Peculiarities of angiogenesis in testicular embryonal carcinoma

Despite the relatively low incidence of testicular germ cell tumors (TGCT), which amount only 1% of all cancers in men worldwide in the epidemiological aspect, unlike tumors of other localizations, it does not become more frequent with age, but reaches its peak in young men of working age what attaches to the problem not only great medical, but also social significance.Estimation of angiogenesis in the tumor is considered as one of the markers for predicting the course of disease, presence of metastases and sensitivity to antitumor antiangiogenic therapy. At the same time, data concerning the study of the mechanisms of blood vessels formation, the work out of methods for estimation of tumorous angiogenesis as well as the use habits of IHC markers of endothelial cells (CD31 and CD34) for assessing the aggressiveness and prognosis of TGCT and, in particular, EC, are absent in the available literature sources.Investigation of peculiarities of neoangiogenesis in the dynamics of testicular embryonal carcinoma progression revealed: significant increasing of relative area of CD31 and CD34 expression as well as vascular density during transition from the initial to the late stages of tumor progression; formation of intratumoral vessels in the embryonal carcinoma occurs by angiogenesis and vasculogenesis with participation of progenitor endothelial cells; embryonal carcinoma is characterized by vasculogenic mimicry in the form of channels formation that do not have endothelial lining

Swelling-Activated Ca2+ Channels Trigger Ca2+ Signals in Merkel Cells

Merkel cell-neurite complexes are highly sensitive touch receptors comprising epidermal Merkel cells and sensory afferents. Based on morphological and molecular studies, Merkel cells are proposed to be mechanosensory cells that signal afferents via neurotransmission; however, functional studies testing this hypothesis in intact skin have produced conflicting results. To test this model in a simplified system, we asked whether purified Merkel cells are directly activated by mechanical stimulation. Cell shape was manipulated with anisotonic solution changes and responses were monitored by Ca2+ imaging with fura-2. We found that hypotonic-induced cell swelling, but not hypertonic solutions, triggered cytoplasmic Ca2+ transients. Several lines of evidence indicate that these signals arise from swelling-activated Ca2+-permeable ion channels. First, transients were reversibly abolished by chelating extracellular Ca2+, demonstrating a requirement for Ca2+ influx across the plasma membrane. Second, Ca2+ transients were initially observed near the plasma membrane in cytoplasmic processes. Third, voltage-activated Ca2+ channel (VACC) antagonists reduced transients by half, suggesting that swelling-activated channels depolarize plasma membranes to activate VACCs. Finally, emptying internal Ca2+ stores attenuated transients by 80%, suggesting Ca2+ release from stores augments swelling-activated Ca2+ signals. To identify candidate mechanotransduction channels, we used RT-PCR to amplify ion-channel transcripts whose pharmacological profiles matched those of hypotonic-evoked Ca2+ signals in Merkel cells. We found 11 amplicons, including PKD1, PKD2, and TRPC1, channels previously implicated in mechanotransduction in other cells. Collectively, these results directly demonstrate that Merkel cells are activated by hypotonic-evoked swelling, identify cellular signaling mechanisms that mediate these responses, and support the hypothesis that Merkel cells contribute to touch reception in the Merkel cell-neurite complex

Особливості експресії металопротеіназ в герміногенних пухлинах яєчка.

Background. Increasing of the testicular germ cell tumors (TGCT)incidence in combination with the young age of the patients attaches to this problem high medical and social importance. Objective. The aim of investigation was to establish peculiaritiesof MMP-1, MMP-3, MMP-9 and TIMP-1 expression in testicular postpubertal-type yolk sac tumor (YSTPT), postpubertal-type teratoma (TPT), spermatocytic tumor (ST) and teratoma with somatic-type malignancy (TSTM). Methods. YSTPT, TPT, ST and TSTM as well as medical histories of patientswere studied. All TGCTwere divided into groups according to the pTNM classification of WHO. Using antibodies to MMP-1, MMP-3, MMP-9 and TIMP-1 the state of extracellular matrix was investigated. Statistical data processing was performed using the statistical package "STATISTICA 13.3 EN trial version".Results. It is proved that MMP are involved in carcinogenesis starting with the early stages of tumor progression.A more expressive expression of MMP in YSTPT indicates its inclination for an aggressive course. It was identified that in patients with YSTPT and TPT who had vascular invasion, lymphogenous and distant metastases the relative area (S) and intensity (L) of expression of all investigated MMP (with the exception of S of MMP-3) were significantly higher than in patients without these signs of tumor aggressiveness. In ST the S of MMP-1 expression was lower than that in YSTPT and TPT, while the S of MMP-3 expression, on the contrary, was higher than the corresponding index in TPT, and was at the same level with the YSTPT. L of MMP-3 expression was at the border of moderate values.S of MMP-9 expression was greater than that in YSTPT and TPT, and its L was at a high level. In TSTM of group «4» S of MMP-1, MMP-3 and MMP-9 expression was higher (p<0,001) than in TSTM of group «1». In all investigated TGCT reaction with TIMP-1 was negative. Conclusion. In YSTPT and TPT at transition from the initial to the late stages of tumorous progression increasing of MMP synthesis, as well as a complete absence of TIMP-1 expression were detected. Increasing of MMP expression leads to the development of vascular invasion, as well as lymphogenous and distant metastases. Parameters of MMP expression may be independent factors in prognosis of metastasis and progression of TGCT.Актуальность. Рост заболеваемости герминогенными опухолями яичка (ГОЯ) в сочетании с молодым возрастом пациентов придает данной проблеме высокую медицинскую и социальную значимость. Целью работы было установить особенности экспрессии MMP-1, MMP-3, MMP-9 и TIMP-1 в опухоли желточного мешка постпубертатного типа (ОЖМПТ), тератоме постпубертатного типа (ТПТ), сперматоцитной опухоли (СО) и тератоме с малигнизацией соматического типа (ТМСТ) яичка. Методы. Были исследованы ОЖМПТ и ТПТ, СО и ТМСТ, а также истории болезни пациентов. Все ГОЯ были разделены на группы в соответствии с pTNM класификацией ВОЗ. С помощью антител к MMP-1, MMP-3, MMP-9 и TIMP-1 изучали состояние экстрацеллюлярного матрикса. Статистическую обработку цифровых данных осуществляли с помощью пакета статистического анализа триал-версии STATISTICA 13.3 EN. Результаты. Доказано, что ММР принимают участие в канцерогенезе уже на ранних стадиях опухолевой прогрессии. Более выразительная экспрессия ММР в ОЖМПТ свидетельствует о ее склонности к агрессивному течению. Установлено, что у больных ОЖМПТ и ТПТ, которые имели сосудистую инвазию, лимфогенные и отдаленные метастазы, показатели относительной площади (S) и интенсивности (L) экспрессии всех исследованных MMP (за исключением показателя S MMP-3) были достоверно больше, чем у пациентов без этих признаков агрессивности опухоли. В СО показатель S экспрессии ММР-1 был ниже таковой в ОЖМПТ и ТПТ, а показатель S экспрессии ММР-3, напротив, был выше соответствующего в ТПТ, а с показателем ОЖМПТ находился на одном уровне. L экспрессии маркера MMP-3 была на границе умеренных значений. S экспрессии ММР-9 оказалась больше таковой в ОЖМПТ и ТПТ, а его L находилась на высоком уровне. В ТМСТ группы «4» S экспрессии MMP-1, MMP-3 и MMP-9 были выше (р<0,001), чем в ТМСТ группы «1». Во всех ГОЯ обнаружена негативная реакция с TIMP-1. Выводы. При переходе от начальных до поздних стадий опухолевой прогрессии в ОЖМПТ и ТПТ происходит усиление синтеза MMP в сочетании с полным отсутствием экспрессии TIMP-1. Увеличение экспрессии MMP приводит к развитию сосудистой инвазии, а также лимфогенных и отдаленных метастазов. Показатели экспрессии MMP могут быть независимыми факторами прогноза метастазирования и прогрессии ГОЯ.Актуальність. Зростання захворюваності на герміногенні пухлини яєчка (ГПЯ)в поєднанні з молодим віком пацієнтів надає даній проблемі високу медичну і соціальну значимість. Метою роботи було встановити особливості експресії MMP-1, MMP-3, MMP-9 і TIMP-1 в пухлині жовткового мішка постпубертатного типу (ПЖМПТ), тератомі постпубертатного типу (ТПТ), сперматоцитній пухлині (СП) і тератомі з малігнізацією соматичного типу (ТМСТ)яєчка. Методи. Були досліджені ПЖМПТ і ТПТ, СП і ТМСТ, а також історії хвороби пацієнтів. Всі ГПЯ були розподілені на групи у відповідності до pTNM класифікації ВООЗ. За допомогою антитіл до MMP-1, MMP-3, MMP-9 і TIMP-1 вивчали стан екстра целюлярного матриксу. Статистичну обробку цифрових даних здійснювали за допомогою пакету статистичного аналізу тріал-версії STATISTICA 13.3 EN. Результати. Доведено, що ММР приймають участь в канцерогенезі вже на ранніх стадіях пухлинної прогресії. Більш виразна експресія ММР в ПЖМПТ свідчить про її схильність до агресивного перебігу. Встановлено, що у хворих на ПЖМПТ і ТПТ, які мали судинну інвазію, лімфогенніі віддалені метастази, показники відносної площі (S) та інтенсивності (L) експресії всіх досліджених MMP (за винятком показника S MMP-3) були достовірно більшими, ніж у пацієнтів без цих ознак агресивності пухлини. В СП показник S експресії ММР-1 був нижчим за такий в ПЖМПТ і ТПТ, а показник S експресії ММР-3, навпаки, був вищим за відповідний в ТПТ, а з показником ПЖМПТ знаходився на одному рівні. L експресії маркера MMP-3 були на межі помірних значень. S експресії ММР-9 виявилась більшою за таку в ПЖМПТ і ТПТ, а його L знаходилась на високому рівні. В ТМСТ групи «4» S експресії MMP-1, MMP-3 і MMP-9 були вищими (р<0,001), ніж в ТМСТ групи «1». В усіх ГПЯ виявлена негативна реакція з TIMP-1. Підсумок. При переході від початкових до пізніх стадій пухлинної прогресії в ПЖМПТ і ТПТ відбувається посилення синтезу MMP у поєднанні з повною відсутністю експресії TIMP-1.Збільшення експресії MMP призводить до розвитку судинної інвазії, а також лімфогенних і віддалених метастазів. Показники експресії MMP можуть бути незалежними факторами прогнозу метастазування і прогресії ГПЯ

A narrative review on haptic devices: relating the physiology and psychophysical properties of the hand to devices for rehabilitation in central nervous system disorders

Purpose. This paper provides rehabilitation professionals and engineers with a theoretical and pragmatic rationale for the inclusion of haptic feedback in the rehabilitation of central nervous system disorders affecting the hand.Method. A narrative review of haptic devices used in sensorimotor hand rehabilitation was undertaken. Presented papers were selected to outline and clarify the underlying somatosensory mechanisms underpinning these technologies and provide exemplars of the evidence to date.Results. Haptic devices provide kinaesthetic and/or tactile stimulation. Kinaesthetic haptics are beginning to be incorporated in central nervous system rehabilitation, however, there has been limited development of tactile haptics. Clinical research in haptic rehabilitation of the hand is embryonic but initial findings indicate potential clinical benefit. Conclusions. Haptic rehabilitation offers the potential to advance sensorimotor hand rehabilitation but both scientific and pragmatic developments are needed to ensure that its potential is realised.<br/

Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis