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Journal of Pathology

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https://www.readbyqxmd.com/read/29235674/loss-of-cyld-promotes-cell-invasion-via-alk5-stabilization-in-oral-squamous-cell-carcinoma
#1
Satoru Shinriki, Hirofumi Jono, Manabu Maeshiro, Takuya Nakamura, Jianying Guo, Jian-Dong Li, Mitsuharu Ueda, Ryoji Yoshida, Masanori Shinohara, Hideki Nakayama, Hirotaka Matsui, Yukio Ando
Oral squamous cell carcinoma (OSCC) has a very poor prognosis because of its highly invasive nature, and the 5-year survival rate has not changed appreciably for the past 30 years. Although cylindromatosis (CYLD), a deubiquitinating enzyme, is thought to be a potent tumour suppressor, its biological and clinical significance in OSCC is largely unknown. This study aimed to clarify the roles of CYLD in OSCC progression. Our immunohistochemical analyses revealed significantly reduced CYLD expression in invasive areas in OSCC tissues, whereas CYLD expression was conserved in normal epithelium and carcinoma in situ...
December 13, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29230817/ebv-encoded-mirnas-target-atm-mediated-response-in-nasopharyngeal-carcinoma
#2
Raymond W-M Lung, Pok-Man Hau, Ken H-O Yu, Kevin Y Yip, Joanna H-M Tong, W-P Chak, Anthony W-H Chan, Ka-Hei Lam, Angela K-F Lo, Edith K-Y Tin, Shuk-Ling Chau, Jesse C-S Pang, Johnny S-H Kwan, Pierre Busson, Lawrence S Young, Lee-Fah Yap, Sai-Wah Tsao, Ka-Fai To, Kwok-Wai Lo
Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignancy that is prevalent in southern China and Southeast Asia. It is consistently associated with latent Epstein-Barr virus (EBV) infection. In NPC, miR-BARTs, the EBV-encoded miRNAs derived from BamH1-A rightward transcripts are abundantly expressed and contribute to cancer development by targeting various cellular and viral genes. In this study, we establish a comprehensive transcriptional profile of EBV-encoded miRNAs in a panel of NPC patient-derived xenografts and an EBV-positive NPC cell line by small RNA sequencing...
December 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29230811/whole-exome-sequencing-of-oral-mucosal-melanoma-reveals-mutational-profile-and-therapeutic-targets
#3
Jiong Lyu, Zhijian Song, Jianhua Chen, Matthew J Shepard, Hao Song, Guoxin Ren, Zhiqiang Li, Wei Guo, Zhengping Zhuang, Yongyong Shi
Oral mucosal melanoma (OMM) is rare and aggressive subtype of melanoma with little known about its pathogenesis carcinogenesis. We therefore performed whole-exome sequencing (WES) on 19 matched OMM tumor/normal pairs in order to gain insight on potential genetic drivers of tumor formation. For the first time we describe the comprehensive mutational profile of OMM. Our data suggests that the genetic background of OMM differs from those of other melanoma subtypes. We identified recurrent mutations involving KIT, POLE,PTPRD, PTCHD2 and DMXL2...
December 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29214629/targeting-early-pkc%C3%AE-dependent-t-cell-infiltration-of-dystrophic-muscle-reduces-disease-severity-in-a-mouse-model-of-muscular-dystrophy
#4
Biliana Lozanoska-Ochser, Anna Benedetti, Giuseppe Rizzo, Valeria Marrocco, Rosanna Di Maggio, Piera Fiore, Marina Bouche
Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy and contributes to muscle fibre injury and disease progression. Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate mdx mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis. Based on our comprehensive analysis of the kinetics of the immune response, we further identify the early pre-necrotic stage of muscular dystrophy as the relevant time frame for T cell-based interventions...
December 7, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29210073/interleukin-17-regulates-matrix-metalloproteinase-activity-in-human-pulmonary-tuberculosis
#5
Shivani Singh, George Maniakis-Grivas, Utpal K Singh, Radha M Asher, Francesco Mauri, Paul T Elkington, Jon S Friedland
Tuberculosis (TB) is characterised by extensive pulmonary matrix breakdown. Interleukin-17 (IL-17) is key in host defence in TB but its role in TB-driven tissue damage is unknown. We investigated the hypothesis that respiratory stromal cell matrix metalloproteinase (MMP) production in TB is regulated by T helper-17 (TH -17) cytokines. Biopsies of patients with pulmonary TB were analysed by immunohistochemistry (IHC) and patient bronchoalveolar lavage fluid (BALF) MMP and cytokine concentrations measured by Luminex assays...
December 6, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29205775/donor-derived-metastatic-urothelial-cancer-after-kidney-transplantation-associated-with-a-potentially-oncogenic-bk-polyomavirus
#6
David C Müller, Maarit Rämö, Klaudia Naegele, Sebastian Ribi, Christian Wetterauer, Valeria Perrina, Luca Quagliata, Tatjana Vlajnic, Christian Ruiz, Beate Balitzki, Rainer Grobholz, Rainer Gosert, Elvis T Ajuh, Hans H Hirsch, Lukas Bubendorf, Cyrill A Rentsch
BK polyomavirus has been linked to urothelial carcinoma in immunosuppressed patients. Here, we performed comprehensive genomic analysis of a BK polyomavirus -associated, metachronous, multifocal and metastatic micropapillary urothelial cancer in a kidney transplant recipient. Dissecting cancer heterogeneity by sorting technologies prior to array-comparative genomic hybridization followed by short tandem repeat analysis revealed that the metastatic urothelial cancer was of donor-origin (4 year-old male). The top 50 cancer-associated genes displayed no key driver mutations as assessed by next generation sequencing...
December 4, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29205368/cyclic-amp-dependent-protein-kinase-catalytic-subunit-a-prkaca-the-expected-the-unexpected-and-what-might-be-next
#7
Constantine A Stratakis
Protein kinase A (PKA) or cyclic-AMP (cAMP)-dependent kinase was among the first serine-threonine kinases to be molecularly and functionally characterized. For years, it was investigated as the enzyme that mediates cAMP functions in almost all cell systems and organisms studied to date. Despite PKA's critical role in signaling and the long history of investigations of cAMP in oncogenesis (dating back to the 1970's), it was not until relatively recently that PKA defects were found to be directly involved in tumor predisposition...
December 4, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29205362/anti-oncostatin-m-antibody-inhibits-the-pro-malignant-effects-of-oncostatin-m-receptor-over-expression-in-squamous-cell-carcinoma
#8
Justyna A Kucia-Tran, Valtteri Tulkki, Cinzia G Scarpini, Stephen Smith, Maja Wallberg, Marta Paez-Ribes, Angela M Araujo, Jan Botthoff, Maria Feeney, Katherine Hughes, Maria M Caffarel, Nicholas Coleman
The oncostatin M receptor (OSMR) shows frequent gene copy-number gain and over-expression in cervical squamous cell carcinomas (SCCs), associated with adverse clinical outcomes. In SCC cells that overexpress OSMR, the major ligand OSM induces multiple pro-malignant effects, including invasion, secretion of angiogenic factors and metastasis. Here we demonstrate, for the first time, that OSMR over-expression in SCC cells activates cell-autonomous feed-forward signalling, via further expression of OSMR and OSM and sustained STAT3 activation despite expression of the negative regulator SOCS3...
December 4, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29205354/podocytes-are-new-cellular-targets-of-hemoglobin-mediated-renal-damage
#9
Alfonso Rubio-Navarro, Maria Dolores Sanchez-Niño, Melania Guerrero-Hue, Cristina García-Caballero, Eduardo Gutiérrez, Claudia Yuste, Ángel Sevillano, Manuel Praga, Javier Egea, Elena Román, Pablo Cannata, Rosa Ortega, Isabel Cortegano, Belén de Andrés, María Luisa Gaspar, Susana Cadenas, Alberto Ortiz, Jesús Egido, Juan Antonio Moreno
Recurrent and massive intravascular hemolysis induces proteinuria, glomerulosclerosis and progressive impairment of renal function, suggesting podocyte injury. However, the effects of hemoglobin (Hb) on podocytes remain unexplored. Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the megalin-cubilin receptor system, thus resulting in increased intracellular Hb catabolism, oxidative stress, activation of the intrinsic apoptosis pathway and altered podocyte morphology, with decreased expressionof the slit diaphragm proteins nephrin and synaptopodin...
December 4, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29178260/origin-of-clear-cell-carcinoma-nature-or-nurture
#10
David L Kolin, Daniela M Dinulescu, Christopher P Crum
A rare but serious complication of endometriosis is the development of carcinoma, and clear cell and endometrioid carcinomas of the ovary are the two most common malignancies which arise from endometriosis. They are distinct diseases, characterized by unique morphologies, immunohistochemical profiles, and responses to treatment. However, both arise in endometriosis and can share common mutations. The overlapping mutational profiles of clear cell and endometrioid carcinoma suggests that their varied histologies may be due to a different cell of origin which gives rise to each type of cancer...
November 27, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29160922/igf1r-signalling-in-testicular-germ-cell-tumour-cells-impacts-on-cell-survival-and-acquired-cisplatin-resistance
#11
Joanna Selfe, Neil C Goddard, Alan McIntyre, Kathryn R Taylor, Jane Renshaw, Sergey D Popov, Khin Thway, Brenda Summersgill, Robert A Huddart, Duncan C Gilbert, Janet M Shipley
Testicular germ cell tumours (TGCT) are the most frequent malignancy and cause of death from solid tumours in the 20-40 year age group. Although most cases show sensitivity to cis-platinum-based chemotherapy, this is associated with long-term toxicities and chemo-resistance. Roles for receptor tyrosine kinases other than KIT are largely unknown in TGCT. We therefore conducted a phosphoproteomic screen and identified the insulin growth factor receptor-1 (IGF1R) as both highly expressed and activated in TGCT cell lines representing the non-seminomatous subtype...
November 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29160908/connective-tissue-growth-factor-induces-renal-fibrosis-via-epidermal-growth-factor-receptor-activation
#12
Sandra Rayego-Mateos, José Luis Morgado-Pascual, Raúl R Rodrigues-Diez, Raquel Rodrigues-Diez, Lucas Falke, Sergio Mezzano, Alberto Ortiz, Jesús Egido, Roel Goldschmeding, Marta Ruiz-Ortega
Connective tissue growth factor (CCN2/CTGF) is a matricellular protein overexpressed in progressive human renal diseases, mainly in fibrotic areas. In vitro studies have demonstrated that CCN2 regulates production of extracellular matrix (ECM) proteins and epithelial mesenchymal transition (EMT), and therefore could contribute to renal fibrosis. CCN2 blockade ameliorates experimental renal damage, including diminution of ECM accumulation. We have described that CCN2 and its C-terminal degradation product CCN2(IV), bind to epidermal growth factor receptor (EGFR) to modulate renal inflammation...
November 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29149504/mybl1-rearrangements-and-myb-amplification-in-breast-adenoid-cystic-carcinomas-lacking-the-myb-nfib-fusion-gene
#13
Jisun Kim, Felipe C Geyer, Luciano G Martelotto, Charlotte K Y Ng, Raymond S Lim, Pier Selenica, Anqi Li, Fresia Pareja, Nicola Fusco, Marcia Edelweiss, Rahul Kumar, Rodrigo Gularte-Merida, Andre N Forbes, Ekta Khurana, Odette Mariani, Sunil Badve, Anne Vincent-Salomon, Larry Norton, Jorge S Reis-Filho, Britta Weigelt
Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer (TNBC), has been shown to be driven by MYB pathway activation, most often underpinned by the MYB-NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB-NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB-NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1-ACTN1 and MYBL1-NFIB), which were associated with MYBL1 overexpression...
November 17, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29144553/blocking-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-in-endometrial-cancer-a-potential-novel-endocrine-therapeutic-approach
#14
Gonda Fj Konings, Karlijn Mc Cornel, Sofia Xanthoulea, Bert Delvoux, Margaretha A Skowron, Loes Kooreman, Pasi Koskimies, Camilla Krakstad, Helga B Salvesen, Kim van Kuijk, Yannick Jm Schrooders, Marc Vooijs, Arjan J Groot, Marlies Y Bongers, Roy Fpm Kruitwagen, Andrea Romano
The enzyme type 1 17β-hydroxysteroid dehydrogenase (17β-HSD-1), responsible for generating active 17β-estradiol (E2) from low-active estrone (E1), is over-expressed in endometrial cancer (EC) thus implicating an increased intra-tissue generation of E2 in this estrogen-dependent condition. In this study we explored the possibility of inhibiting 17β-HSD-1 and impairing the generation of E2 from E1 in EC using in vitro, in vivo and ex vivo models. We generated EC cell lines derived from the well-differentiated endometrial adenocarcinoma Ishikawa cell line and expressing levels of 17β-HSD-1 similar to human tissues...
November 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29144541/genetic-landscape-of-papillary-thyroid-carcinoma-in-the-chinese-population
#15
Jialong Liang, Wanshi Cai, Dongdong Feng, Huajing Teng, Fengbiao Mao, Yi Jiang, Shanshan Hu, Xianfeng Li, Yujie Zhang, Baoguo Liu, Zhong Sheng Sun
Improvement in the clinical outcome of human cancers requires characterization of genetic alterations underlying their pathogenesis. Large-scale genomic and transcriptomic characterization of papillary thyroid carcinomas (PTCs) in Western populations has revealed multiple oncogenic drivers which are essential for understanding pathogenic mechanisms of this disease; while so far, the genetic landscape in Chinese patients with PTC remains uncharacterized. Here, we conducted a largescale genetic analysis of PTCs from patients in China to determine the mutational landscape of this cancer...
November 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29124765/lipocalin-type-prostaglandin-d-synthase-derived-pgd2-attenuates-malignant-properties-of-endothelial-cells-in-tumor
#16
Keisuke Omori, Teppei Morikawa, Akiko Kunita, Tatsuro Nakamura, Kosuke Aritake, Yoshihiro Urade, Masashi Fukayama, Takahisa Murata
Endothelial cells (ECs) are a key component of the tumor microenvironment. They have abnormal characteristics compared to the ECs in normal tissues. Here, we found a marked increase in lipocalin-type prostaglandin D synthase (L-PGDS) mRNA (Ptgds) expression in ECs isolated from mouse melanoma. Immunostaining of mouse melanoma revealed expression of L-PGDS protein in the ECs. In situ hybridization also showed L-PGDS (PTGDS) mRNA expression in the ECs of human melanoma and oral squamous cell carcinoma. In vitro experiments showed that stimulation with tumor cell-derived IL-1 and TNF-α increased L-PGDS mRNA expression and its product prostaglandin D2 (PGD2 ) in human normal ECs...
November 10, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29105096/nthl1-and-mutyh-polyposis-syndromes-two-sides-of-the-same-coin
#17
REVIEW
Robbert D A Weren, Marjolijn J L Ligtenberg, Ad Geurts van Kessel, Richarda M De Voer, Nicoline Hoogerbrugge, Roland P Kuiper
It is well-established now that germline genomic aberrations can underlie high-penetrant familial polyposis and colorectal cancer syndromes, but a genetic cause has not yet been found for the major proportion of patients with polyposis. Since next generation sequencing has become widely accessible, several novel, but rare, high-penetrant risk factors for adenomatous polyposis have been identified, all operating in pathways responsible for genomic maintenance and DNA repair. One of these is the base excision repair (BER) pathway...
November 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29086922/myoepithelial-cell-specific-expression-of-stefin-a-as-a-suppressor-of-early-breast-cancer-invasion
#18
Hendrika M Duivenvoorden, Jai Rautela, Laura E Edgington-Mitchell, Alex Spurling, David W Greening, Cameron J Nowell, Timothy J Molloy, Elizabeth Robbins, Natasha K Brockwell, Cheok Soon Lee, Maoshan Chen, Anne Holliday, Cristina I Selinger, Min Hu, Kara L Britt, David A Stroud, Matthew Bogyo, Andreas Möller, Kornelia Polyak, Bonnie F Sloane, Sandra A O'Toole, Belinda S Parker
Mammography screening has increased the detection of early pre-invasive breast cancers, termed ductal carcinoma in situ (DCIS), increasing the urgency of identifying molecular regulators of invasion as prognostic markers to predict local relapse. Using the MMTV-PyMT breast cancer model and pharmacological protease inhibitors, we reveal that cysteine cathepsins have important roles in early-stage tumorigenesis. To characterize the cell-specific roles of cathepsins in early invasion, we developed a DCIS-like model, incorporating an immortalized myoepithelial cell line (N1ME) that restrained tumor cell invasion in 3D culture...
October 31, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29083488/c-ebp%C3%AE-controls-osteoclast-terminal-differentiation-activation-function-and-postnatal-bone-homeostasis-through-direct-regulation-of-nfatc1
#19
Wei Chen, Guochun Zhu, Jun Tang, Hou-De Zhou, Yi-Ping Li
Osteoclast lineage commitment and differentiation have been studied extensively, although the mechanism by which transcription factor(s) control osteoclast terminal differentiation, activation and function remains unclear. CCAAT/enhancer-binding protein α (C/ebpα) has been reported to be a key regulator of osteoclast cell lineage commitment, yet C/ebpα's roles in osteoclast terminal differentiation, activation and function and bone homeostasis, under physiological or pathological conditions, have not been studied because newborn C/ebpα null mice die within several hours after birth...
October 30, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29057478/dcr3-promotes-cell-adhesion-and-enhances-endometriosis-development
#20
Hsiao-Wen Tsai, Ming-Ting Huang, Peng-Hui Wang, Ben-Shian Huang, Yi-Jen Chen, Shie-Liang Hsieh
Endometriosis is a multifactorial inflammatory disease with persistent activation of NF-κB signaling pathway. Aberrant adhesion of endometrium is the essential step in the progression of endometriosis, but the molecular mechanism for ectopic growth of endometrium is still unclear. Decoy receptor 3 (DcR3)/TNFRSF6B, a pleiotropic immunomodulator regulated by estrogen, is able to activate focal adhesion kinase (FAK) to promote cell adhesion. We found that DcR3 is upregulated in human ectopic endometrial cells via activation of the Akt/NF-κB signaling pathway, and its expression level correlates positively with that of adhesion molecules ICAM-1 (intercellular adhesion molecule 1) and HCAM (homing cell adhesion molecule, CD44)...
October 23, 2017: Journal of Pathology
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