natural killer (NK) cells of the innate lymphocytes that play an important role in preventing the development of cancer by monitoring immune system to eradicate the abnormal cells. Since the ex vivo expanded NK cell cytotoxic activity against a variety of cancers, including breast cancer, their clinical potential as an immune-oncogenic therapy has been studied widely.
Here, we report that the chemical pyrazole XRP44X, inhibiting the activation of Ras / ERK from ELK3, stimulates the cells NK-92MI to increase the cytotoxic activity against breast cancer cells. Under XRP44X stimulation, NK cells did not show the famous apoptosis or cell cycle progression disorders. We show that XRP44X enhanced interferon gamma expression in NK-92MI cells.
We also explained that the potentiation of the cytotoxic activity of NK cell-92MI by XRP44X kinase activation induced by c-Jun N-terminal (JNK) signaling pathway. Our data provide insight into the evaluation XRP44X as immune stimulant and XRP44X a potential candidate compounds for the development of NK cell therapy.
Predictive factors for treatment-related mortality and major adverse events after autologous haematopoietic stem cell transplantation for systemic sclerosis: results of a long-term follow-up multicentre study.
Autologous haematopoietic stem cell transplantation (HSCT) increase the viability of systemic sclerosis (SSC) with a poor prognosis, but is hampered by a treatment-related death (TRM) .To evaluate event-free survival (EFS), TRM, response to treatment, disease progression and patient characteristics associated with events.
All patients treated with HSCT for SSC in the Netherlands until 2017 (n = 92) were included. Data on the skin involvement (modified Rodnan score the skin (mRSS), lung function (forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO)), the extent of lung disease Interstitial on high-resolution CT using score Goh and left ventricular ejection fraction (LVEF) were collected at baseline, 1, 2 and 5 years.
the occurrence of the events, defined as death or major organ failure, collected until 2019 as a control, a comparison between patients treated with cyclophosphamide (CYC) and patients with HSCT participating in Stem Cell Transplantation International Scleroderma (astis) autologous trial is performed.
Median follow-up was 4.6 years. EFS forecast at 5, 10 and 15 years was 78%, 76% and 66%, respectively. twenty the death occurred. Mean FVC, DLCO, mRSS and Goh scores all improved significantly. progression of the disease occurred in 22 patients. the frequency of TRM decreased over time and occur more frequently p No male.
The event was independently associated with ma le sex, LVEF <50% and an older age. In astis, patients treated with HSCT (n = 23) 7 events occurred against 13 in the CYC group (n = 22) .We data confirm the long-term efficacy in improving survival HSCT, skin and lung involvement in SSC. male sex, lower LVEF and older age at the beginning is identified as a risk factor for the event.