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Anat Klein Hila Schwartz Orit Sagi‐Assif Tsipi Meshel Sivan Izraely Shlomit Ben Menachem Roman Bengaiev Amir Ben‐Shmuel Clara Nahmias Pierre‐Olivier Couraud Isaac P Witz Neta Erez 《The Journal of pathology》2015,236(1):116-127
Melanoma is the leading cause of skin cancer mortality. The major cause of melanoma mortality is metastasis to distant organs, frequently to the brain. The microenvironment plays a critical role in tumourigenesis and metastasis. In order to treat or prevent metastasis, the interactions of disseminated tumour cells with the microenvironment at the metastatic organ have to be elucidated. However, the role of brain stromal cells in facilitating metastatic growth is poorly understood. Astrocytes are glial cells that function in repair and scarring of the brain following injury, in part via mediating neuroinflammation, but the role of astrocytes in melanoma brain metastasis is largely unresolved. Here we show that astrocytes can be reprogrammed by human brain‐metastasizing melanoma cells to express pro‐inflammatory factors, including the cytokine IL‐23, which was highly expressed by metastases‐associated astrocytes in vivo. Moreover, we show that the interactions between astrocytes and melanoma cells are reciprocal: paracrine signalling from astrocytes up‐regulates the secretion of the matrix metalloproteinase MMP2 and enhances the invasiveness of brain‐metastasizing melanoma cells. IL‐23 was sufficient to increase melanoma cell invasion, and neutralizing antibodies to IL‐23 could block this enhanced migration, implying a functional role for astrocyte‐derived IL‐23 in facilitating the progression of melanoma brain metastasis. Knocking down the expression of MMP2 in melanoma cells resulted in inhibition of IL‐23‐induced invasiveness. Thus, our study demonstrates that bidirectional signalling between melanoma cells and astrocytes results in the formation of a pro‐inflammatory milieu in the brain, and in functional enhancement of the metastatic potential of disseminated melanoma cells. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
83.
PurposeRecent publications suggested that the risk for pre-eclampsia (PE) is higher with frozen-thawed embryo transfers (FETs) compared to fresh transfers (IVF-ETs). These studies were based on old data that reflects outdated practices. In this paper, we wanted to assess the incidence of PE in current assisted reproductive technology (ART) practice.MethodsIn this cohort study, we present the incidence of PE in all births in the province of Ontario, Canada, for the years 2013–2017 for FET, IVF-ET, and natural conceptions (NC). We also compare our findings to previous studies in a meta-analysis that includes over 4 million births.ResultsThe results of our study show that contemporary practice of ART results in comparable risk for PE between FET and IVF-ET; however, the risk is higher than NC.ConclusionCurrent ART practice is associated with a lower risk for PE in frozen embryo transfer; this RR can be further attenuated by using ovulatory endometrial preparation for FETs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-021-02061-z. 相似文献
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Sheetal Shroff Girish S. Shroff Shlomit Yust‐Katz Adriana Olar Sudhakar Tummala Ivo W. Tremont‐Lukats 《Clinical Case Reports》2014,2(3):113-114
In immunocompromised patients, the pulmonary computed tomography halo sign is highly suggestive of angioinvasive aspergillosis. Early recognition may be life‐saving. 相似文献
87.
Ben-Abraham R Keller N Teodorovitch N Barzilai A Harel R Barzilay Z Paret G 《The Journal of infection》2004,49(4):4028-323
OBJECTIVES: To retrospectively delineate predictors of adverse outcome by looking at the demographic features, therapy and outcome of systemic candida infection in a large tertiary care university-affiliated medical center. METHODS: We reviewed the clinical data on 186 inpatients with candidemia over a 6-year period. The major reason for their hospital admission was an underlying malignancy or an infection other than candidemia. RESULTS: Candida albicans, tropicalis, parapsilosis, glabrata and krusei caused 54, 22, 13, 8 and 3% of the candidemia episodes, respectively. The overall mortality was 42% and it was highest in patients suffering from candidemia of the glabrata species (73%). Forty-eight (63%) of the 76 patients who received no anti-fungal treatment died compared to 38 (34%) of 110 patients who were treated (P < 0.05). Predictors of adverse outcome were intensive care unit stay, renal failure, thrombocytopenia and the need for mechanical ventilation or inotropic support. CONCLUSIONS: We identified four predictors of mortality from candidemia infection. Their validity should be further assessed and the specific candida strains and their susceptibility need to be methodically identified. Our data support immediate initiation of therapy at first identification of infection. 相似文献
88.
Transplants across human leukocyte antigen barriers. 总被引:14,自引:0,他引:14
Massimo F Martelli Franco Aversa Ester Bachar-Lustig Andrea Velardi Shlomit Reich-Zelicher Antonio Tabilio Hilit Gur Yair Reisner 《Seminars in hematology》2002,39(1):48-56
Clinical experience with full haplotype-mismatched stem cell transplants has a 20-year history. Early results in leukemia patients were disappointing because of a high incidence of severe graft-versus-host disease (GvHD) in T-replete transplants or high rejection rates in T-cell-depleted transplants. The breakthrough came with introduction of a megadose T-cell-depleted progenitor cell transplant following a high-intensity conditioning regimen and the realization that donor natural killer (NK) cell alloreactivity also plays a role in facilitating engraftment and in preventing relapse. Treating end-stage patients inevitably confounded clinical outcome in early pilot studies. Today, high-risk acute leukemia patients are treated at less advanced stages of disease, receive a reasonably well-tolerated conditioning regimen, and benefit from advances in post-transplant immunological reconstitution. These factors have markedly reduced transplant-related mortality. Overall, event-free survival (EFS) and transplant-related mortality (TRM) compare favorably with reports from unrelated matched transplants. T-cell-depleted megadose stem cell transplant from a mismatched family member, who is immediately available, can now be offered as a viable option to candidates with high-risk acute leukemias. 相似文献
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P Cohen N Barzilai R Bar-Ilan K Yassin E Karnieli 《The Journal of clinical endocrinology and metabolism》1986,63(6):1411-1413
The regulation of insulin secretion in patients with insulinoma is known to be abnormal. For example, physiological and pharmacological stimuli often fail to stimulate insulin in such patients. Recently, insulin has been found to inhibit its own secretion in normal subjects. To determine if insulin has this effect in patients with insulinoma, we infused insulin at rates of 1 and 10 mU/kg X min in such a patient and in eight normal subjects. Euglycemia was maintained by the euglycemic glucose clamp technique, and endogenous insulin secretion was estimated by measuring plasma C-peptide levels. In the normal subjects, plasma C-peptide declined from 1.60 +/- 0.22 (+/- SEM) to 1.16 +/- 0.17 and 0.82 +/- 0.11 ng/ml during the low and high dose insulin infusions, respectively, indicating 27% (P less than 0.01) and 48% (P less than 0.001) decreases in endogenous insulin secretion at moderately elevated and extremely elevated insulin levels, respectively. In the insulinoma patient, plasma C-peptide was 2.6 ng/ml basally, did not change during the low dose insulin infusion, and rose to 3.4 ng/ml during the high dose insulin infusion. We conclude that the feedback regulation of insulin secretion by insulin that occurs in normal subjects is absent in insulinoma patients. This finding could have pathophysiological and possibly diagnostic significance. 相似文献