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Altan Ahmed John A. Stauffer Jordan D. LeGout Justin Burns Kristopher Croome Ricardo Paz-Fumagalli Gregory Frey Beau Toskich 《Journal of gastrointestinal oncology.》2021,12(2):751
BackgroundNeoadjuvant yttrium-90 transarterial radioembolization (TARE) is increasingly being used as a strategy to facilitate resection of otherwise unresectable tumors due to its ability to generate both tumor response and remnant liver hypertrophy. Perioperative outcomes after the use of neoadjuvant lobar TARE remain underinvestigated.MethodsA single center retrospective review of patients who underwent lobar TARE prior to major hepatectomy for primary or metastatic liver cancer between 2007 and 2018 was conducted. Baseline demographics, radioembolization parameters, pre- and post-radioembolization volumetrics, intra-operative surgical data, adverse events, and post-operative outcomes were analyzed.ResultsTwenty-six patients underwent major hepatectomy after neoadjuvant lobar TARE. The mean age was 58.3 years (17–88 years). 62% of patients (n=16) had primary liver malignancies while the remainder had metastatic disease. Liver resection included right hepatectomy or trisegmentectomy, left or extended left hepatectomy, and sectorectomy/segmentectomy in 77% (n=20), 8% (n=2), and 15% (n=4) of patients, respectively. The mean length of stay was 8.3 days (range, 3–33 days) and there were no grade IV morbidities or 90-day mortalities. The incidence of post hepatectomy liver failure (PHLF) was 3.8% (n=1). The median time to progression after resection was 4.5 months (range, 3.3–10 months). Twenty-three percent (n=6) of patients had no recurrence. The median survival was 28.9 months (range, 16.9–46.8 months) from major hepatectomy and 37.6 months (range, 25.2–53.1 months) from TARE.ConclusionsMajor hepatectomy after neoadjuvant lobar radioembolization is safe with a low incidence of PHLF. 相似文献
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Ahmed Elhassanny Rene Escobedo Daniel Ladin Colin Burns Rukiyah Van Dross 《Oncotarget》2020,11(52):4788
Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ12,14 prostamide J2 (15dPMJ2). As such, the current study investigates whether 15dPMJ2 induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ2 caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ2 also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ2 to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ2-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ2-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ2 and the ER stress pathway. These results demonstrate that 15dPMJ2 is a tumor-selective inducer of DAMP signaling in melanoma. 相似文献
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This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function. 相似文献
7.
Conditionally replicating luciferase reporter phages: improved sensitivity for rapid detection and assessment of drug susceptibility of Mycobacterium tuberculosis. 总被引:7,自引:1,他引:6
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C Carrire P F Riska O Zimhony J Kriakov S Bardarov J Burns J Chan W R Jacobs Jr 《Journal of clinical microbiology》1997,35(12):3232-3239
TM4 is a lytic mycobacteriophage which infects mycobacteria of clinical importance. A luciferase reporter phage, phAE40, has been constructed from TM4 and was previously shown to be useful for the rapid detection and drug susceptibility testing of Mycobacterium tuberculosis. However, the lytic nature of the phage results in a loss of detectable light output and limits the sensitivity of detection. We describe several strategies aimed at improving the luciferase activity generated by TM4 luciferase phages, including (i) varying the position of the luciferase gene in the phage genome, (ii) isolating host-range mutants of the phage, and (iii) introducing temperature-sensitive mutations in the phage such that it will not replicate at the infecting temperature. Several new phages generated by these methods show increased intensity of luciferase production compared to the first-generation reporter phage phAE40, and one phage, phAE88, also demonstrates an enhanced duration of luciferase activity. This has allowed the detection of as few as 120 BCG cells and the determination of drug susceptibilities of M. tuberculosis in as little as 1 day. 相似文献
8.
Nafarelin controlled release injectable (CRI) releases a decapeptide drug for target one month therapy. Nafarelin, a luteinizing hormone releasing hormone agonistic analogue, is microencapsulated in biodegradable poly(lactide-co-glycolide) microspheres and given by intramuscular injection. Clinical data from a human single dose Phase I clinical study are modelled to develop theoretical multiple dose profiles and theoretical single dose profiles from mixtures of two or three formulations. Single dose injections of nafarelin CRI microspheres (4 mg nafarelin) containing 2, 4, or 7 per cent nafarelin all achieve useful plasma drug levels throughout the target 30 day interval. Therapeutic suppression of testosterone levels was observed in all subjects participating in the phase I clinical study. Highest plasma nafarelin levels are achieved in the 0-10 and 20-35 day post-injection intervals. Theoretical multiple dosing profiles generated from the single dose clinical results show significant oscillations in plasma nafarelin levels depending on the particular dosing interval selected. Thirty or forty day dosing intervals yield significant variability in plasma nafarelin levels at steady state; 15 day dosing intervals show less variability. Therapeutic testosterone suppression was observed in the single dose study, so the nafarelin dose per injection can be reduced in multiple dosing therapies. Theoretical plasma nafarelin profiles from certain mixtures of 2 and 4 per cent nafarelin microspheres or 2 and 7 per cent nafarelin microspheres indicate that a 60 day product could be achieved. In general, all three formulations yield their lowest plasma drug levels during the 10-20 day post-injection interval. Therefore any mixture of these formulations will likewise exhibit low plasma drug levels during this interval. 相似文献
9.
OBJECTIVE: To determine the most frequent clinical causes of a prolonged activated partial thromboplastin time (APTT) result, and to determine whether a new heparin-removal device (the Hepchek, Pall Biomedical, Glen Cove, NY 11542) is capable of efficiently detecting the causes of these values. DESIGN: A combination of chart review and laboratory testing comparing the criterion standard--the heparin chromogenic substrate assay--with the Hepchek. Laboratory investigations were blinded and controlled. SETTING: Inpatient, acute-care hospital. PATIENTS: A total of 1,000 hospital patients with a variety of hemostatic disorders. MAIN OUTCOME MEASURE: The extent to which the Hepchek accurately identified the etiology of a prolonged APTT result. RESULTS: The APTT was prolonged in 25.2% of samples. The presence of heparin in the sample was confirmed by chromogenic assay or by using the Hepchek heparin-removal filter. The presence of heparin was confirmed in 12.8% of all samples and in more than 50% of all abnormal samples. The cause of the abnormal APTT was often unappreciated by the clinician. Bayesian analysis of the Hepchek's ability to diagnose heparin correctly as the cause of the abnormal APTT showed a sensitivity of 100% and specificity of 99.9%. CONCLUSION: Use of the Hepchek in the routine clinical laboratory is an efficient and rapid method of detecting heparin as a cause of isolated prolonged APTT results, and should reduce demands for unwarranted coagulation analyses and inappropriate treatment with blood products. 相似文献
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The effects of hyponatraemia and subarachnoid haemorrhage on the cerebral vasomotor responses of the rabbit 总被引:1,自引:0,他引:1
R J Nelson S Perry A C Burns J Roberts J D Pickard 《Journal of cerebral blood flow and metabolism》1991,11(4):661-666
Impairment of cerebral autoregulation and development of hyponatraemia are both implicated in the pathogenesis of delayed cerebral ischaemia and infarction following subarachnoid haemorrhage (SAH) but the pathophysiology and interactions involved are not fully understood. We have studied the effects of hyponatraemia and SAH on the cerebral vasomotor responses of the rabbit. Cerebrovascular reactivity to hypercapnia and cerebral autoregulation to trimetaphan-induced hypotension were determined in normal and hyponatraemic rabbits before and 6 days after experimental SAH produced by two intracisternal injections of autologous blood. Hyponatraemia (mean plasma sodium of 119 mM) was induced gradually over 48 h by administration of Desmopressin and intraperitoneal 5% dextrose. Sham animals received normal saline. The cerebrovascular reactivity (% change +/- SD in cortical CBF/mm Hg PaCO2, measured by hydrogen clearance) of hyponatraemic (4.8 +/- 3.0%) and SAH (1.3 +/- 2.0%) animals was significantly less (p less than 0.05) than control (11.6 +/- 4.0%) and sham (8 +/- 2.0%) animals, whereas the reactivity of hyponatraemic-SAH animals was preserved (9.8 +/- 6.0%). Hyponatraemia and SAH alone each significantly impaired CBF autoregulation but their combined effects were not additive. Systemic hyponatraemia impairs normal cerebral vasomotor responses but does not augment the effects of experimental SAH in the rabbit. 相似文献