Protein kinase C zeta suppresses low ‐ or high‐grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring
Abstract
Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interde...
Source: The Journal of Pathology - March 9, 2018 Category: Pathology Authors: Ravi Kiran Deevi, Arman Javadi, Jane McClements, Jekaterina Vohhodina, Kienan Savage, Maurice Bernard Loughrey, Emma Evergren, Frederick Charles Campbell Tags: Original Paper Source Type: research
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The Journal of Pathology, Ahead of Print. (Source: The Journal of Pathology)
Source: The Journal of Pathology - March 7, 2018 Category: Pathology Source Type: research
Is high ‐grade prostatic intraepithelial neoplasia (HGPIN) a reliable precursor for prostate carcinoma? Implications for clonal evolution and early detection strategies
Abstract
High‐grade prostatic intraepithelial neoplasia (HGPIN) is a documented putative precursor lesion for invasive prostate adenocarcinoma. However, the precise mechanisms of the carcinoma's development from HGPIN are unclear. Many studies have attempted a comparative molecular genetic characterisation of HGPIN and its corresponding carcinoma to study this transformation. However, to date, some HGPIN mimickers, such as intraductal carcinoma, which can engage in retrograde colonisation of the prostatic acini in an HGPIN‐like manner, have been described. In this work, we hypothesise that the lesion formerly known as ...
Source: The Journal of Pathology - March 7, 2018 Category: Pathology Authors: Yuri Tolkach, Glen Kristiansen Tags: Perspective Source Type: research
Re: K öbel and Nelson, Implementation or integration of molecular subclasses?
Abstract
We thank Drs. Köbel and Nelson for their deep reading and thoughtful comments on our recent review [1]. Although they raised significant concerns, their letter, in which they outline their current practice, indicates their agreement with our basic proposition that molecular, TCGA‐based classification is the most important advance in endometrial cancer pathology in a very long time, and is immediately clinically actionable. (Source: The Journal of Pathology)
Source: The Journal of Pathology - March 7, 2018 Category: Pathology Authors: Jessica McAlpine, Tjalling Bosse Tags: Letter to the Editor Source Type: research
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The Journal of Pathology, Ahead of Print. (Source: The Journal of Pathology)
Source: The Journal of Pathology - March 6, 2018 Category: Pathology Source Type: research
Role of Wnt signalling in advanced prostate cancer
The Journal of Pathology, EarlyView. (Source: The Journal of Pathology)
Source: The Journal of Pathology - March 1, 2018 Category: Pathology Source Type: research
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The Journal of Pathology, Ahead of Print. (Source: The Journal of Pathology)
Source: The Journal of Pathology - March 1, 2018 Category: Pathology Source Type: research
Exome sequencing reveals the genetic landscape and frequent inactivation of PCDHB3 in Chinese rectal cancers
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, with more than 1.3 million new cases and 690,000 deaths each year. In China, the incidence of CRC has increased dramatically due to dietary and lifestyle changes, to become the fifth leading cause of cancer‐related death. Here, we performed whole‐exome sequencing in 50rectal cancer cases among the Chinese population as part of the International Cancer Genome Consortium research project. Frequently‐mutated genes and enriched pathways were identified. Moreover, a previously unreported gene, PCDHB3, was found frequently mutated in 5.19% cases. A...
Source: The Journal of Pathology - March 1, 2018 Category: Pathology Authors: Wen Ye, Shaoping Ling, Ran ‐Yi Liu, Zhi‐Zhong Pan, Gaoyuan Wang, Shijuan Gao, Jiangxue Wu, Lihua Cao, Lili Dong, Yingchang Li, Yi Zhou, Wuying Du, Xiangqi Meng, Jinna Chen, Xinyuan Guan, Yulong He, Changchuan Pan, X.F. Steven Zheng, Xuemei Lu, Shuai C Tags: Original Paper Source Type: research
Microenvironment of proliferative diabetic retinopathy supports lymphatic neovascularization
We describe here a clinically relevant model, whereby the native multicellular PDR landscape and neo(fibro)vascular processes can be analyzed ex vivo and related to clinical data. As characterized by 3D whole‐mount immunofluorescence and electron microscopy, heterogeneity in patient‐derived PDR neovascular tissues included discontinuous capillaries coupled with aberrantly differentiated, lymphatic‐like, and tortuous endothelia. Spatially‐confined apoptosis and proliferation co‐existed with inflammatory cell infiltration and unique vascular islet formation. Ex vivo‐cultured explants sustained multicellularity, i...
Source: The Journal of Pathology - March 1, 2018 Category: Pathology Authors: Erika Gucciardo, Sirpa Loukovaara, Ani Korhonen, Pauliina Repo, Beatriz Martins, Helena Vihinen, Eija Jokitalo, Kaisa Lehti Tags: Original Paper Source Type: research
The advanced glycation endproduct N ε‐carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes‐associated risk and its prevention
Abstract
Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, Western diet and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation endproducts (AGEs), which characterizes all the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumor‐promoting role of RAGE, the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation. To this end, we investigated the effects of the AGE Nε‐carboxymethyllysine (CML) in human...
Source: The Journal of Pathology - March 1, 2018 Category: Pathology Authors: Stefano Menini, Carla Iacobini, Luisa de Latouliere, Isabella Manni, Vittoria Ionta, Claudia Blasetti Fantauzzi, Carlo Pesce, Paola Cappello, Francesco Novelli, Giulia Piaggio, Giuseppe Pugliese Tags: Original Paper Source Type: research
Epithelial ER α Is Dispensable for the Development of Estrogen−Induced Cervical Neoplastic Diseases
Human papillomavirus (HPV) is required but not sufficient for cervical carcinoma (CxCa). Estradiol (E2) promotes CxCa development in K14E7 transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin 14 (K14) promoter. E2 mainly works through estrogen receptor α (ERα). However, the role of ERα in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of Esr1 (the ERα‐coding gene) in the cervical stroma of K14E7 mice promotes regression of cervical intraepithelial neoplasia (CIN), the precursor lesion of CxCa. Here, we deleted Es...
Source: The Journal of Pathology - March 1, 2018 Category: Pathology Authors: Jieun Son, Yuri Park, Sang ‐Hyuk Chung Tags: Brief Definitive Report Source Type: research
Implementation or integration of molecular subclasses?
Abstract
Drs McAlpine and Bosse have written a comprehensive review entitled: “The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses” in the Journal of Pathology [1]. In summary, they propose an implementation of molecular subclasses/subtypes for all endometrial carcinomas, regardless of the histotype. We acknowledge the provocative value of this contribution. (Source: The Journal of Pathology)
Source: The Journal of Pathology - March 1, 2018 Category: Pathology Authors: Martin K öbel, Gregg Nelson Tags: Letter to the Editor Source Type: research
Pyloric metaplasia, pseudopyloric metaplasia, ulcer ‐associated cell lineage and spasmolytic polypeptide‐expressing metaplasia: reparative lineages in the gastrointestinal mucosa.
Summary
The gastrointestinal mucosae provide a critical barrier between the external and internal milieu. Thus, damage to the mucosa requires an immediate response to provide appropriate wound closure and healing. Metaplastic lineages with phenotypes similar to the mucous glands of the distal stomach or Brunner’s glands have been associated with various injurious scenarios in the stomach, small bowel and colon. These lineages have been assigned various names including pyloric metaplasia, pseudopyloric metaplasia, ulcer‐associated cell lineage (UACL) and spasmolytic polypeptide‐expressing metaplasia (SPEM). A re‐exa...
Source: The Journal of Pathology - March 1, 2018 Category: Pathology Authors: James R. Goldenring Tags: Invited Perspective Source Type: research
Precious GEMMs: Emergence of faithful models for ovarian cancer research
Abstract
The development of Genetically Engineered Mouse Models (GEMMs) has catalyzed tremendous progress in cancer research. However, it has been difficult to design adequate mouse models for high‐grade serous carcinoma (HGSC), the most common and lethal form of ovarian cancer. The genetic complexity of the disease, as well as the recent appreciation that most HGSCs arise from the fallopian tube (FT) secretory epithelium rather than the ovarian surface epithelium, has stifled the development of robust GEMMs. In a recent issue of this journal, Zhai et al presented an elegant mouse model for ovarian cancer that uses Ovgp1...
Source: The Journal of Pathology - March 1, 2018 Category: Pathology Authors: Sarah Stuckelberger, Ronny Drapkin Tags: Invited Commentary Source Type: research
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The Journal of Pathology, Ahead of Print. (Source: The Journal of Pathology)
Source: The Journal of Pathology - February 28, 2018 Category: Pathology Source Type: research
