The gut microbiota are frequently reported to be associated with colorectal cancer, while less attention has been paid to precancerous tumors. This study aimed to characterize the intestinal bacteria in patients with colorectal lesions and to assess the potential of bacteria as noninvasive biomarkers of colorectal tumors We prospectively collected and sequenced 463 fecal samples from Zhongshan Hospital, Xiamen University, by targeting 16S rRNA V3_V4 on a Hiseq instrument with PE250 reagents. We analyzed the gut bacterial communities, determined the bacterial characteristics, and constructed models to classify colorectal tumors after feature selection, especially for precancerous lesions. There was a significant difference in fecal bacterial communities among the controls with normal colons (healthy subjects; HS) and the four stages of colorectal tumors. The fecal bacterial diversity increased in colorectal tumors. The phylum Firmicutes was significantly decreased, while Bacteroidetes was increased in colorectal tumors vs. HS. Correspondingly, a total of 81 genera, 589 operational taxonomic units, and 157 predicted pathways were remarkably different in relative abundances among the five groups. Relatively weak differences were observed among colorectal hyperplastic or inflammatory polyps (CRP), small adenomas (CRA), and advanced adenomas (Adv_CRA). Based on feature selection from genera, operational taxonomic units, pathways, and age, the models achieved an area under the receiver operating characteristic curve of 0.92 for classifying colorectal tumors vs. HS, 0.91 for the precancerous tumors vs. CRC, 0.80 for Adv_CRA vs. CRP, and 0.70 for CRA vs. CRP. Alterations in the bacterial diversity, composition, and predicted pathways were identified across multistep colorectal tumorigenesis. The selected bacterial features represent potential noninvasive predictors of colorectal tumors, especially in discriminating benign polyps and adenomas. Full article

Health risks from exposure to asbestos fibers have been evaluated based on professional histories, when fiber concentrations at workplaces were greater than today. A linear no-threshold model was used for risk estimation, although its relevance has not been proven. Asbestos fibers are often detected in lungs and pleura during autopsy, but finding evidence of fibers does not prove that a disease has been caused by asbestos. Thus, targeted detection of mesothelioma and other conditions associated with asbestos exposures has resulted in an increase in the reported incidence of mesothelioma among high-risk groups. Histological and immunochemical characteristics of malignant mesothelioma partially overlap with other cancers, which may also contribute to the overdiagnosis in exposed populations. Differences in carcinogenicity of various asbestos types are discussed here. Prohibitions of asbestos in some developed countries must be reconsidered on the basis of independent research. Life-long bioassays are the most promising way to obtain reliable information regarding asbestos-related malignancy. It should be stressed that non-use of asbestos contributes to an increase of harm from fires, armed conflicts, and traffic accidents. Full article

Lung cancer (LC), with its high incidence and less effective treatment strategies, is often not detected until it is in an advanced stage, which contributes to its high mortality rate. Hence, screening the DNA and RNA content in exosomes offers a promising method for its early diagnosis. New technologies for the early detection of LC are absolutely necessary to improve patient outcomes. Such an approach could be the exploitation of exosomes and their content. Exosomes contain DNA, different RNA species, proteins, ceramides, and cholesterol. They can transport their oncogenetic cargo derived from tumor cells to healthy cells over a range of distances to help propagate genetic information that could contribute to the initiation of cancer. This review provides an overview of the involvement of exosomes and their DNA/RNA together with cell-free DNA, summarizes potential biomarkers and describes the application of technologies for the characterization of exosomes with their possible tumor markers. Current radiological and scanning methods for the early detection of LC are also described and compared with nucleic acid analysis. The strengths and weaknesses of both approaches are considered. Full article

In recent years, miRNAs have been shown to play an important role in many diseases, most notably cancers. Traditional experiments for cancer diagnostics are time-consuming and expensive, thus more attention is being diverted towards discovering computational methods for predicting miRNA–disease association and using them in cancer diagnostics. miRNA numerical sequence information and genes targeted by miRNA were used for the construction of descriptors for machine-learning models. Next, we generated a table of miRNA descriptors using all of the miRNAs in a specific cancer dataset for disease classification. To show the effectiveness of the system, we constructed miRNA descriptor systems for pancreatic cancer, lung cancer, and breast cancer. With the Random Forest classifier, we obtained classification accuracies of 86.9%, 86.3%, and 85.1% for the above-mentioned cancers, respectively. Next, different disease datasets were tested on each model, including new miRNA sets for each cancer type from other studies. The models were able to classify the corresponding cancer miRNAs with >90% accuracy and other disease and cancer datasets with <60% accuracy. With this information, we constructed a hard-voting scheme using the three cancer classification models that is able to perform cancer diagnostics. The results suggest that our method is effective in miRNA–disease association prediction and performing cancer diagnostics. Full article

DNA methylation is essential for regulating tissue-specific gene expression, genomic imprinting, X chromosome inactivation and retroviral element silencing. The transformation from normal to cancer cells is accompanied by changes in DNA methylation resulting in the activation of oncogenes and inactivation of tumor suppressor genes. This process is regulated by methylation and contributes to the support and development of tumors. Epigenetic modifications account for the development of resistance in cancer cells treated with anticancer drugs. Dysregulated signaling pathways involved in tumor drug resistance include the Wnt canonical and non-canonical pathways and the PI3K/PTEN/AKT/mTOR pathway. This review considers the mechanisms and specific methylated biomarkers that participate in such resistances and how resistance to individual treatments for breast, ovarian, uterine and cervix tumors are introduced. Full article

Regulatory T cells (Tregs) are a vital cell subset that induces immune tolerance in the tumor microenvironment by secreting suppressive cytokines and inhibiting innate immune cells. Transforming growth factor-beta (TGF-β) plays an important role in this process. However, the effect of TGF-β blockade on intratumoral Tregs and its specific biological role remains unclear. Quantitative and functional changes in Tregs were evaluated after TGF-β blockade with gradient doses of monoclonal antibody 1D11 in a murine pancreatic ductal adenocarcinoma model. The number of tumor infiltrating Tregs decreased significantly (high dose, low dose and control, 38.6 ± 8.1, 38.6 ± 1.8, 74.6 ± 4.9 /40× field, p = 0.024) after 1D11 administration, while CD8⁺ T cells in the tumor microenvironment significantly increased in the low dose group but reversed in the high dose group (3.1 ± 1.4, 12.3 ± 2.1, 5.4 ± 0.5 /40× field, p = 0.016). The frequency of CD4⁺, CD8⁺ or Treg cells in the peripheral blood and spleen showed no significant change. The typical cytokines TGF-β and inerleukin-10 secreted by Tregs as well as interferon-γ produced by cytotoxic T cells in tumor tissues did not change compared with the controls. TGF-β blockade with a monoclonal antibody can reduce Tregs in the tumor niche, however, its therapeutic efficacy in PDAC patients remains limited. Further investigation of combination therapies is required. Full article