HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer

Introduction: Metastases to the brain from breast cancer have a high mortality, and basal-like breast cancers have a propensity for brain metastases. However, the mechanisms that allow cells to colonize the brain are unclear.Methods: We used morphology, immunohistochemistry, gene expression and somatic mutation profiling to analyze 39 matched pairs of primary breast cancers and brain metastases, 22 unmatched brain metastases of breast cancer, 11 non-breast brain metastases and 6 autopsy cases of patients with breast cancer metastases to multiple sites, including the brain.Results: Most brain metastases were triple negative and basal-like. the brain metastases over-expressed one or more members of the HER family and in particular HER3 was significantly over-expressed relative to matched primary tumors. Brain metastases from breast and other primary sites, and metastases to multiple organs in the autopsied cases, also contained somatic mutations in EGFR, HRAS, KRAS, NRAS or PIK3CA. This paralleled the frequent activation of AKT and MAPK pathways. in particular, activation of the MAPK pathway was increased in the brain metastases compared to the primary tumors.Conclusions: Deregulated HER family receptors, particularly HER3, and their downstream pathways are implicated in colonization of brain metastasis. the need for HER family receptors to dimerize for activation suggests that tumors may be susceptible to combinations of anti-HER family inhibitors, and may even be effective in the absence of HER2 amplification (that is, in triple negative/basal cancers). However, the presence of activating mutations in PIK3CA, HRAS, KRAS and NRAS suggests the necessity for also specifically targeting downstream molecules.Ludwig Institute of Cancer ResearchNational Breast Cancer FoundationUniv Queensland, Clin Res Ctr, Brisbane, Qld 4029, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, AustraliaUniversidade Federal de São Paulo, EPM, Dept Anat Patol, BR-04024000 São Paulo, BrazilGriffith Univ, Brisbane, Qld 4011, AustraliaUniv Queensland, Ctr Magnet Resonance, Brisbane, Qld 4072, AustraliaEijkman Inst, Jakarta 10430, IndonesiaInst Nacl Canc, Dept Patol, BR-20230130 Rio de Janeiro, BrazilLab Salomao & Zoppi, Dept Patol, BR-04104000 São Paulo, BrazilCharles Univ Prague, Fac Med, Dept Pathol, Plzen 30605, Czech RepublicUniv Sydney, Inst Clin Pathol & Med Res, Sydney W Area Hlth Serv, Sydney, NSW 2145, AustraliaUniv Sydney, Westmead Millennium Inst, Sydney W Area Hlth Serv, Sydney, NSW 2145, AustraliaPeter MacCallum Canc Ctr, Dept Pathol, Melbourne, Vic 3002, AustraliaUniv Queensland, Queensland Brain Inst, Brisbane, Qld 4072, AustraliaRoyal Brisbane & Womens Hosp, Brisbane, Qld 4029, AustraliaUniversidade Federal de São Paulo, EPM, Dept Anat Patol, BR-04024000 São Paulo, BrazilWeb of Scienc

ИССЛЕДОВАНИЕ ИЗМЕНЕНИЯ КОНСИСТЕНЦИИ ПРОДУКТА ПРИ ЕГО ОБРАБОТКЕ УЛЬТРАЗВУКОМ

This article presents the results of studying the effect of ultrasound on the consistency of products. The task of the study was to identify the possibility of using ultrasound to change the consistency of the product from puree to homogenized. For this purpose, laboratory samples of apple puree were periodically processed on an ultrasonic generator at a frequency of 21.7 kHz, for different duration of exposure to ultrasound from 1 minute to 20 minutes. After processing, measurements of physicochemical parameters were carried out the mass fraction of soluble solids, temperature and viscosity. When analyzing the obtained results, it was found that, depending on the exposure time, the indicators of the mass fraction of dry substances in samples No.1, No.2, No.3 slightly increased relative to the control sample from a value of 11.9 to 12.4 V of sample No.4, in which the duration of exposure to ultrasound was 20 minutes, the indicator of the mass fraction of dry substances increased more significantly up to 13.8%. The same dynamics is observed in the obtained values of the viscosity of the product, which gradually increases in proportion to the exposure time from sample No.1 to sample No.4 (4600-6500 Centipoise (CP)). In addition, a comparative assessment of the organoleptic characteristics of experimental samples (taste, color, aroma and texture) was carried out after their ultrasonic treatment, depending on the duration of exposure. It was found that all the organoleptic characteristics of apple puree with an increase in the duration of ultrasonic treatment with a given parameter at a frequency of 21.7 kHz, changed depending on the time of exposure. Thus, the consistency changed from a “granular” structure (in the control sample) to a homogeneous homogenized (in sample No.3). In sample No.4 (with an exposure time of 20 minutes), mashed potatoes were obtained with a fine, finely divided creamy mass. Consequently, the effect of ultrasound with a given frequency of 21.7 kHz for at least 10 minutes allows a pureed product with a puree-like structure to obtain a homogenized puree.В статье приведены результаты изучения влияния ультразвука на консистенцию продукции. Задача исследования состояла в выявлении возможности применения ультразвука для изменения консистенции продукта из пюреобразной в гомогенизированную. С этой целью изготовленные лабораторные образцы яблочного пюре были подвергнуты периодической обработке на ультразвуковом генераторе на частоте 21,7 кГц, при различной продолжительности воздействия ультразвуком – в течение 1-20 мин. После обработки были проведены измерения физико-химических показателей: массовой доли растворимого сухого вещества, температуры и вязкости. При анализе полученных результатов была установлено, что в зависимости от времени воздействия показатели массовой доли сухого вещества в образцах №1, №2, №3 незначительно повышались относительно контрольного образца – от значения 11,9 до 12,4%. В образце №4, в котором продолжительность воздействия ультразвуком составляла 20 мин, показатель массовой доли сухого вещества увеличился более значительно – до 13,8%. Такая же динамика прослеживается и в полученных значениях вязкости продукта, которая постепенно повышается, пропорционально времени воздействия: от образца №1 до образца №4 (от 4600 сП до 6500 сП). Кроме того, была проведена сравнительная оценка органолептических показателей экспериментальных образцов (вкус, цвет, аромат и консистенция) после их ультразвуковой обработки в зависимости от продолжительности воздействия. Было установлено, что все органолептические характеристики яблочного пюре при увеличении продолжительности обработки продукта ультразвуком с заданным параметром на частоте 21,7 кГц изменялись в зависимости от времени воздействия. Так, консистенция изменялась от «зернистой» структуры (в контрольном образце) до однородной гомогенизированной (в образце №3). В образце №4 (при продолжительности воздействии 20 мин) было получено пюре с тонкоизмельченной кремообразной массой. Следовательно, воздействие ультразвука с заданным значением частоты 21,7 кГц в течение не менее 10 мин позволяет из протёртого продукта с пюреобразной структурой получить гомогенизированное пюре

Polymorphous adenocarcinoma of the salivary glands : reappraisal and update

Although relatively rare, polymorphous adenocarcinoma (PAC) is likely the second most common malignancy of the minor salivary glands (MiSG). The diagnosis is mainly based on an incisional biopsy. The optimal treatment comprises wide surgical excision, often with adjuvant radiotherapy. In general, PAC has a good prognosis. Previously, PAC was referred to as polymorphous low-grade adenocarcinoma (PLGA), but the new WHO classification of salivary gland tumours has also included under the PAC subheading, the so-called cribriform adenocarcinoma of minor salivary glands (CAMSG). This approach raised controversy, predominantly because of possible differences in clinical behaviour. For example, PLGA (PAC, classical variant) only rarely metastasizes, whereas CAMSG often shows metastases to the neck lymph nodes. Given the controversy, this review reappraises the definition, epidemiology, clinical presentation, diagnostic work-up, genetics, treatment modalities, and prognosis of PAC of the salivary glands with a particular focus on contrasting differences with CAMSG.Peer reviewe

A comparative study between mixed-type tumours from human salivary and canine mammary glands

<p>Abstract</p> <p>Background</p> <p>In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours.</p> <p>Methods</p> <p>Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin.</p> <p>Results</p> <p>After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions.</p> <p>Conclusion</p> <p>There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations.</p

Bacterial laccases: some recent advances and applications

Laccases belong to the large family of multi-copper oxidases (MCOs) that couple the one-electron oxidation of substrates with the four-electron reduction of molecular oxygen to water. Because of their high relative non-specific oxidation capacity particularly on phenols and aromatic amines as well as the lack of requirement for expensive organic cofactors, they have found application in a large number of biotechnological fields. The vast majority of studies and applications were performed using fungal laccases, but bacterial laccases show interesting properties such as optimal temperature above 50 °C, optimal pH at the neutral to alkaline range, thermal and chemical stability and increased salt tolerance. Additionally, bacterial systems benefit from a wide range of molecular biology tools that facilitates their engineering and achievement of high yields of protein production and set-up of cost-effective bioprocesses. In this review we will provide up-to-date information on the distribution and putative physiological role of bacterial laccases and highlight their distinctive structural and biochemical properties, discuss the key role of copper in the biochemical properties, discuss thermostability determinants and, finally, review biotechnological applications with a focus on catalytic mechanisms on phenolics and aromatic amines.info:eu-repo/semantics/publishedVersio

Omics-based molecular techniques in oral pathology centred cancer: Prospect and challenges in Africa

: The completion of the human genome project and the accomplished milestones in the human proteome project; as well as the progress made so far in computational bioinformatics and “big data” processing have contributed immensely to individualized/personalized medicine in the developed world.At the dawn of precision medicine, various omics-based therapies and bioengineering can now be applied accurately for the diagnosis, prognosis, treatment, and risk stratifcation of cancer in a manner that was hitherto not thought possible. The widespread introduction of genomics and other omics-based approaches into the postgraduate training curriculum of diverse medical and dental specialties, including pathology has improved the profciency of practitioners in the use of novel molecular signatures in patient management. In addition, intricate details about disease disparity among diferent human populations are beginning to emerge. This would facilitate the use of tailor-made novel theranostic methods based on emerging molecular evidences

human NKR-P1:LLT1 SEC-SAXS raw data

The file contains SEC-SAXS raw data (small angle X-ray scattering) of human NKR-P1 and LLT1 in equimolar mixture. The data were used for OLIGOMER analysis, in order to study complexation capability of both proteins, as described in: Blaha et al., Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse, Nat. Comm. 2022. Preprint available at Biorxiv (https://doi.org/10.1101/2021.06.16.448687).THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

C-type lectin-(like) fold

Review on C-type lectin-(like) fold – protein-protein interaction patterns and utilization potential. The xls table shows PDB ids and basic characteristics of PDB structures containing at least one C-type lectin-(like) domain, 2021