第949回千葉医学会例会・第19回千葉大学第三内科懇話会

<p>Accuracy of chlorogenic acid, rutin and isoquercitrin.</p

In vitro Anti-Tumor Effects of Statins on Head and Neck Squamous Cell Carcinoma: A Systematic Review

<div><p>Background</p><p>Statins are commonly used against arteriosclerotic disease, but recent retrospective analyses have suggested that statins also prevent cancer. The aim of this systematic review is to verify the vitro anti-tumor effects of statins on head and neck squamous cell carcinoma.</p><p>Methods</p><p>Studies were gathered by searching Cochrane, MEDLINE, EMBASE, LILACS, and PubMed, up until May 9, 2015, with no time or language restrictions. Only in vitro studies that discuss the effect of statins on head and neck carcinoma were selected.</p><p>Results</p><p>Of 153 identified papers, 14 studies met the inclusion criteria. These studies demonstrated that statins had a significant effect on head and neck squamous cell carcinoma cell lines and influenced cell viability, cell cycle, cell death, and protein expression levels involved in pathways of carcinogenesis, which corroborates with the potential in vitro anti-tumor effects. It provides highlights about the biological mechanisms of statins used alone or associated with traditional therapy for cancer.</p><p>Conclusions</p><p>Though there are few studies on the topic, currently available evidence suggests that statins shows that preclinical experiments supports the potentiality of statin as an adjuvant agent in chemotherapy and/or radiotherapy approaches routinely used in the management of HNSCC and should undergo further clinical assessment.</p></div

Summary of descriptive characteristics of included articles (n = 14).

<p>The statin clinical application was classified as (1) potential effect in HNSCC treatment; (2) inconclusive, and (3) evidence not supportive as a drug to HNSCC treatment. Abbreviations: U87MG—Human primary glioblastoma cell line; Gy–Gray; ISR—Integrated stress response; HNSCC—Head and neck squamous cell carcinomas; CC—Cervical carcinoma; EGFR—Epidermal growth factor receptor; LKB1- The Liver Kinase B1; AMPK- AMP-Activated Protein Kinase; RhoC—a GTPase belonging to the Ras superfamily; SCC—Squamous cell carcinomas; EGF—Epidermal growth factor; ATF3- activation of transcription factor; mRNA- Messenger RNA; 5-FU 5-fluorouracil; NPC–Nasopharyngeal Carcinoma; LMP1 –latent membrane protein 1; NPC.- Nasopharyngeal Cancer; GGPP- Geranyl pyrosphosphate; ERK- Extracellular-signal-regulated kinases; RT PCR- Reverse transcription polymerase chain reaction; UM- SCC-1—Squamous cell carcinoma cell lines derived from floor of the mouth; UM-SCC-47—Squamous cell carcinoma cell lines derived from tongue; DMSO—Dimethyl sulfoxide; SCC9 (Homo sapiens tongue squamous cell carcinoma); SCC25 (Homo sapiens tongue squamous cell carcinoma); HeLa (cervical carcinoma); A549 (lung carcinoma); MEFs/LKB1 -/- (Murine Embryonic Fibroblast); CCL-30 (Nasopharyngeal carcinoma cells); 293T (Human Embryonic Kidney); Tu167 (Squamous cell carcinoma cell lines derived from floor of the mouth); JMAR (Squamous cell carcinoma cell lines derived from floor of the mouth); CAL27 (Oral Squamous Cell Carcinoma); SIHA (Cervical Carcinoma); Cos-7 (monkey Kidney Cell Line); SCC4 (Oral epithelial cell lines); SCC15 (Oral epithelial cell lines); C15 (Nasopharyngeal Carcinoma Cells); C17 (Nasopharyngeal Carcinoma Cells); A431 cell (epidermoid carcinoma); GM-38 (Diploid fibroblasts cell line).</p><p>Summary of descriptive characteristics of included articles (n = 14).</p

Flow Diagram of literature search and selection criteria adapted from PRISMA [16].

<p>Flow Diagram of literature search and selection criteria adapted from PRISMA [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130476#pone.0130476.ref016" target="_blank">16</a>].</p

Interventions used to test head and neck carcinoma cell lines viability in cell culture.

<p>Cells: Head and Neck Squamous Cell Carcinoma cell lines, (immortalized or primary cell lines). C: Control. O: Outcomes S: Study (RCT or Comparable baselines). Yes- √”, No “–“. Percentage of cell viability: 1 = 0 to 49% of viable cells; 2 = 50 to 100% of viable cells.</p><p>Interventions used to test head and neck carcinoma cell lines viability in cell culture.</p

Metabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trials

<p>Data about harms or benefits associated with the consumption of aspartame, a nonnutritive sweetener worldwide consumed, are still controversial. This systematic review and meta-analysis of randomized controlled clinical trials aimed to assess the effect of aspartame consumption on metabolic parameters related to diabetes and obesity. The search was performed on Cochrane, LILACS, PubMed, SCOPUS, Web of Science databases, and on a gray literature using Open Grey, Google Scholar, and ProQuest Dissertations & Theses Global. Searches across all databases were conducted from the earliest available date up to April 13, 2016, without date and language restrictions. Pooled mean differences were calculated using a random or fixed-effects model for heterogeneous and homogenous studies, respectively. Twenty-nine articles were included in qualitative synthesis and twelve, presenting numeric results, were used in meta-analysis. Fasting blood glucose (mmol/L), insulin levels (μU/mL), total cholesterol (mmol/L), triglycerides concentrations (mmol/L), high-density lipoprotein cholesterol (mmol/L), body weight (kg), and energy intake (MJ) were considered as the main outcomes in subjects that consumed aspartame, and results were presented as mean difference; % confidence interval, range. Aspartame consumption was not associated with alterations on blood glucose levels compared to control (−0.03 mmol/L; 95% CI, −0.21 to 0.14) or to sucrose (0.31 mmol/L; 95% CI, −0.05 to 0.67) and on insulin levels compared to control (0.13 μU/mL; 95% CI, −0.69 to 0.95) or to sucrose (2.54 μU/mL; 95% CI, −6.29 to 11.37). Total cholesterol was not affected by aspartame consumption compared to control (−0.02 mmol/L; 95% CI, −0.31 to 0.27) or to sucrose (−0.24 mmol/L; 95% CI, −0.89 to 0.42). Triglycerides concentrations were not affected by aspartame consumption compared to control (0.00 mmol/L; 95% CI, −0.04 to 0.05) or to sucrose (0.00 mmol/L; 95% CI, −0.09 to 0.09). High-density lipoprotein cholesterol serum levels were higher on aspartame compared to control (−0.03 mmol/L; 95% CI, −0.06 to −0.01) and lower on aspartame compared to sucrose (0.05 mmol/L; 95% CI, 0.02 to 0.09). Body weight did not change after aspartame consumption compared to control (5.00 kg; 95% CI, −1.56 to 11.56) or to sucrose (3.78 kg; 95% CI, −2.18 to 9.74). Energy intake was not altered by aspartame consumption compared to control (−0.49 MJ; 95% CI, −1.21 to 0.22) or to sucrose (−0.17 MJ; 95% CI, −2.03 to 1.69). Data concerning effects of aspartame on main metabolic variables associated to diabetes and obesity do not support a beneficial related to its consumption.</p

IC₅₀ values of tyrosinase inhibition assay.

<p>Kojic acid as positive control. *<i>p</i><0.05 <i>vs</i> Positive control. L: leaf; F: fruit; SB: stem bark; P: peel. Crude extract: (e) ethanol; (h) hexane; (a) aqueous.</p

Evaluation of the potential activity of 33 crude extracts on tyrosinase.

1<p>L: leaf;</p>2<p>S: stem;</p>3<p>F: fruit;</p>4<p>SB: stem bark;</p>5<p>P; peel. Crude extracts: (e) ethanol; (h) hexane; (a) aqueous. NI: no inhibition. Results are represented by mean of inhibition at concentration 1000 µg/mL.</p>*<p>Positive control for tyrosinase tests.</p

HPLC/DAD chromatogram of aqueous leaf extract of <i>P. torta</i> (A) and <i>E. dysenterica</i> (B).

<p>HPLC/DAD chromatogram of aqueous leaf extract of <i>P. torta</i> (A) and <i>E. dysenterica</i> (B).</p

Crude extracts tested against tyrosinase.

1<p>L: leaf;</p>2<p>S: stem;</p>3<p>F: fruit;</p>4<p>SB: stem bark;</p>5<p>P; peel. Crude extract: (e) ethanol; (h) hexane; (a) aqueous.</p