Measurement of circulating tumor cells in squamous cell carcinoma of the head and neck and patient outcomes.

OBJECTIVES: We report the outcomes of patients with squamous cell carcinoma of the head and neck (HNSCC) whose circulating tumor cells (CTCs) were quantified using surface-enhanced Raman scattering (SERS) nanotechnology. METHODS: SERS tagged with EGF was used to directly measure targeted CTCs. Patient charts were retrospectively reviewed. An optimal cut point for CTCs in 7.5 ml of peripheral blood predictive of for distant metastasis-free survival (DMFS) was identified by maximizing the log-rank statistic. An ROC analysis was also performed. RESULTS: Of 82 patients, 13 experienced metastatic progression. The optimal cut point for DMFS was 675 CTCs (p = 0.047). For those with distant recurrence (n = 13) versus those without distant recurrence (n = 69), the CTC cut point which results in the largest combined sensitivity and specificity values is also 675 (sensitivity = 69%, specificity = 68%). CONCLUSION: Liquid biopsy techniques in HNSCC show promise as a means of identifying patients at greater risk of disease progression.

Significant interaction of APOE rs4420638 polymorphism with HDL-C and APOA-I levels in coronary heart disease in Han Chinese men.

Apolipoprotein E (APOE) is recognized for its importance in lipoprotein metabolism and cardiovascular disease. We evaluated the association between APOE rs4420638 genotypes and circulating lipid concentrations along with the risk of coronary heart disease (CHD). We conducted a case-control study involving 1508 individuals to investigate the contribution of rs4420638 to the risk of CHD in Han Chinese. In addition, we performed a meta-analysis to evaluate the association between rs4420638 and CHD in Europeans and Asians. The results show that rs4420638 is significantly correlated with increased CHD risk in male Han Chinese [P = 0.040, odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 1.01-1.78] and is likely to increase the risk of CHD under the dominant model in males (P = 0.036, OR = 1.38, 95%CI = 1.02-1.88). A further subgroup analysis by rs4420638 genotype found a significant association of rs4420638 AA with high-density lipoprotein cholesterol (HDL-C) (P = 0.012) and APOA-I levels (P = 0.0001) in males. The meta-analysis suggests that rs4420638 significantly increases the risk of CHD (OR = 1.18, 95%CI = 1.14-1.22, P < 0.0001, fixed-effect method). Our case-control study shows that rs4420638 genotype AA has a significant association with the concentrations of circulating HDL-C and APOA-I in CHD in Han Chinese males. The meta-analysis suggests that rs4420638 is associated with CHD risk in Europeans and Asians.

AMP-activated protein kinase regulates autophagic protection against cisplatin-induced tissue injury in the kidney.

Although the nephrotoxicity of cisplatin has been well documented as a major side effect of chemotherapy, the exact mechanism by which prosurvival and apoptotic pathways interplay to determine renal pathology remains elusive. Recent studies suggested that autophagy might serve as an adaptive mechanism to promote cell survival during acute kidney injury (AKI). We have used AKI as a disease model to investigate the mechanism regulating the cytoprotective role of autophagy in cisplatin-induced tissue damage. Pharmacological inhibitors such as chloroquine were used to manipulate autophagy during AKI, and DNA damage was evaluated by using the cellular marker γH2AX. Cisplatin induced extensive DNA damage during AKI. Autophagy activation served as a survival strategy to suppress cisplatin-induced DNA damage in the pathology of AKI both in vitro and in vivo. Interestingly, in the kidney, cisplatin treatment can activate AMP-activated protein kinase (AMPK), a signaling molecule that is also critical for p53-mediated inactivation of mammalian target of rapamycin (mTOR) pathways. As a result, inhibition or knockdown of AMPK can lead to repressed autophagy in cisplatin-induced AKI, resulting in more DNA damage. Activation of AMPK regulates autophagy during cisplatin-induced AKI. Given the fact that p53 can regulate autophagy by inactivating mTOR via AMPK, our results suggest that the p53 pathway may also play a critical role in the pathogenesis of cisplatin-induced renal damage. This study may further our understanding of the physiological roles of autophagy in the pathogenesis of renal injuries, and thus may have pathological implications in the clinical setting.

Administration of Flumazenil in a Patient with Acute Abamectin Intoxication: Case Report and Review of the Literature.

Abamectin is used in several countries as a type of macrocyclic lactone insecticide to control nematodes and other pests in livestock and agriculture. This medicine, used for animals and crops, would be highly toxic to human if a person has intentional poisoning. We report a case of a 47-year old man who was admitted to the hospital after ingestion of a large dose of abamectin on purpose, and who rapidly recovered consciousness after administration of flumazenil. Although flumazenil is not the antidote of abamectin, we may hypothesize that it could reduce recovery time and shorten expenditures in hospital. This is the first report that focusses on a specific treatment which could possibly accelerate recovery of consciousness for patients with abamectin intoxication.

Activity of matrix metalloproteinases 2 and 9 in cultured rabbit corneal epithelium cells stimulated by tumor necrosis factor alpha.

We studied the activity of matrix metalloproteinases (MMP) 2 and 9 generated by cultured rabbit corneal epithelium cells that had been stimulated with tumor necrosis factor alpha (TNF-α), to investigate the possible regulative mechanisms of MMP-2/9 and their potential effect on corneal inflammatory diseases. The rabbit corneal epithelium cells were cultured in vitro and incubated with different concentrations of TNF-α (0, 1, 10, and 100 ng/mL) for 24 h. The activity of MMP-2/9 was examined using gelatin zymography. The results were analyzed by computer image analysis and statistical tests. TNF-α stimulated the secretion of MMP-2/9 in a dose-dependent manner, and MMP-2 was activated by TNF-α. Inflammatory factors such as TNF-α can stimulate MMP-2/9 activity in corneal epithelium cells. This may be a potential manipulating mechanism of MMP expression in the pathogenesis of corneal diseases, and could play an important role in the prevention and treatment of corneal inflammatory diseases.

Association between IRF5 polymorphisms and autoimmune diseases: a meta-analysis.

In this study, we investigated the association between 5 interferon regulatory factor-5 (IRF5) single nucleotide polymorphisms (SNPs) and autoimmune diseases using the Medline citation index. Twenty-eight studies with 74 comparisons, including 16 rheumatoid arthritis (RA), 43 systemic lupus erythematous (SLE), 2 juvenile idiopathic arthritis (JIA), 6 multiple sclerosis (MS), and 5 systemic sclerosis (SSc) studies, were examined in the meta-analysis. The SNP rs2004640 was significantly associated with SLE, MS, and SSc, but not with JIA [odds ratio (OR)=1.06, 95% confidence interval (CI)=0.90-1.24, P=0.48] or RA (OR=1.03, 95%CI=0.95-1.11, P=0.44). A significant association was observed between rs2280714 and SLE, MS, and SSc, but not RA (OR=1.01, 95%CI=0.94-1.09, P=0.80). Rs10954213 was associated with the pathogenesis of SLE, RA, MS, and SSc. rs2070197 and the exon 6 insertion were significantly associated with SLE. Haplotypes containing rs2004640T and rs2280714T were significantly associated with an increased risk of SLE, but not with RA. This meta-analysis certified that IRF5 polymorphisms confer susceptibility to SLE, MS, and SSc. To further confirm the correlations between polymorphisms of IRF5 and autoimmune disease susceptibility, studies involving a larger number of patients worldwide are necessary.

Cytogenetic and molecular analysis of infertile Chinese men: karyotypic abnormalities, Y-chromosome microdeletions, and CAG and GGN repeat polymorphisms in the androgen receptor gene.

Chromosome abnormalities, Y-chromosome microdeletions, and androgen receptor gene CAG and GGN repeat polymorphisms in infertile Chinese men featuring severe oligospermia and azoospermia were analyzed. Ninety-six fertile men and 189 non-obstructive infertile men, including 125 patients with azoospermia and 64 with severe oligozoospermia, were studied. Seventeen infertile men (9.0%) carried a chromosome abnormality. Twenty (10.6%) carried a Y-chromosome microdeletion. In the remainder of the patients and controls, GGN and CAG repeats were sequenced. Short GGN repeats (n < 23) appeared to be associated with defective spermatogenesis, with the number of GGN repeats strongly correlated with sperm counts. No significant difference in CAG repeats was found between patients and controls, nor were CAG repeats correlated with sperm counts. However, for CAG repeats ranging between 24 and 25, there was a >2.5-fold risk (OR = 2.539, 95%CI = 1.206-5.344, P < 0.05) of severe oligospermia and azoospermia. Our results confirmed the significant role of chromosome abnormalities, Y-chromosome microdeletions, and GGN repeats in Chinese male infertility.

Association study between Y-chromosome haplogroups and susceptibility to spermatogenic impairment in Han People from southwest China.

The non-recombining portion of the Y-chromosome contains numerous polymorphisms; therefore, it is now the most informative haplotyping system with wide-ranging applications. Idiopathic azoospermia and oligospermia are among the most important causes of male infertility. Different haplogroups may have different genetic backgrounds, which may be either susceptible or unsusceptible to idiopathic azoospermia or oligospermia. This study investigated the possible association between Y-chromosome haplogroup distribution and susceptibility to spermatogenic impairment. Peripheral blood was collected from 193 men with normozoospermia, 193 men with idiopathic azoospermia and 105 men with idiopathic oligospermia. All of the subjects underwent karyotyping, azoospermia factor (AZF) deletion analysis by 15 AZF-specific sequence-tagged sites and Y-chromosome haplotype analysis by 17 binary markers. Excluding men with AZF deletions and abnormal karyotypes, the remainder of these 3 groups was named Group i, Group ii, and Group iii, respectively. The comparisons of 17 Y-haplogroup distributions between Group i and Group ii, Group iii or Group ii + iii were performed with the SPSS V.18.0 software. Significantly different Y-haplogroup distributions were observed between Group i and Group ii in N1* (P = 0.002), between Group i and Group iii in F*, K*, P*, and O3* (P = 0.002, 0.001, 0.004, and 0.007, respectively), and between Group i and Group ii + iii in K*, N1* and O3* (P = 0.008, 0.012, and 0.009, respectively). These results suggest that Y-chromosome haplogroups play a role in spermatogenic impairment.