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  • 1
    In: Blood, American Society of Hematology, Vol. 127, No. 8 ( 2016-02-25), p. 1067-1071
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 2
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 58, No. 5 ( 2014-05), p. 2856-2865
    Abstract: Piperacillin-tazobactam is often given to infants with severe infection in spite of limited pharmacokinetics (PK) data. We evaluated piperacillin-tazobactam PK in premature and term infants of ages 〈 61 days with suspected systemic infection. Infants received intravenous piperacillin-tazobactam (80 to 100 mg/kg of body weight every 8 h [q 8 h]) based on gestational and postnatal age. Sparse plasma samples were obtained after first and multiple doses. Drug concentrations were measured by tandem mass spectrometry. PK data were analyzed using population nonlinear mixed-effect modeling. Target attainment rates for the time unbound piperacillin concentrations remained above the MIC for 50% and 75% of the dosing interval at steady state were evaluated. Bias in population PK parameter estimates was assessed for dried blood spot (DBS) samples, and a comparability analysis was performed for DBS and plasma drug concentrations using linear regression. We obtained 128 plasma samples from 32 infants, median gestational age of 30 weeks (range, 23 to 40 weeks) and postnatal age of 8 days (range, 1 to 60). Piperacillin and tazobactam PK models included body weight (WT) and postmenstrual age (PMA) as covariates for clearance and WT for volume of distribution and were used to optimize dosing in infants. DBS drug concentrations were 50 to 60% lower than those in plasma, but when combined with plasma concentrations and a matrix effect, the data generated PK model parameters similar to those for plasma alone. With PMA-based dosing (100 mg/kg q 8 h, 80 mg/kg q 6 h, and 80 mg/kg q 4 h for PMA of ≤30, 30 to 35, and 35 to 49 weeks, respectively), 90% of simulated infants achieved the surrogate therapeutic target of time above the MIC (≤32 mg/liter) for 75% of the dosing interval.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
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    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2014
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e20544-e20544
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e20544-e20544
    Abstract: e20544 Background: Malignant pleural mesothelioma (MPM), arising from the serosal lining of the thoracic cavity, is a rare malignancy with limited treatment options and very poor prognosis. Recent progress in immunotherapy and innovative devices have advanced treatment fields of MPM. To help investigators understand the landscape of MPM clinical research, characteristic and trends of globally registered trials in the past decades were analyzed in our study. Methods: This is a cross-sectional analysis of MPM trials registered on ClinicalTrials.gov between January 1996 and December 2022. Characteristics pertaining to trail phase, enrollment number, study design, type, funding source, age of population, trial purpose, and participating country were extracted, and chronological shifts were analyzed. Clinical trial variables were enumerated using descriptive statistics and categorical data were presented as frequencies and percentages. Chi-square trend analysis (Cochran–Armitage trend test) was used to evaluate the trend of MPM trials. Results: 267 registered MPM trials were analyzed involving 40 participating countries among which the United States, the United Kingdom, and Italy were top 3. 8.2% trials were phase 3 and 18.7% were randomized. 74 trials had publications by the December 2022. The trial purposes concerning surgery, radiotherapy, chemotherapy, target therapy, immunotherapy, photodynamic therapy, cryotherapy, tumor treating fields (TTF)and non-anticancer research accounted for 2.6%, 5.2%, 20.2%, 25.5%, 31.1%, 1.1%, 0.7%, 0.7% and 12.7% respectively. In the past 27 years, the numbers of chemotherapy and targeted therapy trials declined while immunotherapy trails steadily escalated (all above p trend 〈 0.05). There are no significant changes for the trends of each trial phase. 205 drug therapy trials involved 26 cytotoxic drugs, 44 targeted drugs and 11 immune checkpoint inhibitors and 34 other drugs. Pemetrexed-cisplatin with TTF and ipilimumab-nivolumab have changed the frontline treatment space while improvement for regulatory approvals has been far slower in salvage treatment, with the median overall survival all less than 11 months in phase 3 trials. There are no definitive trials that justify the use of predictive biomarkers for systemic therapy in MPM. Conclusions: Immunotherapy and TTF have reshaped the standard of care landscape over the past 27 years. With the enhanced understanding of molecular characteristics and mechanism of MPM, it is anticipated that ongoing immunotherapy combined with target therapy, chemotherapy or other novel treatment can improve the frontline and post-line therapeutic effect.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 4
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 5
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1720-1720
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1720-1720
    Abstract: PPARγ, originally cloned as a transcription factor involved in fat cell differentiation, is activated by endogenous ligands, such as fatty acids produced by sterol response element binding protein 1 (SREBP1) and fatty acids synthase (FASN) pathways and synthetic ligands including the thiazolidinediones (TZD). PPARγ is expressed in a variety of cancer cells. Independent lines of evidence support a role for PPARγ to either inhibit or promote tumorigenesis. Human breast cancer is associated with ErbB2 amplification or overexpression in & gt;30% of patients. Although PPARγ is reduced in ErbB2 induced tumor, the role of PPARγ in growth control of ErbB2-induced tumorigenesis is poorly understood. The addition of ligand activates the receptor by inducing a conformational change in the receptor, which can be recapitulated by mutation. To investigate the role of activated PPARγ signaling in breast cancer, we compared the function of a constitutively active PPARγ (PγCA) mutant with the wild-type PPARγ in ErbB2-induced mammary tumorigenesis in vivo. Tumor cells transduced with either PPARγ or PγCA were implanted into immune competent FVB mice. Enhanced tumor growth was observed in PγCA-transduced cells, which was associated with increased angiogenesis and endothelial stem cells as evidenced by increased number of cells stained with von Willebrand factor (vWF), c-Kit, CD133 and CD31. Genome-wide expression profiling identified a group of genes within the angiogenesis pathway, including Angptl4, as targets of activated PPARγ. PγCA also induced Angptl4 protein secretion in ErbB2-transformed mammary epithelial cells. Angptl4 promoted vascular endothelial cell migration and conversely immuno-depletion of Angptl4 reduced PγCA-mediated cellular migration. Collectively, these studies suggest that activated PPARγ induces Angptl4 to promote tumor growth through enhanced angiogenesis in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1720.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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    detail.hit.zdb_id: 410466-3
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15603-e15603
    Abstract: e15603 Background: Neoadjuvant chemoradiotherapy (nCRT) not only could bring tumor downsizing and downstaging but also could achieve clinical complete response (cCR) or pathological complete response (pCR). Although immunotherapy benefits MSI-H/dMMR rectal cancer patients, little response is observed in MSS/pMMR patients. Several clinical trials including VOLTAGE trial demonstrated that a combination of PD-1 inhibitor and nCRT could result in a promising pathological response even in MSS/pMMR patients. But the elucidation regarding organ preservation after treatment is lacking. Watch and Wait (W & W) is an effective strategy in rectal cancer patients showing cCR after nCRT to preserve organs. This study was designed to explore the efficacy, safety, and organ preservation rate of a combination of nCRT and PD-1 inhibitor(sintilimab) in MSS/pMMR patients with ultra-low rectal cancers. Methods: This was a single-arm, phase II trial. Patients with ultra-low rectal cancer that was confirmed as MSS/pMMR T 1- 3a N 0-1 M 0 and received 50 Gy (25×2 Gy) chemoradiotherapy and 2 cycles of sintilimab, followed by 6 cycles of capecitabine or CAPOX regimen plus 2 cycles of sintilimab as consolidation therapy. Patients with cCR were managed using the W & W strategy, patients with ncCR were given local excision. The primary outcome was cCR rate and secondary outcomes were anal preservation rate, organ preservation rate, tumor regression grade (TRG), and safety profile. Results: From 2021 January to 2021 December, a total of 23 patients were enrolled. The median age was 55 y (range; 38 to 75). Male patients were 61%. cT2 was 56.5% (13/23), cT3 was 43.5% (10/23), cN0 was 69.6% (16/23), and cN1 was 30.4% (7/23). All patients completed 50Gy chemoradiotherapy. Nineteen patients received 4 cycles of sintilimab treatment, 3 patients received 3 cycles of sintilimab, and 1 patient received 1 cycle of sintilimab. cCR was 43.5% (10/23), ncCR was 26.1% (6/23), and cPR was 30.4% (7/23). The anal preservation rate was not assessed in 1 patient due to cerebral ischemic stroke. The anal preservation rate was 95.5% (21/22), rectal preservation rate was 59.1% (13/22). Ten patients underwent surgery. Among them, two patients achieved pCR, and the major pathologic response rate (TRG0-1) was 60.0% (6/10). The overall CR(cCR+pCR) rate was 52.2% (12/23). Grade 3/4 treatment-related adverse events occurred in 17.4% (4/23) of patients. No unexpected adverse events or deaths were observed. Conclusions: Given the favorable tolerability and encouraging cCR rate, nCRT plus sintilimab could be a feasible and safe option for patients with pMMR/MSS, ultra-low rectal cancer who have a strong desire to preserve the anus. Based on these results, a prospective, randomized, controlled, multicenter, phase III study is currently in progress (NCT05215379). Clinical trial information: ChiCTR2100042785.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 7
    Online Resource
    Online Resource
    SAGE Publications ; 2020
    In:  Acta Radiologica Vol. 61, No. 1 ( 2020-01), p. 101-109
    In: Acta Radiologica, SAGE Publications, Vol. 61, No. 1 ( 2020-01), p. 101-109
    Abstract: The use of weight-adapted pediatric computed tomography (CT) tube voltage protocols has been suggested, but a consensus standard has not been established and clinical available studies are not sufficient. Purpose To determine the best tube voltage for low dose abdominal CT imaging in children. Material and Methods Eighty-seven cases who needed three CT exams in a 1–3-month interval between scans were enrolled (mean age = 4.69 ± 3.20 years). The three scans were performed with three different tube voltages at 80 kV, 100 kV, and 120 kV, keeping the same radiation dose and same contrast injection protocol. Patients were divided into five groups for analysis based on their body weight. The subjective image quality of the three exams were evaluated using a 4-point scale (4 being the best) for image noise and image quality. The objective evaluation in terms of CT values and standard deviation in aorta, liver, spleen, pancreas, and kidney were measured to calculate the degree of enhancement and contrast-to-noise ratio (CNR) of organs. One-way ANOVA was used to compare the subjective and objective image quality with respect to different tube voltages and different patient weights. Result The 80-kV tube voltage provided the highest overall enhancement and CNR for the entire patient population and the best objective image quality for the 6.1–28.0 kg subgroup. Conclusion Patient weight-dependent tube voltage selection maximizes image quality for abdominal enhanced CT in children. The optimal tube voltage for children with weight 〈 28 kg is 80 kV; higher voltages should be selected for children weighing 28.1–50.0 kg.
    Type of Medium: Online Resource
    ISSN: 0284-1851 , 1600-0455
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    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 8
    In: The American Journal of Pathology, Elsevier BV, Vol. 174, No. 2 ( 2009-02), p. 613-629
    Type of Medium: Online Resource
    ISSN: 0002-9440
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
    detail.hit.zdb_id: 1480207-7
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  • 9
    In: The American Journal of Pathology, Elsevier BV, Vol. 174, No. 3 ( 2009-03), p. 746-761
    Type of Medium: Online Resource
    ISSN: 0002-9440
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
    detail.hit.zdb_id: 1480207-7
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  • 10
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 14 ( 2013-07-15), p. 4548-4558
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 14 ( 2013-07-15), p. 4548-4558
    Abstract: Hepatic metastasis is responsible for the majority of colorectal cancer (CRC)-related mortalities. Although Gankyrin (PSMD10) has been implicated in cancer metastasis, its exact role and underlying mechanisms of CRC hepatic metastasis remain largely unknown. Herein, we showed that the expression of Gankyrin was higher in primary CRC with hepatic metastasis compared with CRC without metastasis. RNAi-mediated silencing of Gankyrin expression in highly metastatic human CRC cells impaired their migratory and metastatic capacity in vivo. Genome-wide transcriptome profiling revealed activation of the interleukin (IL)-8 signaling pathway by Gankyrin. Protein levels of IL-8 and cyclin D1 (CCND1), the two important molecules in the IL-8 pathway, were positively correlated with Gankyrin expression in human CRC specimens. Furthermore, genetic deletion of cyclin D1 showed its requirement in Gankyrin-mediated cell migration. Finally, administration of recombinant IL-8 rescued the migratory defect of CRC cells where Gankyrin expression was silenced. Together, our findings highlight the importance of Gankyrin in hepatic metastasis of CRC and point out its candidature as a potential prognostic marker and therapeutic target to improve the clinical management of metastatic CRC. Cancer Res; 73(14); 4548–58. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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