The long non-coding RNA CCAT1 promotes erlotinib resistance in cholangiocarcinoma by inducing epithelial-mesenchymal transition via the miR-181a-5p/ROCK2 axis.

Cholangiocarcinoma (CCA) is a common malignancy of the digestive system, and its treatment is greatly challenged by rising chemoresistance. Long non-coding RNAs (lncRNAs) have been shown to play critical roles in the development of drug resistance in tumors. However, the role of the lncRNA CCAT1 in erlotinib resistance in CCA remains unclear. In this investigation, we identified CCAT1 as a pivotal factor contributing to erlotinib resistance in CCA. Furthermore, we uncovered that lncRNA CCAT1 modulated epithelial-mesenchymal transition (EMT) through Rho-associated coiled-coil-forming protein kinase 2 (ROCK2), thereby conferring erlotinib resistance upon CCA cells. Mechanistically, we demonstrated that miR-181a-5p interacted with CCAT1 to modulate the expression of ROCK2. Collectively, these findings shed light on the significant role of CCAT1 in the development of erlotinib resistance in CCA. The functional suppression of CCAT1 holds promise in enhancing the sensitivity to erlotinib by reversing EMT through the miR-181a-5p/ROCK2 signaling pathway. These findings provide valuable insights into the mechanisms underlying erlotinib resistance in CCA and the potential strategies for its treatment.

Advances in immune regulation of the G protein-coupled estrogen receptor.

Estrogen and related receptors have been shown to have a significant impact on human development, reproduction, metabolism and immune regulation and to play a critical role in tumor development and treatment. Traditionally, the nuclear estrogen receptors (nERs) ERα and ERß have been thought to be involved in mediating the estrogenic effects. However, our group and others have previously demonstrated that the G protein-coupled estrogen receptor (GPER) is the third independent ER, and estrogen signaling mediated by GPER is known to play an important role in normal physiology and a variety of abnormal diseases. Interestingly, recent studies have progressively revealed GPER involvement in the maintenance of the normal immune system, abnormal immune diseases, and inflammatory lesions, which may be of significant clinical value primarily in the immunotherapy of tumors. In this article, we review current advances in GPER-related immunomodulators and provide a theoretical basis and potential clinical targets to ameliorate immune-related diseases and immunotherapy for tumors.

Exploring genetic associations of Crohn's disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations.

Background: Previous studies have reported associations of Crohn's disease (CD) and ulcerative colitis (UC) with the risks of extraintestinal cancers, but the causality remains unclear. Methods: Using genetic variations robustly associated with CD and UC extracted from genome-wide association studies (GWAS) as instrumental variables. Nine types of extraintestinal cancers of European and Asian populations were selected as outcomes. We used the inverse variance weighted method as the primary approach for two-sample Mendelian randomization analysis. Sensitivity analyses were carried out to evaluate the reliability of our findings. Results: In the European population, we found that CD showed a potential causal relationship with pancreatic cancer (OR: 1.1042; 95% CI: 1.0087-1.2088; P=0.0318). Meanwhile, both CD (outliers excluded: OR: 1.0208; 95% CI: 1.0079-1.0339; P=0.0015) and UC (outliers excluded: OR: 1.0220; 95% CI: 1.0051-1.0393; P=0.0108) were associated with a slight increase in breast cancer risk. Additionally, UC exhibited a potential causal effect on cervical cancer (outliers excluded: OR: 1.1091; 95% CI: 1.0286-1.1960; P=0.0071). In the East Asian population, CD had significant causal effects on pancreatic cancer (OR: 1.1876; 95% CI: 1.0741-1.3132; P=0.0008) and breast cancer (outliers excluded: OR: 0.9452; 95% CI: 0.9096-0.9822; P=0.0040). For UC, it exhibited significant causal associations with gastric cancer (OR: 1.1240; 95% CI: 1.0624-1.1891; P=4.7359×10-5), bile duct cancer (OR: 1.3107; 95% CI: 1.0983-1.5641; P=0.0027), hepatocellular carcinoma (OR: 1.2365; 95% CI: 1.1235-1.3608; P=1.4007×10-5) and cervical cancer (OR: 1.3941; 95% CI: 1.1708-1.6599; P=0.0002), as well as a potential causal effect on lung cancer (outliers excluded: OR: 1.1313; 95% CI: 1.0280-1.2449; P=0.0116). Conclusions: Our study provided evidence that genetically predicted CD may be a risk factor for pancreatic and breast cancers in the European population, and for pancreatic cancer in the East Asian population. Regarding UC, it may be a risk factor for cervical and breast cancers in Europeans, and for gastric, bile duct, hepatocellular, lung, and cervical cancers in East Asians. Therefore, patients with CD and UC need to emphasize screening and prevention of site-specific extraintestinal cancers.

Visualization of breast cancer-related protein synthesis from the perspective of bibliometric analysis.

Breast cancer, as a daunting global health threat, has driven an exponential growth in related research activity in recent decades. An area of research of paramount importance is protein synthesis, and the analysis of specific proteins inextricably linked to breast cancer. In this article, we undertake a bibliometric analysis of the literature on breast cancer and protein synthesis, aiming to provide crucial insights into this esoteric realm of investigation. Our approach was to scour the Web of Science database, between 2003 and 2022, for articles containing the keywords "breast cancer" and "protein synthesis" in their title, abstract, or keywords. We deployed bibliometric analysis software, exploring a range of measures such as publication output, citation counts, co-citation analysis, and keyword analysis. Our search yielded 2998 articles that met our inclusion criteria. The number of publications in this area has steadily increased, with a significant rise observed after 2003. Most of the articles were published in oncology or biology-related journals, with the most publications in Journal of Biological Chemistry, Cancer Research, Proceedings of the National Academy of Sciences of the United States of America, and Oncogene. Keyword analysis revealed that "breast cancer," "expression," "cancer," "protein," and "translation" were the most commonly researched topics. In conclusion, our bibliometric analysis of breast cancer and related protein synthesis literature underscores the burgeoning interest in this research. The focus of the research is primarily on the relationship between protein expression in breast cancer and the development and treatment of tumors. These studies have been instrumental in the diagnosis and treatment of breast cancer. Sustained research in this area will yield essential insights into the biology of breast cancer and the genesis of cutting-edge therapies.

Visualization of the relationship between fungi and cancer from the perspective of bibliometric analysis.

The relationship between cancer and microorganisms has been extensively studied, with bacteria receiving more attention than fungi. However, fungi have been shown to play a significant role in cancer development and progression. Understanding the underlying mechanisms is crucial for identifying new avenues in prevention and treatment. To evaluate the current state of research on fungi and cancer, we conducted a comprehensive bibliometric analysis. Using the Web of Science Core Collection database, we searched for English-language articles published between 1998 and 2022. Analyzing the resulting publication data, we identified trends, patterns, and research gaps. Our analysis encompassed co-authorship networks, citation analysis, and keyword co-occurrence analysis. With 8283 publications identified, averaging 331.32 publications per year, our findings highlight China, the United States, India, Japan, and Germany as the top contributing countries. The Chinese Academy of Sciences, Sun Yat-Sen University, and University of São Paulo emerged as the most productive institutions. Key themes in the literature included "cancer," "cytotoxicity," "apoptosis," "metabolites," and "fungus." Recent trends indicate increased interest in keywords such as "green synthesis," "molecular docking," "anticancer activity," "antibacterial," "anticancer," and "silver nanoparticles." Our study provides a comprehensive assessment of the current research landscape in the field of fungi and cancer, offering insights into collaborative networks, research directions, and emerging hotspots. The growing publication rate demonstrates the rising interest in the topic, while identifying leading countries, institutions, and research themes serves as a valuable resource for researchers, policymakers, and funders interested in supporting investigations on fungi-derived compounds as potential anti-cancer agents.

Appraising the causal association between Crohn's disease and breast cancer: a Mendelian randomization study.

Background: Previous research has indicated that there may be a link between Crohn's disease (CD) and breast cancer (BC), but the causality remains unclear. This study aimed to investigate the causal association between CD and BC using Mendelian randomization (MR) analysis. Methods: The summary data for CD (5,956 cases/14,927 controls) was obtained from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). And the summary data for BC (122,977 cases/105,974 controls) was extracted from the Breast Cancer Association Consortium (BCAC). Based on the estrogen receptor status, the cases were classified into two subtypes: estrogen receptor-positive (ER+) BC and estrogen receptor-negative (ER-) BC. We used the inverse variance weighted method as the primary approach for two-sample MR. MR-PRESSO method was used to rule out outliers. Heterogeneity and pleiotropy tests were carried out to improve the accuracy of results. Additionally, multivariable MR was conducted by adjusting for possible confounders to ensure the stability of the results. Results: The two-sample MR indicated that CD increased the risks of overall (OR: 1.020; 95% CI: 1.010-1.031; p=0.000106), ER+ (OR: 1.019; 95%CI: 1.006-1.034; p=0.006) and ER- BC (OR: 1.019; 95%CI: 1.000-1.037; p=0.046) after removal of outliers by MR-PRESSO. This result was reliable in the sensitivity analysis, including Cochran's Q and MR-Egger regression. In multivariate MR analyses, after adjusting for smoking and drinking separately or concurrently, the positive association between CD and the risks of overall and ER+ BC remained, but it disappeared in ER- BC. Furthermore, reverse MR analysis suggested that BC did not have a significant impact on CD risk. Conclusion: Our findings provide evidence for a possible positive association between CD and the risk of BC. However, further studies are needed to fully understand the underlying mechanisms and establish a stronger causal relationship.

Experimental determination of the effective point of measurement of cylindrical ionization chambers for high-energy photon and electron beams.

Measurements of depth-dose curves in water phantom using a cylindrical ionization chamber require that its effective point of measurement is located at the measuring depth. Recommendations for the position of the effective point of measurement with respect to the central axis valid for high-energy electron and photon beams are given in dosimetry protocols. According to these protocols, the use of a constant shift P(eff) is currently recommended. However, this is still based on a very limited set of experimental results. It is therefore expected that an improved knowledge of the exact position of the effective point of measurement will further improve the accuracy of dosimetry. Recent publications have revealed that the position of the effective point of measurement is indeed varying with beam energy, field size and also with chamber geometry. The aim of this study is to investigate whether the shift of P(eff) can be taken to be constant and independent from the beam energy. An experimental determination of the effective point of measurement is presented based on a comparison between cylindrical chambers and a plane-parallel chamber using conventional dosimetry equipment. For electron beams, the determination is based on the comparison of halfvalue depth R(50) between the cylindrical chamber of interest and a well guarded plane-parallel Roos chamber. For photon beams, the depth of dose maximum, d(max), the depth of 80% dose, d(80), and the dose parameter PDD(10) were used. It was again found that the effective point of measurement for both, electron and photon beams Dosimetry, depends on the beam energy. The deviation from a constant value remains very small for photons, whereas significant deviations were found for electrons. It is therefore concluded that use of a single upstream shift value from the centre of the cylindrical chamber as recommended in current dosimetry protocols is adequate for photons, however inadequate for accurate electron beam dosimetry.