Environmental/Occupational Exposure to Radon and Non-Pulmonary Neoplasm Risk: A Review of Epidemiologic Evidence

Although Radon (Rn) is a known agent for lung cancer, the link between Rn exposure and other non-pulmonary neoplasms remains unclear. The aim of this review is to investigate the role of Rn in the development of tumors other than lung cancer in both occupational and environmental exposure. Particularly, our attention has been focused on leukemia and tumors related to brain and central nervous system (CNS), skin, stomach, kidney, and breast. The epidemiologic literature has been systematically reviewed focusing on workers, general population, and pediatric population. A weak increase in leukemia risk due to Rn exposure was found, but bias and confounding factors cannot be ruled out. The results of studies conducted on stomach cancer are mixed, although with some prevalence for a positive association with Rn exposure. In the case of brain and CNS cancer and skin cancer, results are inconclusive, while no association was found for breast and kidney cancers. Overall, the available evidence does not support a conclusion that a causal association has been established between Rn exposure and the risk of other non-pulmonary neoplasms mainly due to the limited number and heterogeneity of existing studies. To confirm this result, a statistical analysis should be necessary, even if it is now not applicable for the few studies available.

Near-Infrared MAO A Inhibitor (NMI) Outperformed FDA-Approved Chemotherapeutic Agents in Brain and Other Cancers: A Bioinformatic Analysis of NCI60 Screening Data

Our previous work has shown that monoamine oxidase A (MAO A) is overexpressed in glioma and prostate cancer. Near-infrared dye conjugate MAO A Inhibitor (NMI) inhibited the growth of these cancers. This study investigated the effects of NMI on other cancers by NCI60 screening. Our results showed that 48 out of 59 screened cell lines from nine types of cancer had 100% growth inhibition at 10 μM NMI treatment. The in vitro efficacy of NMI determined by growth inhibition (GI50 and TGI) and lethal doses (LC50) has been further studied in various cell lines of CNS cancer, prostate cancer, and non-small cell lung cancer (NSCLC), these three cancers showed increased MAO A expression in tumors compared to normal tissues. Based on the waterfall plots and the 3D scatter plot of GI50, TGI, and LC50 data, NMI showed higher potency to several CNS cancer and NSCLC cell lines than prostate cancer cell lines. In vitro efficacy of NMI outperformed FDA-approved drugs for CNS cancer, prostate cancer, and NSCLC, respectively. The Pairwise Pearson Correlation Coefficient (PCC) showed that NMI has a unique mechanism compared to the existing anticancer drugs. This study shows that NMI is a novel theragnostic drug with high potency and unique mechanisms for brain, prostate, NSCLC, and other cancers.

Synthesis and Anticancer Evaluations of Novel Thiazole Derivatives Derived from 4-Phenylthiazol-2-amine

Many novel thiazole derivatives were designed and synthesized using 4-phenylthiazol-2-amine. The reactivity of the latter compound toward different chemical reagents was studied. The structure of the newly synthesized compounds was established based on elemental analysis and spectral data. Furthermore, twenty compounds of the synthesized systems were selected and evaluated in (μM) as significant anticancer agents towards three human cancer cell lines [MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and SF-268 (CNS cancer)] and normal fibroblasts human cell line (WI-38). The results showed that compounds 9 and 14a displayed higher effeciency than the reference doxorubicin.

Synthesis and anticancer properties of 5-(1H-benzoimidazol-2-ylmethylene)-4-oxo-2-thioxothiazolidin-3-ylcarboxilic acids

The reaction of 1H-benzoimidazole-2-carbaldehyde with 4-oxo-2-thioxothiazolidin-3-ylcarboxilic acids was studied and the combinatorial library of 5-(1H-benzoimidazol-2-ylmethylene)-4-oxo-2-thioxothiazolidin-3-ylcarboxilic acids has been prepared. The structures of target compounds 8a-f, 9 and 10a, b were confirmed by using 1H NMR spectroscopy and elemental analysis. The synthesized compounds were selected by the National Cancer Institute (NCI) Developmental Therapeutic Program for the in vitro cell line screening to investigate their anticancer activity. The tested compounds displayed a weak to medium anticancer activity. The most sensitive cell lines turned out to be SNB-75 of CNS Cancer (GP = 74.84–85.73%) and UO-31, Renal cancer (GP = 71.53–82.16%) and to compound 10a K-562 Leukemia cell lines (GP = 57.14). Graphical abstract

A Comprehensive Bioinformatic Analysis of RFC1/2/3/4/5 As Significant Clinical Indicators in The Diagnosis and Prognosis of Low-Grade Glioma

Background: Replication factor C (RFC) proteins play a very important role in nuclear DNA replication, mismatch repair and cell cycle checkpoint pathways. However, the relationship between RFCs and brain tumors is still unclear, especially the diagnostic and prognostic significance of RFCs in low-grade glioma. Methods: In our study, we applied the Oncomine, GEPIA, Human Protein Atlas, cBioPortal, STRING, LinkedOmics and Tumor Immune Estimation Resource (TIMER) databases to analyze the transcriptional and survival data of RFCs in brain and central nervous system (CNS) cancer, especially in low-grade glioma.Results: We found that RFCs were highly expressed in brain and CNS cancer, including low-grade glioma. The transcriptional levels of RFCs were also associated with the tumor stages. Moreover, the survival analysis of RFCs in low-grade glioma patients revealed that enhanced expression of RFCs led to poorer prognosis. RFCs and their 50 frequently altered neighbor genes were found enriched in certain pathways. We also discovered the kinase targets, transcription factor targets and miRNA targets of RFCs in low-grade glioma. RFCs also showed positive correlation with certain infiltrated immune cells in low-grade glioma.Conclusions: These implied that RFCs are the possible biomarkers of the diagnosis and prognosis of low-grade glioma.

Central Nervous System Tumors

This chapter provides an overview of behavioral presentations of central nervous system (CNS) neoplasms in adults. Epidemiology of CNS tumors is briefly reviewed. Complications including cognitive dysfunction and emotional disturbances including mood disorders, anxiety, and psychosis are described. The behavioral adverse effects of treatments for CNS cancer, including radiation therapy and steroids, are discussed. The chapter reviews the differential diagnosis of behavioral presentations in this setting as well as an approach to workup and treatment, including neuropsychological testing, psychotherapy, and pharmacotherapy. The potential effects of CNS cancer on caregivers and staff, and possible assistance for them, are covered.