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American Journal of Pathology

Frederick Charles Campbell, Maurice Bernard Loughrey, Jane McClements, Ravi Kiran Deevi, Arman Javadi, Lisa Rainey
Colorectal cancer (CRC) diagnosis and prognostic stratification are based on histopathological assessment of cell or nuclear pleomorphism, aberrant mitotic figures, altered glandular architecture, and other phenomic abnormalities. This complexity is driven by oncogenic perturbation of tightly coordinated spatiotemporal signaling to disrupt multiple scales of tissue organization. This review clarifies molecular and cellular mechanisms underlying common CRC histological features and help understand how the CRC genome controls core aspects of tumor aggressiveness...
July 17, 2018: American Journal of Pathology
(no author information available yet)
The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
July 17, 2018: American Journal of Pathology
Lindsey Kennedy, Gianfranco Alpini
This commentary highlights the article by Liu et al that provides novel mechanistic insights in how conjugated bile acids promote invasive growth of esophageal adenocarcinoma.
July 17, 2018: American Journal of Pathology
Sowmiya Kumaradevan, Shin Yin Lee, Sean Richards, Chimera Lyle, Qing Zhao, Umit Tapan, Yilan Jiangliu, Shmyle Ghumman, Joshua Walker, Mostafa Belghasem, Nkiruka Arinze, Angela Kuhnen, Janice Weinberg, Jean Francis, Kevan Hartshorn, Vijaya B Kolachalama, Daniel Cifuentes, Nader Rahimi, Vipul C Chitalia
The proto-oncogene β-catenin drives colorectal cancer (CRC) tumorigenesis. Casitas B-lineage lymphoma (c-Cbl) inhibits CRC tumor growth through targeting nuclear β-catenin by a poorly understood mechanism. In addition, the role of c-Cbl in human CRC remains largely underexplored. Using a novel quantitative histopathologic technique, we demonstrate that patients with high c-Cbl-expressing tumors had significantly better median survival (3.7 years) compared with low c-Cbl-expressing tumors (1.8 years; P = 0...
July 13, 2018: American Journal of Pathology
Henk van Ooijen, Marten Hornsveld, Christa Dam-de Veen, Rick Velter, Meng Dou, Wim Verhaegh, Boudewijn Burgering, Anja van de Stolpe
The PI3K pathway is commonly activated in cancer. Tumors are potentially sensitive to PI3K pathway inhibitors but reliable diagnostic tests assessing functional PI3K activity are lacking. As PI3K pathway activity negatively regulates FOXO transcription factor activity, FOXO target gene expression is inversely correlated to PI3K activity. A knowledge-based Bayesian computational model was developed to infer PI3K activity in cancer tissue samples from FOXO target gene mRNA levels, and validated in cancer cell lines treated with PI3K inhibitors...
July 6, 2018: American Journal of Pathology
Lauren Richardson, Ramkumar Menon
Amnion epithelial cell (AEC) shedding causes microfractures in human placental membranes during gestation. However, microfractures are healed to maintain membrane integrity. To better understand the cellular mechanisms of healing and tissue remodeling, scratch assays were performed using primary AECs derived from normal term not in labor membranes. AECs were grown under different conditions: i) normal cultures (control), ii) oxidative stress (OS) induction by cigarette smoke extract (CSE), iii) co-treatment of CSE and antioxidant N-acetyl-l-cysteine, and iv) treatment with amniotic fluid (AF)...
July 6, 2018: American Journal of Pathology
Takanobu Sakurai, Kyohei Kamio, Kazuhiko Sasaki, Tomohiro Nishimoto, Jun-Ichi Yamaguchi, Minoru Sasaki, Shunsuke Tsutsumi
Drug-induced phospholipidosis is a lysosomal storage disorder characterized by the excess accumulation of tissue phospholipids. Although azithromycin can be used to treat drug-induced phospholipidosis, no experimental studies evaluating the relationship between drug accumulation and phospholipid localization have been performed. In this study, azithromycin was orally administered to rats for seven days, and the relationship between drug and phospholipids accumulation was performed using imaging mass microscopy...
July 5, 2018: American Journal of Pathology
Cristina Beltrami, Kate Simpson, Mark Jesky, Alexa Wonnacott, Christopher Carrington, Peter Holmans, Lucy Newbury, Robert Jenkins, Thomas Ashdown, Colin Dayan, Simon Satchell, Peter Corish, Paul Cockwell, Donald Fraser, Timothy Bowen
Effective diabetic kidney disease (DKD) biomarkers remain elusive, and urinary microRNAs (miRNAs) represent a potential source of novel non-invasive disease sentinels. We profiled 754 miRNAs in pooled urine samples from DKD patients (n = 20), detecting significantly increased miR-126, miR-155, and miR-29b compared to controls (n = 20). These results were confirmed in an independent cohort of 89 DKD patients, 62 diabetic patients without DKD and 41 controls: miR-126 (2.8-fold increase; P 0 .0001), miR-155 (1...
July 5, 2018: American Journal of Pathology
Runping Liu, Xiaojiaoyang Li, Phillip B Hylemon, Huiping Zhou
Esophageal adenocarcinoma (EAC) is the sixth leading cause of cancer deaths worldwide and dramatically increasing in incidence over the last decade. Gastroesophageal reflux and Barret's esophagus are well-established risk factors for disease progression. Conjugated bile acids (CBAs), including taurocholate (TCA), represent the major bile acids in the gastroesophageal refluxate of advanced Barret's esophagus and EAC patients. Our previous studies suggested that CBA-induced activation of sphingosine 1-phosphate receptor 2 (S1PR2) plays a critical role in promoting cholangiocarcinoma cell invasive growth...
June 29, 2018: American Journal of Pathology
Martrez Ebrahim, Hans-Joachim Anders
This commentary highlights the article by Fan et al that provides mechanistic insights into MDM2’s anti-inflammatory role in intraocular inflammation.
June 28, 2018: American Journal of Pathology
Osamu Ichii, Teppei Nakamura, Taro Horino, Akira Yabuki, Yaser Hosny Ali Elewa, Yasuhiro Kon
The distal tubule (DT) helps regulate blood pressure and electrolytes. We describe a novel, autosomal recessive, morpho-functional DT abnormality in inbred mice evident as columnar alternations and age-related cystic changes. This abnormality developed in both sexes of DBA/2Cr mice. Similar phenotypes were observed in A/J, C3H/He, DBA/1J, and FVB/N strains, but not in AKR/N, BALB/c, or C57BL/6N strains. In DBA/2Cr mice, abnormal DT localized to straight and convoluted segments and showed interleukin (IL)-36α/IL-1F6 DT injury marker expression...
June 20, 2018: American Journal of Pathology
Kirsten L Moek, Rudolf S N Fehrmann, Bert van der Vegt, Elisabeth G E de Vries, Derk Jan A de Groot
Glypican 3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is overexpressed in ∼70% to 80% of hepatocellular carcinomas (HCCs), but uncommonly expressed in healthy tissues. This raised interest in GPC3 as drug target, and several GPC3-targeting drugs are in clinical development. We therefore predicted GPC3 protein overexpression across tumors and validated these predictions. Functional genomic mRNA profiling was applied to expression profiles of 18,055 patient-derived tumor samples to predict GPC3 overexpression at the protein level in 60 tumor types and subtypes using healthy tissues as reference...
June 20, 2018: American Journal of Pathology
Tristen T Chun, Chun-Shiang Chung, Eleanor A Fallon, Noelle A Hutchins, Erlyana Clarke, Anne-Lise Rossi, William G Cioffi, Daithi S Heffernan, Alfred Ayala
Sepsis remains a major public health concern, characterized by marked immune dysfunction. Innate lymphoid cells develop from a common lymphoid precursor, but have a role in orchestrating inflammation during innate response to infection. Here we investigate the pathological contribution of the group 2 innate lymphoid cells (ILC2s) in a murine model of acute septic shock (cecal ligation and puncture). Flow cytometric data revealed that ILC2s increase in number and percentage in the small intestine and in the peritoneal cells, and inversely decline in the liver, at 24 hours following septic insult...
June 20, 2018: American Journal of Pathology
Adelaide Tawiah, France Moreau, Manish Kumar, Sameer Tiwari, Jan Falguera, Kris Chadee
Intestinal epithelial cell wound healing involves cell migration, proliferation, and differentiation. Although numerous studies have analyzed the migration of absorptive epithelial cells during wound healing, it remains unclear how goblet cells restitute and how MUC2 mucin production affects this process. In this study, we examined the role of high MUC2 production in goblet cell migration during wound healing and demonstrated that during high MUC2 output, goblet cells migrated slower due to impaired production of wound healing factors and endoplasmic reticulum (ER) stress...
June 20, 2018: American Journal of Pathology
Hidenori Shimizu, Masayuki Shimoda, Satsuki Mochizuki, Yuka Miyamae, Hitoshi Abe, Miyuki Chijiiwa, Hiroyuki Yoshida, Jun Shiozawa, Muneaki Ishijima, Kazuo Kaneko, Arihiko Kanaji, Masaya Nakamura, Yoshiaki Toyama, Yasunori Okada
Hyaluronan-binding protein involved in hyaluronan depolymerization (HYBID), also called KIAA1199 or CEMIP, plays a key role in degradation of hyaluronan (HA) in skin and arthritic synovial fibroblasts, but its functions in osteoarthritic (OA) cartilage remain elusive. Here, we investigated the expression and roles of HYBID in human OA cartilage. HYBID was highly expressed by chondrocytes in the HA-depleted area of OA cartilage, and the HYBID immunoreactivity directly correlated with Mankin score, the histopathological severity of OA lesions of cartilage...
June 20, 2018: American Journal of Pathology
Keren Kaufman-Francis, Julianne T Djordjevic, Pierre-Georges Juillard, Sophie Lev, Desmarini Desmarini, Georges E R Grau, Tania C Sorrell
The innate immune system is the primary defense against cryptococcal infection, but paradoxically it promotes infection of the central nervous system. We performed a detailed longitudinal study of neurocryptococcosis in normal, chimeric, green fluorescent protein phagocyte-positive mice and phagocyte-depleted mice and interrogated the central nervous system innate immune response to Cryptococcus neoformans H99 using confocal microscopy, histology, flow cytometry, and quantification of brain cytokine/chemokines and fungal burdens...
June 18, 2018: American Journal of Pathology
Ivonne Koeck, Ali Hashemi Gheinani, Ulrich Baumgartner, Erik Vassella, Rémy Bruggmann, Fiona C Burkhard, Katia Monastyrskaya
Bladder outlet obstruction (BOO) and the ensuing clinical lower urinary tract dysfunction are common in elderly patients. BOO is accompanied by urodynamic changes in bladder function and leads to organ fibrosis and ultimately loss of contractility. Comprehensive transcriptome analysis of bladder samples from human patients with different urodynamically defined phenotypes of BOO revealed tumor necrosis factor (TNF)-α as the top upstream signaling pathway regulator. Herein, we validated next-generation sequencing and pathway analysis in cell-based models using bladder smooth muscle and urothelial cells exposed to TNF-α...
June 18, 2018: American Journal of Pathology
Chhavi Chauhan
The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
June 16, 2018: American Journal of Pathology
Laura Molina, Danielle Bell, Junyan Tao, Morgan Preziosi, Tirthadipa Pradhan-Sundd, Sucha Singh, Minakshi Poddar, Jianhua Luo, Sarangarajan Ranganathan, Maria Chikina, Satdarshan P Monga
Hepatoblastoma (HB) is the most common pediatric liver malignancy. Previously, we reported co-activation of β-catenin and YAP1 in 80% of HB. Hepatic co-expression of active β-catenin and YAP1 via sleeping beauty transposon/transposase and hydrodynamic tail vein injection (SB-HTVI) led to HB development in mice. Here, we identify lipocalin 2 (LCN2) as a target of β-catenin and YAP1 in HB and show that serum LCN2 values positively correlated with tumor burden. Lcn2 was strongly expressed in HB tumor cells in our mouse model...
June 16, 2018: American Journal of Pathology
Hung-Cheng Tsai, Tzu-Hao Li, Chia-Chang Huang, Shiang-Fen Huang, Ren-Shyan Liu, Ying-Ying Yang, Yun-Cheng Hsieh, Kuei-Chuan Lee, Yi-Hsiang Huang, Ming-Chih Hou, Han-Chieh Lin
Recent studies have reported that peroxisome proliferator-activated receptor α (PPARα) agonist decreases intrahepatic resistance, whereas PPARγ agonist reduces portosystemic shunts (PSSs) and splanchnic angiogenesis in cirrhotic rats. The present study investigated the effects of a 21-day treatment with the dual PPARα/γ agonist aleglitazar (Ale) on progressive abnormalities in bile-duct-ligated and thioacetamide-induced cirrhotic rats with portal hypertension (PH). In vivo and in vitro effects were evaluated...
June 13, 2018: American Journal of Pathology
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