Human Papillomavirus and the use of nanoparticles for immunotherapy in HPV-related cancer: A review

Human Papillomavirus (HPV) remains one of the most commonly contracted sexually transmitted diseases around the world. There are a multitude of HPV types, some of which may never present any symptoms. Others, however, are considered high-risk types, which increase the chance of the person infected to develop cancer. In recent years, the utilization of nanotechnology has allowed researchers to employ and explore the use of nanoparticles in immunotherapies.The new nanoparticle frontier has opened many doors in this area of research as a form of prevention, diagnosis, and treatment in cancers resulting from HPV. This review will provide a brief background of HPV, its relationship to head and neck cancer (HNC) and present some insight into the field of immunotherapeutic nanoparticles.     

HSPA5 negatively regulates lysosomal activity through ubiquitination of MUL1 in head and neck cancer

HSPA5/GRP78/BiP plays an important role in cell survival or tumor progression. For these reasons, HSPA5 is an emerging therapeutic target in cancer development. Here we report that HSPA5 contributes to head and neck cancer (HNC) survival via maintenance of lysosomal activity; however, a nonthermal plasma (NTP, considered as a next-generation cancer therapy)-treated solution (NTS) inhibits HNC progression through HSPA5-dependent alteration of lysosomal activity. HSPA5 prevents NTS-induced lysosome inhibition through lysosomal-related proteins or regulation of gene expression. However, NTS-induced MUL1/MULAN/GIDE/MAPL (mitochondrial ubiquitin ligase activator of NFKB 1) leads to downregulation of HSPA5 via K48-linked ubiquitination at the lysine 446 (K446) residue. MUL1 knockdown hinders NTS-induced lysosome inhibition or cytotoxicity through the reduction of HSPA5 ubiquitination in HNC cells. While MUL1 was suppressed, HSPA5 was overexpressed in tissues of HNC patients. NTS strongly inhibited HNC progression via alterations of expression of MUL1 and HSPA5, in vivo in a xenograft model. However, NTS did not induce inhibition of tumor progression or HSPA5 reduction in MUL1 knockout (KO) HNC cells which were generated by CRISPR/Cas9 system. The data provide compelling evidence to support the idea that the regulation of the MUL1-HSPA5 axis can be a novel strategy for the treatment of HNC.     

Association between the CYP1A1 T3801C polymorphism and risk of cancer: Evidence from 268 case–control studies

T3801C is a common polymorphism in CYP1A1, showing differences in its biological functions. Case–control studies have been performed to elucidate the role of T3801C in cancer, although the results are conflicting and heterogeneous. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and T3801C (55,963 cases and 76,631 controls from 268 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.09–1.19; recessive model: OR = 1.23, 95% CI = 1.12–1.34; CC vs. TT: OR = 1.31, 95% CI = 1.19–1.45; TC vs. TT: OR = 1.12, 95% CI = 1.07–1.18; additive model: OR = 1.14, 95% CI = 1.09–1.19) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of cervical cancer, head and neck cancer, hepatocellular cancer, leukemia, lung cancer, prostate cancer and breast cancer. In addition, significantly decreased colorectal cancer risk was also observed. In summary, this meta-analysis suggests that the participation of CYP1A1 T3801C is a genetic susceptibility for some cancer types. Moreover, our work also points out the importance of new studies for T3801C association in some cancer types, such as gallbladder cancer, Asians of acute myeloid leukemia, and thyroid cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the CYP1A1 T3801C polymorphism in cancer development.     

Hcn and Hnc in Comets C/2000 Wm1 (Linear) and C/2002 C1 (Ikeya-Zhang)

Comets have been suggested as a possibly significant source of organic molecules to the early Earth. Hydrogen cyanide (HCN) is important in models of prebiotic chemistry, but may be difficult to form in the early terrestrial environment, while hydrogen isocyanide (HNC) is a `classical' tracer of interstellar ion-molecule chemistry. We have observed both HCN and HNC in 2 recent comets, bringing the number of comets with published measurements of the HNC/HCN abundance ratio to 6. The HNC/HCN ratio in comet Ikeya-Zhang appears to increase with decreasing heliocentric distance, as was previously observed for comet Hale-Bopp, indicating that the HNC is produced at least in part by processes in the cometary coma (atmosphere) and is not simply a constituent of the nuclear ices. Both comets C/2000 WM1 (Linear) and C/2002 C1 (Ikeya-Zhang) exhibit values of the HNC/HCN ratio that appear to be too large (0.09–0.19) tobe matched by current models of coma chemistry. Cometary HNC maybe a photodissociation product of organic grains or large organic polymers stored in the nucleus. We have also set a limit on the emission from the NO radical in comet WM1.     

Genetic variability of Xrcc3 and Rad51 modulates the risk of head and neck cancer

A case-control study was conducted to analyze the possible associations between the head and neck cancer (HNC) risk and fourteen single nucleotide polymorphisms (SNPs) and haplotypes in Xrcc3 and Rad51 genes. This study involved 81 HNC cases and 111 healthy control subjects. A significant risk-increasing effect of rs3212057 (p.Arg94His) SNP in Xrcc3 (OR=6.6; p<0.01) was observed. On the other hand, risk-decreasing effect was found for rs5030789 (g.3997A>G) and rs1801321 (c.-60G>T) in 5' near gene and 5'UTR regions of Rad51, respectively (OR=0.3 and OR=0.2, p<0.05, respectively). Moreover, these effects were shown to be modulated by tobacco-smoking status and gene-gene interactions. Concluding, the genetic variability of Xrcc3 and/or Rad51 genes might be of relevance with respect to HNC risk.