Clinical Characteristics and Prognosis of Patients with Hematological Malignancies Superimposed with Solid Tumors / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and prognosis of hematological malignancies superimposed patients with solid tumors.@*METHODS@#The clinical data of 30 patients with more than two kinds of malignancy (the second is hematological malignancy) from October 2011 to October 2020 in Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University were collected and analyzed retrospectively. The overall survival time was used as the prognostic evaluation standard, and the survival of patients were analyzed by KaplanMeier method. Logrank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 30 patients.@*RESULTS@#Among 30 cases, 20 were male, 10 were female, the median age of onset of the second tumor was 70 years old. The common types of the secondary hematological malignancies to solid tumors are myelodysplastic syndrome, acute myeloid leukemia, multiple myeloma. Univariate analysis showed that patients' gender, age, type of solid tumors, the onset of interval between two kinds of tumor, chromosome karyotype were not related to do with the patients' overall survival time. Type of hematologic disease, ECOG score were associated with patients' overall survival time, and the multivariate analysis showed that the type of hematologic disease and ECOG score were independent risk factors for patients with poor prognosis.@*CONCLUSION@#Patients superimposed with solid tumors complicated with myelodysplastic syndrome or acute leukemia and ECOG score ≥3 have poor prognosis and shorter overall survival time, which are independent risk factors influencing the prognosis. Bone marrow injury, immune dysfunction and genetic susceptibility after chemoradiotherapy may be the main causes of these diseases.

Estradiol inhibits differentiation of mouse macrophage into a pro-inflammatory phenotype by upregulating the IRE1α-XBP1 signaling axis / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which estradiol modulates the immunophenotype of macrophages through the endoplasmic reticulum stress pathway.@*METHODS@#Peritoneal macrophages isolated from C57 mice were cultured in the presence of 60 ng/mL interferon-γ (IFN-γ) followed by treatment with estradiol (1.0 nmol/L) alone, estradiol with estrogen receptor antagonist (Acolbifene, 4 nmol/L), estradiol with IRE1α inhibitor (4 μ 8 C), or estradiol with IRE1α agonist. After the treatments, the expression levels of MHC-Ⅱ, iNOS and endoplasmic reticulum stress marker proteins IRE1α, eIF2α and ATF6 in the macrophages were detected with Western blotting, and the mRNA levels of TGF-β, IL-6, IL-10 and TNF-α were detected with RT-PCR.@*RESULTS@#Estrogen treatment of the macrophages significantly decreased the expressions of M1-related proteins MHC-Ⅱ (P=0.021) and iNOS (P < 0.001) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.004), increased the mRNA expression of TGF-β (P=0.002) and IL-10 (P=0.008), and up-regulated the protein expressions of IRE1α (P < 0.001) and its downstream transcription factor XBP-1 (P < 0.001). Addition of the estrogen inhibitor obviously blocked the effect of estrogen. Compared with estrogen treatment alone, combined treatment of the macrophages with estrogen and the IRE1α inhibitor 4 μ 8 C significantly up-regulated the protein expressions of MHC-Ⅱ (P=0.002) and iNOS (P=0.003) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.024), and obviously down-regulated the mRNA expression of TGF-β (P < 0.001) and IL-10 (P < 0.001); these changes were not observed in cells treated with estrogen and the IRE1α agonist.@*CONCLUSION@#Estrogen can inhibit the differentiation of murine macrophages into a pro-inflammatory phenotype by up-regulating the IRE1α-XBP-1 signaling axis, thereby producing an inhibitory effect on inflammatory response.

Prevalence of Human T-Cell Lymphotropic Virus Type 1 and 2 among Blood Donors in Jiangsu from 2016 to 2019 / 中国实验血液学杂志

OBJECTIVE@#To investigate the prevalence of human T-cell lymphotropic virus (HTLV) type-I/II infection among voluntary blood donors in Jiangsu (Nanjing, Suzhou, Xuzhou).@*METHODS@#From 2016 to 2019, 408 262 samples of voluntary blood donors from four blood stations in Jiangsu Province (Jiangsu Province Blood Center, Nanjing Red Cross Blood Center, Suzhou Central Blood Station, and Xuzhou Central Blood Station) were screened for HTLV-I/II antibody by ELISA. The positive samples were sent to National Center for Clinical Laboratories for confirmation by RT-PCR and Western blot.@*RESULTS@#The positive rate of HTLV-I/II screened by ELISA was 0.20‰ (82/408 262), and three HTLV-I positive samples were confirmed. The prevalence of HTLV-1 infection was 0.74 per 100 000 (3/408 262). All three donors were female repeated blood donors of childbearing ages.@*CONCLUSION@#Jiangsu is a low prevalence area of HTLV, and a reasonable blood screening strategy for HTLV can further reduce the risk of transfusion-transmitted virus infection.

Clinical and Cytogenetical Characteristics in Acute Myeloid Leukemia with Myelodysplasia-Related Changes / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical and cytogenetic characteristics of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) based on morphology define.@*METHODS@#A total of 180 newly diagnosed acute myeloid leukemia (AML) patients were enrolled and retrospectively analyzed, and marrow cell morphology of 126 patients were re-evaluated. The clinical and cytogenetic characteristics, including ages, sex, WBC count, HGB level, PLT count, blasts percentage, abnormal karyotype detection rate of the patients in AML with multilineage dysplasia (AML-MRC-1), secondary AML from myelodysplastic/ myeloproliferative neoplasms (MDS/MPN) (AML-MRC-2), and AML not otherwise specified (AML-NOS) groups were investigated.@*RESULTS@#There was no significant differences between the patients in three groups in terms of sex, age and platelet count (P=0.898, P=0.365, P=0.853), but AML-MRC-2 group (73.2%) was higher than AML-MRC-1 (60.0%) and AML-NOS (56.4%) in the percentages of patients over 60 years old (P=0.228); there were statistically significant differences on WBC count, HGB level, and blasts percentage (P=0.000, P=0.022, P=0.000, AML-MRC-2

Analysis of Non-genetic Factors Influencing the Overall Survival of Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the non-genetic factors of overall survival in patients with multiple myeloma (MM).@*METHODS@#Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 51 patients who were newly diagnosed with MM and had complete follow-up data in the Department of Hematology, the Affiliated Jiangning Hospital of Nanjing Medical University from November 2011 to October 2019.@*RESULTS@#Fifty-one patients included 29 males and 22 females. Followed up to December 2019, 21 cases died and 30 cases survived. The univariate analysis showed that the overall survival time of the patients was influenced by age, disease stage, standard treatment, new drugs, maintenance treatment, hypercalcemia, globulin, albumin, and hemoglobin. The overall survival time of patients with age <65 years old, ISS stage I and II, standardized treatment, new drugs, normal or below normal blood calcium, normal or below normal globulin, albumin ≥35 g/L or hemoglobin ≥100 g/L was prolonged significantly (P<0.05). The multivariate analysis showed that maintenance treatment, hypercalcemia (≥2.6 mmol/L), and hemoglobin (<100 g/L) were independent risk factors influencing the prognosis of MM patients.@*CONCLUSION@#Patients with blood calcium ≥2.6 mmol/L, hemoglobin <100 g/L, and who do not undergo regular maintenance therapy show a poor prognosis.

Analysis of Relevant Factors of Refractory and Relapse DLBCL Treated by Rituximab Combined with CHOP/EPOCH Regimen / 中国实验血液学杂志

OBJECTIVE@#To analyze the efficacy of rituximab combined with CHOP/EPOCH regimen for treatment of diffuse large B-cell lymphoma（DLBCL） patients, and to explore the high risk factors of refractory and relapsed patients.@*METHODS@#The clinical data of 72 patients with de novo DLBCL from December 2012 to December 2018 in the Department of Hematology, Zhongda Hospital Affiliated to Southeast University were retrospectively analyzed. The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH was analyzed, and survival analysis was conducted to explore the risk factors influencing refractory recurrence.@*RESULTS@#45 cases among 72 patients achieved complete remission (CR), 11 cases achieved partial remission (PR), the total remission rate was 77.78%. 25 cases (34.2%) refractory and relapsed. Single factor analysis showed that the B symptoms, low Hb, high NLR, low MLR, high β@*CONCLUSION@#The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH regimen is high, but about one third of the patients still show refractory and relapsed. B Symptoms, anemia, high β

Characteristics and Clinical Significance of RAG1 Expression in Adult B-Cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#RAG1 plays important roles in lymphopoiesis and immune system, its dysfunction may result in the malignancies of hemopoietic system. The aim of this study was to investigate the characteristics of RAG1 expression in adult B-cell acute lymphoblastic leukemia (B-ALL), and to analyze the clinical significances.@*METHODS@#Quantitative PCR (q-PCR) was performed to evaluate the expression of RAG1 in 104 newly diagnosed, 22 relapsed adult B-ALL patients and 30 normal controls, the clinical significances of RAG1 expression were analyzed.@*RESULTS@#Compared with normal controls, newly diagnosed and relapsed adult B-ALL patients showed higher RAG1 expression level (3.94 vs 1.23) (P＜0.01), (5.86 vs 1.23) (P＜0.01). The analysis of paired simples from 6 cases of newly diagnosed and relapsed B-ALL showed that the expression level of RAG1 at relapse was significantly higher than that at new diagnosis (13.65 vs 2.31) (P＜0.01). The RAG1 expression level in IK6 positive patients was higher than that in IK6 negative patients (5.30 vs 2.11) (P＜0.05). The ratio of patients with LDH＞1 000 U/L in RAG1 high expression group was higher than that in RAG1 low expression group (42.2% vs 20.5%) (P＜0.05).@*CONCLUSION@#RAG1 up-regulation may play an important role in the development of adult B-ALL especially when relapsed, which may also take part in the formation of Ik6. Monitoring RAG1 expression may provide a new method to evaluate the prognosis of adult B-ALL patients.

Advance of Research on the Immunotherapy Targeting B Cell Maration Antigen for Multiple Myeloma--Review / 中国实验血液学杂志

Abstract　　B cell maturation antigen (BCMA) is an ideal target for precise treatment due to its highly selective expression on malignant myeloma cells. This review summarizes briefly the advances in the latest research progress on biological activity of BCMA, its significance as a biomarker and immunotherapy direcited against BCMA, such as bispecific antibodies, antibody drug conjugates, chimeric antigen receptor T cell therapy against mature B cell antigens.

Application of alkaloids in reversing multidrug resistance in human cancers / 中国天然药物

Multidrug resistance (MDR) in human cancer is one of greatest challenges in cancer therapy. Natural products, especially the alkaloids, exert reversed effects on MDR with low toxicity, by interacting with various targets. In this review article, we summarize the recent progress made in the research of the main alkaloids, including classification, function, mechanism, research status, and application in reversing MDR.

Anticancer activity and underlying mechanism of neogambogic acid / 中国天然药物

Garcinia, a kind of dry resin secreted by Garcinia hanburyi Hook. F. G., is a traditional Chinese medicine with various biological functions such as detoxification, anti-inflammatory, and anthelmintic activities. Recent studies suggest that garcinia has potential anticancer activity. Increasing evidences indicate that the main active monomer gambogic acid isolated from garcinia can inhibit the growth of various cancer cells. Neogambogic acid is an isolated compound with a similar chemical structure as gambogic acid. Preliminary studies show that the neogambogic acid can selectively inhibit the growth of various cancer cells, and has a broader antitumor activity and lower toxicity than gambogic acid. In this review, we summarize the advances made in the investigation of the anti-tumor effect of neogambogic acid in recent years.

Gambogic acid induces cell apoptosis through endoplasmic reticulum stress triggered inhibition of Akt signaling pathways in extranodal NK/T-cell lymphoma cells / 中国天然药物

As the chemotherapeutic resistance of extranodal NK/T-cell lymphoma (ENKTL) rises year by year, searching for novel chemoprevention compounds has become imminent. Gambogic acid (GA) has recently been shown to have anti-tumor effects, but its role and underling mechanism in ENKTL are rather elusive. In the present study, we showed that GA inhibited the cell growth and potently induced the apoptosis of ENKTL cells in vitro in a time- and concentration-dependent manner. Furthermore, GA induced cell death through endoplasmic reticulum stress (ERS) mediated suppression of Akt signaling pathways and finally the release of the caspase-3 proteases. Overall, our data provided evidences supporting GA as a potential therapeutic agent for ENKTL, which may facilitate further preclinical development of anti-tumor drugs.

Acute eosinophilic leukemia transformed from myelodysplastic syndrome: a case report and literature review / 临床检验杂志

Objective To summarize and explore the morphological characteristics,genetic alterations,immunophenotype and characteristics of molecular marker of acute eosinophilic leukemia (AEL),and improve the awareness for AEL.Methods A case of refractory hematopoietic dysplasia (MDS-RCMD) transformed to AEL in our hospital was retrospectively reviewed.Results The MDS-RC-MD patient transformed to AEL in 12 months after diagnosis.In his special bone marrow 10.4％ was blasts,while 70.8％ of bone marrow cells were eosinophils including 69.3％ of promyelocyte,myelocyte and metamyelocyte.Eosinophils accounted for 13.5％ in his peripheral blood.The blasts in bone marrow expressed CD34,CD117,HLA-DR,CD33,CD38 and CD13,and accompanied by complex chromosomal abnormalities.FI1L1/PDGFRα and ETV6/PDGFRβ fusion gene were negative.The patient died two months later following treating with AML regimen.Conclusion The AEL patient with negative FI1L1/PDGFRα and ETV6/PDGFRβ gene rearrangement,imatinib treatment is ineffectual.

Efficacy Analysis of Unrelated Umbilical Cord Blood Transplantation for the Treatment of Wiskott-Aldrich Syndrome / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) for the treatment of Wiskott-Aldrich syndrome(WAS).@*METHODS@#Five pediatric patients with WAS received single UCBT were retrospectively analyzed. The median age of these male patients was 268 days (range, 3 days -695 days). Among them, 2 patients were transplanted with a 6/6 matched cord blood graft，the other 3 patients received a 5/6 matched cord blood graft. Myeloablative conditioning regimen was applied, and all patients received a combination of cyclosporine and mycophenolate mofetil for the prophylaxis of graft versus host disease (GVHD). The recovery time of neutrophils and platelets as well as chimerism after transplantation were taken as the evidence of hematopoietic reconstruction.@*RESULTS@#All the five pediatric patients had hematopoietic recovery. A median time of neutrophil cells after transplantation was at 15.8 days (range,11 days -25 days), and platelet recovery was at a median of 20.4 days(range,12 days-30 days). Chimerism data were available for 5 patients at 30 days after UCBT, 4 out of the 5 patients had full donor chimerism and only one patient had mixed chimerism. There were 2 cases with pre-engraftment syndrome, 3 cases with acute GVHD gradeⅠ-Ⅲ, 4 cases with pulmonary infection and cytomegalovirus infection, but chronic GVHD was not observed in 5 cases. Four patients were alive with a median follow-up of 12.3 months (range, 5 months-17 months), and one patient had died at 22 days after UCBT.@*CONCLUSION@#Unrelated umbilical cord blood transplantation is a safe and effective treatment method for Wiskott-Aldrich syndrome.

Application of alkaloids in reversing multidrug resistance in human cancers / 中国天然药物

Multidrug resistance (MDR) in human cancer is one of greatest challenges in cancer therapy. Natural products, especially the alkaloids, exert reversed effects on MDR with low toxicity, by interacting with various targets. In this review article, we summarize the recent progress made in the research of the main alkaloids, including classification, function, mechanism, research status, and application in reversing MDR.

Anticancer activity and underlying mechanism of neogambogic acid / 中国天然药物

Garcinia, a kind of dry resin secreted by Garcinia hanburyi Hook. F. G., is a traditional Chinese medicine with various biological functions such as detoxification, anti-inflammatory, and anthelmintic activities. Recent studies suggest that garcinia has potential anticancer activity. Increasing evidences indicate that the main active monomer gambogic acid isolated from garcinia can inhibit the growth of various cancer cells. Neogambogic acid is an isolated compound with a similar chemical structure as gambogic acid. Preliminary studies show that the neogambogic acid can selectively inhibit the growth of various cancer cells, and has a broader antitumor activity and lower toxicity than gambogic acid. In this review, we summarize the advances made in the investigation of the anti-tumor effect of neogambogic acid in recent years.

Gambogic acid induces cell apoptosis through endoplasmic reticulum stress triggered inhibition of Akt signaling pathways in extranodal NK/T-cell lymphoma cells / 中国天然药物

As the chemotherapeutic resistance of extranodal NK/T-cell lymphoma (ENKTL) rises year by year, searching for novel chemoprevention compounds has become imminent. Gambogic acid (GA) has recently been shown to have anti-tumor effects, but its role and underling mechanism in ENKTL are rather elusive. In the present study, we showed that GA inhibited the cell growth and potently induced the apoptosis of ENKTL cells in vitro in a time- and concentration-dependent manner. Furthermore, GA induced cell death through endoplasmic reticulum stress (ERS) mediated suppression of Akt signaling pathways and finally the release of the caspase-3 proteases. Overall, our data provided evidences supporting GA as a potential therapeutic agent for ENKTL, which may facilitate further preclinical development of anti-tumor drugs.

Apigenin's anticancer properties and molecular mechanisms of action: Recent advances and future prospectives / 中国天然药物

Cancer is a major health concern and leading burden on economy worldwide. An increasing effort is devoted to isolation and development of plant-derived dietary components as effective chemo-preventive products. Phytochemical compounds from natural resources such as fruits and vegetables are responsible for decreasing the risk of certain cancers among the consuming populations. Apigenin, a flavonoid phytochemical found in many kinds of fruits and vegetables, has been shown to exert significant biological effects, such as anti-oxidant, anti-inflammatory and most particularly anti-neoplastic properties. This review is intended to summarize the most recent advances in the anti-proliferative and chemo-preventive effects of apigenin in different cancer models. Analysis of the data from the studied cancer models has revealed that apigenin exerts its anti-proliferative effects through multiple and complex pathways. This guided us to discover some controversial results about the exact role of certain molecular pathways such as autophagy in the anticancer effects of apigenin. Further, there were cumulative positive evidences supporting the involvement of certain pathways such as apoptosis, ROS and DNA damage and repair. Apigenin possesses a high potential to be used as a chemosensitizing agent through the up-regulation of DR5 pathway. According to these preclinical findings we recommend that further robust unbiased studies should consider the possible interactions between different molecular pathways.

Research Advances in Treatment of Myeloma Nephropathy-Review / 中国实验血液学杂志

Myeloma nephropathy is a common complication in patients with myltiple myeloma (MM) that causes high morbidity. In the majority of cases, renal impairment is caused by the accumulation and precipitation of light chains, which form casts in the distal tubules, resulting in renal obstruction. This review discusses the recent advances on its treatment, so as to provide reference for clinical treatment of MM induced-renal failure.

Analysis of Clinical Characteristics and Therapeutic Efficacy in 61 Adult Patients with Acute Lymphoblastic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and curative effect in 61 adult patients with acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>The clinical data of 61 patients (≥15 years old) with ALL enrolled from January 2010 to December 2014 were studied retrospectively. The relationship between clinical characteristics and curative effect was analyzed. The univariate and multivariate analyses related with the overall survival (OS) and disease free survival (DFS) were conducted by using the method of COX regression analysis.</p><p><b>RESULTS</b>Forty-four patients obtained complete remission (CR) in all 61 cases. The total CR rate was 72.13%. Age of onset, WBC count at first visit, CNS involvement or not, status of myeloid antigen expression and Ph chromosome condition were the important factors affecting the CR rate (P<0.05). The 2 years OS rate of all the 61 cases was 28.13%, the median OS time was 11 months (95% CI 9.58-12.42). The 2 years OS rate and DFS rate of the 44 patients in CR were 39.57% and 34.29% respectively. As showed by univariate analysis, the age of onset, WBC count at first visit, whether achieved CR or not after induction chemotherapy, and whether accepted consolidation therapy or allo-HSCT therapy after CR were factors affecting the prognosis of adult ALL patients. The result of multivariate analysis showed that the older age (P=0.001), induction chemotherapy did not achieve CR (P=0.018) and patients did not received consolidation after CR(P=0.005) , all these were independent risk factors for DFS.</p><p><b>CONCLUSION</b>The CR rate after induction chemotherapy is high in adult ALL patients, but the OS rate is low. To achieve CR and to maintain consolidation treatment after CR may be helpful to improve the long-term survival.</p>

Research Advances on Treatment of Multiple Myeloma Bone Disease--Review / 中国实验血液学杂志

The main features of multiple myeloma bone disease (MBD) are hyperactivity of systemic bone destruction and inhibition of new bone formation. Its clinical manifestations include pain, osteoporosis, pathologic fractures and associated nerve compression symptoms etc. MBD is one of the most common complications of multiple myeloma (MM). Its misdiagnosis rate is higher, and the patients' quality of life and prognosis are poor. This review discusses the most recent advancement on its pathogenesis and novel therapies, so as to provide reference for clinical treatment of MBD.