Aberrant nuclear and cellular structures are hallmarks of malignant transformation. Thus it is not surprising that the three-dimensional structure of the cell both affects and is affected by changes in gene expression. Here we review the role of the cytoskeleton, nuclear matrix, and chromatin structure in the genesis of cancer. The shape of a cell is governed by a dynamic tissue matrix, which includes extracellular matrix, cytoskeleton and nuclear matrix. Mechanical and chemical signals are transmitted to the nucleus, resulting in alterations in the three-dimensional chromatin organization of genes. The signal transduction pathways affect histone modifications, such as acetylation and phosphorylation, resulting in a relaxed chromatin structure observed in oncogene-transformed cells.
Solitary fibrous tumours are uncommon spindle cell neoplasms generally associated with serosal surfaces, especially the pleura (‘localized fibrous mesothelioma’). Recently, these tumours have been documented in extraserosal sites. We report two solitary fibrous tumours, including one occurring in the paediatric age group, arising in two previously unreported locations, parapharyngeal space and epiglottis. These cases expand the range of sites where this tumour may originate and confirm the tendency of extrapleural cases to involve the upper respiratory tract and adjacent structures.
Abstract The tissue adjacent to breast tumors has been referred to as “normal-like” tissue despite exhibiting many alterations at epigenetic and gene expression levels consistent with enhanced proliferation and wound healing signatures. However, the influence of such alterations on the proliferation and differentiation of healthy breast progenitors is currently unknown. Fibroblasts are a major component of microenvironment for the healthy and malignant breast cells. We therefore, isolate fibroblast from primary breast tumors, tissue adjacent to tumors (TAT) and the healthy breast tissue and examine their ability to support proliferation of healthy and malignant breast cells. To characterize the TAT samples we first utilized clonal co-culture assays using breast cells obtained from the healthy breast tissue (reduction mammoplasty sample, RM) and the healthy fibroblasts. Our results suggested that the TAT samples surprisingly contained significantly decreased pool of progenitors compared to the RM samples. In order to study the underlying mechanism, we characterized fibroblasts derived from either the breast tumours (TAFs) or the TAT samples (TATF) or the RM normal samples (NAFs) and assessed their role on breast progenitor cell functions. Fibroblasts were isolated from the ER+ and ER- breast tumours and their adjacent breast tissue. We observed that matrigel co-cultures consisting of RM samples and NAFs led to a 5.5-fold expansion of the progenitors, whereas the co-cultures of TAT or the RM samples with either TAFs or TATFs failed to show expansion of epithelial progenitors. The comparative secretome analysis of the NAFs and the TATFs identified TGFβ as a candidate molecule primarily secreted only by the TATFs and not by NAFs. Interestingly, blocking TGFβ signaling restored both TAFs' and TATFs' ability to support the expansion of healthy progenitors in matrigel cultures. Lastly, we found that TAFs were able to enhanced breast cancer cell proliferation in vivo and in vitro but to a lesser extent than the TAFs. Our observations suggest that the tissues adjacent to breast tumours are transformed into a TGFβ-enriched environment that is supportive of breast tumour growth while suppressing the proliferation and differentiation potentials of the healthy breast progenitors. Our data also suggest that the use of TGFβ blockers may be important in reducing risk of local breast tumour recurrence. Citation Format: Chatterjee S, Berdnikov A, Lee-Wing V, Safneck J, Buchel E, Raouf A. Fibroblasts isolated from the “normal-like” tissue adjacent to breast tumours suppress healthy epithelial progenitor cell proliferation while supporting tumour cell growth [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-11.
Human breast cancer cells are known to activate adjacent "normal-like" cells to enhance their own growth, but the cellular and molecular mechanisms involved are poorly understood. We now show by both phenotypic and functional measurements that normal human mammary progenitor cells are significantly under-represented in the mammary epithelium of patients' tumor-adjacent tissue (TAT). Interestingly, fibroblasts isolated from TAT samples showed a reduced ability to support normal EGF-stimulated mammary progenitor cell proliferation in vitro via their increased secretion of transforming growth factor β. In contrast, TAT fibroblasts promoted the proliferation of human breast cancer cells when these were co-transplanted in immunodeficient mice. The discovery of a common stromal cell-mediated mechanism that has opposing growth-suppressive and promoting effects on normal and malignant human breast cells and also extends well beyond currently examined surgical margins has important implications for disease recurrence and its prevention.
Les opioïdes jouent un rôle important dans le traitement de la douleur de nombreux patients, mais sont de plus en plus associés au trouble de l’utilisation de substances et à des effets indésirables en Amérique du Nord. Dans cette étude de cas, nous décrivons le premier cas canadien de séquelles significatives intranasales et pharyngiques suite à l’utilisation d’opioïdes intranasaux. Les approches de diagnostic et de traitement sont ensuite décrites. Chez les patients présentant des représentations atypiques, les lésions tissulaires induites par les opioïdes intranasaux devraient être envisagées dans le diagnostic différentiel des lésions tumorales otolaryngologiques. Ce cas souligne l’importance de pouvoir reconnaître les complications otolaryngologiques de la mauvaise utilisation des opioïdes intranasaux et traiter ainsi de manière appropriée en utilisant une approche multidisciplinaire. ABSTRACT Opioids play an important part in the pain management of many patients, but are increasingly associated with substance use disorder and adverse events in North America. In this case report, we describe the first noted Canadian case of significant intranasal and pharyngeal sequelae of intranasal opioid use. Diagnostic and treatment approaches are then described. In patients with atypical presentations, intranasal opioid-induced tissue damage should be considered in the differential diagnosis of otolaryngologic tissue damage. This case highlights the importance of being able to recognize the otolaryngologic complications of intranasal opioid misuse and thereby appropriately treat using a multidisciplinary approach.
To study the fine needle aspiration cytology of lymphoepithelial carcinoma of salivary gland (LECSG).Needle aspirates from five primary and two metastatic LECSGs were reviewed.Three aspirates showed very scant cellularity with rare tumor cells originally misinterpreted as lymphohistiocytic cells. Six fine needle aspiration biopsies (FNABs) contained medium to large polygonal and spindled cells with one or more prominent nucleoli. Five aspirates also displayed a heterogeneous population of lymphoid cells, while a sixth had much necrotic debris and only a few lymphocytes admixed with tumor cells.In the clinical setting of an Inuit or Chinese patient with a salivary gland mass, an FNAB with these features should suggest the possibility of LECSG.
