GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Material
Language
  • 1
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3002-3002
    Abstract: Aggressive natural killer cell leukemia (ANKL) is a rare and highly aggressive subtype of mature NK-cell neoplasms. Similar with extranodal NK/T-cell lymphoma, nasal type (ENKL), another subtype of NK-cell neoplasm, ANKL is also an Asian-prevalent and Epstein-Barr virus (EBV)-related neoplasm. In contrast, our knowledge of ANKL, especially about EBV biological behavior in this rare leukemia, lags far behind that of ENKL and other EBV-related hematopoietic malignancies, such as Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and post-transplant lymphoproliferative disorder (PTLD). Dissection of the virus-host crosstalk in ANKL could contribute to better understanding the mechanism and finding out effective therapy for this neoplasm. In the present study, we investigated EBV-associated biological behavior in serial ANKL patients, including the clinical presentation, EBV genomic DNA, EBV antigens expression, cytogenetic-molecular aberrations, and leukemia-associated microenvironment. A total of 28 ANKL patients were collected upon review of the clinical database in Nanfang hospital. Different items of EBV infection evidence consisted of EBV viremia (n=9), EBV genomic DNA (n=20), and EBER/EBNA/LMP1/LMP2A expression (n=23). EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) was the predominant clinical feature. Bone marrow smear was infiltrated with large granular lymphocyte (LGL) with LMP1/LMP2a-positive bulb, indicating the presence of EBV viral inclusions bodies. Positron emission tomographic (PET)-computed tomographic (CT) scan revealed bone marrow, liver and spleen as the most frequently involved organs, compared with nose and nasopharynx in ENKL. Cytogenetic analysis demonstrated 7q10-32 (n=4) was the “hotspot” of chromosome aberrations in ANKL. PCR analysis with EBNA-2/LMP1 specific primers on reserved DNA samples (n=20) revealed ANKL cells were infected with type-1 EBV strain with wide-type LMP1 (n=20), compared with 30bp-deleted LMP1 gene in ENKL. Integrated mutation analysis (n=20) identified recurrent mutations in Src homology 2 (SH2) domains of STAT5a (n=7) and p16inka (exon 3/4, n=20), but no mutation in SH2 domains of ID2, STAT1, and STAT3. Immunochemical (IHC) analysis on formalin-fixed paraffin-embedded tissues (n=23) revealed latency type-3 EBV expression in ANKL cells, with latency antigens of EBER, EBNA, LMP-1, and LMP-2. Furthermore, LMP-1/LMP-2-positive leukemia/lymphoma-associated macrophages (LAMs, n=23) were enriched in ANKL microenvironment. Notably, EBV-positive LAMs were significantly associated with poor prognosis and disease progression. Univariate analysis revealed significant difference (p 〈 0.05) in overall survival (OS) between High-Ratio of CD68+LAMs/CD56+ANKLs (HMA, n=13) and Low-Ratio LAM/ANKLs cohorts (LMA, n=10). Furthermore, IHC analysis on paired presentation and progression samples (n=3) showed that EBV-positive LAMs increased in pace with disease progression. Conclusions: Our data demonstrate that type-1 EBV strain as being latency type-3 expression infected both leukemia cells and microenvironment and thus linked the pathogen-microenvironment-host crosstalk in ANKL. EBV-infected leukemia-associated microenvironment, particularly LAMs, might not only play a critical role in prognosis classification but also contribute to the leukemogenesis of NK transformation in ANKL, which it’s still poorly understood and deserves more research efforts. Disclosures Zhou: Guangzhou Pearl River of Science and Technology New Star Project: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 21 ( 2022-11-02), p. 3974-3986
    Abstract: Resistance to HER2-targeted therapy represents a significant challenge for the successful treatment of patients with breast cancer with HER2-positive tumors. Through a global mass spectrometry–based proteomics approach, we discovered that the expression of the N6-methyladenosine (m6A) demethylase ALKBH5 was significantly upregulated in HER2-targeted therapy-resistant breast cancer cells. Elevated expression of ALKBH5 was sufficient to confer resistance to HER2-targeted therapy, and specific knockdown of ALKBH5 rescued the efficacy of trastuzumab and lapatinib in resistant breast cancer cells. Mechanistically, ALKBH5 promoted m6A demethylation of GLUT4 mRNA and increased GLUT4 mRNA stability in a YTHDF2-dependent manner, resulting in enhanced glycolysis in resistant breast cancer cells. In breast cancer tissues obtained from patients with poor response to HER2-targeted therapy, increased expression of ALKBH5 or GLUT4 was observed and was significantly associated with poor prognosis in the patients. Moreover, suppression of GLUT4 via genetic knockdown or pharmacologic targeting with a specific inhibitor profoundly restored the response of resistant breast cancer cells to trastuzumab and lapatinib, both in vitro and in vivo. In conclusion, ALKBH5-mediated m6A demethylation of GLUT4 mRNA promotes resistance to HER2-targeted therapy, and targeting the ALKBH5/GLUT4 axis has therapeutic potential for treating patients with breast cancer refractory to HER2-targeted therapies. Significance: GLUT4 upregulation by ALKBH5-mediated m6A demethylation induces glycolysis and resistance to HER2-targeted therapy and represents a potential therapeutic target for treating HER2-positive breast cancer.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 5 ( 2020-02-04), p. 2560-2569
    Abstract: De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains 〈 1% of variation. While we are underpowered to see small differences, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, we did find significantly fewer DNMs in Amish individuals, even when compared with other Europeans, and even after accounting for parental age and sequencing center. Specifically, we found significant reductions in the number of C→A and T→C mutations in the Amish, which seem to underpin their overall reduction in DNMs. Finally, we calculated near-zero estimates of narrow sense heritability ( h 2 ), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Food Chemistry, Elsevier BV, Vol. 309 ( 2020-03), p. 125737-
    Type of Medium: Online Resource
    ISSN: 0308-8146
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1483647-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    In: Frontiers in Psychology, Frontiers Media SA, Vol. 14 ( 2023-3-9)
    Abstract: The purpose of this study was to assess the psychological status of medical workers from other locations who helped support the fight against COVID-19 in Shanghai and to provide a basis for psychological crisis intervention plans under designated emergencies. Methods While supporting the Shanghai Lingang Shelter Hospital, we investigated 1,097 medical staff from other cities working in the hospital. A questionnaire comprising the general information questionnaire, health questionnaire depression scale, generalized anxiety scale, insomnia severity index scale, and mental health self-assessment questionnaire was used. Results There were no statistically significant differences in the incidence rates of anxiety, depression, and sleep disorders among subjects of different genders, ages, and educational levels. There were statistically significant differences in the incidences of anxiety, depression, stress response, and sleep disturbance among subjects with different levels of worry about COVID-19. Conclusion During the COVID-19 pandemic, the Lingang Shelter Hospital team experienced more psychological pressure, suggesting that medical institutions should pay attention to the mental health of frontline medical workers during COVID-19 and prepare psychological intervention measures for team members.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2563826-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2483-2483
    Abstract: BACKGROUND: Acute hemorrhagic cystitis (HC), a severe complication of hematopoietic stem cell transplantation (HSCT), being considered mainly as a result of cyclophosphamide (CTX), seriously affects the quality of life of patients. Mesna, whose half-life is about 70min, is widely used to prevent HC. OBJECTIVE: Our previous work proved that the continuous intravenous injection of Mesna using micro pump can help prevent HC in HSCT. This study expanded the sample size to research further,Mesna concentration in urine or serum were detected to explore the mechanism of action. METHODS: (1) 394 patients who underwent allogenic HSCT in Nanfang hospital from January 2003 to June 2014were recruited into this study (247male and 147 female). All patients received BuCy or TBI-Cy basedconditioning regimens, in which CTX were given 60mg/kg·d, d-3,-2: or GIAC regimen, in which CTX were given 1.8g/m2, d-5, -4. Intravenous injection of Mesna was used to prevent HC continuously using micro pump (continuous group, n=234) or intermittently (intermittent group, n=160). (2) Patients in two groups received the same daily dose of Mesna. In the intermittent group, 25% of Mesna’s daily dosage was injected at 0h, 3h, 6h and 9h after the use of CTX at each time-point; while in the continuous group, 25% of Mesna’s daily dosage was injected before the use of CTX, with the rest of the dosage being continuously injected intravenously for 24hs using micro-infusion pump (25% daily dosage of Mesna dissolved in 40ml 0.9% sodium chloride lasting for 8h was given, q8h), from the first dose of CTX till 48hs after the last injection of CTX. Incidences and grades of HC in the two groups were followed up and analyzed. (3)The Mesna concentration in urine and serum of the continuous group was detected by High Performance Liquid Chromatography (HPLC), with the test of the mean concentration at four time points. As all the patients were changed from the intermittent to the continuous group since 2009, hence, we are now testing for the Mesna concentration in the continuous group only. Patients in other hospitals will be involved in trials for future research. RESULTS: (1) Within 30d after transplantation, HC occurs in 30 of the 160 (18.75%) cases in the intermittent group vs. 17 of 234(7.26%) in the continuous group (P=0.001). Within 60d after transplantation, HC occurs in 45 of 160 (28.13%) cases in the intermittent group (17 cases of I°, 18 cases of II°, 8 cases of III°, 2 cases of IV°) with the mean occurrence time being +19.77d (-5-+42d); while only 30 of 234 (12.82%) cases (17 cases of I°, 9 cases of II°, 4 cases of III°, 0 cases of IV°) in the continuous group with the mean time of +27.20d (-3d-+58d). There were statistical significances of the incidence within 60d (P=0.000123) and occurrence time (P=0.037), however there was no statistical significances of grade/severity (P=0.063) of HC between the two groups. (2) Logistic regression analysis shows that within 30d after transplantation, the HC occurrences were related with the procedure of Mesna infusion (P=0.001), with continuous Mesna injection being a protective factor (OR=0.270, 95% CI=0.121-0.599); while age, sex, 24h mean liquid intake, 24h mean excretion, 24h mean urinary volume (each P 〉 0.2) and HLA matching (P=0.093) were unrelated factors. Within 60d after transplantation, the HC occurrences relate with with the procedure of Mesna infusion (P 〈 0.001)and GVHD (P=0.001); continuous Mesna injection is a protective factor (OR=0.266, 95% CI=0.135-0.524) and GVHD occurrence is a risk factor (OR=2.951, 95%CI=1.598-5.451). 3) As the half-life of Mesna is 70mins, therefore, we must maintain the Mesna concentration at a certain level at all times. The five observation points were the first day before and after CTX use, the second day before and after CTX use and the third day morning. The mean concentration of Mesna were as follows: 0±0, 298.06±299.76, 317.08±234.22, 415.18±463.75, 271.40±265.02 in urine,and 0±0, 75.04±56.93, 62.93±47.04, 57.39±39.14, 55.84±34.97 in serum. CONCLUSION: Continuous intravenous injection of Mesna is efficient in the prevention of HC in HSCT. Maintaining the Mesna concentration at a certain level in urine or serum is the key factor in reducing the incidence rate of HC significantly. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 217, No. 11 ( 2018-05-05), p. 1708-1717
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 1473843-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    In: Cell Research, Springer Science and Business Media LLC, Vol. 28, No. 2 ( 2018-2), p. 172-186
    Type of Medium: Online Resource
    ISSN: 1001-0602 , 1748-7838
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2082402-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    In: Cell Biology International, Wiley, Vol. 45, No. 1 ( 2021-01), p. 74-82
    Abstract: Deregulation of tripartite motif (TRIM) family proteins contribute to multiple biological processes such as neurodegeneration, development, inflammation, cell survival, apoptosis, and carcinogenesis. However, the biological function and molecular mechanism of TRIM family proteins in osteosarcoma chemoresistance remain unclear. In the current study, we found the protein expression of TRIM10 was markedly overexpressed in cisplatin resistance's osteosarcoma tissues and TRIM10 overexpression was inversely correlated with osteosarcoma patient survival. Furthermore, overexpression of TRIM10 confers cisplatin resistance on osteosarcoma cells; however, repressing TRIM10 sensitized osteosarcoma cell lines to cisplatin cytotoxicity in vitro. Mechanically, TRIM10 upregulated the nuclear levels of p65, thereby activating canonical NF‐κB signaling. Taken together, our results suggest that TRIM10 contributed to cisplatin resistance in osteosarcoma cells, and targeting the TRIM10/p65 axis may represent a promising strategy to enhance cisplatin response in osteosarcoma patients with chemoresistance.
    Type of Medium: Online Resource
    ISSN: 1065-6995 , 1095-8355
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1462519-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    In: Physics Letters B, Elsevier BV, Vol. 719, No. 1-3 ( 2013-02), p. 29-41
    Type of Medium: Online Resource
    ISSN: 0370-2693
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
    detail.hit.zdb_id: 1466612-1
    detail.hit.zdb_id: 208866-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...