Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2023 ASH annual meeting.

Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) often exhibit limited responses to traditional chemotherapy, resulting in poor prognosis. The combination of venetoclax (VEN) with hypomethylating agents has been established as the standard treatment for elderly or medically unfit AML patients unable to undergo intensive chemotherapy. Despite this, the availability of novel VEN-based therapies specifically tailored for those with R/R AML remains scarce. Here, we provide a comprehensive overview of the latest data presented at the 65th American Society of Hematology Annual Meeting, shedding light on the progress and efficacy of VEN-based therapies for R/R AML.

Exosomal miR-222-3p contributes to castration-resistant prostate cancer by activating mTOR signaling.

Despite the clinical benefits of androgen deprivation therapy, most patients with advanced androgen-dependent prostate cancer (ADPC) eventually relapse and progress to lethal androgen-independent prostate cancer (AIPC), also termed castration-resistant prostate cancer (CRPC). MiRNAs can be packaged into exosomes (Exos) and shuttled between cells. However, the roles and mechanisms of exosomal miRNAs involved in CRPC progression have not yet been fully elucidated. Here, we find that miR-222-3p is elevated in AIPC cells, which results in remarkable enhancement of cell proliferation, migration, and invasion ability. Furthermore, Exos released by AIPC cells can be uptaken by ADPC cells, thus acclimating ADPC cells to progressing to more aggressive cell types in vitro and in vivo through exosomal transfer of miR-222-3p. Mechanistically, Exos-miR-222-3p promoted ADPC cells transformed to AIPC-like cells, at least in part, by activating mTOR signaling through targeting MIDN. Our results show that AIPC cells secrete Exos containing miRNA cargo. These cargos can be transferred to ADPC cells through paracrine mechanisms that have a strong impact on cellular functional remodeling. The current work underscores the great therapeutic potential of targeting Exo miRNAs, either as a single agent or combined with androgen receptor pathway inhibitors for CRPC treatment.

Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2022 ASH annual meeting.

Venetoclax (VEN), the first selective Bcl-2 inhibitor, has shown efficacy and safety both as monotherapy and in combination with other agents in the treatment of newly diagnosed acute myeloid leukemia (AML), while its role in relapsed or refractory (R/R) disease is not well defined. Here, we reviewed the latest advances of VEN-based therapy for R/R AML from the 2022 American Society of Hematology (ASH) Annual Meeting, including some novel and encouraging regimes, such as VCA, VAH, and HAM regimes, etc. Further research is still needed to fully understand the optimal use of these agents in R/R AML treatment.

Adefovir dipivoxil inhibits APL progression through degradation of the oncoprotein PML-RARA.

Acute promyelocytic leukemia (APL) is highly aggressive and is frequently associated with disseminated intravascular coagulation and high early death rates. Although all-trans retinoic acid (RA) induces complete remission in a high proportion of patients with APL, there are limited treatments for APL patients with RA resistance. Here we report an atypical APL patient, with an APL-like disease that developed very slowly without anti-leukemia therapy for nearly 2 years. During that time, the patient only intermittently received anti-HBV drugs, i.e., the combination of adefovir dipivoxil (ADV) and entecavir (ETV), leading us to hypothesize that ADV and/or ETV could inhibit APL progression. Our results showed that anti-HBV drugs ADV and ETV both exhibited significantly inhibitory effects on APL cells, and ADV indicated a much greater cytotoxic effect than ETV on APL cells. We further found that ADV significantly promoted APL cell differentiation and apoptosis, thereby restraining the progression of APL. Most importantly, our study uncovered a novel mechanism of ADV prohibiting APL progression, which was mediated, at least in part, by inhibition of TRIB3 and degradation of the oncoprotein PML-RARA, therefore leading to APL cell differentiation and apoptosis. Taken together, our study demonstrated that ADV, an anti-HBV drug, had significantly inhibitory effects on APL, and provided a novel therapeutic strategy for APL patients with RA resistance.

Linalool inhibits the growth of human T cell acute lymphoblastic leukemia cells with involvement of the MAPK signaling pathway.

Linalool can inhibit the malignant proliferation of numerous human malignant solid tumors, including hepatocellular carcinoma, breast cancer, small cell carcinoma and malignant melanoma. However, the role of linalool in T cell acute lymphoblastic leukaemia (T-ALL) remains unclear. In the present study, human T-ALL cell lines (Jurkat, H9, Molt-4 and Raji cells) and peripheral blood mononuclear cells (PBMCs) from healthy donors were treated with various concentrations of linalool (3.75, 7.50, 15.00, 30.00, 60.00 and 120.00 µM, respectively). A CCK-8 assay was used to analyse cell viability and it demonstrated that linalool inhibited the growth of T-ALL cells in a dose-dependent manner, but did not significantly affect normal PBMCs. Flow cytometry was used to detect the cell cycle and apoptosis and demonstrated that linalool reduced the percentage of T-ALL cells at the G0/G1 phase, and induced the apoptosis of T-ALL cells. RNA sequencing was conducted on an Illumina HiSeq X Series 2500 before and after treatment with linalool followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. It was demonstrated that the mitogen-activated protein kinase (MAPK) pathway was involved in the effect of linalool on T-ALL cells. Real-time quantitative PCR and western blotting were performed to verify the mRNA and protein levels, respectively of the genes in the signaling pathway identified. In addition, it was found that linalool significantly inhibited phosphorylated (p)-ERK1/2 protein expression and enhanced p-JNK protein expression of T-ALL cells. In conclusion, the present study revealed that linalool inhibits T-ALL cell survival with involvement of the MAPK signaling pathway. JNK activation and ERK inhibition may play a functional role in apoptosis induction of T-ALL cells. Linalool may be developed as a novel anti T-ALL agent.

Clinical and laboratory characteristics of lymphoid neoplasms in serous effusions: a single centre experience in China.

BACKGROUND: Lymphoid neoplasms in serous effusions are uncommon, and the details of lymphoid neoplasms in serous effusions from China are still unclear. METHODS: Between January 2004 and December 2019, all patients with lymphoid neoplasms in pleural effusions, ascites, and pericardial effusions in our hospital, were reviewed. RESULTS: A total of 65 patients with lymphoid neoplasms were collected during this period. The top three neoplasms were diffuse large B-cell lymphoma (DLBCL) (n = 20, 30.7%), myeloma (n = 13, 20.0%), and T-lymphoblastic lymphoma (n = 7, 10.8%). In pleural effusions involving DLBCL, the cytomorphology of DLBCL cells was diverse; most pleural effusions were present during the tumor course (92.9%); bilateral pleural effusions were predominant (57.2%); and the median survival time was only 1.23 months after the effusion. In pleural effusions involving myeloma, 90.9% of cases (10/11) had a high ratio (> 1.0) of immature to mature plasma cells; paraprotein types of IgA (36.4%) and light chain λ (36.4%) were the most frequently found; bilateral pleural effusions were easily found (n = 10, 90.9%); and the median survival time was only 1.4 months after the effusion. CONCLUSION: In pleural effusions involving DLBCL, most of our patients with effusions are present during the tumor course, and bilateral pleural effusions are predominant. In pleural effusions involving myeloma, the paraprotein types of IgA and light chain λ are the most frequently found, and it has a high ratio of immature to mature plasma cells in pleural effusions.

Unusual findings of acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): A multicenter study.

INTRODUCTION: AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) [inv(3)/t(3;3)] was very rare. Currently, most reports of AML-inv(3)/t(3;3) were from Western countries, and few reports were from Asian countries. Racial differences in patients with AML-inv(3)/t(3;3) are still unknown. METHODS: Between January 1996 and April 2018, a total of 37 AML cases with inv(3)/t(3;3) were studied retrospectively. They were collected from 2229 primary AML cases performed with conventional cytogenetic analysis (37/2229, 1.66%). RESULTS: Here, some differences were found by comparing our data with those from Western countries. In our series, AML with inv(3)(q21q26) had a lower incidence than that with t(3;3)(q21;q26) (11 vs 26 cases). Our patients seemed to be more younger (median, 43 years) and have lower hemoglobin concentrations (median, 73 g/L) and higher platelet count (median, 351 × 109 /L). A higher incidence of acute monoblastic and monocytic leukemia (45.9%) was observed in our patients. Immunophenotypic studies showed that CD38 (30.8%) was not so frequently expressed as that in the earlier reports. Mutations analysis showed a high frequency of NRAS mutations (45.0%), followed by SF3B1(15.0%), GATA2(15.0%), FLT3-ITD(10.0%), C-Kit/D816(5.0%), and CEBPA(5.0%), without mutation of NPM1(Exon12)or JAK2V617. CONCLUSION: Ethnic differences do exist between the Chinese and Western patients with AML-inv(3)/t(3;3), and more attention should be paid involving different ethnic populations and geographic regions.

Increased interleukin-22 levels in lupus nephritis and its associated with disease severity: a study in both patients and lupus-like mice model.

OBJECTIVES: Interleukin-22 (IL-22) has been considered as an inflammatory cytokine. In the present study, we investigated the potential role of IL-22 in lupus nephritis (LN). METHODS: We examined the IL-22 levels of serum and kidney tissue from LN patients and MRL/lpr mice. An intraperitoneal injection of saline, isotype control antibody (IgG), prednisone (3mg/kg/mouse), or anti-IL-22 mAb (5µg/kg/mouse or 25µg/kg/mouse) was administered twice a week from 6 to 18 weeks of age. RESULTS: IL-22 levels in both serum and kidney were significantly higher in LN patients as compared with those in healthy controls. The serum and renal levels of IL-22 in MRL/lpr mice were significantly increased over time. After MRL/lpr mice were treated with anti-IL-22 monoclonal antibody (mAb) for 12 weeks, significantly less urine protein and lower serum levels of creatinine and urea nitrogen were found. In addition, less renal injury score and few number of inflammatory cells per glomerulus were observed in MRL/lpr mice treated with anti-IL-22 mAb as compared with control groups. CONCLUSIONS: Our results suggest that IL-22 as a pathogenic cytokine might be a potential target for treatment of lupus nephritis.

Secondary mixed phenotype acute leukemia following chemotherapy for diffuse large B-cell lymphoma: a case report and review of the literature.

Therapy-related mixed phenotype acute leukemia (MPAL) following non-Hodgkin's lymphoma (NHL) is extremely rare. We present here the case of an elderly man, diagnosed with diffuse large B-cell lymphoma (DLBCL) through a tonsil biopsy. After treatment with seven cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) like regimen, the patient developed to MPAL (B/myeloid) with del(7)(q22), t(6;9)(p23;q34), DEK/NUP214 fusion, as well as EZH2 and TET2 mutations. The patient was successively treated with chemotherapy and allogenetic hematopoietic stem cell transplantation. Until recently he is still alive more than 23 months without relapse.

Chronic myelogenous leukemia following small lymphocytic lymphoma: a case report and review of literature.

Chronic myelogenous leukemia (CML) following non-Hodgkin's lymphoma (NHL) is extremely rare. Here we report a unique case of CML after small lymphocytic lymphoma (SLL). A 64-years-old Asian female was firstly diagnosed as SLL by biopsies of the retroperitoneal and the mesenteric root lymph nodes, with bone marrow (BM) involvement. BM chromosome showed no abnormalities, and the rearrangement of IgDH (DH1-6-JH) and IgK (Vk-Jk) gene were present. After treatment with three courses of fludarabine, cyclophosphamide, and rituximab (FCR) regimens, the patient achieved complete response. However, she progressed to CML 35 months later, with Philadelphia translocation and the major BCR/ABL fusion transcript (p210), and she has a good prognosis with imatinib. It is not clear whether BCR-ABL1 gene was present at the time of primary diagnosis for SLL, so we extracted genomic DNA from the patient's paraffin-embedded BM biopsies at the first diagnosis of SLL for comparison, but real-time quantitative PCR assay for BCR-ABL1 gene was negative. Taken together, there is a strong possibility that FCR therapy caused the BCR-ABL1 gene rearrangement, and then became CML in 35 months.

Chronic myeloid leukemia following repeated diagnostic X-ray exposure for the treatment of recurrent spontaneous pneumothorax in a patient with ankylosing spondylitis: A case report and literature review.

Previous studies have indicated that X-ray irradiation may increase the risk of chronic myeloid leukemia (CML), and the incidence of spontaneous pneumothorax in patients with ankylosing spondylitis (AS) is higher than in the general population. Patients with AS usually develop spontaneous pneumothorax several years after the diagnosis of AS. The present study reports the unusual case and complicated clinical history of a 29-year-old man with recurrent pneumothorax and AS, who developed CML following repeated exposure to low doses of radiation via diagnostic X-rays and chest computed tomography imaging. Pneumothorax was diagnosed prior to AS in this patient; the present case report highlights the importance of recognizing AS as a possible underlying cause of recurrent spontaneous pneumothorax. Patients with AS may be more sensitive to injury via X-ray-derived radiation, and even small diagnostic doses may be associated with CML. Diagnostic X-ray exposure should therefore be limited to reduce the risk of radiation-associated malignancies, including CML, particularly in patients with AS.

Chronic myeloid leukaemia following repeated exposure to chest radiography and computed tomography in a patient with pneumothorax: A case report and literature review.

It is well known that radioactive rays may cause damage to the human body. Progress in modern medicine has led to an increased risk of therapeutic and diagnostic radiation exposure of patients. Although clear evidence of a radiation dose-dependent risk of chronic myeloid leukaemia, particularly for patients exposed to radiation at a young age, has been established, it is not known whether radiation exposure during diagnostic imaging also increases the risk of cancer. The present study reports the case of a patient who underwent several diagnostic imaging tests (including repeated chest radiography and computed tomography) for recurrent pneumothorax. At around one year subsequent to these tests, the patient was diagnosed with chronic myeloid leukaemia. The patient exhibited an increase in white blood cell count over time, and a bone marrow smear test showed a myeloid/erythroid ratio of 13.9:1. In addition, the qualitative breakpoint cluster region (BCR)/Abelson (ABL) gene test revealed positive results for BCR/ABL fusion (p210). Based on the data reported in the current case, research aimed at elucidating the potential risks associated with diagnostic radiation is urgently required. It is crucial that medical professionals consider the potential harmful side effects of diagnostic radiation when ordering radiation-based diagnostic imaging examinations.

Increased urinary interleukin 22 binding protein levels correlate with lupus nephritis activity.

OBJECTIVE: Interleukin 22 (IL-22) plays an important role in the promotion of antimicrobial immunity. However, dysregulated IL-22 action leads to inflammation and is involved in autoimmune diseases, including systemic lupus erythematosus (SLE). IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We investigated the expression and potential significance of serum and urinary IL-22BP levels in patients with SLE. METHODS: A total of 112 patients with SLE and healthy control subjects participated in our study. Patients were classified according to kidney involvement and disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, complement factor 3 (C3), C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The concentrations of IL-22BP and IL-22 were measured by ELISA. The expression of IL-22BP in the renal tissue was detected by immunohistochemistry. RESULTS: Patients with active renal disease had urinary levels of IL-22BP higher than (1) patients with active SLE but no renal involvement, (2) patients with a history of lupus nephritis in remission with no systemic disease activity and no history of renal involvement, and (3) control subjects. There was no difference in serum levels of IL-22BP among the groups. Urinary levels of IL-22BP in patients with active renal disease were positively correlated with SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics renal activity score, and histological activity index. IL-22BP was highly expressed in renal tissue of patients with active renal disease. After 6 months of treatment, urinary IL-22BP levels decreased significantly in patients with complete response, but remained unchanged in those with partial or no response. CONCLUSION: Urinary but not serum IL-22BP levels were associated with active renal disease. Urinary levels of IL-22BP might be a potential marker for the presence of renal involvement in patients with SLE.

Clinicopathologic characteristics of prefibrotic-early primary myelofibrosis in Chinese patients.

The clinicopathologic features of patients with prefibrotic-early primary myelofibrosis (PEPMF) are still uncertain, and the characteristics of PEPMF in Asian patients are rarely reported. This study analyzed the clinicopathologic characteristics of 42 Chinese patients with PMF newly diagnosed according to the 2008 World Health Organization criteria. Some clinical and laboratory features of the patients differed significantly from those of the predominantly white patients in Western countries. Chinese patients with PEPMF were more often male (1.28:1) and younger, less likely to have higher median hemoglobin concentrations (126 g/L), less frequently had palpable spleens (35.7%), and had longer median times between prefibrotic-early and classical PEPMF (64 months). On bone marrow trephine sections, Chinese patients were more likely to have increased granulopoiesis (78.6%) and less frequently had balloon-like megakaryocytes (61.9%), giant and staghorn megakaryocytes (35.7%), or megakaryocytes with hyperchromatic and dysplastic nuclei (40.4%). In conclusion, some clinicopathologic characteristics of PEPMF in Chinese patients in China differ substantially from those seen in predominantly white patients in Western countries, and more clinicopathologic studies involving different ethnic populations and geographic regions of the world should help unfold the characteristics of this disease.

[The morphology features of bone marrow in the prefibrotic-early primary myelofibrosis].

OBJECTIVE: To compare the morphologic features of bone marrow (BM) between the prefibrotic-early primary myelofibrosis (PMF) and essential thrombocythaemia (ET). METHOD: Seven cases of prefibrotic-early PMF were selected and analyzed. Based on the diagnostic standard of prefibrotic-early PMF by WHO, BM aspirate smears, trephine biopsy sections and imprints of 156 uncertain ET cases conducted simultaneously were recruited into this study, the BM morphologic features between the prefibrotic-early PMF and ET groups were analyzed. The morphological difference in 22 cases of prefibrotic-early PMF and 27 ET were compared between the JAK2V617F mutation positive and negative groups. RESULTS: Of the 156 uncertain ET cases, it was reclassified 61 prefibrotic-early PMF (34 MF-0, 27 MF-1), 12 PMF and 83 ET. The platelet count and LDH level in MF-1 group were obviously higher than that of ET group (P < 0.05). The blast percentage of BM smear in MF-1 group was also higher than that of ET group (P < 0.05). As to BM section, cases with increased nucleated cells (granulocyte), compact megakaryocytic cluster, megakaryocyte near bone trabecula, cloud-like megakaryocyte, small bare nucleus of megakaryocyte and large ball-like megakaryocyte in MF-0 and MF-1 group were significantly higher than that of ET group (all P < 0.05), cases with megakaryocytic cluster of various size in MF-1 group were significantly higher than that of MF-0 and ET groups (P < 0.05). The JAK2V617F mutation rate in prefibrotic-early PMF and ET groups were 54.5% and 48.1%, respectively. Hb level in JAK2V617F mutation positive group was obviously higher than the negative group (P < 0.05), no special change with megakaryocytic morphology was found between the positive and negative groups. CONCLUSION: Morphology of BM section, especially megakaryocytic morphologic characteristics are the main basis in distinguishing prefibrotic-early PMF from ET. The importance of morphologic index were megakaryocytic cluster with various size, cloud-like megakaryocyte, large ball-like megakaryocyte, increased nucleated cells (granulocyte), small bare nucleus, megakaryocyte near bone trabecula and compact megakaryocytic cluster in order. JAK2V617F mutation provides no specific effect on the megakaryocytic morphology.

[Value of imprint in bone marrow morphological examination].

OBJECTIVE: To explore the role of bone marrow (BM) imprint in the diagnosis of hematological diseases. METHODS: Between January 2002 and June 2008, a total of 3024 cases with BM smears, imprints and sections conducted simultaneously were recruited. There were 1667 males and 1357 females with a median age of 55 years old (range: 7 to 92). The cellularity on imprint and smear was evaluated with the standard cellularity on BM section. With the integrative diagnosis (including all examinations and clinical outcomes) as the standard, the diagnostic accuracy of hematological diseases were compared between BM imprint, smear and section groups. Another 79 cases of lymphoma and 114 cases of plasma cell myeloma (PCM) were selected for a correlation analysis of tumor cell infiltration patterns. RESULTS: BM imprint contained hematopoietic and non-hematopoietic regions and cells retained integrated structure. The cellularity evaluation by imprint was superior to smear overall. In BM imprint group, the diagnostic accuracy for hypersplenism (n = 130), metastatic carcinoma (n = 67), refractory anemia with excess blasts, myeloproliferative neoplasm (n = 174), and PCM (n = 94) were better than smear group (96.9% vs 80.7%, 91.0% vs 76.1%, 92.6% vs 81.5%, 92.5% vs 76.4%, and 97.8% vs 92.6% respectively, all P < 0.05); And the diagnostic accuracy for megaloblastic anemia (n = 69), acute myeloid leukemia (n = 104), refractory cytopenia with unilineage dysplasia (n = 15), refractory cytopenia with multilineage dysplasia (n = 22), and lymphoplasmacytic lymphoma (n = 12) were higher than biopsy section group (100% vs 84.0%, 91.3% vs 74.0%, 86.7% vs 60.0%, 90. 9% vs 72.7%, and 66.6% vs 50.0% respectively, all P < 0.05); And the diagnostic accuracy for myelodysplastic/myeloproliferative neoplasm (n = 26) was higher than smear group (76.3%, P < 0.05) and biopsy section group (78.2%, P < 0.05). Excellent correlations existed between BM imprint and section of the patients with lymphoma or with PCM (r = 0.90, r = 0.78, both P < 0.05). CONCLUSIONS: BM imprint contains the characteristics of both smear and section. BM imprint is superior to smear for an evaluation of cellularity. And it is also better than section for an analysis of cytological changes.

[Improvement of Phi bodies stain and its clinical significance].

The aim of this study was to improve the dyeing method of hydroperoxidase (HPO), to analyze the morphologic features of Phi bodies and to evaluate the clinical application of this method. 128 bone marrow or peripheral blood smears from patients with myeloid and lymphoid malignancies were stained by improved HPO staining. The Phi bodies were observed with detection rate of Phi bodies in different leukemias. 69 acute myeloid leukemia (AML) specimens were chosen randomly, the positive rate and the number of Phi bodies between the improved HPO and POX stain based on the same substrate of 3, 3'diaminobenzidine were compared. The results showed that the shape of bundle-like Phi bodies was variable, long or short. while the nubbly Phi bodies often presented oval and smooth. Club-like Phi bodies were found in M(3). The detection rates of bundle-like Phi bodies in AML M(1)-M(5) were 42.9% (6/14), 83.3% (15/18), 92.0% (23/25), 52.3% (11/21), 33.3% (5/15) respectively, and those of nubbly Phi bodies were 28.6% (4/14), 66.7% (12/18), 11.1% (3/25), 33.3% (7/21), 20.0% (3/15) respectively. The detection rate of bundle-like Phi bodies in M(3) was significantly higher than that in (M(1) + M(2)) or (M(4) + M(5)) groups. The detection rate of nubbly Phi bodies in (M(1) + M(2)) group was higher than that in M(3) group. In conclusion, after improvement of staining method, the HPO stain becomes simple, the detection rate of Phi bodies is higher than that by the previous method, the positive granules are more obvious, and the results become stable. This improved method plays an important role in differentiating AML from ALL, subtyping AML, and evaluating the therapeutic results.

[Cerulenin changes apoptosis related genes expression in multiple myeloma cell line U266].

OBJECTIVE: To study the expression changes of apoptosis related genes induced by cerulenin in multiple myeloma cell line U266 and explore its molecular mechanism. METHODS: The expression changes of 96 apoptosis related genes were analyzed by superArray cDNA in U266 cells treated with cerulenin (20 microg/ml) for 12 h. Semi-quantitative RT-PCR was used to confirm the representative expression changes genes, Rip2, caspase 9 and TRAF2. RESULTS: After treated with cerulenin for 12 h, 44 apoptosis related genes expression in the U266 cells were changed, among which 41 were over 2 fold increase and 3 over 2 fold decrease. The expression of caspase 9 was increased markedly, indicating that mitochondria pathway played a key role in cerulenin inducing apoptosis and TRAF2 expression change suggested that nuclear factor (NF) participates in cerulenin inducing apoptosis. CONCLUSION: The death acceptor signaling pathway and the death acceptor non-dependence signaling pathway co-regulate cerulenin inducing apoptosis in U266 cells. Mitochondria pathway played the key role and nuclear factor (NF) participates in the apoptosis process.

Novel distribution pattern of fibrinolytic components in rabbit tissues extract: a preliminary study.

OBJECTIVE: The purpose of this work was to investigate the distribution pattern of fibrinolytic factors and their inhibitors in rabbit tissues. METHODS: The components of the fibrinolytic system in extracts from a variety of rabbit tissues, including tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), plasminogen (Plg), plasmin (Pl) and alpha(2) plasmin inhibitor (alpha(2)PI), were determined by colorimetric assay. RESULTS: The tissue extracts in renal, small intestine, lung, brain and spleen demonstrated strong fibrinolytic function, in which high activity of tPA, Plg and Pl was manifested; whereas in skeletal muscle, tongue and stomach, higher activity of PAI-1 and alpha(2)PI showed obviously. Also excellent linear correlations were found between levels of tPA and PAI-1, Pl and alpha(2)PI, Plg and Pl. In related tissues, renal cortex and renal marrow showed distinctly higher activity of tPA and lower activity of PAI-1, with the levels of Plg and Pl in renal cortex being higher than those in renal marrow, where the alpha(2)PI level was higher than that in renal cortex. Similarly, the levels of tPA, Plg and Pl in small intestine were higher than those in large intestine, but with respect to PAI-1 and alpha(2)PI, the matter was reverse. In addition, the fibrinolytic activity in muscle tissue was lower, however, the levels of tPA, Plg, and Pl in cardiac muscle were obviously higher than those in skeletal muscles, and the levels of PAI-1 and alpha(2)PI were significantly lower than those in skeletal muscle. CONCLUSION: Our data demonstrate that a remarkable difference of the fibrinolytic patterns exists in rabbit tissues, which has probable profound significance in understanding the relationship between the function of haemostasis or thrombosis and the physiologic function in tissues.

Clinical study of plasma thrombomodulin detection.

The purpose of this study was to investigate the clinical value of plasma thrombomodulin (PTM) in different diseases or in different severity or complications of diseases, PTM in 979 patients and 60 healthy controls was determined by ELISA method. The results showed that the PTM level in the control group was 20.40 +/- 7.72 microg/L, there was no difference in sex and ages. In chronic primary glomerular disease, the PTM level in chronic renal failure (CRF) group was higher than that in non-CRF group (P < 0.01). PTM level > 70 microg/L was defined as its positive criterion. The sensitivity, specificity and positive predictive value in PTM were 85.7%, 82.4% and 77.8% respectively. The PTM level in septemia group was higher than that in non-septemia group (P < 0.01), the sensitivity, specificity and positive predictive value were 86.6%, 89.5% and 76.5% respectively (> 50 microg/L as its positive criterion). With respect of multiple trauma, the PTM level in multiple organ failare (MOF) group was higher than that in non-MOF group (P < 0.01), while the sensitivity, specificity and positive predictive value were 77.8%, 77.3% and 73.7% respectively (> 40 microg/L as its positive criterion). For systemic lupus erythematosus (SLE), the PTM level in the patients with albuminuria was higher than that in the patients without albuminuria (P < 0.01), and the sensitivity, specificity and positive predictive value were 77.8%, 92.3% and 93.3% respectively (> 35.54 microg/L as its positive criterion). For diabetes, the PTM level in complication group was higher than that in group without complications, the sensitivity, specificity and positive predictive value were 53.4%, 97.1% and 98.6% respectively (> 35.54 microg/L as its positive criterion). The PTM level in microangiopathy group was higher than that in macroangiopathy group (P < 0.01). The sensitivity, specificity and positive predictive value were 71.2%, 97.1% and 97.9% respectively. Acute leukemia (AL) and multiple myeloma (MM) had higher PTM level and PTM level was extremely high when renal failure developed (P < 0.01). As compared the acute stage with the restoration stage in stroke, pre-chemotherapeutics with post-chemotherapeutics in AL and MM, and pre-operation with post-operation in cancer, the PTM level was connected with clinical development. The PTM level in the patients with microangiopathy was higher than that in the patients with macroangiopathy (P < 0.01). The defined PTM level was higher than its normal upper limit as PTM positive criterion in microangiopathy diseases, the sensitivity, specificity and positive predictive value were 77.7%, 71.2% and 75.6% respectively. It is concluded that PTM level is a good criterion in evaluating the microangiopathy, and PTM is also a valuable indicator in prediction or assessment of the severity of diseases, or evaluation of therapeutic effectiveness.