Vaccines for Non-Viral Cancer Prevention

Cancer vaccines are a type of immune therapy that seeks to modulate the host’s immune system to induce durable and protective immune responses against cancer-related antigens. The little clinical success of therapeutic cancer vaccines is generally attributed to the immunosuppressive tumor microenvironment at late-stage diseases. The administration of cancer-preventive vaccination at early stages, such as pre-malignant lesions or even in healthy individuals at high cancer risk could increase clinical efficacy by potentiating immune surveillance and pre-existing specific immune responses, thus eliminating de novo appearing lesions or maintaining equilibrium. Indeed, research focus has begun to shift to these approaches and some of them are yielding encouraging outcomes.

Exclusion of patients living with HIV from cancer immune checkpoint inhibitor trials

Emerging retrospective and prospective studies indicate that immune checkpoint inhibitors (ICIs) can be safe and effective cancer treatments among people living with human immunodeficiency virus (PLWH), however this high-cancer-risk population has often been excluded from groundbreaking cancer ICI trials. Our study aimed to characterize the current rate of exclusion and conditional inclusion of PLWH in cancer ICI trials by tumor type, trial phase, and year. ClinicalTrials.gov cancer ICI trials with planned starts between 1/1/2019 and 10/20/2020 were identified. Based on trial eligibility criteria, trials were categorized as “excluded” if PLWH could not enroll, “conditionally included” if only PLWH with adequate immune function were allowed, or “included/not specified” if HIV was not mentioned in the eligibility criteria. Trials from 2014 were separately collected for comparison over time. The number of trials excluding PLWH were compared to the included/not specified group using Fisher’s exact test. Of 809 trials analyzed from 2019 to 2020, 74.4% excluded, 6.9% conditionally included, and 18.7% included/did not specify PLWH. Early phase trials excluded PLWH more frequently than late phase trials. The 2019–2020 trial cohort showed no significant change in exclusion of PLWH compared to 2014. Despite increasing evidence for safe and effective ICI use for PLWH, most cancer ICI trials exclude PLWH and few studies permit PLWH to participate, even if HIV is well-controlled.

Farmlands Degradation with Intensive Agricultural Practices and Human Health Risk Assessment: A Case Study of Province Punjab, Pakistan

Farmlands contamination with heavy metals (HMs) can be considered as a global issue especially in developing countries. The current study investigates the various pollution indices, potential ecological risk index (PERI) and human health risk caused by HMs in some selected regions of Punjab Province, Pakistan. Farmlands soil samples were collected, acid extracted and analyzed via ICP-MS (Agilent 7500c) for selected HMs. All the HMs were found within permissible limits set by worldwide regulatory authorities except Cd which exceeded its limit in 68% agricultural soils of the study area. The CF values for Cd showed high (CF≥6) degree of contamination to considerable contamination (3≤CF≤6). The CD values indicated low (CD≤6) contamination to moderate (6dermal>inhalation. Furthermore, the RI values were observed higher than 1.0×10–4 for Cd (Lahore and Faisalabad regions) and Cr (Multan and Faisalabad regions) in children working in farmlands and likely exposed to high cancer risk. So, minimization of pollutants must be the top priority of the state to reduce contaminants inputs and immobilization in soil through environmental protection laws and regulations

Elucidation of molecular links between obesity and cancer through microRNA regulation

Background Obesity contributes to high cancer risk in humans and the mechanistic links between these two pathologies are not yet understood. Recent emerging evidence has associated obesity and cancer with metabolic abnormalities and inflammation where microRNA regulation has a strong implication. Methods In this study, we have developed an integrated framework to unravel obesity-cancer linkage from a microRNA regulation perspective. Different from traditional means of identifying static microRNA targets based on sequence and structure properties, our approach focused on the discovery of context-dependent microRNA-mRNA interactions that are potentially associated with disease progression via large-scale genomic analysis. Specifically, a meta-regression analysis and the integration of multi-omics information from obesity and cancers were presented to investigate the microRNA regulation in a dynamic and systematic manner. Results Our analysis has identified a total number of 2,143 unique microRNA-gene interactions in obesity and seven types of cancer. Common interactions in obesity and obesity-associated cancers are found to regulate genes in key metabolic processes such as fatty acid and arachidonic acid metabolism and various signaling pathways related to cell growth and inflammation. Additionally, modulated co-regulations among microRNAs targeting the same functional processes were reflected through the analysis. Conclusion We demonstrated the statistical modeling of microRNA-mediated gene regulation can facilitate the association study between obesity and cancer. The entire framework provides a powerful tool to understand multifaceted gene regulation in complex human diseases that can be generalized in other biomedical applications.

Nation wide increase of polycyclic aromatic hydrocarbons in ultrafine particles during winter over China

Polycyclic aromatic hydrocarbons (PAHs) are toxic compounds in the atmosphere and have adverse effects on public health, especially through the inhalation of particulate matter (PM). At present, there are limited understandings in size distribution of particulate-bound PAHs and its health risk on a continental scale. In this study, we carried out a one-year PM campaign and simultaneously measured size-segregated PAHs at 12 sites across six regions of China. The annual averages of total 24 PAHs (∑24PAHs) and benzo[a]pyrene (BaP) carcinogenic equivalent concentration (BaPeq) ranged from 7.56 to 205 ng m−3 with a mean of 53.5 ng m−3 and 0.21 to 22.2 ng m−3 with a mean of 5.02 ng m−3, respectively. At all the sites, ∑24PAHs and BaPeq were dominated in the ultrafine particles with aerodynamic diameter <1.1 μm, followed by those in the size ranges of 1.1–3.3 µm and >3.3 µm. Compared with the southern China, the northern China witnessed much higher ∑24PAHs (87.36 ng m−3 vs. 17.56 ng m−3), BaPeq (8.48 ng m−3 vs. 1.34 ng m−3) and PAHs inhalation cancer risk (7.4 × 10−4 vs. 1.2 × 10−4). Nationwide increases in both PAH levels and inhalation cancer risk occurred in winter. The unfavorable meteorological conditions and enhanced emissions of coal combustion and biomass burning together led to severe PAHs pollution and high cancer risk in the atmosphere of the northern China, especially during winter. Our results suggested that the reduction of coal and biofuel consumption in the residential sector could be crucial and effective to lower PAH concentrations and its inhalation cancer risk in China.

The genetics of inherited cancers

All cancer can be termed ‘genetic’ as the disease is caused by somatic cell mutations (alterations in the DNA code), which result in abnormal cellular growth and/or proliferation. Most of these mutations are sporadic (only occurring in the cancer cell), but some are due to the inheritance of a germline mutation in a cancer predisposition gene. Cancer predisposition genes can be rare and confer a high cancer risk (about 10-fold lifetime relative risk), or common and confer a low to moderately increased risk (from just over onefold, up to two- to threefold). They have been shown to be involved in causing some of most common cancers as well as some rare cancers. Cancer genetics will become part of mainstream clinical pathways for cancer care in the coming years and is likely to contribute to healthcare that is tailored to individual patients.