Biomedical subjects
Publications and source records attributed to Bing Xu.
N-(Fluorenyl-9-Methoxycarbonyl) dipeptides form supramolecular hydrogels via hydrogen bonding and hydrophobic interactions. These hydrogels respond to a ligand-receptor interaction as well as to thermal or pH perturbation and also exhibit chiral recognition.
Dimers of vancomycin (Van), linked by a rigid metal complex, [Pt(en)(H(2)O)(2)](2+), exhibit potent activities (MIC approximately 0.8 mug/mL, approximately 720 times more potent than that of Van itself) against vancomycin-resistant enterococci (VRE). The result suggests that combining metal complexation and receptor/ligand interaction offers a useful method to construct multivalent inhibitors.
OBJECTIVE: To explore the benefit of autologous transplantation of interleukine-2 activated bone marrow (ABM) in acute promyelocytic leukemia (APL) as consolidation therapy. METHODS: 31 patients with APL, 27 in first complete remission (CR1), 3 in CR2, and 1 in partial remission (PR) after the second relapse, were treated with autologous transplantation of ABM. The conditioning regimens included MACC protocol (Melphalan, Ara-C, CTX, and CCNU) in 26 patients and TBI + CY protocol in 5 patients. The PML/RARa fusion gene was measured by fluorescence in situ hybridization. Kaplan-Meier survival analysis model was used to estimate the disease-free survival (DFS) rate at 5 years post-transplantation and COX regression model was used to analyze the DFS-influencing factors, including sex, PML/RARa positive state, pre-transplantation state (CR1, CR2, or PR), white blood cell (WBC) count, and platelet (PBC) count. RESULTS: The 27 patients in CR1 had a DFS time of 3 to 113 months (with a mean DFS time of 46 months), and a 5-year DFS rate of 100%; none of them suffered a relapse after transplantation. One of the 3 patients in CR2 relapsed in 19 months after the transplantation and the other two patients had been in DFS state for 7 and 33 months respectively. The patient in PR obtained CR and relapsed 8 months after the transplantation. All the patients showed reconstitution of hematopoiesis. None of the patients died of transplantation-related complication. Multivariate analysis showed that long-term survival was correlated with the pre-transplantation statues and not with sex, positivity of PML/RARa, and WBC and PBC counts. CONCLUSION: Autologous transplantation of ABM reduces the relapse and increases the long-term survival in the patients with APL in CR, especially in CR1.
A vancomycin (Van) derivative self-assembles in a phosphate buffer as a divalent Van and on cell surfaces as a multivalent Van, which offers potent activity against VRE.
After conjugation to vancomycin (Van), chemically stable and highly magnetic anisotropic FePt magnetic nanoparticles (approximately 4 nm) become water-soluble and capture E. coli at 15 cfu mL(-1).
This paper reports a simple, additive process to generate patterned polymer films without using any solvent. This process involves a highly efficient catalyst, a Grubbs's catalyst, and a volatile monomer, norbornene. The catalyst and monomers have higher local concentrations inside the microchannels, formed by contacting poly(dimethylsiloxane) stamps to a solid surface, and allow the polymeric thin films to be defined by the microchannels. The patterned thin film serves as an excellent resistant to reactive ion etching, which promises that this process is a complementary, useful alternative to spin-coating and plasma polymerization in microfabrication.
Segmented conducting polymers based upon a calix[4]arene scaffold are reported. The cone conformation creates a zigzag orientation of the polymer segments. Their acid-dependent conductivities are similar to the strong pH conductivity dependence of polyaniline which is said to be acid dopable. On the other hand, they have a segmented structure that imposes greater localization of the carriers. The conductivity of such a system can be considered to result from rapid self-exchange between discrete units. Hence, electron exchange between radical cations and p-diquinone salts produces the high conductivity of these polymers.
The cribriform-morular variant (C-MV), an unusual and peculiar subtype of papillary thyroid carcinoma (PTC), has been observed frequently in familial adenomatous polyposis (FAP)-associated thyroid carcinoma and also in sporadic thyroid carcinoma. In this paper, five young women with the C-MV of PTC, aged 22-34 years at cancer diagnosis, are reported; two of them had attenuated FAP. Grossly, one FAP-associated tumour and one sporadic tumour were multicentric and the others were solitary. Histologically, the tumours were encapsulated and exhibited a combination of cribriform, follicular, trabecular, solid, and papillary patterns of growth, with morular areas. Immunohistochemically, the tumour cells showed cytoplasmic expression of thyroglobulin, neuron-specific enolase, epithelial membrane antigen, high- and low-molecular-weight cytokeratins, vimentin, and bcl-2 protein; nuclear expression of oestrogen and progesterone receptors, and retinoblastoma protein; and cytoplasmic and nuclear accumulation of beta-catenin. Germline mutations of the adenomatous polyposis coli (APC) gene were investigated using the protein truncation test in four subjects, including two FAP individuals. Germline APC mutation was identified in only one FAP patient with the multicentric C-MV of PTC, who had a thymidine deletion at codon 512, resulting in a frameshift leading to a premature stop codon. No loss of heterozygosity of loci close to the APC gene was detected in tumour tissues from these four patients. Somatic mutation analysis of exon 3 of the beta-catenin gene (CTNNB1) revealed alterations in seven tumours from all five individuals: one at a serine residue (codon 29), three at amino acids adjacent to serine or threonine residues (codons 22, 39, and 44), and three at other amino acids (codons 49, 54, and 56). Moreover, each of two different tumours examined from two patients with the multicentric C-MV of PTC, had different somatic mutations of the CTNNB1 gene. Taken together, these data suggest that accumulation of mutant beta-catenin contributes to the development of the C-MV of PTC.
We report an unusual case of spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid present in a 6-year-old boy. The tumor, located at both the left lobe and isthmus, was a circumscribed mass with slightly gritty whorled appearance. Microscopically, the lobulated, highly cellular, spindle cell neoplasm was arranged in intersecting bundles and fascicles separated by fibrous bands. Benign-appearing glands entrapped within fibrous bands and foci of squamous differentiation within spindle cells were observed. Immunohistochemically, the spindle cells were diffusely positive for cytokeratins, vimentin, and alpha-smooth muscle actin and patchily reactive for muscle-specific actin and epithelial membrane antigen, exhibiting myoepithelial differentiation. The spindle cells were also patchily immunopositive for p53 protein. Molecular genetic analysis revealed Ki-ras gene mutations at codons 13 (GGC(gly) to AGC(ser)) and 15 (GGC(gly) to AGC(ser)) on the same allele. Mutation of the p53 gene was not detected. This is the first report on Ki-ras oncogene mutations in a case of SETTLE.
BACKGROUND & OBJECTIVE: The aim of this study was to investigate the clonal T cell receptor (TCR) gene rearrangement in the patients with non-Hodgkin's lymphoma (NHL) and its clinical significance. METHODS: TCRVgammaI-Jgamma gene rearrangement were detected in 43 patients with polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP). RESULTS: Of 43 cases of NHL, 26 (60.5%) were found with clonal TCRVgammaI-Jgamma gene rearrangement. Among 16 cases without bone marrow morphologic involvement,3 cases (18.8%) were found with clonal TCRVgammaI-Jgamma gene rearrangement. These 3 cases presented bone marrow morphologic involvement 4-9 months later. Clonal TCRVgammaI-Jgamma gene rearrangement were detected in 85.2%(23/27) cases with bone marrow morphologic involvement. Among 26 cases with clonal TCRVgammaI-Jgamma gene rearrangement, 7 cases (26.9%) was found with oligoclonal/subclonal rearrangement after PCR-SSCP analysis. Of 7 cases with oligoclonal/subclonal rearrangement, 5 (71.4%) developed to leukemia 3-11 months later. The number of NHL patients with oligoclonal/subclonal rearrangement developed to leukemia was significantly higher than that (10.5%) of NHL patients without oligoclonal/subclonal rearrangement (P< 0.005) within 1 year. CONCLUSION: The detection of clonal TCRVgammaI-Jgamma gene rearrangement by PCR methods can be used to find bone marrow minimal disease in NHL patients without morphologic abnormality. NHL patients with oligoclonal/subclonal rearrangement are more likely to develop to leukemia; it can also develop to acute nonlymphoblastic leukemia. Further investigation was needed in this respect.
BACKGROUND & OBJECTIVE: Glivec was approved by Food & Drug Administration (FDA) in May 2001 as a gene target drug for treatment of chronic myeloid leukemia (CML) and showed a good curative effect for patients with chronic myeloid leukemia in chronic phase. But its effectiveness was poor in patients with CML blast phase treated with Glivec alone. Glivec was reported having synergetic effect with other chemical agents in vitro, but there is few report in clinical combined application. In this paper, we analyzed effectiveness of Glivec in combination with homoharringtonine (HHT) and cytarabine (Ara-C) for patients with Ph chromosome positive acute leukemia (Ph(+)-AL), and investigated patients' tolerance to side effects of this trial. METHODS: A total of 20 patients (16 males and 4 females, median age was 43 years) were eligible. Blasts in peripheral blood (PB) or bone marrow (BM) were both more than 30%, bcr/abl fusion genes were detected positive in 90% cells by analysis of karyotype or fluorescence in situ hybridization (FISH). Five patients showed t(9;22) and other 15 patients showed more complicated chromosome abnormality. Of these 20 patients, 17 patients developed Ph(+)-ANLL from CML, 1 case developed Ph(+)-ALL, and other 2 cases were primary Ph(+)-ALL. The median interval from diagnosis to Glivec treatment was 4 months. Eighteen of 20 patients received different chemotherapy regimens for 2-4 treatment cycles, but no one reached hematological complete remission (HCR). All patients were given oral Glivec daily at the doses of 0.3-0.6 g in a median treatment time of 2.5 months (range, 1-6.5 months). Ph(+)-ANLL patients were infused with HHT over 6-24 hours daily at the doses of 1-2 mg intravenously and Ara-C 30-50 mg daily subcutaneously for 10-14 days; 3 patients with Ph(+)-ALL received HOAP or DOP combination treatment regimens (One cycle consists of HA with the same dosage described above for Ph(+)-ANLL patients for 7 days, daunorubicin at the dose of 40 mg/d intravenously for 3 days, vincristine at the dose of 2 mg/wk for two weeks, and prednisone at the doses of 60-80 mg/d for 14 days). Median treatment cycle was 2 (range, 1-3). The dosage of Glivec could be reduced or treatment was suspended when bone marrow inhibition happened. G-CSF was used when necessary. The curative effect was evaluated by international hematology and cytogenetics standards, in which bone marrow was examined every chemotherapy cycle and chromosome was analyzed 3 months later. RESULTS: Among the 20 patients receiving Glivec, 40% achieved HCR, and 25% achieved hematological partial remission (HPR), but only 15% patients approached a partial cytogenetic remission and no cytogenetic responses were found in other 85% patients. White blood cells (WBC) in peripheral blood reduced from 41+/-31 x 10(9)/L to normal level within 1 week. The blasts decreased from (50+/-30)% to(1.9+/-2.9)% (P< 0.001) in median time of 21.0+/-16.8 days. Three patients with high fever recovered normal temperature after 3 days treatment. When follow-up median time at 8 months, the total survival rate reduced to 40%, the rate of death and lost follow-up number of patients added to 60%. CONCLUSION: Regimen of Glivec in combination with HA could increase chemotherapy effect for the patients with Ph(+)-AL, prolong their life time and the side-effects were tolerable.
Microtus fortis(Taxonomy ID: 100897), also named as reed vole, is classified as Microtus, Micotinae, Cricetidae, Rodentia, Mammalia on taxonomy. Microtus fortis mainly distributes in China. Some areas of Russia, North Korea and Mongolia close to Northeast borderland of China also have a small number of Microtus fortis in distribution. Microtus fortis in China has principally 4 subspecies, and most of them live is the drainage area of Yangtse River. Schistosoma japonicum (one of commonly parasites in China) can infect about 40 kinds of mammalian animals, including the human being, but could not infect Microtus foris. It is known as the only animal in Dongting Lake region of China which has the ability of natural resistance to Schistosoma japonicum. The Microtus fortis domesticated in laboratory has the same biological characteristics as the wild one and these characteristics could be inherited to its progeny steadily. We got a specific DNA fragment from genomic library of Microtus fortis. This DNA fragment in genomic DNA of human beings, Kunming mice, Balb/c mice and C57BL/6J mice could not be detected by dot blot hybridization and PCR, apart from genomic DNA of Microtus fortis. In this report, the differences of genomic DNA in 34 Microtus fortis were compared between Microtus fortis calamorum(Dongting Lake region of southern China) and Microtus fortis fortis (Ningxia province of northern China). The residing localion of these two subspecies is far away about 1,200 kilometers from each other. The genomic DNA of Microtus fortis calamorum and Microtus fortis fortis were extracted and amplified by PCR according to the specific genomic DNAs sequence of Microtus fortis reported previously (Accession number in GenBank: AF277394). The amplified DNA fragments were inserted into pGEM-T easy vector and sequenced. The DNA fragment sequencing results from the two subspecies were compared to detect whether there was any difference. 19 alleles were found from Microtus fortis (20 of Microtus fortis calamorum and 14 of Microtus fortis fortis). The results of multiple sequence alignment showed that 25 single nucleotide polymorphism (SNP) sites were existed in the different Microtus fortis individuals, including transition (G-->A,A-->G,T-->C,C-->T), transversion(G-->T,A-->T,T-->A,C-->A), insertion (CA) and deletion (TGTTTT). The difference of genomic DNA from two subspecies were obvious, especially on the sites of 146, 192, 223, 224 and 235. The insertion of CA on the sites of 223 and 224 as well as A-->G transition on the site of 235 was only occurred in Microtus fortis fortis. They are not found in Microtus fortis calamorum so far. They could be divided into two groups according to phylogenetic tree analysis results, one was the genomic DNA of Microtus fortis calamorum and the other one was that of Microtus fortis fortis. However, the homologues reached up to 98% between two subspecies. These results are very important for us to further understand the genetic background, biological characteristics, evolutionary rule and the anti-schistosoma japonicum mechanism of Microtus fortis at the molecular levels. The specific base changes of the DNA fragment between the two subspecies are probably correlative with the animal immigration, survival conditions, and species evolution.
OBJECTIVE: To analyze the prognostic factors in patients with refractory acute myeloid leukemia, so as to provide theoretical basis for choosing an appropriate chemotherapy. METHODS: This study included 48 patients with refractory acute myeloid leukemia who received two standard DA regimens followed by chemotherapy with median dose of Ara-C and mitoxantrone. The factors such as age, gender, responses to the standard chemotherapy, cytogenetic abnormalities, blast cell counts in the bone marrow, peripheral blood cell counts, extramedullary infiltration exhibition and LDH were examined in light of their respective impact on the patients' survival. Cox regression model was used to analyze the prognostic factors. RESULTS: The results revealed that the factors such as achievement of the first complete remission after standard induction chemotherapy, the remission duration longer than 6 months, favorable cytogenetic abnormalities, blast cell counts less than 50% in bone marrow, absence of severe anemia, absence of liver or pancreatic enlargement or central nerves system (CNS) leukemia, and LDH less than 360 U/L, all indicated favorable prognosis of the patients. Age, gender, white cell counts in periphery blood or lymphadenopathy were not related to the survival of the patients. CONCLUSION: The patients with favorable prognostic factors should receive intensive chemotherapy for prolonged survival; allogeneic bone marrow transplantation should be performed as soon as possible in patients with unfavorable prognostic factors.
OBJECTIVE: To study the immunophenotyping of adult patients with acute leukemia and its association with the prognosis. METHODS: Immunophenotyping was performed in 106 adult patients with acute leukemia by three-color flow cytometry analysis using CD34/SSC gating. RESULTS: The antigens expressed in 71 patients with acute myeloid leukemia (AML) were mainly CD13, CD33, HLA-DR, CD34 and CD117. Lymphoid antigen expression was identified in 23.9% adult AML patients and CD56 antigen expression in 15.5% of the AML patients. In 29 patients with acute lymphoblastic leukemia (ALL), the expressed antigens were mainly HLA-DR, CD10, CD19, CD34 and CD7, and 34.5% of these patients were found to be positive for myeloid antigen expression. Complete remission (CR) rate in AML patients with lymphoid antigen expression after chemotherapy was lower than that in AML patients without lymphoid antigen expression (52.9% vs 77.8%, P<0.05), and no significant impact was noted of myeloid antigen expression in ALL on the CR of the patients (70.0% vs 94.7%, P>0.05). The CR rate in AML with CD56 antigen expression was lower than that in AML without CD56 expression (36.4% vs 78.3%, P<0.025), and the CR rate in CD34+ AML was lower than that in CD34- AML (56.0% vs 80.4%, P<0.05). CONCLUSIONS: Gating of CD45/SSC can eliminate the interference of normal cells to render more reliable immunophenotyping results. The expressions of CD56+, CD34+, lymphoid antigen in adult AML patients, who have lower CR rate, often signify poor prognosis.
OBJECTIVE: To evaluate the therapeutic effect of modified FLAG regimen in the management of refractory acute myeloid leukemia (AML). METHODS: Sixteen patients with refractory AML were divided into two groups. In modified FLAG regimen group (n=10), the patients received fludarabine (Flu, 50 mg/d, VDx5 d) and Ara-c (200 mg/d, VDx5 or 7 d). The regimen for classic FLAG group (n=6) consisted of Flu (50 mg/d, VDx5d), Ara-C (500 or 1,000 mg/d, VDx5d) and G-CSF (300 microg/d, x5 d, subcutaneously injected 4-6 hours before chemotherapy). Each patient received subcutaneous G-CSF (300 microg/d) when the white blood cell count was lower than 1.0x10(9)/L till the condition was corrected. RESULTS: The total complete remission(CR) rate of the 16 patients was 50% (8/16). Seven patients in modified group achieved CR (70%) and only one of the classic group did (17%, P<0.05). Episodes of infections were lower in modified group than in the classic group (50% vs 83%). CONCLUSION: Modified FLAG regimen is more likely than classic FLAG regimen to achieve CR and reduce infections in patients with refractory AML.
OBJECTIVE: To evaluate the efficacy of quadruple therapy with cyclosporine (CsA), methotrexate (MTX), mycophenolate mofetil (MMF) and low-dose antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis in unrelated donor hematopoietic stem cell transplantation (URD-HSCT). METHODS: Thirteen patients with leukemia received URD-HSCT, of whom 11 had HLA genotypes and 2 had mismatch for 1 genetic locus. Another 11 leukemia patients all serologically matched underwent related donor (RD)-HSCT. Total body irradiation (TBI) plus cyclophosphamide (CTX) was adopted in 19 cases and modified BuCY conditioning regimen (hydroxyurea, busulfan, Ara-C, Cyclophosphamide ) in the other 5 cases. All the patients received CsA+MTX protocal for GVHD prophylaxis, and in those undergoing URD-HSCT, additional MMF and low-dose ATG were used. RESULTS: The incidence and severity of regimen-related toxicity differed little between unrelated and related transplantation. Acute GVHD (aGVHD) occurred in 46.2% of the patients undergoing URD- HSCT and in 55.6% of those with RD-HSCT, respectively. Four patients had chronic GVHD (cGVHD), in the 7 ones who could be followed up after URD-HSCT; 6 of the 9 patients with RD-HSCT developed cGVHD postoperatively. One patient with URD-HSCT died of hemorrhagic cystitis and another with RD-HSCT died of cytomegalovirus (CMV) pneumonia. The at one-year disease-free survival rate was 87.5% and 90.9% in patients with unrelated and related transplantation respectively. Significant difference was not noted in the positivity rate of CMV antigen between the patients receiving URD-HSCT or RD-HSCT. CONCLUSION: CsA+MTX in combination with MMF and low-dose ATG may decrease the incidence and severity of aGVHD without increasing transplant-related mortality or CMV infection.
OBJECTIVE: To compare the therapeutic effects of STI 571 in treating Philadelphia chromosome (Ph)-positive patients with chronic-phase and acceleration phase chronic myeloid leukemia (CML-CP and CML-AP, respectively). METHODS: A total of 19 CML patients with Ph chromosome and/or fluorescence in situ hybridization (FISH)-bcr/abl fusion gene positivity rates over 90% and a median age of 38 years were recruited in this study, 12 of whom had previously failed to respond to interferon-alpha. Five of the 19 patients were in accelerated phase and 14 in chronic phase, 9 of the latter patient group in early stage of CML-CP (within 1 year since diagnosis) and 5 in advanced stage (3-6 years since diagnosis). All the patients were given oral STI 571 at the dose of 300-500 mg/d for a median treatment course of 5 months, and the 5 patients with CML-AP also received homoharringtonine at dose of 1-2 mg/d for an average of 1.5 treatment cycles (7-14 d for a complete treatment cycle). The Ph chromosome and the FISH-bcr/abl were analysed again 3 months after the treatment. RESULTS: STI 571 induced 100% complete hematological remission (CHR) and 79% major cytogenetic responses (MCR) in these patients. The complete cytogenetic remission (CCR) rates of CML-AP patients and CML-CP patients in advanced stage were lower than that of CML- CP patients in early stage (0% and 40% vs 88.9%). CONCLUSION: STI 571 can achieve high rate of CHR and MCR in CML-CP patients, especially in those in early stage of the disease.
OBJECTIVE: This study retrospectively analyzed the clinical data of 11 patients with intraosseous neurilemmoma of the jaw, with the purpose of improve its diagnosis and treatment. METHODS: 11 patients with intraosseous neurilemmoma of the jaw treated from January 1993 to February 2002 were reviewed, including the clinical features, pathological findings, immunohistochemical findings, imaging examinations and treatment methods. 8 patients with benign lesions were treated with radical curettage and cautery. 2 patients with mandibular malignant lesions were treated with extended resection and neck dissection. 1 patient with maxillary malignant lesion concomitant with neurofibrostosis was treated with extensive resection and middle split skin graft and neck dissection, followed by chemotherapy and radiotherapy after surgery. RESULTS: The lesions were located in the maxilla in 5 patients (1 was malignant). 6 patients had mandibular lesions (2 were malignant). The X ray findings had some specificity. 10 patients were followed up for 7 to 122 months without recurrence. 1 patient with maxillary malignant lesion died of multiple metastasis 11 months after treatment. CONCLUSIONS: Intraosseous neurilemmoma of the jaw was rarely seen clinically. CT, MRI and fine needle aspiration biopsy were beneficial for early diagnosis. Surgery is still the dominant choice of treatment. The prognosis of the patients was generally good. Adjuvant radiotherapy or chemotherapy had limited value, especially for patients with neurofibrostosis. A novel regime called CYVADICDE was recently invoked much clinical interest.