Ancuta Jurj

Background: Psidium guajava L. (Psidium guajava) is an edible plant; its parts are widely used to cure and prevent many health disorders. Psidium guajava leaves contain a wide array of polyphenols that inhibit peroxidation and may play a role in the prevention and treatment of common, degenerative chronic disorders such as diabetes, cardiovascular disease, and cancer. Colon cancer is the third most common type of cancer diagnosed and the second most common cause of cancer-related deaths globally. In contrast, prostate cancer is the second most diagnosed cancer and the fifth leading cause of cancer-related death worldwide. This study aims to evaluate the pharmacological potential of the Psidium guajava plants cultivated in Romania on colon and prostate cancer cell lines. Methods: Phenolic compounds extraction was made using an average sample of all nine Psidium guajava varieties. Analyses were carried out using a HP-1200 liquid chromatograph. The effect of the alcoholic extract of Psidium guajava leaves was tested on two colon cancer and one prostate cancer cell line as in vitro models. Results: The Psidium guajava leaf extract exhibited anticancer activity against the tested cell lines, with decreased proliferation, increased apoptosis, and cell cycle arrest. The extract reduced the cancer cell line’s migration and invasion capacity, demonstrating greater selectivity for the colon cancer cell line than for the prostate cancer cell lines. Conclusions: This study provides further proof of the Psidium guajava plant’s anticancer properties against colon cancer cell lines. Further studies are needed to confirm its use either alone or in conjunction with conventional cancer treatments as an alternate treatment for certain kinds of malignancies.

Monocationic arene ruthenium complexes (RuL₁–RuL₄) incorporating phenothiazinyl-hydrazinyl-thiazole ligands (L₁–L₄) have been synthesized, characterized and evaluated as anticancer agents. Their cytotoxicity, antiproliferative activity and alteration of apoptotic gene expression were studied on three cancer cell lines, a double positive breast cancer cell line MCF-7 and two triple negative breast cancer cell lines Hs578T and MDA-MB-231. All arene ruthenium complexes were able to reduce the viability of the breast cancer cell lines, with the highest cytotoxicities being recorded for the [(p-cymene)RuL₃Cl]⁺ (RuL₃) complex on the MCF-7 (IC₅₀ = 0.019 µM) and Hs578T cell lines (IC₅₀ = 0.095 µM). In the double positive MCF-7 breast cancer cells, the complexes [(p-cymene)RuL₁Cl]⁺ (RuL₁) and [(p-cymene)RuL₂Cl]⁺ (RuL₂) significantly upregulated pro-apoptotic genes including BAK, FAS, NAIP, CASP8, TNF, XIAP and BAD, while downregulating TNFSF10. In the triple negative breast cancer cell line Hs578T, RuL₁ reduced TNFSF-10 and significantly upregulated BAK, CASP8, XIAP, FADD and BAD, while complex RuL₂ also increased BAK and CASP8 expression, but had limited effects on other genes. The triple negative MDA-MB-231 cancer cells treated with RuL₁ upregulated NOD1 and downregulated p53, while RuL₂ significantly downregulated p53, XIAP and TNFSF10, with minor changes in other genes. The significant alterations in the expression of key apoptotic genes suggest that such complexes have the potential to target cancer cells.

Raman spectroscopy recently proved a tremendous capacity to identify disease-specific markers in various (bio)samples being a non-invasive, rapid, and reliable method for cancer detection. In this study, we first aimed to record vibrational spectra of salivary exosomes isolated from oral and oropharyngeal squamous cell carcinoma patients and healthy controls using surface enhancement Raman spectroscopy (SERS). Then, we assessed this method’s capacity to discriminate between malignant and non-malignant samples by means of principal component–linear discriminant analysis (PC-LDA) and we used area under the receiver operating characteristics with illustration as the area under the curve to measure the power of salivary exosomes SERS spectra analysis to identify cancer presence. The vibrational spectra were collected on a solid plasmonic substrate developed in our group, synthesized using tangential flow filtered and concentrated silver nanoparticles, capable of generating very reproducible spectra for a whole range of bioanalytes. SERS examination identified interesting variations in the vibrational bands assigned to thiocyanate, proteins, and nucleic acids between the saliva of cancer and control groups. Chemometric analysis indicated discrimination sensitivity between the two groups up to 79.3%. The sensitivity is influenced by the spectral interval used for the multivariate analysis, being lower (75.9%) when the full-range spectra were used.

The lack of estrogen or progesterone receptors and absence of HER2 amplification/overexpression in triple-negative breast cancer (TNBC) restricts therapeutic options used in clinical management. MicroRNAs (miRNAs) are small, non-coding transcripts which affect important cellular mechanisms by regulating gene expression at the post-transcriptional level. Among this class, attention was focused on miR-29b-3p with a high profile in TNBC and correlated with the overall survival rates, as TCGA data revealed. This study aims to investigate the implication of the miR-29b-3p inhibitor in TNBC cell lines by identifying a potential therapeutic transcript, improving the clinical outcomes of this disease. The experiments were performed on two TNBC cell lines (MDA-MB-231 and BT549) as in vitro models. An established dose of 50 nM was used for all functional assays performed on the miR-29b-3p inhibitor. A decreased level of miR-29b-3p determined a significant reduction in cell proliferation and colony-forming capacity. At the same time, the changes occurring at the molecular and cellular levels were highlighted. We observed that, when inhibiting the expression level of miR-29b-3p, processes such as apoptosis and autophagy were activated. Further, microarray data revealed that the miRNA expression pattern was altered after miR-29b-3p inhibition, pointing out 8 overexpressed and 11 downregulated miRNAs specific for BT549 cells and 33 upregulated and 10 downregulated miRNAs that were specific for MDA-MB-231 cells. As a common signature for both cell lines, three transcripts were observed, two downregulated, miR-29b-3p and miR-29a, and one upregulated, miR-1229-5p. According to DIANA miRPath, the main predicted targets are related to ECM (extracellular matrix) receptor interaction and TP53 signaling. An additional validation step through qRT-PCR was performed, which showed an upregulation of MCL1 and TGFB1. By inhibiting the expression level of miR-29b-3p, it was shown that complex regulatory pathways targeted this transcript in TNBC cells.

Background: Colorectal cancer is highly common and causes high mortality rates. Treatment for colorectal cancer is multidisciplinary, but in most cases the main option remains surgery. Intriguingly, in recent years, a number of studies have shown that a patient’s postoperative outcome may be influenced by certain anesthetic drugs. Our main objective was to compare the effect of propofol–total intravenous anesthesia (TIVA) with sevoflurane anesthesia and to investigate the potential role of intravenous lidocaine on colon cancer cell functions. We tested the effects of serum from colorectal cancer patients undergoing TIVA vs. sevoflurane anesthesia with or without lidocaine on HCT 116 cell lines; on proliferation, apoptosis, migration, and cell cycles; and on cancer-related gene expressions. Methods: 60 patients who were scheduled for colorectal cancer surgery were randomized into four different groups (two groups with TIVA and two groups with sevoflurane anesthesia with or without intravenous lidocaine). Blood samples were collected at the start and at the end of surgery. HCT 116 cells were exposed to the patients’ serum. Results: 15 patients were included in each of the study groups. We did not find any significant difference on cell viability or apoptosis between the study groups. However, there was an increased apoptosis in propofol groups, but this result was not statistically significant. A significant increase in the expression profile of the TP53 gene in the propofol group was registered (p = 0.029), while in the other study groups, no significant differences were reported. BCL2 and CASP3 expressions increased in the sevoflurane–lidocaine group without statistical significance. Conclusions: In our study, serum from patients receiving different anesthetic techniques did not significantly influence the apoptosis, migration, and cell cycle of HCT-116 colorectal carcinoma cells. Viability was also not significantly influenced by the anesthetic technique, except the sevoflurane–lidocaine group where it was increased. The gene expression of TP53 was significantly increased in the propofol group, which is consistent with the results of similar in vitro studies and may be one of the mechanisms by which anesthetic agents may influence the biology of cancer cells. Further studies that investigate the effects of propofol and lidocaine in different plasma concentrations on different colon cancer cell lines and assess the impacts of these findings on the clinical outcome are much needed.

Neo-adjuvant therapy (NAT) is increasingly used in the clinic for the treatment of breast cancer (BC). Pathological response to NAT has been associated with improved patients’ survival; however, the current techniques employed for assessing the tumor response have significant limitations. Small EVs (sEVs)-encapsulated miRNAs have emerged as promising new biomarkers for diagnosis and prediction. Therefore, our study aims to explore the predictive value of these miRNAs for the pathological response to NAT in BC. By employing bioinformatic tools, we selected a set of miRNAs and evaluated their expression in plasma sEVs and BC biopsies. Twelve miRNAs were identified in sEVs, of which, miR-21-5p, 221-3p, 146a-5p and 26a-5p were significantly associated with the Miller–Payne (MP) pathological response to NAT. Moreover, miR-21-5p, 146a-5p, 26a-5p and miR-24-3p were independent as predictors of MP response to NAT. However, the expression of these miRNAs showed no correlation between sEVs and tissue samples, indicating that the mechanisms of miRNA sorting into sEVs still needs to be elucidated. Functional analysis of miRNA target genes and drug interactions revealed that candidate miRNAs and their targets, can be regulated by different NAT regimens. This evidence supports their role in governing the patients’ therapy response and highlights their potential use as prediction biomarkers.

Background and Objectives: The research aimed at evaluating the capacity of salivary exosomal miR-10b-5p and miR-486-5p for oral and oropharyngeal cancer detection. Materials and Methods: The saliva samples were harvested from histopathological diagnosed oral and oropharyngeal squamous cell carcinoma patients and healthy volunteer subjects. The exosomes were isolated by differential ultracentrifugation and quantified by Nano Track Analysis. The microRNAs were extracted and quantified from salivary exosomes by quantitative Real-Time Polymerase Chain Reaction. Results: This research comprised fifty participants. When compared to healthy controls, salivary exosomal miR-486-5p was elevated and miR-10b-5p was reduced in oral and oropharyngeal squamous cell carcinoma. Moreover, miR-486-5p had a high expression level in stage II of cancer in comparison to the other cancer stages. The cancer samples presented an increased exosome dimension compared to the control samples. Conclusions: Salivary exosomal miR-10b-5p and miR-486-5p have an altered expression in oral and oropharyngeal cancer.

Lung cancers are broadly divided into two categories: non-small-cell lung carcinoma (NSCLC), which accounts for 80–85% of all cancer cases, and small-cell lung carcinoma (SCLC), which covers the remaining 10–15%. Recent advances in cancer biology and genomics research have allowed an in-depth characterization of lung cancers that have revealed new therapy targets (EGFR, ALK, ROS, and KRAS mutations) and have the potential of revealing even more biomarkers for diagnostic, prognostic, and targeted therapies. A new source of biomarkers is represented by non-coding RNAs, especially microRNAs (miRNAs). MiRNAs are short non-coding RNA sequences that have essential regulatory roles in multiple cancers. Therefore, we aim to investigate the tumor microenvironment (TME) and miRNA tumor profile in a subset of 51 early-stage lung cancer samples (T1 and T2) to better understand early tumor and TME organization and molecular dysregulation. We analyzed the immunohistochemistry expression of CD4 and CD8 as markers of the main TME immune populations, E-cadherin to evaluate early-stage epithelial-to-mesenchymal transition (EMT), and p53, the main altered tumor suppressor gene in lung cancer. Starting from these 4 markers, we identified and validated 4 miRNAs that target TP53 and regulate EMT that can be further investigated as potential early-stage lung cancer biomarkers.