Circulating serum microRNAs as biomarkers of drug resistance in multiple myeloma patients treated with bortezomib-based regimens - pilot study.

Despite advances in multiple myeloma (MM) treatment, drug resistance remains a clinical challenge. We aimed to develop a prognostic model for bortezomib resistance based on miRNA expression profiling. The study included 40 previously untreated MM patients receiving bortezomib-based regimens (20 treatment-sensitive, 20 resistant). Pretreatment venous blood samples were analyzed for miRNA expression. Differential expression analysis revealed upregulated miR-27b-3p (FC 1.45, p = 0.017) and let-7b-5p (FC 1.44, p = 0.025) in the resistant group. Univariate analysis identified let-7b-5p (OR 3.17, 95%CI: 1.19-11.4, p = 0.04) and miR-27b-3p (OR 4.73, 95%CI: 1.4-26.6, p = 0.036) as risk factors for resistance. The final multivariate model included miR-27b-3p (OR 23.1, 95% CI: 2.8-452, p = 0.015), let-7b-5p (OR 4.38, 95% CI: 1.28-22.2, p = 0.038), and miR-103a-3p (OR 15.3, 95% CI: 1.33-351, p = 0.049). These miRNAs may serve as biomarkers of treatment response in MM. However, external validation is necessary to confirm the clinical utility of our model.

The Relationship between Serum miRNAs and Early Mortality in Multiple Myeloma Patients Treated with Bortezomib-Based Regimens.

Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow (BM) microenvironment. Despite the progress made in treatment, some MM patients still die within the first year of diagnosis. Numerous studies investigating microRNA (miRNA) expression patterns suggest they may be good prognostic markers. The primary aim of this study was to analyze the expression of selected miRNAs in the serum of MM patients who were later treated with bortezomib-based regimens, and to determine their potential to predict early mortality. The study was conducted in 70 prospectively recruited patients with newly diagnosed MM admitted to the Department of Hematology of the Copernicus Memorial Hospital, Lodz (Poland) between 2017 and 2021. Among them, 17 patients experienced death within 12 months of diagnosis. The expression of 31 selected miRNAs was determined using a miRCURY LNA miRNA Custom PCR Panel. The obtained clinical data included patient characteristics on diagnosis, treatment regimen, response to treatment, and follow-up. Differential expression analysis found two miRNAs to be significantly downregulated in the early mortality group: hsa-miR-328-3p (fold change-FC: 0.72, p = 0.0342) and hsa-miR-409-3p (FC: 0.49, p = 0.0357). Univariate and multivariate logistic regression analyses were performed to assess the early mortality rate. The final model consisted of hsa-miR-409-3p, hsa-miR-328-3p, age, and R-ISS 3. It yielded an area under the curve (AUC) of 0.863 (95%CI: 0.761-0.965) with 88.2% sensitivity and 77.5% specificity. Further external validation of our model is needed to confirm its clinical value.

The Significance of mRNA in the Biology of Multiple Myeloma and Its Clinical Implications.

Multiple myeloma (MM) is a genetically complex disease that results from a multistep transformation of normal to malignant plasma cells in the bone marrow. However, the molecular mechanisms responsible for the initiation and heterogeneous evolution of MM remain largely unknown. A fundamental step needed to understand the oncogenesis of MM and its response to therapy is the identification of driver mutations. The introduction of gene expression profiling (GEP) in MM is an important step in elucidating the molecular heterogeneity of MM and its clinical relevance. Since some mutations in myeloma occur in non-coding regions, studies based on the analysis of mRNA provide more comprehensive information on the oncogenic pathways and mechanisms relevant to MM biology. In this review, we discuss the role of gene expression profiling in understanding the biology of multiple myeloma together with the clinical manifestation of the disease, as well as its impact on treatment decisions and future directions.

Hairy cell leukemia: a brief update on current knowledge and treatment prospects.

PURPOSE OF REVIEW: This article provides a brief update on the recommended diagnosis and treatment strategies for patients with the classic form of hairy cell leukemia (HCL) and HCL variant (HCLv). RECENT FINDINGS: HCL is a chronic B-cell malignancy with multiple treatment options. In recent years, many novel drugs have been assessed for HCL treatment with promising results. The investigated nonchemotherapy options include moxetumomab pasudotox, which targets CD22; vemurafenib or dabrafenib, which target the BRAFV600E protein; trametinib, which targets mitogen-activated protein kinase enzyme; and ibrutinib, which targets Bruton tyrosine kinase. SUMMARY: Purine analogs significantly improve survival in patients with HCL. However, patients often relapse, require multiple treatments, and may become refractory. The introduction of novel agents has expanded the spectrum of therapy possibilities in those patients. In the coming years, they will assist standard therapy for patients with HCL who may currently have suboptimal results.

MicroRNA in Multiple Myeloma - A Role in Pathogenesis and Prognostic Significance.

Multiple myeloma (MM) is a common malignant hematological malignancy. Recently, interest has grown in the role of non-coding regions in disease pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs containing 19-25 bases that play a crucial role in messenger RNA silencing and post-transcriptional regulation of gene expression. Several miRNAs demonstrate markedly dysregulated expression in MM, suggesting that they may act as both tumor suppressors and oncogenes. microRNAs are also reportedly involved in the regulation of other epigenetic mechanisms of gene expression. Additionally, some miRNAs have been associated with drug resistance, and therefore a further exploration of their activity may lead to its reversal. Moreover, miRNA expression patterns in either MM cells or serum exosomes have been shown to be good prognostic markers. This review describes the roles of miRNAs in MM and examines their potential to predict MM prognosis and play a role in novel therapeutic strategies.

Efficacy and safety of B-cell receptor signaling pathway inhibitors in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis of randomized clinical trials.

Ibrutinib and idelalisib, B-cell receptor (BCR) signaling pathway inhibitors, have been recently approved for use against relapsed/refractory chronic lymphocytic leukemia (CLL). To assess the efficacy and safety of BCR pathway inhibitors in relapsed/refractory CLL, we conducted a systematic review and meta-analysis of five randomized controlled trials (1866 patients). Our study demonstrated that BCR pathway inhibitors significantly prolonged progression-free survival (PFS; pooled HR = 0.24; 95% CI: 0.19-0.30) and overall survival (HR = 0.58; 0.46-0.73) compared with control treatment. BCR pathway inhibitors increased the probability of response (RR = 3.54; 95% CI: 1.69-7.41) and decreased the risk of progression (RR = 0.21, 95% CI: 0.13-0.34). However, BCR pathway inhibitors increased the risk of grade 3 and 4 adverse events (AEs; RR = 1.25; 95% CI: 1.08-1.44) and serious AEs (RR = 1.32; 95% CI: 1.17-1.50). AEs causing discontinuation (RR = 1.26; 95% CI: 0.88-1.81) or death (RR = 1.06; 95% CI: 0.72-1.57) were not significantly increased. No statistically significant difference in any aspect of meta-analysis was noted between ibrutinib and idelalisib.

PancreApp: An Innovative Approach to Computational Individualization of Nutritional Therapy in Chronic Gastrointestinal Disorders.

Medical nutrition therapy has a pivotal role in the management of chronic gastrointestinal disorders, like chronic pancreatitis, inflammatory bowel diseases (Lesniowski-Crohn's disease and ulcerative colitis) or irritable bowel syndrome. The aim of this study is to develop, deploy and evaluate an interactive application for Windows and Android operating systems, which could serve as a digital diet diary and as an analysis and a prediction tool both for the patient and the doctor. The software is gathering details about patients' diet and associated fettle in order to estimate fettle change after future meals, specifically for an individual patient. In this paper we have described the process of idea development and application design, feasibility assessment using a phone survey, a preliminary evaluation on 6 healthy individuals and early results of a clinical trial, which is still an ongoing study. Results suggest that applied approximative approach (Shepard's method of 6-dimensional metric interpolation) has a potential to predict the fettle accurately; as shown in leave-one-out cross-validation (LOOCV).

Patients' Awareness Of The Prevention And Treatment Of Colorectal Cancer.

UNLABELLED: The aim of the study was to assess patients' awareness of the prevention and treatment of colorectal cancer. MATERIAL AND METHODS: Patients diagnosed with colorectal cancer, hospitalised at the Department of General and Colorectal Surgery of the Medical University in Lódz during the period from January 2015 to April 2015, were asked to complete a questionnaire concerning their families' medical case record, factors predisposing them to the development of colorectal cancer, the tests applied in diagnostics, and the treatment process. The questionnaire comprised 42 closed-ended questions with one correct answer. A statistical analysis of all answers was carried out. RESULTS: The study group consisted of 30 men and 20 women aged 27-94 years old. A strong, statistically significant negative correlation between a patient's age and his/her awareness of the prevention and treatment of colorectal cancer was noted (p<0.001; r= -0.51). The study demonstrated a statistically significant relationship between the occurrence of neoplasms in a patient's family (p=0.009) or, more specifically, the occurrence of colorectal cancer (p=0.008), and the awareness of the prevention programme. The women's group was characterised by statistically significantly greater awareness of colonoscopy as a screening examination (p=0.004). CONCLUSIONS: Patients need more information on colorectal cancer, its risk factors, prevention, the treatment process, and postoperative care. Lack of awareness of the colorectal cancer issue can be one of the major factors contributing to the high incidence of this disease.