CircSEPT9 promotes breast cancer progression by regulating PTBP3 expression via sponging miR-625-5p.

BACKGROUND: Breast cancer (BC) is a common malignancy which threatens the health of women. Circular RNAs (circRNAs) are critical factors in multiple cancers, including BC. The aim of this experiment was to investigate the molecular mechanisms of circRNA Septin 9 (circSEPT9) in the progression of BC. METHODS: CircSEPT9, microRNA-625-5p (miR-625-5p) and polypyrimidine tract-binding protein 3 (PTBP3) levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was performed to detect the protein levels of PTBP3, E-cadherin and vimentin. Cell counting kit-8 assay (CCK8) and thymidine analog 5-ethynyl-2'-deoxyuridine (EDU) was utilized for proliferation examination. Flow cytometry was conducted to measure apoptosis. Transwell assay and wound healing assay to investigate the migration of BC cells. Glucose uptake and lactate production were determined by specific kits. Additionally, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized to verify the interaction. A murine xenograft model was established to investigate the function of circSEPT9 in BC in vivo. RESULTS: Overexpression of circSEPT9 was found in BC tissues and cells. Silencing circSEPT9 impeded BC cell proliferation, migration, epithelial-mesenchymal transition (EMT) and glycolytic metabolism but facilitated cell apoptosis in vitro. Meanwhile, circSEPT9 knockdown constrained tumor growth in vivo. MiR-625-5p was targeted by circSEPT9. The influence of silencing circSEPT9 on BC cell function was regained by miR-625-5p inhibitor. Furthermore, miR-625-5p regulated BC cell malignant phenotypes via downregulating PTBP3. CONCLUSION: circSEPT9 contributed to the malignant progression of BC by up-regulating PTBP3 via sponging miR-625-5p.

B-Cell Lymphoma Associated with COVID-19 Infection: A Case Report.

PURPOSE: Most common publications are related to COVID-19 diagnosis in hematological malignancy patients. However, here we report a case involving a patient diagnosed with B-cell lymphoma while undergoing treatment for COVID-19, including the changes in major clinical symptoms and medical examinations, then explain the probable causes of the case. CASE PRESENTATION: A 74-year-old woman with a previous history of oesophageal cancer was admitted to the hospital after having cough and sputum for 15 days. Despite the COVID-19 symptoms, this patient did not have a fever at the time of the onset. Results of routine blood tests were normal at first but then declined with persistent fever, and A whole-body C.T. examination ruled out the possibility of tumor-metastasis-related fever. This patient had no hepatosplenomegaly or regional lymphadenopathy, and there was no concrete evidence of haemophagocytic lymphohistiocytosis or lymphoma until bone marrow biopsy results confirmed the latter. CONCLUSION: We describe an uncommon case of COVID-19 who was finally diagnosed with B-cell lymphoma. An awareness of persistent fever and declined routine blood tests caused by hematological malignancies instead of COVID-19 itself can aid in providing appropriate guidelines for management and treatment.

Protective Effect and Possible Mechanisms of Astragaloside IV in Animal Models of Diabetic Nephropathy: A Preclinical Systematic Review and Meta-Analysis.

Astragaloside IV (AS-IV) has a variety of biological activities and is widely used to treat kidney diseases. We conducted a systematic review of 24 animal studies including 424 animals to evaluate the efficacy of AS-IV for diabetic nephropathy (DN); all current possible mechanisms were summarized. A search strategy was applied to eight databases from inception to June 2020. The CAMARADES 10-item quality checklist and Rev-Man 5.3 software were used to analyze the risks of bias of each study and data regarding outcome measures, respectively. The mean study quality score was 5.4 points (range 3-8 points). Meta-analyses data and comparisons between groups showed that AS-IV significantly slowed the progression of pathological signs in the kidney including glomeruli and tubules, increasing creatinine clearance rate, decreasing blood urea nitrogen, serum creatinine, 24-h urinary neutrophil gelatinase-associated lipocalin and N-acetyl-ß-D-glucosaminidase, 24-h urinary albumin, 24-h urinary microalbumin and HbA1c. There were no significant differences between experimental and control groups with respect to mortality or levels of alanine aminotransferase and aspartate aminotransferase. In terms of the possible mechanisms of treatment of DN, AS-IV acts through antifibrotic, antioxidant, and antiapoptotic mechanisms, thereby alleviating endoplasmic reticulum stress, inhibiting mitochondrial fission, and increasing autophagic activity. Taken together, our findings suggest that AS-IV is a multifaceted renoprotective candidate drug for DN.

Successful Treatment of Severe Heparin-induced Thrombocytopenia with Intravenous Immunoglobulin, Platelet Transfusion and Rivaroxaban: A Case Report.

Heparin-induced thrombocytopenia (HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin (IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.

Fasudil, a Rho-Kinase Inhibitor, Exerts Cardioprotective Function in Animal Models of Myocardial Ischemia/Reperfusion Injury: A Meta-Analysis and Review of Preclinical Evidence and Possible Mechanisms.

Fasudil, a Rho-kinase inhibitor, has shown outstanding therapeutic effects against cerebral vasospasm after subarachnoid hemorrhage (SAH) in humans. Studies show various biological effects of fasudil in the cardiovascular system. We conducted a preclinical systematic review to determine the efficacy and possible mechanisms of fasudil on animal models of myocardial ischemia/reperfusion (I/R) injury. Nineteen studies involving 400 animals were identified after searching 8 databases for articles published till June 2018. The methodological quality was assessed by the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) 10-item checklist. The data were analyzed using Rev-Man 5.3 software, and the score of study quality ranged from 3 to 6 points. Compared to the control group, fasudil treated animals showed reduced myocardial infarct size (P < 0.05), lower levels of cardiac enzymes (P < 0.05) and cardiac troponin T (P < 0.05), improved systolic and diastolic functions (P < 0.05), and increased degree of decline in the ST-segment (P < 0.05). The possible mechanisms of fasudil action against myocardial I/R injury are improvement in coronary vasodilation, inhibition of apoptosis and oxidative stress, relieving inflammation, and reduction in endoplasmic reticulum stress and metabolism. In conclusion, fasudil exerts a cardio-protective function through multiple signaling pathways in animal models of myocardial I/R injury.

Down-regulated miR-148b increases resistance to CHOP in diffuse large B-cell lymphoma cells by rescuing Ezrin.

BACKGROUND: Aberrant microRNA (miRNAs) have recently been proposed as important regulators in acquiring resistance to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to establish the role of miR-148b in the development of CHOP resistance in DLBCL. METHODS: The expression patterns of miR-148b, HDAC6, and Ezrin were detected in CHOP-resistant clinical specimens and a DLBCL cell line. miR-148b, HDAC6, and Ezrin in DLBCL cells were manipulated by cell transfection to explore the functional correlation between them. Cell viability was determined using a CCK-8 assay. RESULTS: We found that miR-148b levels were markedly reduced and that the protein expressions of HDAC6 and Ezrin were increased in DLBCL CHOP-resistant clinical specimens and the cell line CRL2631/CHOP. Indeed, HDAC6 decreased the acetylation of histones H3 and H4 in the miR-148b promoter to inhibit miR-148b expression in DLBCL. Moreover, down-regulated miR-148b encouraged CHOP resistance in CRL2631 cells and miR-148b sensitized CRL2631 cells. We further revealed that Ezrin was negatively regulated by miR-148b and that the knockdown of Ezrin significantly attenuated CHOP resistance in CRL2631 cells induced by miR-148b silencing. MiR-148b also sensitized CRL2631/CHOP cell xenografts to CHOP in mice. CONCLUSION: Our data indicated that the high level of HDAC6 inhibited miR-148b via maintaining the low acetylation of histones H3 and H4 in the miR-148b promoter, thus rescuing Ezrin expression and promoting CHOP resistance in DLBCL.

Effects of preemptive interferon-α monotherapy in acute leukemia patients with relapse tendency after allogeneic hematopoietic stem cell transplantation: a case-control study.

Interferon-α (IFN-α) inhibits tumor growth and mimics graft-versus-leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the current case-control study, we compared treatment responses in acute leukemia patients with relapse tendency post-allo-HSCT receiving preemptive IFN-α after withdrawal of immunosuppressants (n = 31) vs. receiving no IFN-α (n = 67). In the IFN-α group, 25 patients responded to the treatment without progressing to hematological relapse. In the non-IFN-α group, only 22 patients responded to the treatment. The response rate differed significantly (80.6 vs. 32.8%, P < 0.001). The 2-year cumulative incidence of relapse was 31.6 and 61.2% in the IFN-α and the non-IFN groups, respectively (P = 0.006). The 2-year leukemia-free survival and overall survival rate was 57.4 vs. 28.4% (P < 0.001) and 67.6 vs. 32.9% (P = 0.001), respectively. Among the 31 patients in the IFN-α group, 18 patients (58.1%) developed graft-versus-host disease (GVHD): 6 acute and 12 limited chronic GVHD. Patients who developed GVHD had higher treatment response rate than patients without GVHD (88.9 vs. 53.8%, P = 0.022). In conclusion, preemptive IFN-α therapy is a safe and effective treatment to prevent disease progression in high-risk patients with relapse tendency post-allo-HSCT.

Bufalin Enhances the Cytotoxity of Human Multiple Myeloma Cells H929 to AKT Inhibitor MK2206: The Role of Protein AKT Phosphorylation.

This study was purposed to investigate bufalin combined with AKT inhibitor MK2206 on growth inhibition and apoptosis of multiple myeloma cell line H929. CCK-8 assay and Annexin/PI staining were used to access the effects of bufalin and MK2206 in single or in combination, on inhibition of proliferation and induction of apoptosis in H929 cells. The apoptotic cells markedly increased after treated with nM bufalin and µM MK2206, including caspase3 and PARP1 proteins activated. The difference was statistically significant (P < 0.05) when compared with these drugs in single use. The apoptosis associated proteins and AKT/p-AKT proteins were determined by Western blots. We confirmed that AKT performed contradictory results in H929 with the two agents, and concluded p-AKT was vital in the synergy. The underlying mechanisms warrant further investigation.

LncRNA PDIA3P interacts with c-Myc to regulate cell proliferation via induction of pentose phosphate pathway in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic malignancy, is an incurable disease characterized by the accumulation of malignant plasma cells within the bone marrow. Though great progresses have been made in understanding the mechanisms of MM, metabolic plasticity and drug resistance remain largely unknown. In this study, we found lncRNA Protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) is highly expressed in MM and is associated with the survival rate of MM patients. PDIA3P regulates MM growth and drug resistance through Glucose 6-phosphate dehydrogenase (G6PD) and the pentose phosphate pathway (PPP). Mechanistically, we revealed that PDIA3P interacts with c-Myc to enhance its transactivation activity and binding to G6PD promoter, stimulating G6PD expression and PPP flux. Our study identified PDIA3P as a novel c-Myc interacting lncRNA and elucidated crucial roles for PDIA3P in metabolic regulation of MM, providing a potential therapeutic target for MM patients.

Co-existence of isodicentric Ph chromosomes and the three-way Ph chromosome variant t(3;9;22)(p21;q34;q11) in a rare case of chronic myeloid leukemia.

More than 90% of patients with chronic myeloid leukemia (CML) have the chromosomal translocation t(9;22)(q34;q11), while 5-8% of patients have complex variant translocations that have previously been thought not to affect the efficacy of imatinib therapy. The present study reports a patient with CML in B-lymphoid blast crisis who had a rare three-way Philadelphia (Ph) variant t(3;9;22)(p21;q34;q11), in addition to isodicentric Ph chromosomes. The patient was initially treated with imatinib for >2 months with a very poor response. When no T315I or F317L mutations in the ABL proto-oncogene 1 region were detected, the patient received dasatinib treatment (140 mg daily) and achieved a complete hematologic response. Following allo-hematopoietic stem cell transplantation, the patient displayed clinical, hematological and cytogenetic remission, with complete molecular response and complete donor chimerism, and stopped taking dasatinib at the last follow-up. The present data suggest that BCR-ABL gene amplification may be associated with imatinib resistance, which can be overcome with dasatinib. The present analysis suggests an alternative therapy strategy for CML involving isodicentric Ph chromosomes.

Quantification and pharmacokinetics of alpinetin in rat plasma by UHPLC-MS/MS using protein precipitation coupled with dilution approach to eliminate matrix effects.

Alpinetin, a bioactive flavonoid, has attracted great attention due to its diverse therapeutic effects, namely anti-oxidant, anti-tumor and anti-inflammatory effects with low systemic toxicity. Various determination methods have been developed in quality control and plant chemistry areas. However, quantification and pharmacokinetics of alpinetin in biological matrix have not been studied. In the present research, a sensitive, efficient and reliable ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of alpinetin in rat plasma was developed and validated. Plasma samples were processed with protein precipitation (PP) followed by a 5-fold acetonitrile/water (50:50, v/v) dilution to significantly decrease matrix effect which exited in one step PP method. Determination of alpinetin was conducted using positive electrospray ionization tandem mass spectrometry in multiple reaction monitoring mode. Results demonstrated that the method was precise (3.3%-12.3%), accurate (-5.8% to 10.8%) and linear in the range of 1-1000 ng/mL. The new developed method was subsequently applied to a pharmacokinetic research of alpinetin following oral and intravenous dosing to healthy Sprague-Dawley rats. Alpinetin was demonstrated rapid absorption after oral administration with an absolute bioavailability of ∼15.1% and extensive distribution after dosing.

Increased histone deacetylase 6 expression serves as a favorable prognostic factor for diffuse large B-cell lymphoma.

OBJECTIVE: This study aims to investigate ectopic expression of histone deacetylase 6 (HDAC6) in diffuse large B-cell lymphoma (DLBCL). METHODS: This study analyzed patients with DLBCL (n=132) and reactive lymph node hyperplasia (n=32) diagnosed in our hospital from December 2007 to May 2016. Correlation between HDAC6 expression and clinical pathologic features was analyzed by χ2 test. The significant differences between the 5-year overall survival (OS) or progression-free survival (PFS) and high HDAC6 expression as well as DLBCL clinic-pathological features including age, International Prognostic Index (IPI) score, Eastern Cooperative Oncology Group score, lactate dehydrogenase (LDH), and germinal center B-cell-like were assessed by univariate and multivariate analyses. RESULTS: HDAC6 high-expression percentage in DLBCL was significantly higher than that in the control group. The proportion of IPI score of 0-2, 5-year OS, and PFS in the high-expression group, which had lower percentage of patients with increased LDH and ß2-microglobulin, were significantly higher than those in the low-expression group. Moreover, HDAC6 mRNA expression in HDAC6 protein low expression was markedly lower than that in protein high expression. The multivariate analysis demonstrated that HDAC6 high expression was an independent prognostic factor for patients with DLBCL. CONCLUSION: HDAC6 high expression might be a prognostic factor for DLBCL.

[Analysis of isodicentric Ph chromosomes in chronic myeloid leukemia blast crisis].

OBJECTIVE: To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC). METHODS: Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH). Variations of acute lymphoblastic leukemia-related genes including CDKN2A/AB and PAX5 were detected by multiplex ligation-dependent probe amplication (MLPA). RESULTS: Deletions and duplications on derivative chromosome 9 detected by FISH were confirmed by SNP array analysis. The distances between the BCR/ABL fusion signals on the idic(Ph) chromosomes in the two patients have differed greatly. The idic(Ph) in the second patient was supposed to be formed by two Ph chromosomes joined at their q terminals, where as the idic(Ph) in the first patient have been shown to be fused at the satellite regions of their p arms. CONCLUSION: The idic(Ph) chromosomes presented in CML-BLC may predict resistance to Imatinib and response to Dasatinib.

A Meta-Analysis for Effects of Elevated Pre-Transplantation Serum Ferritin on the Outcomes in Patients Undergoing Hematopoietic Stem Cell Transplantation.

The level of pre-transplantation serum ferritin (SF) is one of the factors related to outcome for patients undergoing allogeneic hematopoietic stem cell transplantation. We searched PubMed and Cochrane Library databases from 2000 to 2014. The primary efficacy outcome was overall survival rate and non-relapse mortality. Twenty clinical trials were selected from 189 studies identified. The combined hazard ratio indicated a significantly lower overall survival rate and a higher non-relapse mortality rate in patients with elevated SF before transplantation. This indicates that elevated pre-transplantation SF affects outcome in patients undergoing allogeneic hematopoietic stem cell transplantation.

Role of caspase-10 in the death of acute leukemia cells.

Autophagy can protect cells from stress, but can also induce cancer cell death. Caspase-10 is now considered to be a factor that is associated with autophagy in cancer. The present study therefore investigated whether caspase-10 affects autophagy in acute leukemia cells. The rates of survival vs. apoptosis in acute leukemia HL-60 and Jurkat cells treated with drugs were tested using cell viability assays and flow cytometry, and the levels of caspase-3 and -10 were tested by western blotting. In HL-60 cells that were treated with chemotherapy drugs combined with a caspase-10 inhibitor, the rate of survival decreased significantly compared with HL-60 cells treated with chemotherapy drugs alone. In contrast, the rate of survival of Jurkat cells treated with chemotherapy drugs combined with the caspase-10 inhibitor increased significantly compared with Jurkat cells treated with chemotherapy drugs alone. The results of the flow cytometry and western blotting showed that the changes in the survival rate may be caused by a change in the amount of apoptosis occurring in the Jurkat cells treated with chemotherapy drugs combined with the caspase-10 inhibitor. However, in HL-60 cells undergoing this combination treatment, the change in the survival rate was not caused by a change in the rate of apoptosis. When HL-60 cells were treated with the chemotherapy drugs combined with the caspase-10 inhibitor and the autophagy inhibitor 3-methyl adenine, the survival rate increased, whereas the rate of apoptosis did not change. These results show that caspase-10 may be associated with autophagy in acute myeloid leukemia cells, but not in acute lymphatic leukemia cells.

RhIL-11 treatment normalized Th1/Th2 and T-bet/GATA-3 imbalance in in human immune thrombocytopenic purpura (ITP).

Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by reduction in platelet counts. T helper 1 (Th1) cells polarization with an increased shift of Th1/Th2 ratio has been reported in ITP. This shift is associated with transcription factor T-box expressed in T cells (T-bet) upregulation and GATA-binding protein 3 (GATA-3) downregulation, leading to an increased T-bet/GATA-3 ratio. Our previous in vitro study showed that recombinant human interleukin-11 (rhIL-11) could normalize Th1/Th2 imbalance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients, which co-occurred with T-bet/GATA-3 ratio restoration. In this report, we investigated whether rhIL-11 had therapeutic effect in clinical ITP patients and whether rhIL-11 treatment could normalize Th1/Th2 and T-bet/GATA-3 levels in vivo. We found rhIL-11 treatment had a response rate of 67.7% and significantly decreased Th1 and T-bet levels but increased Th2 and GATA-3 levels in ITP patients who showed good response, normalizing Th1/Th2 and T-bet/GATA-3 ratios similar to that in healthy controls. Thus our study suggested rhIL-11 was effective with tolerable adverse effects in ITP. The treatment strategy warrants further clinical investigation.

CD1d levels in peripheral blood of patients with acute myeloid leukemia and acute lymphoblastic leukemia.

The antitumor effect of natural killer T cells has been reported in several studies analyzing the expression of CD1d on antigen-presenting cells (APCs). Therefore, the present study questioned whether APCs may be abnormal in the peripheral blood (PB) of acute leukemia (AL) patients, particularly the levels of CD1d. To improve the understanding of the role of CD1d on APCs, the levels of CD1d on monocytes were analyzed in healthy controls, AL patients and AL patients with complete remission (CR). In addition, the correlation between the number of CD3+CD56+ T lymphocytes and levels of CD1d on monocytes was analyzed. Flow cytometry was used to determine the levels of CD1d on monocytes and lymphocytes. A significant decrease was observed in the levels of CD1d on monocytes in the PB of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients compared with the healthy controls. Simultaneously, significantly different levels of CD1d on monocytes were identified between the CR-AML and the CR-ALL patients; the levels of CD1d on monocytes remained low in the CR-AML patients, while the levels of CD1d on monocytes recovered in the CR-ALL patients. A significantly negative correlation was observed between the number of CD3+CD56+ T lymphocytes and the levels of CD1d on monocytes in AL patients. However, a significantly positive correlation was identified between the cytotoxicity of the CD3+CD56+ T lymphocytes and the levels of CD1d on monocytes. These results suggested that the significantly low levels of CD1d on monocytes may contribute to AML and ALL progression. In addition, a significant correlation was observed between the levels of CD1d on monocytes and the number/cytotoxicity of CD3+CD56+ T lymphocytes in AML and ALL patients.

Downregulation of T-bet/GATA-3 ratio induced by IL-11 treatment is responsible for Th1/Th2 balance restoration in human immune thrombocytopenic purpura (ITP).

Abnormal cellular immunity induced by deranged Th1/Th2 profile has been revealed to play a critical role in the pathogenesis of immune thrombocytopenic purpura (ITP). Correction of the shifted Th1/Th2 balance represents a potential therapeutic approach to treat ITP. Here, we investigated the effects of IL-11 on the restoration of Th1/Th2 balance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients. As shown here, we observed a higher ratio of T-bet/GATA-3 gene expression by quantitative real-time PCR in the PBMCs from ITP patients, consistent with the presence of an abnormally high Th1/Th2 ratio. Remarkably, upon IL-11 treatment, a reversal of T-bet/GATA-3 ratio in ITP was achieved and was shown to be responsible for the restoration of Th1/Th2 balance, with IL-11 at 100 ng/ml demonstrating the highest efficiency. T-bet and GATA-3 are the two transcriptional factors that have been indicated to be the master regulators for Th1 and Th2 lineage commitment, respectively. In the presence of 100 ng/ml IL-11, GATA-3 transcript abundance rose up to ~85-fold of that measured in untreated cells, whereas T-bet transcripts were lowered merely to ~41%, suggesting that GATA-3 was the major contributor for the reversal of T-bet/GATA-3 ratio. Thus, our findings may very well encourage the development of novel medicines that specifically target and correct the T-bet/GATA-3 imbalance identified in ITP.

Numbers and cytotoxicities of CD3+CD56+ T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia.

Recent reports have highlighted the role of cellular immunity in anti-tumor defenses. T lymphocytes are known to play important part in anti-cancer immunity. The number and function of T lymphocytes are altered in chronic leukemia patients. CD3(+)CD56(+) T lymphocytes have also been found to be abnormal in cancer patients. We therefore investigated changes in the number and cytotoxicity of CD3(+)CD56(+) T lymphocytes in the peripheral blood of acute leukemia (AL) patients (excluding acute promyelocytic leukemia), to improve our understanding of the role of this T lymphocyte subset. We analyzed CD3(+)CD56(+) T lymphocyte numbers and cytotoxicities in healthy controls, AL patients, and AL patients with complete remission. Lymphocyte counts were performed in peripheral blood and flow cytometry was used to determine cell numbers and cytotoxicities. The absolute number of CD3(+)CD56(+) T lymphocytes was increased in AL patients (including acute myeloid [AML] and acute lymphocytic leukemia [ALL]) compared with healthy controls (P<0.05), but their functioning was significantly reduced (P<0.05). The number of CD3(+)CD56(+) T lymphocytes in AML and ALL patients who achieved remission following chemotherapy was close to healthy controls (P>0.05), but their functioning was still significantly reduced (P<0.05). In addition, the number of CD3(+)CD56(+) T lymphocytes increased significantly in AML patients with increased peripheral blood white blood cell (WBC) counts, and in ALL patients without increased WBCs. These results suggest that cellular immunity may respond to AML and ALL, but that lymphocyte cytotoxicity remains impaired. Dysfunction of CD3(+)CD56(+) T lymphocytes in AML and ALL patients may contribute to the failure of the host immune response against leukemic blasts.

Treatment of fungal myositis with intra-lesional and intravenous itraconazole: a case report.

INTRODUCTION: Fungal myositis is very uncommon, even in patients who are immunocompromised. Because of its rarity and a lack of clinical experience, no consensus has been reached about the best means of treating fungal myositis. To the best of our knowledge this is the first description of the treatment of fungal myositis with simultaneous intravenous and intra-lesional itraconazole. CASE PRESENTATION: A 35-year-old Chinese woman with acute myelomonocytic leukemia developed Candida krusei fungemia and fungal myositis in the right biceps brachii after chemotherapy. A course of intravenous itraconazole and subsequently intravenous voriconazole was initiated and her blood cultures became sterile; however, our patient remained febrile and the myositis did not resolve. Intravenous itraconazole was restarted simultaneously with low-dose intra-lesional itraconazole. The pyrexia settled after 48 hours and within 10 days the lesion could be seen to be resolving. After the course of intravenous and intra-lesional anti-fungals was complete, oral itraconazole was administered as maintenance therapy. CONCLUSIONS: To the best of our knowledge this is the first case in which fungal myositis was successfully treated with intravenous and intra-lesional itraconazole in a patient with acute myelomonocytic leukemia. The efficacy and safety of locally-administered itraconazole to treat intractable soft tissue infections requires further evaluation.