Coexistent loss of INI1 and BRG1 expression in a rhabdoid renal cell carcinoma (RCC): implications for a possible role of SWI/SNF complex in the pathogenesis of RCC

In this study, we analyzed the immunohistochemical and molecular profiles of an unusual RCC showed coexistent absence of INI1 and BRG1 expression, rhabdoid morphology, and poor prognosis. Histologically, the tumor had rhabdoid features, which were demonstrated by large round to polygonal cells with eccentric nuclei, prominent nucleoli, and eosinophilic cytoplasm varying from abundant to scanty. Immunohistochemically, the tumor were positive for BRM, PBRM1, ARID1A, CD10, CKpan, Vimentin, carbonic anhydrase IX (CA-IX), and P504S (AMACR) but negative for INI1, BRG1, HMB45, melan A, CK7, CD117, Ksp-cadherin, TFEB, TFE3, and Cathepsin K. We detected all three exons status of the VHL gene of the tumor and observed 1 somatic mutations in 1st exon. Chromosome 3p deletion, coupled with polysomy of chromosome 3 was also found. Based on these findings, it is further indicated that in some cases, rhabdoid RCC may arise from clear cell RCC. SWI/SNF chromatin remodeling complex may be an attractive candidate for being the “second hit” in RCCs and may play an important role during tumor progression. The role of SWI/SNF complex in rhabdoid RCC should be further studied on a larger number of cases.     

Evaluation of HistoCheck as a Predictor of Clinical Outcomes after Haploidentical Hematopoietic Stem Cell Transplantation

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is available for nearly all patients without matching HLA-related or -unrelated donors. There was not a valid evaluation system to predict the most proper donor. HistoCheck was based on the functional similarity of amino acids to estimate the allogenicity of HLA mismatches with a sequence similarity matching (SSM) score. We investigated whether HistoCheck could predict clinical outcomes in 500 patients with acute leukemia or myelodysplastic syndrome receiving haplo-HSCT. The total SSM score of the 5 loci (HLA-A, -B, -C, -DRB1, and -DQB1) had no association with clinical outcomes. HLA-C SSM score was significantly associated with transplant-related mortality (TRM) (hazard ratio [HR], .in691; 95% confidence interval [CI], .520 to .917; P?=?.011), disease-free survival (DFS) (HR, .714; 95% CI, .586 to .869; P?=?.001), and overall survival (OS) (HR, .711; 95% CI, .574 to .881; P?=?.002) by multivariate analysis. No significant associations were observed between other single-locus SSM score and clinical outcomes. In summary, our data demonstrate that a high HLA-C HistoCheck SSM score may lead to lower TRM and improved DFS and OS after haplo-HSCT and inclusion of HLA-C HistoCheck in donor selection criteria may need to be further confirmed in prospective studies.     

Dysfunctional Bone Marrow Mesenchymal Stem Cells in Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Poor graft function (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is characterized by defective hematopoiesis. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis, but little is known about the role of MSCs in the pathogenesis of PGF. In the current prospective case-control study, we evaluated whether the number and function of bone marrow (BM) MSCs in PGF patients differed from those in good graft function (GGF) patients. We found that BM MSCs from PGF patients expanded more slowly and appeared flattened and larger, exhibiting more apoptosis and senescence than MSCs from GGF patients. Furthermore, increased intracellular reactive oxygen species, p-p53, and p21 (but not p38) levels were detected in MSCs from PGF patients. Moreover, the ability of MSCs to sustain hematopoiesis was significantly reduced in PGF patients, as evaluated by cell number, apoptosis, and the colony-forming unit–plating efficiency of CD34⁺ cells. In summary, the biologic characteristics of PGF MSCs are different from those of GGF MSCs, and the in vitro hematopoiesis-supporting ability of PGF MSCs is significantly lower. Although requiring further validation, our study indicates that reduced and dysfunctional BM MSCs may contribute to deficient hematopoiesis in PGF patients. Therefore, improvement of BM MSCs may represent a promising therapeutic approach for PGF patients after allo-HSCT.     

The protective effects of Bacillus licheniformis preparation on gastrointestinal disorders and inflammation induced by radiotherapy in pediatric patients with central nervous system tumor

Purpose

we studied the effect of Bacillus licheniformis preparation (ZCS) on CNST (central nervous system tumor) patients undergoing the gastrointestinal symptoms and inflammation induced by radiotherapy.

Expression of CD62L on Donor CD4<Superscript>+</Superscript> T Cells in Allografts: Correlation with Graft-Versus-Host Disease after Unmanipulated Allogeneic Blood and Marrow Transplantation

Introduction  The aim of this study was to investigate the association of donor CD4⁺ T cells expressing CD62L with transplant outcomes. Materials and Methods  We report a prospective analysis of 31 patients who were treated with a Bu/Cy regimen, followed by unmanipulated blood and marrow transplantation. Results  Median number (range) of CD4⁺CD62L⁺, CD4⁺CD45RA⁺CD62L⁺, and CD4⁺CD45RO⁺CD62L⁺ cells infused were 0.31(0.05–1.10)×10⁸/kg, 0.22(0.03–0.95)× 10⁸/kg, and 0.17(0.01–0.81)×10⁸/kg, respectively. The incidence of grades II to IV aGVHD was 36%. In a multivariate analysis, infusion of >0.22 × 10⁸ CD4⁺CD45RA⁺CD62L⁺ cells infused/kg increased the risk of grades II to IV aGVHD (HR = 4.741, 95% CI = 1.037–21.662, P = 0.045). Thirteen of 31 patients experienced cGVHD, the risk of cGVHD was increased in patients receiving >0.45 × 10⁸ CD4⁺CD45RA⁺ cells infused/kg (HR = 4.614, 95% CI = 1.265–16.829, P = 0.021). Conclusion  Our results suggest that a high cell dose of CD4⁺CD45RA⁺CD62L⁺ cells increase the incidence of grades II–IV aGVHD. A high number of CD4⁺CD45RA⁺ cells infused were associated with increased risk of cGVHD in our transplant settings. Ying-Jun Chang: performed research, analysis and interpretation of data, and drafting of the article, and gave final approval of the version to be published; Xiang-Yu Zhao: performed research, analysis and interpretation of data, and drafting of the article and gave final approval of the version to be published; Ming-Rui Huo: performed research, analysis and interpretation of data, and drafting of the article and gave final approval of the version to be published; Xiao-Jun Huang: involved in conception and design, revising the article critically, and final approval of the version to be published.     

Therapeutic potential of chlorotoxin-like neurotoxin from the Chinese scorpion for human gliomas

Chlorotoxin, one of the key toxins in scorpion Leiurus quinquestriatus venom, has been shown to bind specifically to glioma cell surface as a specific chloride channel blocker. In this study, a purified, recombinant chlorotoxin-like peptide from the scorpion Buthus martensii Karsch (named rBmK CTa) was characterized by in vivo and in vitro studies. The results from cell proliferation assay with human glioma (SHG-44) cells showed that rBmK CTa inhibits the growth of glioma cells in a dose-dependent manner, with an IC₅₀ value of approximately 0.28 μM. Under the same conditions, the IC₅₀ value for normal astrocytes increased to 8 μM. This clearly indicated that rBmK CTa had specific toxicity against glioma cells but not astrocytes. Results from whole-cell patch-clamp recording showed that chloride current in SHG-44 was inhibited by rBmK CTa in a voltage-dependent manner and percent inhibitions for the blocking action of rBmK CTa (0.07 and 0.14 μM) on I_Cl was 17.64 ± 3.06% and 55.86 ± 2.83%, respectively. Histological analysis of rBmK CTa treated mice showed that brain, leg muscle and cardiac muscle were the target organs of this toxin. These results suggest that rBmK CTa may have potential therapeutic application in clinical treatment of human glioma. It represents an approach for developing a novel therapeutic agent.     

Utility of CD10 and RCCma in the diagnosis of metastatic conventional renal-cell adenocarcinoma by fine-needle aspiration biopsy

The cytologic diagnosis of primary conventional renal-cell adenocarcinoma (cRCC) is usually straightforward; however, metastatic cRCC must be distinguished from a variety of neoplasms with clear-cell features. CD10, a cell membrane-associated neutral endopeptidase, and renal-cell carcinoma marker (RCCma), an antibody against human proximal tubular brush border antigen, have recently been shown to be useful in the diagnosis of cRCC. We compared CD10 and RCCma in cell block material from fine-needle aspiration biopsies (FNABs) to assess their utility in the diagnosis of metastatic cRCC, in cytologic specimens. Seven primary and sixteen metastatic cRCCs were immunostained with CD10 and RCCma. The immunoreactivity results were compared with those of a variety of neoplasms originating from other sites such as the liver, lungs, breast, and the gastrointestinal tract. The sensitivity and specificity of CD10 for cRCC were 100% and 59%, respectively. The sensitivity and specificity of RCCma for cRCC were 35% and 100%, respectively. We conclude that CD10 has limited value in confirming the diagnosis of cRCC because of its low specificity. RCCma, when positive, is highly specific for cRCC, but its low sensitivity hinders its diagnostic usefulness.     

Modified Donor Lymphocyte Infusion after HLA-Mismatched/Haploidentical T Cell-replete Hematopoietic Stem Cell Transplantation for Prophylaxis of Relapse of Leukemia in Patients with Advanced Leukemia

We evaluated the safety and efficacy of donor lymphocyte infusion (DLI) with granulocyte colony-stimulating factor priming and short-term immunosuppressive agents for prophylaxis of relapse in patients with advanced leukemia after human leukocyte antigen (HLA)-mismatched T cell-replete hematopoietic stem cell transplantation (HCT). Twenty-nine patients received prophylactic DLI at a median 75 (33–120) days after HCT. Acute graft-vs-host disease (GVHD) grades 3–4 occurred in six patients, and all cases were controlled. Eleven patients were alive and relapse-free with a probability of leukemia-free survival (LFS) of 37.3 ± 9.6% at 3 years. Chronic GVHD was associated with a lower relapse rate and higher probability of LFS. Prophylactic-modified DLI is feasible in patients with advanced leukemia to prevent relapse after HLA-mismatched HCT. Xiao-Jun Huang: involved in conception and design, revising the article critically, and final approval of the version to be published; Dai-Hong Liu: performed research, analysis, and interpretation of data and drafting of the article and gave final approval of the version to be published; the other authors: performed research and gave final approval of the version to be published; the authors reported no potential conflicts of interest.