Infusion of leukocytes from HLA haplo-identical familial donors as an adjuvant in the HLH-2004 protocol to treat the virus-associated adult hemophagocytic lymphohistiocytosis: a retrospective study of 26 patients

Abstract

Adult hemophagocytic lymphohistiocytosis (HLH) is a fatal disease with poor survival and a limited role of drug therapies. To help to recognize virus and enhance survival, we infused leukocytes derived from human leukocyte antigen (HLA) haplo-identical familial donors to patients. We retrospectively investigated 26 adult virus-associated hemophagocytic syndrome (VAHS) patients’ medical records from 2006–2017. Eleven of the 26 patients accepted relatives’ derived leukocytes infusions in addition to drug therapies recommended in the HLH-2004 protocol. The leukocyte doses ranged from 0.75 to 3.30×10⁸ per kilogram of body weight. The other 15 patients accepted immunosuppressive and supportive therapies referred to in the HLH-2004 protocol. We compared the treatment outcomes of the two groups of patients. Patients in the cell infusion group had a lower viral load (P = 0.023) and better laboratory results and prolonged overall survival (60.44 vs. 20.18 weeks, P = 0.047). A factor that might relate to overall survival is platelet count (P = 0.032), except for the leukocyte infusions (P = 0.012). For patients without acceptable donors, infusions of leukocytes from HLA haplo-identical familial donors could be a feasible treatment to prolong overall survival as an adjuvant to drug therapies.

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Is it possible to improve prognostic value of NCCN-IPI in patients with diffuse large B cell lymphoma? The prognostic significance of comorbidities

Abstract

The prognostic value of the International Prognostic Index (IPI) has been re-evaluated in the rituximab-treated diffuse large B cell lymphoma (DLBCL) patients. Accordingly, National Comprehensive Cancer Network-IPI (NCCN-IPI) has been introduced to estimate prognosis of DLBCL patients. However, comorbidities that frequently affect elderly DLBCL patients were not analyzed. The aim of this study was to evaluate the prognostic significance of comorbidities using Charlson Comorbidity Index (CCI) in 962 DLBCL patients. According to CCI, majority of patients (73.6%) did not have any comorbidity, while high CCI (≥ 2) was observed in 71/962 (7.4%) patients, and in 55/426 (12.9%) of the elderly patients aged ≥ 60 years. When the CCI was analyzed in a multivariate model along with the NCCN-IPI parameters, it stood out as a threefold independent risk factor of a lethal outcome. Also, we have developed a novel comorbidity-NCCN-IPI (cNCCN-IPI) by adding additional 3 points if the patient had a CCI ≥ 2. Four risk groups emerged with the following patient distribution in low, low-intermediate, high-intermediate, and high group: 3.4, 34.3, 49.4, and 12.5%, respectively. The prognostic value of the new cNCCN-IPI was 2.1% improved compared to that of the IPI, and 1.3% improved compared to that of the NCCN-IPI (p < 0.05). This difference was more pronounced in elderly patients, in whom the cNCCN-IPI showed a 5.1% better discriminative power compared to that of the IPI, and 3.6% better compared to the NCCN-IPI. The NCCN-IPI enhanced by the CCI and combined with redistributed risk groups is better for differentiating risk categories in unselected DLBCL patients, especially in the elderly.

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The tubby-like proteins kingdom in animals and plants

Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Meng Wang, Zongchang Xu, Yingzhen Kong
Each gene of the tubby-like family is characterized by a signature of C-terminal tubby domain. The wide spread of this family in plants and animals implies they have an important function in various organisms. Even though the tubby-like genes are suggested to be putative transcription factors (TFs), how they execute the function as TFs is not yet clear. The biological functions of most animal tubby-like genes have been well studied, especially for vertebrate TUB, TULP1 and TULP3, but not with TULP2 and TULP4. Plants possess more tubby-like genes than animals, but their functions are still elusive except the idea that they are involved in stress responses with indistinct mechanisms. Here we reviewed the current knowledge of the versatile functions and roles of the tubby-like family members in plants and animals.



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The unrecognized role of tumor suppressor genes in atrial fibrillation

Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Liang Mao, Wenjun Huang, Ping Zou, Xitong Dang, Xiaorong Zeng
Epidemiogical evidence has shown that the incidence of atrial fibrillation in tumor patients is higher than non-tumor patients and general population. The potential risk factors predisposing tumor patients to atrial fibrillation include advanced age, comorbidities, direct anatomic local occupying effect of tumors in the heart or adjacent organs, paraneoplastic manifestations of some tumors, tumor-induced dys-regulation of metabolism, radio-, bio- and chemo-therapeutics, disturbance of autonomous nerve system because of physical pain and psychological sufferings, chronic inflammation typical of most tumors, and surgical interventions among others. However, whether tumor suppressor genes commonly mutated or dys-regulated in tumor play any roles in the pathogenesis of atrial fibrillation remain largely unexplored. Tumor suppressor genes or genes possessing tumor suppressing function have been reported to be constitutively expressed in quiescent heart, and mutations, small nucleotide polymorphisms, or disturbed expression of tumor suppressor genes has been implicated in the pathogenesis of atrial fibrillation. Here, we provide a state-of-the-art overview of the unrecognized roles of tumor suppressor genes in the pathogenesis of atrial fibrillation, focusing mainly on the two well-characterized tumor suppressor genes, zinc finger homeobox protein-3 and esophageal cancer related gene-4.



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Identification and analysis of up-regulated proteins in Lissorhoptrus oryzophilus adults for rapid cold hardening

Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Shuang Yang, Xinxin Zhang, Jinxin Wang, Shang Wang, Yu Pan, Juhong Zhang, Jinghui Xi
Rapid cold hardening (RCH) is a central physiological adaptation in which brief chilling significantly enhances the cold tolerance ability of insects. However, the mechanism of rapid cold stress response remains unknown for rice water weevils. To elucidate the mechanism, a comparative proteomic analysis was applied with two-dimensional gel electrophoresis (2-DE) between RCH and control treatment samples. A total of 21 protein spots were found to be up-regulated in rice water weevil adults for the RCH condition. As an initial work, 16 of these proteins were identified using MALDI TOF/TOF MS. In addition, the expression patterns of 9 proteins (including 2 HSPs that were not identified in the 2-DE experiment) were confirmed by qPCR analysis. Using the geneMANIA app in cytoscape, we constructed a protein-protein interaction network analysis of these up-regulated proteins. Gene ontology (GO) function annotation shows that a “response to heat process,” including 6 HSPs, was related to the identified proteins. These up-regulated, RCH responsive proteins could possibly serve as potential biomarkers to study the molecular mechanisms of the L. oryzophilus response to cold stress.



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The role of TRPV4 in fibrosis

Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Lei Zhan, Jun Li
The transient receptor potential vanilloid 4 (TRPV4) is a highly Ca²⁺-permeable non-selective cation channel in TRPV family. Accumulating evidence hints that TRPV4 play a significant role in a wide diversity of pathologic changes. Fibrosis is a kind of chronic disease which was characterized by the formation of excessive accumulation of extracellular matrix (ECM) components in tissues and organs. In recent years, a growing body of studies showed that TRPV4 acted as a crucial regulator in the progression of fibrosis including myocardial fibrosis, cystic fibrosis, pulmonary fibrosis, hepatic fibrosis and pancreatic fibrosis, suggesting TRPV4 may be a potential therapeutic vehicle in fibrotic diseases. However, the mechanisms by which TRPV4 regulates fibrosis are still undefined. In this review, firstly, we intend to sum up the collective knowledge of TRPV4. Then we provided the latent mechanism between TRPV4 and fibrosis. We also elaborated the distinct signaling pathways focus on TRPV4 with fibrosis. Finally, we discussed its potential as a novel therapeutic target for fibrosis.



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Geometric and dosimetric accuracy of dynamic tumor tracking during volumetric-modulated arc therapy using a gimbal mounted linac

The aim was to examine the feasibility of a dynamic tumor-tracking volumetric modulated arc therapy (DTT-VMAT) technique using a gimbal-mounted linac and assess its positional, mechanical and dosimetric accuracy.

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