A first-in-human phase I trial of daily oral zelenirstat, a N-myristoyltransferase inhibitor, in patients with advanced solid tumors and relapsed/refractory B-cell lymphomas.

Myristoylation, the N-terminal addition of the fatty acid myristate to proteins, regulates membrane-bound signal transduction pathways important in cancer cell biology. This modification is catalyzed by two N-myristoyltransferases, NMT1 and NMT2. Zelenirstat is a first-in-class potent oral small molecule inhibitor of both NMT1 and NMT2 proteins. Patients with advanced solid tumors and relapsed/refractory (R/R) B-cell lymphomas were enrolled in an open label, phase I dose escalation trial of oral daily zelenirstat, administered in 28-day cycles until progression or unacceptable toxicity. The endpoints were to evaluate dose-limiting toxicities (DLT) to establish a maximum tolerated dose (MTD), pharmacokinetic parameters, and anticancer activity. Twenty-nine patients were enrolled (25 advanced solid tumor; 4 R/R B-cell lymphoma) and 24 were DLT-evaluable. Dosing ranged from 20 mg once daily (OD) to 210 mg OD without DLT, but gastrointestinal DLTS were seen in the 280 mg cohort. MTD and recommended phase 2 dose were 210 mg OD. Common adverse events were predominantly Gr ≤ 2 nausea, vomiting, diarrhea, and fatigue. Plasma concentrations peaked at 2 h with terminal half-lives averaging 10 h. Steady state was achieved by day 15, and higher doses achieved trough concentrations predicted to be therapeutic. Stable disease as best response was seen in eight (28%) patients. Progression-free survival and overall survival were significantly better in patients receiving 210 mg OD compared to those receiving lower doses. Zelenirstat is well-tolerated, achieves plasma exposures expected for efficacy, and shows early signs of anticancer activity. Further clinical development of zelenirstat is warranted.

New advances in diagnosis and treatment of primary breast malignant lymphoma / 国际外科学杂志

Breast malignant lymphoma refers to occur in the breast malignant tumor of the lymphoid tissue.Breast malignant lymphoma which belongs to outside of lymph tissue malignant tumor can be divided into two categories:one category is the secondary breast lymphoma (SBL),another kind is the primary malignant lymphoma of the breast (PBL).Because the rate of PBL was low and the difficulty of preoperative diagnosis,illness development is rapid and high malignant degree,we should improve the attention of clinicians.Based on the discussion of primary breast lymphoma pathological changes,histological types,clinical manifestations,this article focuses on the progress of diagnosis and treatment of the PBL.

MRI manifestations of primary muscle non-Hodgkin lymphoma / 中华放射学杂志

Objective To explore and evaluate MRI in diagnosing primary muscle non-Hodgkin lymphoma. Methods Six surgically confirmed primary muscle non-Hod#in lymphoma underwent MR examination including T_1WI, T_2WI and T_1 WI enhanced studies. The acquired images date was reviewed and analysed retrospectively in comparison with surgical and pathological results. Results The locations of 6 cases were cervical part (2), upper extremity (1), lower extremity (3), respectively. All cases involved of more than one anatomical compartment with poorly defined solid masses in 5 cases and well defined in 1 cases, 5 extended to subcutaneous fat and 3 extended along the neurovascular bundle. The mean tumor diameter was 13.9 cm, ranging from 7.3 to 22.5 cm. One was well demarcated and 5 were ill-defined. On T_1 WI, 2 were slighdy high signal intensity and 4 were slighdy low signal intensity. On T_2 WI, 2 were slightly high signal intensity, 3 were intermediate signal intensity and 1 was high signal intensity. Five were inhomogeneous and 1 was homogeneous. The intrinsic structure such as muscle fiber, tendo, spatium intermusculare were detected on 5 cases. Of the 5 dynamic contrast-enhanced cases, it showed moderate enhamcement during arterial phase, 2 were homogeneous and 3 were inhomogeneous. And it showed progressive enhancement during interstitial phase, 3 were homogeneous and 2 were inhomogeneous. Conclusions Primary muscle lymphoma always originated deep to the fascia showing subcutaneous extension and multiple compartment invasion. Typically form poorly defined solid masses with slightly high in signal intensity on MR T_2WI and middle degree dynamic delayed contrasted-enhanced in which intrinsic anatomic structure such as muscle fiber, tendo, spatium intermusculare and so on can be discerned, almost all cases involve more than one muscle compartment and some of tumor extend along the neurovascular bundle.

The classifications of the thymoma and their pathologic diagnosis / 医学研究生学报

The classifications of the thymoma and their pathologic diagnosis is closely related to the clinical treatment of the disease. Similarly, it is a focal on the clinicopathologic study today. In this paper,the classification of the thymoma and their developing process in the histopathological changes was extensively discussed, and various type of the histopatholgic characteristic of the tumor was compared. It was suggested the new edition of the thymoma classifications of WHO should be operated in practical work. Additionally, the B1 type thymom, the thymic lymphoma and the histopathological changes of thymus in myasthenia gravis patients were described respectively, and it was also considered that the new edition of the thymoma classifications of WHO had some incomplete aspects in the pathological diagnosis.

Immunophenotype character of malignant lymphoma with bone marrow involvement / 中国癌症杂志

Purpose:To analyze the immunophenotype character of malignant lymphoma with bone marrow involvement by means of Flow Cytometry (CD45/SSC gate).Methods:Bone marrow of malignant lymphoma patients was detected by Flow Cytometer(CD45/SSC gate),bone marrow smear was simultaneously performed as control.Results:(1) Bone marrow of 34 malignant lymphoma patients was examined by Flow Cytometry.23 cases were detected to have bone marrow involvement.(2) Among these 23 cases,19 cases were non-Hodgkin's lymphoma(NHL),4 cases were Hodgkin's lymphoma(HL).The highest frequency antigen marker of B cell NHL was CD19 and CD20,T cell NHL was CD7,and HL was CD9.Conclusions:(1)Flow Cytometry(CD45/SSC gate) is a feasible and effective method to detect patients with bone marrow involvement.(2) The antigen marker of B cell NHL is CD19 and CD20,T cell NHL is CD7 and HL is CD9.