This study provides a high-level discussion, conclusion, and recommendations on the underutilization of human papilloma virus vaccination (HPVV) in Saskatchewan, Canada, drawing on the findings of individual and group interviews conducted as a part of a qualitative mixed-method study. It is structured in the following way. First, it reiterates key findings from the overall study at the system, provider, and patient levels by locating them in the published literature. Second, it identifies and discusses cross-cutting themes (from the themes identified) at three levels (system, provider, and patient). It then provides a concluding section drawing from our qualitative effort to address the overarching goal of addressing inequitable HPVV uptake by advocating “systems thinking” to enhance overall HPVV uptake. It concludes by providing broad recommendations and implications. Full article

Understanding the characteristics of cancer cells is critical for developing enhanced therapies and diagnoses. The super-enhancer notion has been given from the angle of gene regulation in order to properly appreciate the molecular mechanisms behind the identities of distinct cell types. A variety of distinguishing features of super-enhancers have contributed to the findings which link gene regulation and biomolecular condensates. This is typically mediated via liquid-liquid phase separation. Several lines of evidence have pointed to alterations in molecular and biophysical principles in cancer cells, notably those linked to gene regulation and cell signaling. All these findings hint to biomolecular condensate change as a major mechanism by which cancer cells acquire distinct cancer characteristic traits and offer functional innovation for cancer initiation and progression. Liquid-liquid phase separation has recently been used for sorting all the processes taking place in the cell for the formation of biomolecular condensates (membrane-free organelles). Recent studies on biomolecular condensates have found that their production and regulation are associated with cancer. Here, we review the evidence that production and degradation of biomolecular condensates are linked to cancer development and progression. As they are linked to cancers, they can be used in cancer research and to devise new cancer therapies, for example, condensate perturbation. Full article

Colorectal cancer (CRC) ranks third in incidence and second in mortality worldwide. In Ecuador, there are 2,481 new CRC cases per year and 2,366 cancer deaths yearly. CRC presents in stages III-IV in more than 50% of patients. The standard treatment for CRC is chemotherapy, with an overall survival (OS) of 29–31 months. The status of biomarkers KRAS, NRAS, BRAF, and MSI provides prognostic and predictive value. This study aimed to determine OS and progression-free survival (PFS) for metastatic CRC based on these molecular markers with a minimum follow-up of one year. This was an observational longitudinal analytical study at the Hospital de Especialidades Eugenio Espejo (HEEE). We obtained demographic, anatomopathological-molecular, and clinical data from the medical records of patients with metastatic CRC from July 1, 2018 until December 31, 2020. Data were collected from a total of 177 patients. The median follow-up was 21.6 months. The median PFS was 15 months (11.6–18.3) in those with mutated (MT) markers, 18 months (15.7–20.2) for wild type (WT), and 9 months (4.1–13.8) for not performed markers (NR), with a hazard ratio (HR) for PFS in MT versus WT of 0.76; the 95% confidence interval (CI) (0.4–1.4) with p = 0.4. for OS was 21 months (17.1–24.8) for MT markers, 22 months (17.7–26.2) for WT markers, and 19 months (17.7–20.2) for NR. There were no significant differences in OS for MT vs. WT: HR = 1.38, 95% CI (0.8–2.3) p = 0.6. There was no significant association between OS or PSF and KRAS, NRAS, BRAF, and MSI mutations. KRAS was the most mutated marker, with a frequency of 40.2%. In the first monocentric study of mutations in metastatic CRC patients from Ecuador, patients with WT molecular markers reached the most prolonged OS and PFS, and KRAS had the highest mutation frequency. However, further studies with larger sample sizes are required to corroborate our findings. 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

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

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