleen S. Curran, Jeffrey B. Kopp
BMC Nephrology.2021;[Epub] CrossRef
Intratumoral Fibrosis in Facilitating Renal Cancer Aggressiveness: Underlying Mechanisms and Promising Targets
Chao Hu, Yufeng Zhao, Xuanchuan Wang, Tongyu Zhu
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
What Mediates Fibrosis in the Tumor Microenvironment of Clear Renal Cell Carcinoma
Wenbo Yang, Caipeng Qin, Jingli Han, Songchen Han, Wenjun Bai, Yiqing Du, Tao Xu
Frontiers in Genetics.2021;[Epub] CrossRef
Kidney Cancer and Chronic Kidney Disease: Too Close for Comfort
Pedro Caetano Pinto, Cindy Rönnau, Martin Burchardt, Ingmar Wolff
Biomedicines.2021; 9(12): 1761. CrossRef
The Significance of Fibrosis Quantification as a Marker in Assessing Pseudo-Capsule Status and Clear Cell Renal Cell Carcinoma Prognosis
Caipeng Qin, Huaqi Yin, Huixin Liu, Feng Liu, Yiqing Du, Tao Xu
Diagnostics.2020; 10(11): 895. CrossRef
The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma
Zuzana Strizova, Jirina Bartunkova, Daniel Smrz
Cancer Immunology, Immunotherapy.2019; 68(11): 1831. CrossRef
Procollagen-lysine, 2-oxoglutarate 5-dioxygenases 1, 2, and 3 are potential prognostic indicators in patients with clear cell renal cell carcinoma
Wen-Hao Xu, Yue Xu, Jun Wang, Xi Tian, Junlong Wu, Fang-Ning Wan, Hong-Kai Wang, Yuan-Yuan Qu, Hai-Liang Zhang, Ding-Wei Ye
Aging.2019; 11(16): 6503. CrossRef

Usual Interstitial Pneumonia with Lung Cancer: Clinicopathological Analysis of 43 Cases: Dae Hyun Song, In Ho Choi, Sang Yun Ha, Kang Min Han, Jae Jun Lee, Min Eui Hong, Kyeongman Jeon, Man Pyo Chung, Jhingook Kim, Joungho Han; Korean J Pathol. 2014;48(1):10-16. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.10

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Abstract PDF

Background

Previous studies have suggested an association between usual interstitial pneumonia (UIP) and lung cancer (Ca). However, clinical and histological information is not enough to determine such an association, due to the low incidence and short survival time of patients with both conditions.

Methods

We retrospectively reviewed the clinical and histological records of Ca patients with UIP between January 1999 and August 2013 at the Samsung Medical Center, Seoul, Korea. We found 43 patients who had Ca with UIP (UIP-Ca). Previously reported data of eighty-four patients with UIP-only were included as a comparison group.

Results

Smoking is related to poor prognosis in patients with UIP-Ca, and the number of patients with a high smoking index of more than 30 pack-years significantly increased in UIP-Ca patients compared with UIP-only patients. There is no significant prognostic differentiation between UIP-Ca patients and UIP-only patients. Microscopically, UIP-Ca patients showed characteristically heterogeneous histological patterns and degrees of differentiation. There were many foci of squamous metaplasia or dysplasia at the peripheral area of squamous cell carcinomas.

Conclusions

We report 43 cases of UIP-Ca. Our results suggest that smoking is related to cancer occurrence in UIP patients and poor prognosis in UIP-Ca patients.

Citations

Citations to this article as recorded by

Prognosis of idiopathic pulmonary fibrosis without anti-fibrotic therapy: a systematic review
Yet H. Khor, Yvonne Ng, Hayley Barnes, Nicole S.L. Goh, Christine F. McDonald, Anne E. Holland
European Respiratory Review.2020; 29(157): 190158. CrossRef
Linfoma difuso de células B grandes pulmonar en paciente con neumonía intersticial no específica
Luis Gorospe Sarasúa, Paola Arrieta, Anabelle Chinea-Rodríguez, Carlos de la Puente-Bujidos
Reumatología Clínica.2019; 15(6): e151. CrossRef
Diffuse Large B-cell Lymphoma of the Lung in a Patient With Nonspecific Interstitial Pneumonia
Luis Gorospe Sarasúa, Paola Arrieta, Anabelle Chinea-Rodríguez, Carlos de la Puente-Bujidos
Reumatología Clínica (English Edition).2019; 15(6): e151. CrossRef
Characteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease – analysis of institutional and population data
Joo Heung Yoon, Mehdi Nouraie, Xiaoping Chen, Richard H Zou, Jacobo Sellares, Kristen L Veraldi, Jared Chiarchiaro, Kathleen Lindell, David O Wilson, Naftali Kaminski, Timothy Burns, Humberto Trejo Bittar, Samuel Yousem, Kevin Gibson, Daniel J Kass
Respiratory Research.2018;[Epub] CrossRef
Genomic profiles of lung cancer associated with idiopathic pulmonary fibrosis
Ji An Hwang, Deokhoon Kim, Sung‐Min Chun, SooHyun Bae, Joon Seon Song, Mi Young Kim, Hyun Jung Koo, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Hyeong Ryul Kim, Chang‐Min Choi, Se Jin Jang
The Journal of Pathology.2018; 244(1): 25. CrossRef
Survival after repeated surgery for lung cancer with idiopathic pulmonary fibrosis: a retrospective study
Seijiro Sato, Yuki Shimizu, Tatsuya Goto, Akihiko Kitahara, Terumoto Koike, Hiroyuki Ishikawa, Takehiro Watanabe, Masanori Tsuchida
BMC Pulmonary Medicine.2018;[Epub] CrossRef
Alveolar Squamous Cell Metaplasia: Preneoplastic Lesion?
Adriana Handra-Luca
Journal of Pathology and Translational Medicine.2018; 52(6): 355. CrossRef
Low expression of long noncoding RNA CDKN2B-AS1 in patients with idiopathic pulmonary fibrosis predicts lung cancer by regulating the p53-signaling pathway
Yufeng Du, Xiaoyan Hao, Xuejun Liu
Oncology Letters.2018;[Epub] CrossRef
A clinicopathological study of surgically resected lung cancer in patients with usual interstitial pneumonia
Yasutaka Watanabe, Yoshinori Kawabata, Nobuyuki Koyama, Tomohiko Ikeya, Eishin Hoshi, Noboru Takayanagi, Shinichiro Koyama
Respiratory Medicine.2017; 129: 158. CrossRef
Risk of the preoperative underestimation of tumour size of lung cancer in patients with idiopathic interstitial pneumonias
Mariko Fukui, Kazuya Takamochi, Takeshi Matsunaga, Shiaki Oh, Katsutoshi Ando, Kazuhiro Suzuki, Atsushi Arakawa, Toshimasa Uekusa, Kenji Suzuki
European Journal of Cardio-Thoracic Surgery.2016; 50(3): 428. CrossRef
The Idiopathic Interstitial Pneumonias: Histology and Imaging
Diane C. Strollo, Teri J. Franks, Jeffrey R. Galvin
Seminars in Roentgenology.2015; 50(1): 8. CrossRef
Do Chest Expansion Exercises Aid Re‐shaping the Diaphragm Within the First 72 Hours Following Lung Transplantation in a Usual Interstitial Pneumonia Patient?
Massimiliano Polastri, Erika Venturini, Saverio Pastore, Andrea Dell'Amore
Physiotherapy Research International.2015; 20(3): 191. CrossRef
Scrotal wall metastasis from a primary lung adenocarcinoma
Marie-Louise M. Coussa-Koniski, Pia A. Maalouf, Nehme E. Raad, Noha A. Bejjani
Respiratory Medicine Case Reports.2015; 15: 77. CrossRef
The Ratio KL-6 to SLX in Serum for Prediction of the Occurrence of Drug-Induced Interstitial Lung Disease in Lung Cancer Patients with Idiopathic Interstitial Pneumonias Receiving Chemotherapy
Kosuke Kashiwabara, Hiroshi Semba, Shinji Fujii, Shinsuke Tsumura, Ryota Aoki
Cancer Investigation.2015; 33(10): 516. CrossRef
Idiopathic pulmonary fibrosis will increase the risk of lung cancer
Li Junyao, Yang Ming, Li Ping, Su Zhenzhong, Gao Peng, Zhang Jie
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Transcriptional Regulation of Hepatic Stellate Cell Activation by siRNA for TGF-beta1.: Hoon Kyu Oh, Kyung Hyun Kim, Yoon Sup Keum, Chang Ho Cho, Jae Bok Park, Kwan Kyu Park; Korean J Pathol. 2009;43(6):503-508.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.503

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Abstract PDF

BACKGROUND
The cytokine-induced activation of hepatic stellate cells (HSC) plays a major role in liver fibrosis. Quiescent HSCs undergo phenotypic transformation called "transdifferentiation" in response to viral, chemical or immune insults to the liver. The cytokine TGF-beta1 plays a key role in progressive liver fibrosis. Since small interfering RNA (siRNA) is a powerful tool for silencing gene expression post-transcriptionally, the present study aimed to determine whether synthetic TGF-beta1 siRNA down-regulates the expression of the TGF-beta1 gene in immortalized and activated rat HSCs (HSC-T6s). The study examined whether synthetic TGF-beta1 siRNA prevents rat HSCs activation and extracellular matrix (ECM) production.
METHODS
TGF-beta1 siRNA or a control (pU6) siRNA was added to HSC-T6 culture media. We then performed RT-PCR and western blot analyses for TGF-beta1 and ECM components (fibronectin, type-I collagen, and TIMP-1). RESULTS: TGF-beta1 siRNA significantly down-regulated expression of TGF-beta1 mRNA and protein and attenuated mRNA and protein expressions of type-I collagen, fibronectin, and TIMP-1, as compared to the control. CONCLUSIONS: TGF-beta1 siRNA can effectively down-regulate the expression of TGF-beta1 in rat HSC, resulting in significant inhibition of HSC activation and of ECM production. These data indicate that synthetic TGF-beta1 siRNA can be a useful treatment modality to prevent liver fibrosis.

Citations

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Glaucocalyxin A Attenuates the Activation of Hepatic Stellate Cells Through the TGF-β1/Smad Signaling Pathway
Zhichao Dong, Qi Gao, Hao Guo
DNA and Cell Biology.2018; 37(3): 227. CrossRef

The Effects of Immunosuppressant and Immunostimulant on the Splenic Cell Subset of Rats Having Undergone Experimentally Induced Septal Fibrosis of Liver.: Mee Young Sol, Joon Yeon Kim, Sun Kyoung Lee; Korean J Pathol. 1995;29(5):572-583.

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Abstract: Although there have been many reports about the importance of the spleen's role in hepatic fibrogenesis, the exact mechanism is still uncertain. The author designed this study to evaluate splenic function on hepatic fibrogenesis. The degree of hepatic fibrosis and the population of splenocyte subsets were studied in the experimental animal model with fibrosis produced by injecting normal swine serum intra-peritoneally into Sprague-Dawley rats. The animals were divided into three groups; group A was subjected to injection of swine serum only, group B swine serum and complete Freund's adjuvant and group C swine serum and cyclosporin A. The experimental hepatic fibrogenesis by swine serum was augumented by coinjection with the adjuvant and inhibited by cyclosporin A. The study of the splenocyte subset revealed increased percentages of spienic B cell and CD4+ cell and a decreased percentage of CD8+ cell, and these changes of splenocyte subset were also augumented by the adjuvant and inhibited by cyclosporin A. The percent of monocytes was not significantly altered, although a tendancy of early decrease by the adjuvant was noted.

Case Report

Congenital Hepatic Fibrosis with Caroli's Disease.: Yoon Jung Kim, Soon Ae Oak, In Chul Lee; Korean J Pathol. 1997;31(3):275-279.

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Abstract PDF: Congenital hepatic fibrosis is an inherited, congenital disorder of the liver, and is occasionally associated with cystic disease of the liver and kidney. We present a case of congenital hepatic fibrosis with Caroli's disease. A 21-year-old woman had suffered from an episodic fever with headaches for 3 years. In laboratory examination, the liver function test was within the normal limits. Esophageal varix was noted by an endoscopic examination. Hepatosplenomegaly and multiple dilated bile ducts were seen by abdominal CT scanning. An orthotopic whole liver transplantation was done. The liver was fibrotic and enlarged. Multiple cystically dilated intrahepatic ducts were noted. Microscopically, diffuse portal fibrosis and widening with proliferation of bile ductules were seen. Intrahepatic bile ducts were markedly dilated and tortuous. The liver cell cords were well preserved.

Original Articles

Histopathologic Analysis of the Repeated Renal Biopsies in the Course of Lupus Nephropathy.: Chong Woo Yoo, Hyun Soon Lee; Korean J Pathol. 1997;31(5):436-445.

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Abstract PDF: Lupus nephropathy shows a variable clinical course including remission, relapse and progression to renal failure. To examine the clinical or morphological parameters which might be related to the progression of lupus nephropathy, we have analyzed renal biopsies of 19 patients (M : F=5 : 14), who underwent repeated renal biopsies by morphology and morphometry. The average age of the patients was 22.8+/-9.0 years. The mean interval between two biopsies was 34.5+/-13.3 months. The first renal biopsies of these patients were diagnosed with WHO class IV (74%), class II (11%), class I (5%), class III (5%), and class V (5%). According to the clinical data the patients were divided into 3 groups, static, relapsing and progressive. At the time of the first biopsies, the amount of proteinuria in both the static and relapsing groups was significantly higher than that in the progressive group (P<0.05). The volume density of the renal cortical interstitium of the first biopsies in the progressive group was significantly greater than that in the static and relapsing groups (0.14+/-0.07 micrometer3/micrometer3 vs. 0.05+/-0.02 micrometer3/micrometer3, P<0.05; 0.14+/-0.07 micrometer3/micrometer3 vs. 0.05+/-0.04 micrometer3/micrometer3, P<0.05). The activity index of the second biopsies in the relapsing group was significantly higher than that in the static group (2.7+/-0.6 vs 1.2+/-1.0, P<0.05). In the progressive group, the percentage of glomeruli with global sclerosis and the volume density of the renal cortical interstitium in the second biopsies was elevated over the first biopsies (P<0.05). Half of the patients in the static and relapsing groups underwent a morphologic transformation on the second biopsy. However, of the 7 patients in the progressive group, only one showed a transformation from WHO class IV to class III, suggesting that the transformation is not related to the progression of lupus nephropathy. These results suggest that interstitial expansion and heavy proteinuria at the time of the first renal biopsy may bode for poor prognosis in lupus nephropathy. Furthermore, they suggest that an increased histologic activity index could be related to the relapse of the disease.

Cellular Distribution of TGF-beta1 Peptide in Dimethylnitrosamine Induced Fibrosis of Rat Liver.: Sook Nyo Lee, Do Youn Park, Sun Kyung Lee; Korean J Pathol. 1997;31(11):1157-1165.

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Abstract: Recently attention has been focused on the biology of transforming growth factor-beta1 (TGF-beta1). TGF-beta1, a potent regulator of cell proliferation, stimulates the proliferation of many cell types of mesenchymal origin and inhibits the growth of many epithelial cells. But its cellular distribution and temporal expression remain unknown. The aim of this study was to investigate immunohistochemically the cellular distribution and temporal expression of TGF-beta1 during rat hepatic fibrosis induced by dimethylnitrosamine (DMN). At an early stage of liver fibrosis, there was evidence of multiple centrilobular hemorrhagic necrosis with parenchymal lobular collapse, and at a late stage, there was septal fibrosis with micronodule formation of the parenchyme. TGF-beta1 peptide was first expressed in centrilobular clusters of macrophage which were surrounded by many TGF-beta1 negative fat-storing cells (FSCs). Along with the progression of fibrosis, the TGF-beta1 peptide was expressed in the alpha-smooth muscle actin positive FSCs and also in some peripherally located hepatocytes of micronodules. Serum IFN-gamma was detected in the serum 2 weeks after an initial administration of DMN had reached the peak level at the 4th week and then markedly decreased at the 5th week. We think that TGF-beta1 peptide is produced by macrophages influenced by soluble IFN-gamma, and is expressed in the -smooth muscle actin positive mesenchymal cells and regenerating hepatocytes, and that this cytokine may have an important role in the synthesis of the extracellular matrix and in the regulation of hepatocytic regeneration.

Structural-Functional Relationships in Renal Amyloidosis.: Myeong Cherl Kook, Hyun Soon Lee; Korean J Pathol. 1997;31(11):1190-1199.

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Abstract: The pathogenetic mechanism of renal dysfunction in renal amyloidosis is poorly understood. To evaluate the morphologic parameters which are correlated with renal function in this disorder, we have examined renal biopsies from 14 patients with renal amyloidosis by morphometry. Of the 14 patients, 8 were male and 6 were female. They were between 41 and 70 years of age. The serum concentration of albumin and creatinine were 2.1+/-0.7 mg/dl and 1.1+/-0.5 mg/dl, respectively. The 24-hour excretion of urinary protein was 7.9+/-5.2 g. Creatinine clearance was 62+/-23 ml/min/1.73m2. The mean glomerular volume (MGV) was (2.2+/-1.3) 10(6) micrometer3. The surface density of peripheral glomerular basement membrane [Sv (PGBM/glom)] was 0.049+/-0.027 (micrometer3/micrometer3). Volume density of mesangium [Vv (mes/glom)] was 0.31+/-0.14 (micrometer3/micrometer3) and volume density of glomerular amyloid deposition [Vv (amyl/glom)] was 0.21+/-0.14 (micrometer3/micrometer3). The volume density of cortical interstitium [Vv (int/cortex)] was 0.14+/-0.09 (micrometer3/micrometer3). The serum creatinine concentration was significantly correlated with Vv (int/cortex) (r=+0.66, p<0.05). MGV was correlated with Vv (mes/glom) (r=+0.75, p<0.01) and Vv (amyl/glom) (r= +0.68, p<0.05) but showed negative correlation with Sv (PGBM/glom) (r=-0.79, p<0.01). Sv (PGBM/glom) showed negative correlation with Vv (mes/glom) (r=-0.77, p<0.01) and with Vv (amyl/glom) (r=-0.87, p<0.01). Positive correlation was observed between Vv (mes/glom) and Vv (amyl/glom) (r=+0.95, p<0.01). These results suggest that the decreased renal function in patients with amyloidosis is related to interstitial fibrosis rather than glomerular lesions. In addition, glomerular hypertrophy in these patients is related to amyloid deposition in the mesangium and peripheral glomerular basement membrane.

Pathology of Chronic Interstitial Lung Disease.: Dong Hwan Shin; Korean J Pathol. 1998;32(1):1-8.

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Abstract PDF: Interstitial lung disease is a generic term for a heterogeneous group of lung disease that primarily affect the interstitium although the disease is not clearly restricted to the interstitium. The majority of interstitial lung diseases represent inflammatory insults to the microscopic anatomic space bounded by the basement membrane of epithelial and endothelial cells, which may occur as slowly developing process and ultimately end up as end-stage honeycomb fibrosis. The currently prevalent classification of interstitial pneumonia with practical utility and easy reproducibility pertaining only to idopathic interstitial pneumonia encompasses several different entities some of which may represent different aspects of the same condition. Honeycomb fibrosis is usually caused by a variety of pulmonary disease including chronic interstitial lung disease. It is important to recognize that usual inter-stitial pneumonia and honeycomb fibrosis are not synonymous. In the era of chemotherapy for malignant tumor, aggressive immunosuppression for autoimmune diseases and transplant recipients and acquired immunodeficiency syndrome, lung disease in the immunocompromised host has been common. Diagnostic lung biopsy becomes increasingly needed because proper treatment of interstitial lung disease relies on correct morphologic diagnosis. This review summarizes the pathologic spectrum of idiopathic interstitial pneumonias together with other inflammatory process with known or suggestive etiologies simulating interstitial pneumonias.

Image Standardization and Determination of Gray Level Threshold in the Assessment of the Myocardial Fibrosis by the Computerized Image Analysis.: Nam Young Lee, Young Sik Park, Jin Haeng Chung, Jeong Wook Seo; Korean J Pathol. 1998;32(7):494-503.

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Abstract: The computerized image analysis is a useful tool for the quantitative assessment of histopathologic findings. In contrast to the usual microscopic examination by pathologists, the computerization should be accompanied with the standardization process of the image. We developed an algorithm to standardize images and to determine the optimal gray level threshold, using a myocardial fibrosis model. Sirius red staining was more convenient for the image analysis than Masson's trichrome staining because of a better contrast with the surrounding structures. To get an optimal measurement, light intensity was standardized at each of the fibrosis, myocardium and background. In this study, the most promising method to determine the degree of fibrosis was that of revising the background without tissue to a gray level of 200, obtaining a green component of the color image, revising the myocardial fiber to 163, and defining a partial ratio as fibrosis index when the gray level threshold was 120. These threshold levels and parameters were determined after drawing the binarization index curves according to the change of the gray level threshold and by the morphological examination of the actual binarization figures overlaid to the original color image. Through these processes we could get a consistent result on the myocardial fibrosis and we expect a similar principle applies when we analyze color images in the histopathologic quantitation by computerized image analysis.

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