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1.
Article in Chinese | WPRIM | ID: wpr-988948

ABSTRACT

Primary light-chain (AL) amyloidosis is a rare and fatal plasma cell disease. In recent years, the treatment of AL amyloidosis has changed from the era of bortezomib to the era of daratumumab immunotherapy. However, for the treatment choice of advanced-staged patients, how to achieve organ responses at the early stage and how to monitor the disease are questions that need to be further explored. The 64th American Society of Hematology Annual Meeting in 2022 has reported advances in the diagnosis and treatment of AL amyloidosis, which are briefly reviewed in this article.

2.
Frontiers of Medicine ; (4): 1170-1185, 2023.
Article in English | WPRIM | ID: wpr-1010819

ABSTRACT

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.


Subject(s)
Mice , Animals , Receptors, Tumor Necrosis Factor/physiology , Receptors, OX40 , Membrane Glycoproteins , Ligands , Antibodies, Monoclonal/pharmacology , Antineoplastic Agents/pharmacology
3.
JOURNAL OF RARE DISEASES ; (4): 43-49, 2023.
Article in English | WPRIM | ID: wpr-1005059

ABSTRACT

  Objective  Myocardial fibrosis is a potential mechanism of light-chain myocardial amyloidosis(AL-CA). This research aimed at exploring the correlation between multiparameter cardiac magnetic resonance (CMR) and myocardial fibrosis by relating the CMR myocardial tissue characteristics, the morphological and the functional parameters with gallium-68-labeledfibroblast activation protein inhibitor 04 positron emission tomography (68Ga-FAPI PET).  Methods  We gave the patients diagnosed with AL-CA in Peking Union Medical College Hospital from August to December 2021 the examinations of CMR and 68Ga-FAPI PET/CT. We recorded and analyzed the information on clinical manifestations and examinations of the patients.  Results  A total of 23 patients with AL-CA were included, 15 (65.2%)of which were male and the mean age was 58.3±6.5 years. Patients with high 68Ga-FAPI-04 uptake had shown growth in myocardial extracellular volume (ECV), significantly higher than those in the negative group (P=0.047). In addition, patients' myocardial ECV was positively correlated with myocardial FAPI uptake (r=0.628, P=0.001;r=0.727, P < 0.001;r=0.661, P=0.001). Patients in the positive group showd reduced left ventricular (LV) ejection fraction (EF)(P < 0.001).LVEF (r=-0.798, P < 0.001;r=-0.794, P < 0.001; r=-0.795, P < 0.001) and right ventricular (RV)EF (r=-0.735, P < 0.001;r=-0.739, P < 0.001;r=- 0.684, P < 0.001) showd negatively correlated with myocardial FAPI uptake, LV circumferential strain (r=0.668, P < 0.001;r=0.708, P < 0.001;r=0.705, P < 0.001), LV longitudinal strain (r=0.629, P=0.001;r=0.635, P=0.001; r=0.597, P=0.003), and RV longitudinal strain (r=0.575, P=0.004; r=0.792, P < 0.001;r=0.673, P < 0.001) were negatively correlated with myocardial FAPI uptake.  Conclusions  FAPI-related fibroblast activation is concurrent with CMR-related abnormal myocardial interstitial characteristics that leads to the decreased function of the myocardial movement. Patients with increased FAPI uptake present with increased ECV, decreased EF, and decreased strain with morphological abnormalities.

4.
Article in Chinese | WPRIM | ID: wpr-911472

ABSTRACT

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) featured by clonal proliferation of platelets, thrombosis and hemorrhage. Portal hypertension is a serious complication of ET associated with poor prognosis. We report a patient with ET complicated with acute upper gastrointestinal hemorrhage and intestinal perforation due to portal hypertension. She had an uneventful recovery after surgical and endoscopic treatment.

5.
Article in Chinese | WPRIM | ID: wpr-340078

ABSTRACT

<p><b>OBJECTIVE</b>To study the toxicological effects of benzo[a]pyrene(BaP) on mammalian animal's nerve tissue.</p><p><b>METHODS</b>50 Kunming mice were divided into 5 groups at random, the exposed groups(3 dose level groups), the vehicle control group and standard control group. Every group got 10 mice. The exposed groups were treated by intraperitoneal injection with BaP dissolved in vegetable oil at 7.8, 3.2 and 1.3 mg/kg respectively, 4 times/week, for 10 weeks, the vehicle control group were given vegetable oil and the standard control group were not given any treatment. All the mice were anesthetized with 0.02 mol/L pentobarbital and infused with 1.33 mol/L paraformaldehyde dissolved in PBS through heart after 10 weeks. Then the brain, spinal cord and sciatic nerve were removed. Slices of these tissues were made and morphological changes were observed by optical microscope and electron-microscope. Cell appoptosis was examined by TUNEL(TdT-mediated x-dUTP nick end labeling) method.</p><p><b>RESULTS</b>Morphological observations showed tissue injury in BaP exposed groups. There were focal necrosis areas found in the high-dose group. The cell apoptosis rates in 3.2 and 1.3 mg/kg groups were 90.02%-94.22% and 62.45%-77.54% respectively, significantly higher than those of vehicle control group and standard control group(4.60%-5.57%).</p><p><b>CONCLUSION</b>BaP is neurotoxic. It could damage the nerve tissue as well as induce DNA breaks and cell apoptosis.</p>


Subject(s)
Animals , Mice , Apoptosis , Benzo(a)pyrene , Toxicity , Brain , Pathology , Dose-Response Relationship, Drug , In Situ Nick-End Labeling , Sciatic Nerve , Pathology , Spinal Cord , Pathology
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