Data_Sheet_1_No dose-response relationship of clarithromycin utilization on cardiovascular outcomes in patients with stable coronary heart disease: Analysis of Taiwan’s national health insurance claims data.pdf

BackgroundClarithromycin is widely used to treat various bacterial infections and has been reported to have potential cardiovascular risk. However, it is uncertain whether this association was dose dependent and confounded by indication bias in patients with stable coronary heart disease (CHD).MethodsThis cohort study retrospectively analyzed a national health insurance claims data from Taiwan’s 2005 Longitudinal Generation Tracking Database. We used a new-user design and 1:1 propensity score matching. A total of 9,631 eligible clarithromycin users and 9,631 non-users in 2004–2015 were subject to final analysis. All patients were followed-up after receiving clarithromycin or on the matched corresponding date until occurrence of cardiovascular morbidity in the presence of competing mortality, all-cause and cause-specific mortality, or through the end of 2015. The effect of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes were also addressed.ResultsClarithromycin use, compared with non-use, was associated with higher risk for all-cause [adjusted hazard ratios (aHR), 1.43; 95% confidence interval, 1.29–1.58], cardiovascular (1.35; 1.09–1.67), and non-cardiovascular (1.45; 1.29–1.63) mortality, but not for overall cardiovascular morbidity. Further analysis of individual cardiovascular morbidity demonstrated major risk for heart events (1.25; 1.04–1.51) in clarithromycin users than non-users. However, there was no relationship of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes. Analyses of the effects over time showed that clarithromycin increased cardiovascular morbidity (1.21; 1.01–1.45), especially heart events (1.39; 1.10–1.45), all-cause (1.57; 1.38–1.80), cardiovascular (1.58; 1.20–2.08), and non-cardiovascular (1.57; 1.35–1.83) mortality during the first 3 years. Thereafter, clarithromycin effect on all outcomes almost dissipated.ConclusionClarithromycin use was associated with increased risk for short-term cardiovascular morbidity (especially, heart events) and mortality without a dose-response relationship in patients with stable CHD, which was not dose dependent and confounded by indications. Hence, patients with stable CHD while receiving clarithromycin should watch for these short-term potential risks.</p

Xeroderma pigmentosum, complementation group D expression in H1299 lung cancer cells following benzo[a]pyrene exposure as well as in head and neck cancer patients

<p>DNA repair genes play critical roles in response to carcinogen-induced and anticancer therapy-induced DNA damage. Benzo[a]pyrene (BaP), the most carcinogenic polycyclic aromatic hydrocarbon (PAH), is classified as a group 1 carcinogen by International Agency for Research on Cancer. The aims of this study were to (1) evaluate the effects of BaP on DNA repair activity and expression of DNA repair genes in vitro and (2) examine the role of xeroderma pigmentosum, complementation group D (XPD) mRNA expression in human head and neck cancers. Host cell reactivation assay showed that BaP inhibited nucleotide excision repair in H1299 lung cancer cells. DNA repair through the non-homologous end-joining pathway was not affected by BaP. Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot demonstrated that XPD was downregulated by BaP treatment. BaP exposure did not apparently affect expression of another 11 DNA repair genes. BaP treatment increased the DNA damage marker γ-H2AX and ultraviolet (UV) sensitivity, supporting an impairment of DNA repair in BaP-treated cells. XPD expression was also examined by quantitative RT-PCR in 68 head and neck cancers, and a lower XPD mRNA level was found in smokers’ cancer specimens. Importantly, reduced XPD expression was correlated with patient 5-year overall survival rate (35 vs. 56%) and was an independent prognostic factor (hazard ratio: 2.27). Data demonstrated that XPD downregulation was correlated with BaP exposure and human head and neck cancer survival.</p

Linear regression model of lymph node yield.

*<p>Statistically significant difference (<i>P</i><0.05).</p

Effects of andrographolide and radiation on the expression EMT-related markers (E-cadherin, vimentin) and matrix metalloproteinases MMP-2 and -9.

(A) RAS-transformed cells were treated with 10 uM andrographolide for 6 hours with and without 2 or 4 Gy radiation. After 24 hours, the cells were harvested for preparation of whole-cell protein lysates followed by Western blotting to detect the given proteins. (B) Quantitative analyses of MMP-2 expression evaluated by MMP-2/GAPDH ratio. The results are shown as mean ± SD (n = 3). *p < 0.05 for andrographolide combined with 4 Gy vs. andrographolide alone.</p

Andrographolide with radiation suppressed angiotensin II-induced MMP-2 expression through inhibition of ERK1/2 signaling.

Cells were incubated with 300 nM Ang II for 1 hour and then treated with andrographolide, irradiation, or both for 24 hours. Protein level was determined by Western blotting.</p

Andrographolide with radiation enhanced downregulation of radiation-induced MMP-2 leading to the suppression of ERK signaling.

The cells were treated with 10 uM andrographolide with/without 2Gy or 4 Gy radiation for 24 hours. The figure displays typical data of MMP-2, phosphor-ERK1/2, total-ERK1/2 and NF-κB activity by Western blotting. Relative band intensities were analyzed by the Image J software. β-actin was used as an internal control for normalization. The numbers beneath the blots indicate the relative expression of each band when compared to the respective untreated control.</p

sj-doc-1-ict-10.1177_15347354211044833 – Supplemental material for Chinese Herbal Medicine to Reduce Radiation-Induced Oral Mucositis in Head and Neck Cancer Patients: Evidence From Population-Based Health Claims

Supplemental material, sj-doc-1-ict-10.1177_15347354211044833 for Chinese Herbal Medicine to Reduce Radiation-Induced Oral Mucositis in Head and Neck Cancer Patients: Evidence From Population-Based Health Claims by Hsin-Hua Li, Hanoch Livneh, Wei-Jen Chen, Ming-Chi Lu, Wen-Yen Chiou, Shih-Kai Hung, Chia-Chou Yeh and Tzung-Yi Tsai in Integrative Cancer Therapies</p

Andrographolide plus radiation reduced angiotensin II-induced MMP-2 activation and invasion.

The Ras-transformed cells were incubated with/without 300 nM angiotensin II (Ang II) for 1 hour, and then treated with andrographolide, or radiation, or both for 24 hours. (A) The typical data show the gelatin zymography analysis band of the MMP-2 in conditioned media. (B) Invasion assays were performed using Transwell inserts of 8-micron pore size membrane and matrigel. After treatment, the cells were seeded in Transwell plates for 72 hours. The invaded cells were stained and quantified at an optical density of 560 nm. The experiments have been repeated three times; representative results of three independent experiments were shown. Quantification of cell invasion expressed as the percentage of control; one-way ANOVA was used for statistical analysis.</p

Lung metastatic rate in mice.

Lung metastatic rate in mice.</p

Andrographolide and radiation reduces MMP-2 expression.

Gelatin zymography was performed using the conditioned media that were harvested after 48 hours in the presence or absence of 10 uM andrographolide, and then treated with/without radiation (2 or 4Gy) for 24 hours. The samples were applied without reduction to a 10% polyacrylamide gel containing gelatin, and proteolytic activity was demonstrated by digestion of the gelatin and clearing of the gel.</p