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1.
Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献2.
Coronary artery bypass grafts: visualization with MR imaging 总被引:1,自引:0,他引:1
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4.
D. Chemla P. Démolis M. Thyrault D. Annane Y. Lecarpentier and JF Giudicelli 《Fundamental & clinical pharmacology》1996,10(4):393-399
Summary— The influence of local resistance and cardiac performance on peripheral blood acceleration was investigated in 14 healthy male volunteers. Steady and pulsatile flow was studied in the brachial and in the common carotid arteries, ie, two territories that exhibit marked differences in resistive characteristics. Instantaneous blood velocity (V), mean blood velocity (Vm ) and artery diameter (D) were evaluated at rest by an ultrasonic range-gated pulsed Doppler flowmeter using a double transducer probe, thus allowing the calculation of mean blood flow (Q). Mean local resistance (R) was obtained by dividing the mean arterial pressure by Q. The peak value of the local acceleration of the blood was obtained by computer-assisted calculation of the first derivative of instantaneous blood velocity (Gmax = +dV/dtmax ). Peak aortic blood acceleration (GAo) was simultaneously measured from the suprasternal notch using a pulsed Doppler velocity meter. In the brachial and the common carotid arteries, Gmax was of a similar magnitude (551 ±30 and 555 ± 44 cm/s2 , respectively) despite major differences in the respective D, Vm , Q and R values. In neither artery was there a relationship between Gmax and either resting Q or R. At the brachial artery level, Gmax was positively related to GAo ( r = 0.79, P = 0.0008). At the common carotid artery level, there was a weak, although non significant relationship between Gmax and GAo ( P = 0.08). Our results indicate that the local acceleration of peripheral blood flow in the brachial artery is related rather to upstream central impulse than to downstream hemodynamics, and suggest some regional differences in the hemodynamic determinants of the local acceleration of peripheral blood flow. 相似文献
5.
In a prospective, randomized, double-blind study, 49 patients underwent lumbar myelography using iotrol (24 patients) or metrizamide (25 patients). The diagnostic imaging adequacy of iotrol was comparable with that of metrizamide. After iotrol myelography, adverse reactions were fewer, less severe, and of shorter duration than were those following metrizamide myelography. Thirteen of 24 patients (54%) receiving iotrol reported some adverse reactions compared with 24 of 25 patients (96%) receiving metrizamide. Five moderate and one severe adverse reaction occurred in the group receiving iotrol. Fourteen moderate and eight severe adverse reactions occurred in the group receiving metrizamide. Thirty-eight patients underwent electroencephalography both before and after myelography (19 iotrol and 19 metrizamide). None of the EEGs obtained after iotrol myelography changed from baseline, while seven of the EEGs obtained after metrizamide myelography showed changes from baseline. Iotrol was judged superior to metrizamide as a contrast medium in this patient population. 相似文献
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7.
Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine. 相似文献
8.
Reperfusion pulmonary edema 总被引:5,自引:0,他引:5
Reperfusion following lower-torso ischemia in humans leads to respiratory failure manifest by pulmonary hypertension, hypoxemia, and noncardiogenic pulmonary edema. The mechanism of injury has been studied in the sheep lung lymph preparation, where it has been demonstrated that the reperfusion resulting in pulmonary edema is due to an increase in microvascular permeability of the lung to protein. This respiratory failure caused by reperfusion appears to be an inflammatory reaction associated with intravascular release of the chemoattractants leukotriene B4 and thromboxane. Histological studies of the lung in experimental animals revealed significant accumulation of neutrophils but not platelets in alveolar capillaries. We conclude that thromboxane generated and released from the ischemic tissue is responsible for the transient pulmonary hypertension. Second, it is likely that the chemoattractants are responsible for leukosequestration, and, third, neutrophils, oxygen-derived free radicals, and thromboxane moderate the altered lung permeability. 相似文献
9.
Vasoactive amines and eicosanoids interactively regulate both polymorphonuclear leukocyte diapedesis and albumin permeability in vitro 总被引:2,自引:0,他引:2
Previously we reported that cultured endothelial cells (ECs) can promote or inhibit polymorphonuclear leukocyte (PMN) diapedesis and albumin permeability in vitro by altering monolayer intercellular integrity (an activity influenced by pretreatment with exogenous amines). Endothelial eicosanoid release was also seen to stimulate both PMN motility and diapedesis. We now demonstrate that these endothelial activities are related. Thromboxane (Tx) B2 pretreatment of ECs results in increased diapedesis and permeability across the monolayers whereas 6-keto-PGF1 alpha pretreatment has the opposite effects, demonstrating that these eicosanoids exert direct effects upon ECs, in addition to their direct effects upon PMNs as previously described. Norepinephrine (NE) or serotonin (5HT) pretreatment of ECs inhibits the release of TxB2 and 6-keto-PGF1 alpha, with the result that the stimulation of PMN motility by these EC metabolites is eliminated. In contrast, histamine increases the endothelial release of eicosanoids, resulting in a further increase in PMN motility. We conclude that histamine directly reduces EC monolayer integrity (by altering the endothelial cytoskeleton) and also increases eicosanoid release, actions which both enhance PMN motility and further reduce monolayer integrity. Conversely, NE and 5HT both increase intercellular integrity and decrease eicosanoid release, thereby decreasing PMN motility, diapedesis, and albumin permeability. 相似文献
10.
Pernes JM; Vitoux JF; Brenoit P; Raynaud A; Parola JL; Roth JP; Angel CY; Fiessinger JN; Roncato M; Gaux JC 《Radiology》1986,158(2):481-485
Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases. Only 3% of the patients had major and 6% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK-LYS-PLG is as effective as streptokinase. Its excellent tolerance makes it a good alternative in the treatment of acute ischemia in the lower limbs. 相似文献