Клеточные маркеры непрогредиентности при респираторном оксалозе

Respiratory oxalosis (RO), a special hereditary form of obstructive lung disease accompanied by hyperoxaluria, non-progredient course, absence of allergy and several cytology markers was studied in this comparative prospective study. We have observed 2 groups of non-smoking women (71 patients with RO and 64 patients with asthma accompanied by allergy with progredient course during 5 years). We evaluated the locomotor function of the mononuclear and polynuclear blood phagocytes using the inhibition of lymphocyte migration test as an immunological marker, and the hepatocyte function using AST / ALT ratio as a cytological marker. Their prevalence was the greatest in the 1-st group and constituted 100 % for the immunological marker and 98 % for the cytological one. We assume that function of the mononuclear phagocytes in RO probably results in the non progredient course of the disease. It relates to congenital high threshold of the immunocompetent cell sensitivity to polyclonal mitogens.Респираторный оксалоз (РО) является особой наследственной формой обструктивной болезни легких, сопровождаемой гипероксаурией, непрогредиентным течением, отсутствием аллергических проявлений и наличием ряда цитологических маркеров. Мы проводили сравнительное проспективное исследование в течение 5 лет в 2 группах пациентов (все некурящие женщины): 71 человек с РО и 64 с атопической бронхиальной астмой, аллергическими проявлениями и прогредиентным течением. Оценивали локомоторную функцию моно- и полинуклеарных фагоцитов периферической крови в тесте РТМЛ после инкубации крови с поликлональным митогеном FGA (цитологический маркер) и функцию гепатоцитов в тесте де Ритиса с учетом соотношения трансаминаз АСТ и АЛТ (иммунологический маркер). Встречаемость этих маркеров была максимальной в 1-й группе больных и составила 100 % для иммунологического маркера и 98 % — для цитологического маркера. Таким образом, мы полагаем, что ведущим фактором формирования непрогредиентного течения РО является наследственно обусловленный высокий порог клеточной чувствительности иммунокомпетентных клеток к поликлональному митогену

Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.

The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage

KAI1 suppresses HIF-1α and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer

<p>Abstract</p> <p>Background</p> <p>KAI1 was initially identified as a metastasis-suppressor gene in prostate cancer. It is a member of the tetraspan transmembrane superfamily (TM4SF) of membrane glycoproteins. As part of a tetraspanin-enriched microdomain (TEM), KAI1 inhibits tumor metastasis by negative regulation of Src. However, the underlying regulatory mechanism has not yet been fully elucidated. CUB-domain-containing protein 1 (CDCP1), which was previously known as tetraspanin-interacting protein in TEM, promoted metastasis via enhancement of Src activity. To better understand how KAI1 is involved in the negative regulation of Src, we here examined the function of KAI1 in CDCP1-mediated Src kinase activation and the consequences of this process, focusing on HIF-1 α and VEGF expression.</p> <p>Methods</p> <p>We used the human prostate cancer cell line PC3 which was devoid of KAI1 expression. Vector-transfected cells (PC3-GFP clone #8) and KAI1-expressing PC3 clones (PC3-KAI1 clone #5 and #6) were picked after stable transfection with KAI1 cDNA and selection in 800 <it>μ</it>g/ml G418. Protein levels were assessed by immunoblotting and VEGF reporter gene activity was measured by assaying luciferase activitiy. We followed tumor growth <it>in vivo </it>and immunohistochemistry was performed for detection of HIF-1, CDCP1, and VHL protein level.</p> <p>Results</p> <p>We demonstrated that Hypoxia-inducible factor 1α (HIF-1α) and VEGF expression were significantly inhibited by restoration of KAI1 in PC3 cells. In response to KAI1 expression, CDCP1-enhanced Src activation was down-regulated and the level of von Hippel-Lindau (VHL) protein was significantly increased. In an <it>in vivo </it>xenograft model, KAI1 inhibited the expression of CDCP1 and HIF-1α.</p> <p>Conclusions</p> <p>These novel observations may indicate that KAI1 exerts profound metastasis-suppressor activity in the tumor malignancy process via inhibition of CDCP1-mediated Src activation, followed by VHL-induced HIF-1α degradation and, ultimately, decreased VEGF expression.</p

Writing Communities to (Re-)engage Faculty: The U See I Write Initiative

The COVID-19 pandemic has taken a toll on university faculty, unduly those from underrepresented groups, causing many faculty to disengage. Writing communities represent a promising tool to (re-)engage faculty and build an inclusive climate. As part of U See I Write, a faculty development initiative at the University of California, Irvine, we convened a series of monthly writing retreats between March and June of 2021, with between-retreat weekly writing sessions in smaller groups and an expectation to write daily for at least 30 minutes. In a diverse cohort of 34 faculty writers, program participation resulted in a significant increase in writing and work engagement. Similar initiatives at other institutions of higher education may prove successful in faculty (re-)engagement while also advancing faculty diversity

Writing communities to (re-) engage faculty: The U See I Write Initiative

The COVID-19 pandemic has taken a toll on university faculty, unduly those from underrepresented groups, causing many faculty to disengage. Writing communities represent a promising tool to (re-)engage faculty and build an inclusive climate. As part of U See I Write, a faculty development initiative at the University of California, Irvine, we convened a series of monthly writing retreats between March and June of 2021, with between-retreat weekly writing sessions in smaller groups and an expectation to write daily for at least 30 minutes. In a diverse cohort of 34 faculty writers, program participation resulted in a significant increase in writing and work engagement. Similar initiatives at other institutions of higher education may prove successful in faculty (re-)engagement while also advancing faculty diversity