Biomedical subjects

Shan-Shan Chen

Publications and source records attributed to Shan-Shan Chen.

30 records · Page 2Linked to original sources

PubMed2003

[Follow-up detection of M-bcr/abl and m-bcr/abl fusion transcripts in chronic myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation].

In order to investigate the features of M-bcr/abl and m-bcr/abl fusion transcripts in patients with chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (SCT), M-bcr/abl and m-bcr/abl fusion transcripts were sequentially detected by RT-PCR technique in 72 CML patients after SCT. The results showed that M-bcr/abl positive rate (79.2%, 42/53) within 6 months after SCT was remarkably higher than that in 6-12 months group (34.3%, 11/32) and >or= 12 months group (35.1%, 13/37) (P < 0.001), and the clinical relapse rates in corresponding periods were 1.9% (1/53), 0% (0/32) and 16.2% (6/37) respectively. M-bcr/abl and m-bcr/abl fusion transcripts occurred in 5 of 6 clinically relapsed patients. In period of more than 6 months after transplantation, none of 17 M-bcr/abl(+) samples from 14 patients in cytogenetic remission appeared positive reaction of m-bcr/abl. It is concluded that M-bcr/abl(+) fusion transcript still existed in most patients after SCT, and usually disappeared within 6 months. Existence of M-bcr/abl is not a clinical relapse marker in CML patients. Simultaneous detection of M-bcr/abl and m-bcr/abl fusion transcripts can be helpful for monitoring residual disease.

Adolescent↗

PubMed2002

Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study.

OBJECTIVE: To evaluate the safety and efficacy of once daily doses of tenofovir DF (TDF) administered in combination with other antiretroviral therapy (ART) in treatment-experienced HIV-1-infected patients with incomplete virological suppression. DESIGN: One-hundred and eighty-nine subjects with plasma HIV-1 RNA levels between 400 and 100,000 copies/ml and stable ART (> or = 8 weeks) were randomized (2 : 2 : 2 : 1 ratio) to add TDF 75 mg, 150 mg, or 300 mg or placebo to existing ART in a double-blinded manner. After 24 weeks, patients initially randomized to placebo received blinded TDF 300 mg. METHODS: Efficacy was analyzed by the mean changes HIV-1 RNA levels (log10 copies/ml plasma; DAVG(xx)) from week 0 to weeks 4, 24, and 48. Safety was analyzed by incidence of grade 3 or 4 clinical and laboratory adverse events. RESULTS: At baseline, patients had mean 4.6 years prior ART use with 94% having HIV-1 with nucleoside-associated resistance mutations. There were statistically significant decreases in DAVG(4) and DAVG(24) for all doses of TDF compared with placebo, with the greatest effect seen with TDF 300 mg (DAVG(4), -0.62, P < 0.001; DAVG(24), -0.58; P < 0.001; DAVG(48), -0.62). The incidence of adverse events was similar among the TDF groups and placebo through week 24. Throughout the 48-week study, no significant changes in renal function were observed. CONCLUSIONS: In treatment-experienced patients with baseline nucleoside resistance mutations, TDF provided dose-related, durable reductions in HIV-1 RNA. Through 24 weeks, the safety profile of TDF was similar to that of placebo.

Adenine↗

PubMed2002

Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report.

In the past 6 years, we treated 129 patients who had acute promyelocytic leukemia (APL) with a new arsenic agent, oral tetra-arsenic tetra-sulfide (As(4)S(4)). Nineteen of the patients had newly diagnosed APL, 7 had first relapse, and 103 had hematologic complete remission (HCR). HCR was achieved in all patients with newly diagnosed APL and in all those with hematologic relapse. Of 16 patients with newly diagnosed disease and available cytogenetic and molecular analyses, 14 had cytogenetic and molecular complete remission (CR). Cytogenetic and molecular CR was also obtained in 5 of the 7 patients with hematologic relapse. In the HCR group, 35 of 44 patients positive for PML-RARalpha at baseline became negative. In the newly diagnosed group, estimated disease-free survival (DFS) rates for 1 and 3 years were 86.1% and 76.6%, respectively, with a median follow-up time of 13.5 months (range, 2-40 months). In the HCR group, DFS rates for 1 and 6 years were 96.7% and 87.4%, respectively, with a median follow-up of 23 months (range, 2-71 months). Treatment with As(4)S(4) was well tolerated, with only moderate side effects, including asymptomatic prolongation of corrected QT interval, transient elevation in liver enzyme levels, rash, and mild gastrointestinal discomfort; neither myelosuppression nor appreciable long-term side effects occurred. Degeneration or apoptosis of APL promyelocytes was observed during As(4)S(4) therapy. Pharmacokinetic studies showed that the agent was absorbed rapidly. Most urinary arsenic excretion occurred within the first 24 hours. Both blood and urinary arsenic levels declined after discontinuation of As(4)S(4). Our results show, for the first time, that As(4)S(4) treatment alone is highly effective and safe in both remission induction and maintenance therapy in patients with APL, regardless of disease stage.

Adolescent↗

PubMed2002

[The application of 4-color fluorescence labeling antibodies and its significance in immunophenotyping for leukemia by flow cytometer].

To prove the significance of 4-color fluorescence labeling flow cytometric analysis for leukemia immunophenotyping, bone marrow and peripheral blood samples from 88 cases with acute leukemia were analyzed by means of flow cytometry with 4-color fluorescence labeling monoclonal antibodies (McAbs). More than 90% of cases could be classified into acute myeloid, T- or B-lymphocytic leukemia by staining with 13 different kinds of monoclonal antibodies within 4 tubes of combination of antibodies. AML-M(2) - M(7) could also be identified simultaneously. Another one tube of combination of 4 McAbs could be used for further subtyping of those who were undetermined by the above 4 tubes. Patients with AML-M(0)/M(1) which may be negative of myeloperoxidase (MPO) in cytochemistry can be identified by labeling with both membrane and cytoplasmic antibodies. In conclusion, the accuracy of leukemia immunophenotyping has been improved by 4-color flow cytometry analysis.

Adolescent↗

PubMed2002

[Immunophenotypic characteristics of multiple myeloma cells].

To investigate the immunophenotypic characteristics of multiple myeloma (MM) cells, 20 bone marrow samples from patients with multiple myeloma were analyzed by flow cytometry with three-color direct immunofluorescence staining. Results showed that all of myeloma cells expressed bright CD38, dim or negative CD45 and negative CD19. Most of the cells were CD56(+) and a small portions were ckappa(+) or clambda(+), or CD20(+). The phenotypes of normal plasmocyte, CD19(+) and CD56(-), except CD56(-) in one-third samples, were not appeared in all detected samples. It was concluded that the surface marker analysis of myeloma cells is a useful tool for diagnosis and further evaluating prognosis of multiple myeloma.

ADP-ribosyl Cyclase↗

PubMed2002

[Flowcytometric-immunophenotyping for leukemia needs to be standardized].

Flowcytometer has been flourishing since the passed decade in our nation. Many general hospitals use it for routine tests. One of the main usage is immunophenotyping for hematological malignancies. Flowcytometric immunophenotyping (FCM-IM) facilitates accurate diagnosis in both leukemias and lymphoid proliferative disorders (LPDs). It becomes an indispensable criteria in the diagnosis of hematological malignancies. It may also offer additional therapeutically relevant information. Typical patterns of immunophenotype in leukemias and certain types of LPDs are illustrated in figure 1 and figure 2. But variation or overlapping appears often. In order to reach a definitive diagnosis and to have a common interpretation between laboratory to laboratory the following items need not to be ignored: 1. Direct staining and multi-color or multi-parameter flow cytometric analysis is necessary. 2. The phenotype of abnormal cells should be determined on as pure a population as possible therefore CD45/SSC gating is critical for isolating the blast population (abnormal cells). CD45/SSC gating is much better than FSC/SSC gating especially when percentage of blast is low in the sample. Else, each subtype of leukemia has its special CD45/SSC pattern. 3. The phenotype of this certain population should be described clearly but it is not necessary to count the percentage of each marker. 4. > 20% for positive threshold used in indirect staining method may be confused in multi-color direct staining method. 5. Hybrid leukemia diagnosed by FCM only should be in caution since the divergence of antigen/antibody, the lineage infidelity of antigen expression and the biological characteristics of the leukemic cells. Flowcytometer is not a cell counter. "It provides a pattern of information that must be interpreted by a knowledgeable professional in the context of the clinical situation".

Antigens, CD↗

PubMed2002

[Detection of cytoplasmic antigens by flow cytometry and its implication for leukemia immunophenotyping].

The purpose of this study was to optimize a fixation procedure for detection of cytoplasmic antigens by flow cytometry(FCM) and to evaluate the effect of intracellular CD3, CD22, CD79a and myeloperoxidase(MPO) in lineage assignment. Four kinds of fixation procedure and three or four color direct immunofluorescence staining were used to permeate cell membrane and label cell surface and intracellular antigens by means of FCM. Results showed that percentage of cytoplasmic antigens positive cells was the highest and cell scatter and fluorescence intensity of CD45 were not changed after using of FACS permeabilization solution. MPO protein was positive in 16/18 acute myeloid leukemia(AML) patients. 4 cases of T cell-acute lymphoblastic leukemia (T-ALL) cases were positive for cytoplasmic CD3(c CD3) but surface CD3 was negative. c CD22 was only detected in 9/13 of B-ALL and cCD79a was positive in 5/5 B-ALL. 18/38 cases of acute leukemia were expressed in more than one lineage marker, 8/21 cases of acute non-lymphocytic leukemia(ANLL) were CD7 positive. 7/17 cases of acute lymphocytic leukemia (ALL) expressed CD13. After further cytoplasmic antigen detection, one was considered to be a T/myeloid biphenotypic leukemia, another one was diagnosed as biclonal or mixed leukemia. The results suggest that intracellular CD3,CD22,CD79a and MPO are lineage specific markers, they are very important for biphenotypic and biclonal/mixed acute leukemia identification

Adolescent↗

PubMed2001

[Effect of Autocrine VEGF on Chronic Myeloid Leukemia Cell Line K562]

Vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells. It has been associated with angiogenesis, growth, metastasis and poor prognosis in solid tumors. Lately, it has been known that VEGF expression is higher in bone marrow from chronic myeloid leukemia (CML) patients than that in normal subjects. However, it is not clarified that the effect of VEGF on the abnormal proliferation of CML cells. In order to explore the effect of autocrine VEGF on CML cells, K562 cells were transfected with the VEGF(121) cDNA sense vector (K562/S) or with the VEGF(121) cDNA antisense vector (K562/As). K562 cells were transfected with the pcDNA(3) vector (K562/V) as the control. Cell proliferation was determined by MTT and colony forming assay in vitro. Flow cytometric Annexin-V-FITC/PI dual labeling technique was performed to observe the effect of VEGF(121) cDNA transfection on apoptosis of K562 cells. Results indicated that K562/S transfectants exhibited a 3-fold increase in VEGF secretion, and K562/As transfectants exhibited a 49% reduction in VEGF secretion. K562/As showed a reduced growth rate and colony forming efficiency as compared to K562/V. K562/S showed an increasing growth rate and colony forming efficiency as compared to K562/V. K562/As had more apoptotic cells than K562/V and K562/S in the same culture condition. These data suggest that VEGF plays an important role in the abnormal proliferation and apoptosis in CML cells through an autocrine mechanism.

Journal Article↗

PubMed2001

[Low Concentrations of STI571 Enhances beta1 Integrin Mediated Inhibitory Effect on Proliferation of Myeloid Progenitors in Ph(+)Chronic Myeloid Leukemia]

To investigate whether ABL specific tyrosine kinase specific inhibitor STI571 can restore beta1 integrin mediated negative effect on Ph(+) chronic myeloid leukemia(CML), the inhibitory effect of beta 1 integrin activator (beta1 integrin activating antibody 8A2, cytokines such as GM-CSF, G-CSF and SCF) and/or FN on the granulocyte-macrophage colony forming unit (CFU-GM) from 16 patients with Ph(+)CML and 13 normal individuals were examined; the bone marrow mononuclear cells (BMMNC) before and after ABL kinase specific inhibitor STI571 pretreatment (0.1 micro mol/L for 30-60 minutes) were target cells in this study. The roles which VLA4 and VLA5 played in this process were evaluated through blocking assay. The results showed: (1) beta1 integrin activator(s) or FN alone have no effect on CFU-GM from CML or normal bone marrow mononuclear cells before or after STI571 pretreatment, nor STI571 pretreatment itself. (2) The inhibitory effect of beta1 integrin activator(s) plus FN on CML CFU-GM are significantly lower than that on normal CFU-GM. (3) The inhibitory effect of beta1 integrin activator(s) plus FN on CML CFU-GM after STI571 pretreatment is comparable to that on normal CFU-GM. (4) Monoclonal antibody to VLA4 and VLA5 or to total beta1 integrins almost completely abrogate the above effect of STI571. The results suggested enhancing beta1 integrin mediated negative effect on myeloid progenitors in Ph(+)CML is one of the therapeutic mechanisms of STI571 on Ph(+)CML.

Journal Article↗

PubMed2001

[Follow up Detection of AML/ETO Fushion Transcripts after Chemotherapy or Bone Marrow Transplantation in Leukemia Patients]

Expression of AML1/ETO mRNA was observed in bone marrow cells from 49 untreated leukemic patients, and continuously detected during different periods after chemotherapy (12 cases) or bone marrow transplantation (8 cases). The results showed that AML1/ETO mRNA could be expressed in cells from AML-M(2), AML-M(4) and MDS-RAEB-T patients. The positive expression changed into negative at different duration in patients who achieved complete remission either by chemotherapy (9 cases), allogeneic bone marrow transplantation (5 cases) and autologous peripheral blood stem cell transplantation (1 case), and they were sustained in complete remission status. In chemotherapeutic group, patients whose AML1/ETO expression turning from negative (2 cases) or faint positive (1 case) to positive relapsed later. Two patients treated with Allo-BMT showed continuously positive results and died of GVHD and relapse, respectively. These observations suggest that AML1/ETO chimeric mRNA could disappeared after chemotherapy or bone marrow transplantation. The patients have a great probability to relapse if the results of RT-PCR are continuously positive or change from negative to positive. Regular detection is necessary for leukemic patients.

Journal Article↗

PubMed2001

[Expression of Vascular Endothelial Growth Factor in the Bone Marrow Cells from Adult Chronic Myelogenous Leukemia]

Vascular endothelial growth factor (VEGF) is one of the main angiogenic cytokines and plays an important role in the development of human solid tumors. However, it is not clarified whether VEGF governs the progress of the chronic myelogenous leukemia (CML). This study is to estimate VEGF expression in the bone marrow cells from normal and adult CML patients and various leukemic cell lines. Reverse transcription-polymerase chain reaction (RT-PCR) was used for detection of VEGF mRNA. VEGF concentrations in the cell cultural supernatant and the plasma from normal and CML patient bone marrows were determined by enzyme linked immunosorbent assay (ELISA). VEGF mRNA was positive in 67 of 72 cases of bcr/abl(+) CML patient bone marrow cells (93.1%), in 5 of 10 CML patients post Allo-BMT bone marrow cells (50%), and in 6 of 10 normal bone marrow cells (60%), the expression rate of VEGF mRNA in CML patients bone marrow cells was higher than that in CML patients post Allo-BMT and normal bone marrow cells. VEGF mRNA also expressed in the HL-60, K562, CEM, KG1a, NB4, and Nalm6 cells, but not in the Jurkat cells. The mean VEGF concentration in the plasma (380.6 pg/ml) from 22 untreated CML patients was 9 folds higher than that from 9 CML patients post Allo-BMT (38.0 pg/ml). The mean VEGF concentration in the cultural supernatant (499.8 pg/ml) of 17 newly diagnosed CML bone marrows was 2.5-folds higher than that in 11 normal donors (141.3 pg/ml). The CML marrow cells secrete more VEGF than normal marrow cells do. Our results suggest that the abnormality of VEGF transcription and translation expression may play an important role in the development of CML.

Journal Article↗

PubMed2001

[Expression of AC133 Antigen on Acute Leukemia Cells]

To investigate the expression of AC133 antigen on acute leukemia cells and its clinical significance, samples of 29 patients with acute lymphocytic leukemia (ALL) and 32 patients with acute myelocytic leukemia (AML) were analyzed by flow cytometric three-color direct immunofluorescence methods. It was found that 13 of 29 ALL, 6 of 8 AML-M(0)/M(1), 4 of 16 AML-M(2) and 4 of 8 AML-M(4)/M(5) expressed AC133. The mean fluoresence intensity of AC133 in each subtype of AML-M(0)/M(1), AML-M(2) and AML-M(4)/M(5) was 227.1, 143.1 and 142.5, respectively. Among 27 AC133(+) cases (44.3%), 25 cases coexpressed CD34 (92.6%) and 13 cases coex- pressed CD117 (48.1%). In contrast to other reports, our data do not support the findings that AML-M(4)/M(5) expressed very high levels of AC133. In conclusion, AC133 antigen, coexpressed with CD34 and CD117, appears more frequently and more intensely in AML-M(0)/M(1).

Journal Article↗