Man-made Vitreous Fibres.

This volume reports on the conclusions of a scientific working group of 19 experts from 11 countries convened by the Monographs Programme of the International Agency for Research on Cancer (IARC) on the re-evaluation of the carcinogenic risk of airborne man-made vitreous fibres.

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Some Antiviral and Antineoplastic Drugs, and Other Pharmaceutical Agents.

This monograph evaluates the carcinogenic risks to humans posed by the use of four antiretroviral agents, four DNA topoisomerase II inhibitors used in the treatment of cancer, and an additional three pharmaceutical agents (hydroxyures, phenolphthalein, and vitamin K substances). The volume marks the first IARC evaluation of nucleoside analogs that act as antiviral agents. The evaluation responds in part to recent findings that zidovudine (AZT), an effective antiretroviral agent now being given to pregnant HIV-infected women to prevent maternal-to-fetal transmission of the virus, is a transplacental carcinogen in mice.

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Association of PDCD1 gene markers with susceptibility to thyroid cancer

Abstract

Purpose

PD-1 receptor is a co-signaling molecule with an important role in regulation of T-lymphocyte activity. Correlation between PD-1 gene (PDCD1) polymorphisms and some immune-related diseases has been reported before. In current study, we aimed to investigate the association of PD-1 polymorphisms at positions +7146 G/A (PD-1.3) and +7785 C/T (PD-1.5), as well as the emerged haplotypes with susceptibility to thyroid carcinoma.

Methods

One hundred five patients with confirmed thyroid cancer and 160 healthy individuals as control group were enrolled. Genotypes were identified using PCR–RFLP and nested PCR–RFLP methods. Results were analyzed by Arlequin and SPSS software packages.

Results

Analysis revealed a significant increase in the frequency of PD-1.5 mutant T allele and heterozygous CT genotype in patients with thyroid cancer in comparison with controls [79 (37.7%) vs. 71 (22.2%), and 51 (48.6%) vs. 51 (31.9%), p = 0.0001 and p = 0.009, receptively]. CC genotype at this position observed to be significantly higher among controls than the patients [99 (61.9%) vs. 40 (38.1%), p = 0.0002]. There were no significant differences in the frequencies of genotypes and alleles at locus PD-1.3 between patients and control group. Despite this, GT haplotype emerged from both positions (PD-1.3 G and PD-1.5 T) has also been observed with significant increased frequency between patients and controls [70 (36.8%) vs. 71 (22.2%), p = 0.0005].

Conclusion

As the first study to investigate two mentioned polymorphisms in thyroid cancer, current study confirmed the association of PD-1.5 C/T polymorphism and a haplotype resulted from both loci, PD-1.3 and PD-1.5, with susceptibility of Iranians to thyroid cancer.

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Spontaneous temporomandibular joint herniation: a rare case

Abstract

Spontaneous herniation of temporomandibular joint into the external auditory canal through the foramen of Huschke is a very rare condition. We describe a case of spontaneous temporomandibular joint herniation in a 35-year-old male, who presented with otorrhea and aural fullness. The herniation was repaired using collagen mesh. A literature review of all the previous reported cases of spontaneous temporomandibular joint was done to study the presenting clinical features and the method of surgical repair.

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Immune modulation associated with vascular endothelial growth factor (VEGF) blockade in patients with glioblastoma

Abstract

Background

Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV).

Methods

Eleven patients with newly diagnosed glioblastoma were treated with radiation, TMZ, and BEV, following surgery. We measured immune-related PBMC subsets using multi-parameter flow cytometry and plasma cytokine and growth factor concentrations using electrochemiluminescence-based multiplex analysis at baseline and after 6 weeks of treatment.

Results

The absolute number of peripheral blood regulatory T cells (Tregs) decreased significantly following treatment. The lower number of peripheral Tregs was associated with a CD4+ lymphopenia, and thus, the ratio of Tregs to PBMCs was unchanged. The addition of bevacizumab to standard radiation and temozolomide led to the decrease in the number of circulating Tregs when compared with our prior study. There was a significant decrease in CD8+ cytotoxic and CD4+ recent thymic emigrant T cells, but no change in the number of myeloid-derived suppressor cells. Significant increases in plasma VEGF and placental growth factor (PlGF) concentrations were observed.

Conclusions

Treatment with radiation, TMZ, and BEV decreased the number but not the proportion of peripheral Tregs and increased the concentration of circulating VEGF. This shift in the peripheral immune cell profile may modulate the tumor environment and have implications for combining immunotherapy with anti-angiogenic therapy.

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Cardiovascular effects of exogenous adrenomedullin and CGRP in Ramp and Calcrl deficient mice

Publication date: Available online 8 December 2016
Source:Peptides
Author(s): J.B. Pawlak, S.E. Wetzel-Strong, M.K. Dunn, K.M. Caron
Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) are potent vasodilator peptides and serve as ligands for the G-protein coupled receptor (GPCR) calcitonin receptor-like receptor (CLR/Calcrl). Three GPCR accessory proteins called receptor activity-modifying proteins (RAMPs) modify the ligand binding affinity of the receptor such that the CLR/RAMP1 heterodimer preferably binds CGRP, while CLR/RAMP2 and CLR/RAMP3 have a stronger affinity for AM. Here we determine the contribution of each of the three RAMPs to blood pressure control in response to exogenous AM and CGRP by measuring the blood pressure of mice with genetic reduction or deletion of the receptor components. Thus, the cardiovascular response of Ramp1^−/−, Ramp2^+/−, Ramp3^−/−, Ramp1^−/−/Ramp3^−/− double-knockout (dKO), and Calcrl^+/− mice to AM and CGRP were compared to wildtype mice. While under anesthesia, Ramp1^−/− male mice had significantly higher basal blood pressure than wildtype males; a difference which was not present in female mice. Additionally, anesthetized Ramp1^−/−, Ramp3^−/−, and Calcrl^+/− male mice exhibited significantly higher basal blood pressure than females of the same genotype. The hypotensive response to intravenously injected AM was greatly attenuated in Ramp1^−/− mice, and to a lesser extent in Ramp3^−/− and Calcrl^+/− mice. However, Ramp1^−/−/Ramp3^−/− dKO mice retained some hypotensive response to AM. These results suggest that the hypotensive effect of AM is primarily mediated through the CLR/RAMP1 heterodimer, but that AM signaling via CLR/RAMP2 and CLR/RAMP3 also contributes to some hypotensive action. On the other hand, CGRP's hypotensive activity seems to be predominantly through the CLR/RAMP1 heterodimer. With this knowledge, therapeutic AM or CGRP peptides could be designed to cause less hypotension while maintaining canonical receptor-RAMP mediated signaling.



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Assessment of trace metal concentrations and human health risk in clam ( Tapes decussatus ) and mussel ( Mytilus galloprovincialis ) from the Homa Lagoon (Eastern Aegean Sea)

Abstract

Seasonal variations of trace metal concentrations (Hg, Cd, Pb, Cr, Zn, and Cu) were investigated in the hepatopancreas and soft tissues (remaining parts of bivalves such as gill, mantle, foot, and muscle) of Tapes decussatus and Mytilus galloprovincialis from the Homa Lagoon. The highest metal concentrations were recorded frequently in February and July in M. galloprovincialis and T. decussatus, respectively. Trace metal levels (except Zn) in the hepatopancreas were higher than those in soft tissue for both bivalves. The results showed that the mean concentrations of Hg, Cd, and Zn for M. galloprovincialis were higher compared to T. decussatus in both tissues. The metal concentrations in both bivalves from the Homa Lagoon were generally below the values of provisional tolerable weekly intake (PTWI) estimates, in terms of human health risk. According to hazard quotient (HQ), Cr values for both species and Cd values for only M. galloprovincialis were found greater than one. Also, total hazard index (THI) values were greater than one in both bivalves, having a potential risk for consumers.

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