Dasatinib plus prednisone as induction and consolidation for adults with Ph-positive acute lymphoblastic leukaemia: A single-arm, multicentre, phase 2 trial.

To reducing chemotherapy-related toxicity, the chemo-free regimens become a new trend of Ph + ALL treatment. Therefore, we conducted a phase 2 trial of dasatinib plus prednisone, as induction (Course I) and early consolidation (Courses II and III) treating newly diagnosed Ph + ALL. The trial was registered at www.chictr.org.cn, ChiCTR2000038053. Forty-one patients were enrolled from 15 hospitals. The complete remission (CR) was 95% (39/41), including two elderly induction deaths. By the end of Course III, 25.6% (10/39) of patients achieved a complete molecular response. With a median follow-up of 15.4 months, 2-year disease-free survival (DFS) were 100% and 33% for patients who receiving haematopoietic stem cell transplantation (HSCT) at CR1 and receiving chemotherapy alone respectively. When censored at time of HSCT, 2-year DFS were 51% and 45% for young and elderly patients (p = 0.987). 2-year overall survival were 45%, 86% and 100% for patients without HSCT, receiving HSCT after relapse and receiving HSCT at CR1 respectively. A total of 12 patients had marrow recurrences and one had CNS relapse, with 38% occurred early (between Courses I and III). IKZF1 gene deletion was shown to be associated with relapse (p = 0.019). This chemo-free induction and early consolidation regimen was efficacious and well-tolerated in de novo Ph + ALL. Allogeneic HSCT conferred definite survival advantage after chemo-free induction.

Dietary protein sources, genetics, and cardiovascular disease incidence.

BACKGROUND: To explore the potential correlation between the amount and source of dietary protein and cardiovascular disease (CVD), as well as the potential impact of genetic susceptibility on these connections. METHODS: We performed a prospective analysis of 98,224 participants from the UK. We measured dietary protein intake using two 24-hour dietary recall interviews. To analyze the data, we used multivariable-adjusted Cox regression models and restricted cubic spline models. Additionally, we calculated weighted genetic risk scores. RESULTS: A total of 8818 new cases of CVD were documented, which included 4076 cases of coronary artery disease (CAD) and 1126 cases of stroke. The study found a J-shaped association (p nonlinearity = 0.005) between CVD risk and the percentage of energy obtained from consuming plant protein. Higher intake of plant protein and whole protein was associated with a decreased risk of CVD. On the other hand, larger intakes of animal protein was linked to a higher occurrence of CAD. Additionally, increased intake of plant protein was also linked to a lower incidence of stroke. Replacing 5 % of animal protein-based energy intake with plant protein-based energy intake resulted in a 5 % decrease in CVD risk. LIMITATIONS: There remains an effect of residual confounders. CONCLUSION: The consumption of larger amounts of plant protein, whole protein, and nut protein was found to be associated with a lower risk of CVD events. Conversely, higher intakes of animal protein was associated with an increased risk of CAD events. Furthermore, replacing 5 % of energy intake from animal protein with energy intake from plant protein was found to reduce the risk of CVD by 5 %.

Methods and clinical biomarker discovery for targeted proteomics using Olink technology.

PURPOSE: This paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment. EXPERIMENTAL DESIGN: We discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune-related diseases, and Outlines the advantages and limitations of Olink technology. RESULTS: Olink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments. CONCLUSIONS: Although proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other.

Recent Advances in Nanobiotechnology for the Treatment of Non-Hodgkin's Lymphoma.

Lymphoma is the eighth most common type of cancer worldwide. Currently, lymphoma is mainly classified into two main groups: Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), with NHL accounting for 80% to 90% of the cases. NHL is primarily divided into B, T, and natural killer (NK) cell lymphoma. Nanotechnology is developing rapidly and has made significant contributions to the field of medicine. This review summarizes the advancements of nanobiotechnology in recent years and its applications in the treatment of NHL, especially in diffuse large B cell lymphoma (DLBCL), central nerve cell lymphoma, and follicular lymphoma. The technologies discussed include clinical imaging, targeted drug delivery, photodynamic therapy (PDT), and thermodynamic therapy for lymphoma. This review aims to provide a better understanding of the use of nanotechnology in the treatment of non-Hodgkin's lymphoma.

Development of GPC3 and EGFR-dual-targeting chimeric antigen receptor-T cells for adoptive T cell therapy.

Adoptive transfer of T cells expressing specific anti-glypican-3 (GPC3) chimeric antigen receptors (CARs) has demonstrated therapeutic potential against hepatocellular carcinoma (HCC). However, normal tissues with low expression of neoplasm-associated antigens often show on-target, off-tumor toxicity. Previous studies have revealed that the development of HCC xenografts in mice could be inhibited effectively by GPC3-targeting CAR-T cells. However, these studies did not provide information regarding on-target, off-tumor toxicity. We hypothesized that on-target, off-tumor toxicity may decrease in dual-targeting CAR-T cells that co-express GPC3 with epidermal growth factor receptor (EGFR)-targeted CARs characterized by CD3ζ and 28BB expression. Our research confirmed that dual-targeting CAR-T (CARgpc3-egfr) cells exhibited similar proliferative ability and cytotoxicity to CARgpc3 T cells against GPC3+EGFR+ HCC in vitro. However, EGFR-targeting CAR-T (CARegfr) cells showed poor proliferation activity and cytotoxicity against GPC3+EGFR+ HCC cells, similar to mock CAR-T cells. CARgpc3 and CARgpc3-egfr T cells showed enhanced cytokine secretion compared to CARegfr and mock CAR-T cells in vitro. In vivo, tumor growth suppression was better for CARgpc3-egfr T cells than for CARgpc3 T cells in GPC3+EGFR+ HCC, while it was not observed for CARegfr or mock CAR-T cells. Taken together, our data indicated that dual-targeting CAR-T cells with two CARs against GPC3 and EGFR may maintain relatively effective anti-neoplasm functions in GPC3+EGFR+ HCC in vitro and in vivo, a strategy that may reduce off-tumor toxicity.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Efficacy and safety of sustained-release oxycodone compared with immediate-release morphine for pain titration in cancer patients: A multicenter, open-label, randomized controlled trial (SOCIAL).

BACKGROUND: The study aims to investigate the effect and safety of sustained-release oxycodone hydrochloride as background dose on pain titration in patients with moderate-to-severe cancer pain. MATERIAL AND METHODS: Adult patients scheduled with a regular strong opioid for cancer-related pain were recruited and randomly assigned to sustained-release oxycodone group (tablets, 12 hourly) and immediate-release morphine group (5 mg initially, hourly). All patients were hourly reassessed for efficacy and dose titration. RESULTS: The primary end point was the number of titration cycles required to achieve adequate pain relief (numerical rating scale, NRS ≤ 3). Secondary end points included the proportion of patients achieving adequate pain relief during each cycle, potential predictive factors for titration performance, and side effects. Ninety (94.7%) patients in oxycodone group and 78 (86.7%) patients in morphine group achieved adequate pain control during 1 to 4 cycles of titration. Patients in oxycodone group reached adequate pain control within the first 2 cycles of titration, which was significantly shorter than morphine group wherein the number of titration cycles ranged from 1 to 4 (P = .034). Oxycodone prescription significantly increased the response rate of patients to morphine titration during the first cycle of titration (P = .010). The initial NRS score and oxycodone administration were significantly associated with titration performance. The mild or moderate adverse effects were similar in 2 groups, while severe adverse effects were only identified in morphine group (P = .001). CONCLUSION: Use of background sustained-release oxycodone is more efficient and better tolerated on dose titration than immediate-release morphine.

Association study of inflammatory cytokine and chemokine expression in hand foot and mouth disease.

OBJECTIVE: To determine the relationship of cytokine/chemokine expression with the clinical presentation of hand, foot and mouth disease (HFMD). RESULTS: All cytokine/chemokine levels were higher in severe HFMD patients than in mild HFMD patients or controls (P < 0.01). RANTES, MCP-1, IL-4, IL-12 and IL-18 levels were higher in mild HFMD patients than in the controls (P < 0.05). In severe HFMD, all levels (except IL-8 and IL-4) were higher in patients with encephalitis plus pulmonary edema than in those with encephalitis alone (P < 0.05). All levels (except IL-8) were higher in EV71-positive patients than in EV71-negative patients (P < 0.05). In mild HFMD, all levels (except IL-8 and IL-4) were higher in EV71-positive patients than in EV71-negative patients (P < 0.05). In severe HFMD, only RANTES, IP-10 and IFN-γ levels were higher in EV71-positive patients than in EV71-negative patients (P < 0.05). In the EV71-negative group, all levels were higher in severe HFMD than in mild HFMD (P < 0.01). In the EV71-positive group, all levels (except IL-8) were higher in severe HFMD than in mild HFMD (P < 0.01). MATERIALS AND METHODS: This study involved 28 mild HFMD patients, 44 severe HFMD patients and 26 healthy children. Venous blood was tested for cytokines (IL-4, IL-12, IL-18, TNF-α, IFN-γ) and chemokines (IL-8, RANTES, MCP-1, IP-10). Stool samples from the patients were tested for EV71 nucleic acid using reverse transcription polymerase chain reaction. CONCLUSIONS: Cytokines/chemokines participate in HFMD pathogenesis, and could have potential value in monitoring disease progression and predicting prognosis.