Retrospective comparison between a regular and a split-dose protocol of 5-fluorouracil, cisplatin, and mitoxantrone for the treatment of far advanced hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>In patients with advanced hepatocellular carcinoma (HCC), combination chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone (FMP) could achieve a response rate > 20%, but the beneficial effect was compromised by formidable adverse events. Chemotherapy given in a split-dose manner was associated with reduced toxicities. In this retrospective study, we compared the efficacies and side effects between a regular and a split-dose FMP protocol approved in our medical center.</p> <p>Methods</p> <p>From 2005 to 2008, the clinical data of 84 patients with far advanced HCC, who had either main portal vein thrombosis and/or extrahepatic metastasis, were reviewed. Of them, 65 were treated by either regular (n = 27) or split-dose (n = 38) FMP and had completed at least one therapeutic course. The remaining 19 patients were untreated. Clinical parameters, therapeutic responses, survivals and adverse events were compared.</p> <p>Results</p> <p>The median overall survival was 6.0, 5.2, and 1.5 months, respectively, in patients receiving regular FMP, split-dose FMP, and no treatment (regular versus split-dose group, P = 0.447; regular or split-dose versus untreated group; P < 0.0001). Patients receiving split-dose treatment had a significantly lower risk of grade 3/4 neutropenia (51.9 versus 10.5%, P = 0.0005). When the two treated groups were combined, the median overall survival was 10.6 and 3.8 months respectively for patients achieving disease control and progressive disease (P < 0.001). Cox proportion hazard model identified Child-Pugh stage B (hazard ratio [HR], 2.216; P = 0.006), presence of extrahepatic metastasis (HR, 0.574; P = 0.048), and achievement of disease control (HR, 0.228; P < 0.001) as independent factors associated with overall survival. Logistic regression analysis revealed that anti-hepatitis C virus antibody (odds ratio [OR], 9.219; P = 0.002) tumor size (OR, 0.816; P = 0.036), and previous anti-cancer therapy (OR, 0.195; P = 0.017) were significantly associated with successful disease control.</p> <p>Conclusions</p> <p>Comparable overall survival was observed between patients receiving regular and split-dose FMP therapies. Patients receiving split-dose therapy had a significantly lower risk of grade 3/4 neutropenia. Positive anti-hepatitis C virus antibody, smaller tumor size, and absence of previous anti-cancer therapy were independent predictors for successful disease control.</p

Time for Singapore to Relook Abortion Law

Figure S1. Effect of anti-ITGA2 antibody on cell morphology. The AGS cells were treated with a 3 Οg of the anti-ITGA2 antibodies or isotype control antibodies (negative control) for 48 h, and cell morphology was observed at 200X magnification. Data are representative of three independent experiments. (PPTX 1463 kb

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Intravascular flow decreases erythrocyte consumption of nitric oxide

Nitric oxide (NO) produced by the endothelium diffuses both into the lumen and to the smooth muscle cells according to the concentration gradient in each direction. The extremely high reaction rate between NO and hemoglobin (Hb), k(Hb)= 3–5 × 10(7) M(−1)⋅s(−1), suggests that most of the NO produced would be consumed by Hb in the red blood cells (RBCs), which then would block the biological effect of NO. Therefore, specific mechanisms must exist under physiological conditions to reduce the NO consumption by RBCs, in which the Hb concentration is very high (24 mM heme). By using isolated microvessels as a bioassay, here we show that physiological concentrations of RBCs in the presence of intravascular flow does not inhibit NO-mediated vessel dilation, suggesting that RBCs under this condition are not an NO scavenger. On the other hand, RBCs (50% hematocrit) without intravascular flow reduce NO-mediated dilation to serotonin by 30%. In contrast, free Hb (10 μM) completely inhibits NO-mediated dilation with or without intravascular flow. The effect of flow on NO consumption by RBCs may be attributed to the formation of an RBC-free zone near the vessel wall, which is caused by hydrodynamic forces on particles. Intravascular flow does not affect the reaction rate between NO and free Hb in the lumen, because the latter forms a homogeneous solution and is not subject to the hydrodynamic separation. However, intravascular flow only partially contributes to the reduced consumption of NO by RBCs, because without the flow, the NO consumption by RBCs is already about 3 orders of magnitude slower than free Hb

Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta‐Analysis of Randomized Controlled Trials

Background Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. Methods and Results This meta‐analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta‐analysis. High‐ and low‐dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High‐dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low‐dose regimens, with both doses having similar bleeding risks. Conclusions In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. Registration URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557

Prophylactic Administration of Fucoidan Represses Cancer Metastasis by Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs) in Lewis Tumor-Bearing Mice

Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs

The Effects of Freshwater Clam (Corbicula fluminea) Extract on Serum Tumor Necrosis Factor-Alpha (TNF-&alpha;) in Prediabetic Patients in Taiwan

Freshwater clam extract (FCE) is a functional food that regulates the immune system and has been demonstrated in numerous studies to display desirable anti&ndash;tumor necrosis factor-alpha (TNF-&alpha;) responses. In addition, excess TNF-&alpha; production is positively associated with type 2 diabetes. However, few longitudinal clinical studies evaluating the efficiency and toxicity of FCE are available. This article reports that patients with prediabetes who received FCE had a desirable outcome of a reduction in serum TNF-&alpha; for a long period. This was a double-blind, randomized, parallel clinical trial conducted using FCE intervention and placebo groups, and 36 patients with prediabetes were enrolled. Two grams of FCE or placebo was consumed daily for 180 consecutive days. The serum of the participants was collected at four time points (0M: before the intervention; 3M: after 3 months of intervention; 6M: after 6 months of intervention; 12M: 6 months after cessation of intervention at 6M). A serum TNF-&alpha; concentration higher than 4.05 pg/mL was defined as a cut-off value. FCE reduced serum TNF-&alpha; in all participants at 6M and 12M. Moreover, FCE significantly suppressed serum TNF-&alpha; concentrations at 6M and 12M and inhibited TNF-&alpha; release with time series in subjects with elevated TNF-&alpha; values. FCE intervention effectively reduced serum TNF-&alpha; and persistently sustained the effects for half a year in patients with prediabetes. Gas chromatography&ndash;mass spectrometry (GS-MS) analysis revealed that the major components of FCE were phytosterols and fatty acids, which exerted anti-inflammatory and anti-TNF-&alpha; abilities. Hence, FCE has the potential to be developed as a natural treatment for prediabetic patients in Taiwan