Tumor Resection in Hepatic Carcinomas Restores Circulating T Regulatory Cells.

Background/Objectives: Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) represent major primary liver cancers, affecting one of the most vital organs in the human body. T regulatory (Treg) cells play an important role in liver cancers through the immunosuppression of antitumor immune responses. The current study focuses on the characterization of circulating natural killer (NK) cells and T cell subsets, including Treg cells, in CCA and HCC patients, before and after surgical tumor resection, in order to understand the effect of tumor resection on the homeostasis of peripheral blood NK cells and T cells. Methods: Whole blood assays were performed to monitor immune alterations and the functional competence of circulating lymphocytes in a group of ten healthy individuals, eight CCA patients, and twenty HCC patients, before and one month after the surgical procedure, using flow cytometry, cell sorting, and qRT-PCR. Results: Before tumor resection, both HCC and CCA patients display increased percentages of CD8+ Treg cells and decreased frequencies of circulating CD4+ Treg cells. Notwithstanding, no functional impairment was detected on circulating CD4+ Treg cells, neither in CCA nor in HCC patients. Interestingly, the frequency of peripheral CD4+ Treg cells increased from 0.55% ± 0.49 and 0.71% ± 0.54 (in CCA and HCC, respectively) at T0 to 0.99% ± 0.91 and 1.17% ± 0.33 (in CCA and HCC, respectively) at T1, following tumor resection. Conclusions: Our results suggest mechanisms of immune modulation induced by tumor resection.

Proteomic Profile of Endometrial Cancer: A Scoping Review.

Proteomics can be a robust tool in protein identification and regulation, allowing the discovery of potential biomarkers. In clinical practice, the management of endometrial cancer can be challenging. Thus, identifying promising markers could be beneficial, helping both in diagnosis and prognostic stratification, even predicting the response to therapy. Therefore, this manuscript systematically reviews the existing evidence of the proteomic profile of human endometrial cancer. The literature search was conducted via Medline (through PubMed) and the Web of Science. The inclusion criteria were clinical, in vitro, and in vivo original studies reporting proteomic analysis using all types of samples to map the human endometrial cancer proteome. A total of 55 publications were included in this review. Most of the articles carried out a proteomic analysis on endometrial tissue, serum and plasma samples, which enabled the identification of several potential diagnostic and prognostic biomarkers. In addition, eight articles were analyzed regarding the identified proteins, where three studies showed a strong correlation, sharing forty-five proteins. This analysis also allowed the identification of the 10 most frequently reported proteins in these studies: EGFR, PGRMC1, CSE1L, MYDGF, STMN1, CASP3 ANXA2, YBX1, ANXA1, and MYH11. Proteomics-based approaches pointed out potential diagnostic and prognostic candidates for endometrial cancer. However, there is a lack of studies exploring novel therapeutic targets.

Effectiveness of photodynamic therapy on treatment response and survival in patients with recurrent oral squamous cell carcinoma: A systematic review.

BACKGROUND: This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC). METHODS: Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature. RESULTS: The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, PhotofrinⓇ, FoscanⓇ and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. PhotofrinⓇ and FoscanⓇ were the most used photosensitisers, with more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue. CONCLUSIONS: Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations, which considered four photosensitisers, PhotofrinⓇ was the most used but more recent photosensitisers like FoscanⓇ have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC.

Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells.

Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role in triggering tumorigenesis, disease progression, recurrence, and metastasis, as high aldehyde dehydrogenase (ALDH) activity is associated with invasiveness and chemotherapy resistance. Therefore, this study aimed to evaluate the effects of ALDH inhibition in endometrial CSCs. ECC-1 and RL95-2 cells were submitted to a sphere-forming protocol to obtain endometrial CSCs. ALDH inhibition was evaluated through ALDH activity and expression, sphere-forming capacity, self-renewal, projection area, and CD133, CD44, CD24, and P53 expression. A mass spectrometry-based proteomic study was performed to determine the proteomic profile of endometrial cancer cells upon N,N-diethylaminobenzaldehyde (DEAB). DEAB reduced ALDH activity and expression, along with a significant decrease in sphere-forming capacity and projection area, with increased CD133 expression. Additionally, DEAB modulated P53 expression. Endometrial cancer cells display a distinct proteomic profile upon DEAB, sharing 75 up-regulated and 30 down-regulated proteins. In conclusion, DEAB inhibits ALDH activity and expression, influencing endometrial CSC phenotype. Furthermore, ALDH18A1, SdhA, and UBAP2L should be explored as novel molecular targets for endometrial cancer.

Efficacy of Cold Atmospheric Plasma vs. Chemotherapy in Triple-Negative Breast Cancer: A Systematic Review.

Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast cancer (TNBC) remains a challenge. Considering the recent advances in cold atmospheric plasma (CAP) cancer research, our goal was to evaluate efficacy data from studies based on chemotherapy and CAP in TNBC cell lines and animal models. A search of the literature was carried out in the PubMed, Web of Science, Cochrane Library, and Embase databases. Of the 10,999 studies, there were fifty-four in vitro studies, three in vivo studies, and two in vitro and in vivo studies included. MDA-MB-231 cells were the most used. MTT, MTS, SRB, annexin-V/propidium iodide, trypan blue, and clonogenic assay were performed to assess efficacy in vitro, increasing the reliability and comprehensiveness of the data. There was found to be a decrease in cell proliferation after both chemotherapy and CAP; however, different protocol settings, including an extensive range of drug doses and CAP exposure times, were reported. For both therapies, a considerable reduction in tumor volume was observed in vivo compared with that of the untreated group. The treatment of TNBC cell lines with CAP proved successful, with apoptosis emerging as the predominant type of cellular death. This systematic review presents a comprehensive overview of the treatment landscape in chemotherapy and CAP regarding their efficacy in TNBC cell lines.

Targeting of G-quadruplex DNA with 99mTc(I)/Re(I) Tricarbonyl Complexes Carrying Pyridostatin Derivatives.

The main goal of this work was to elucidate the potential relevance of (radio)metal chelates of 99mTc and Re targeting G-quadruplex structures for the design of new tools for cancer theranostics. 99mTc provides the complexes with the ability to perform single-photon-emission computed tomography imaging studies, while the Re complexes should act as anticancer agents upon interaction with specific G4 DNA or RNA structures present in tumor tissues. Towards this goal, we have developed isostructural 99mTc(I) and Re(I) tricarbonyl complexes anchored by a pyrazolyl-diamine (Pz) chelator carrying a pendant pyridostatin (PDS) fragment as the G4-binding motif. The interaction of the PDF-Pz-Re (8) complex with different G4-forming oligonucleotides was studied by circular dichroism, fluorescence spectroscopy and FRET-melting assays. The results showed that the Re complex retained the ability to bind and stabilize G4-structures from different DNA or RNA sequences, namely those present on the SRC proto-oncogene and telomeric RNA (TERRA sequence). PDF-Pz-Re (8) showed low to moderate cytotoxicity in PC3 and MCF-7 cancer cell lines, as typically observed for G4-binders. Biodistribution studies of the congener PDF-Pz-99mTc (12) in normal mice showed that the complex undergoes a fast blood clearance with a predominant hepatobiliary excretion, pointing also for a high in vitro stability.

In Vitro Characterization of Reversine-Treated Gingival Fibroblasts and Their Safety Evaluation after In Vivo Transplantation.

Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD.

Risk of Second Tumors in Retinoblastoma Survivors after Ionizing Radiation: A Review.

Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene (RB1). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Effectively, RB patients present a higher risk of SMN incidence compared to other oncology patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. Over the decades, some studies have been performed to better understand this subject, evaluating the risk of the development of SMNs in RB patients. Furthermore, this risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB. This review aims to clarify the effect of ionizing radiation in RB patients and to understand the association between the risk of SMN incidence in patients that underwent radiation therapy, especially in hereditary RB individuals.

AZD-7648, a DNA-PK Inhibitor, Induces DNA Damage, Apoptosis, and Cell Cycle Arrest in Chronic and Acute Myeloid Leukemia Cells.

The non-homologous end joining pathway is vital for repairing DNA double-strand breaks (DSB), with DNA-dependent protein kinase (DNA-PK) playing a critical role. Altered DNA damage response (DDR) in chronic (CML) and acute myeloid leukemia (AML) offers potential therapeutic opportunities. We studied the therapeutic potential of AZD-7648 (DNA-PK inhibitor) in CML and AML cell lines. This study used two CML (K-562 and LAMA-84) and five AML (HEL, HL-60, KG-1, NB-4, and THP-1) cell lines. DDR gene mutations were obtained from the COSMIC database. The copy number and methylation profile were evaluated using MS-MLPA and DDR genes, and telomere length using qPCR. p53 protein expression was assessed using Western Blot, chromosomal damage through cytokinesis-block micronucleus assay, and γH2AX levels and DSB repair kinetics using flow cytometry. Cell density and viability were analyzed using trypan blue assay after treatment with AZD-7648 in concentrations ranging from 10 to 200 µM. Cell death, cell cycle distribution, and cell proliferation rate were assessed using flow cytometry. The cells displayed different DNA baseline damage, DDR gene expressions, mutations, genetic/epigenetic changes, and p53 expression. Only HEL cells displayed inefficient DSB repair. The LAMA-84, HEL, and KG-1 cells were the most sensitive to AZD-7648, whereas HL-60 and K-562 showed a lower effect on density and viability. Besides the reduction in cell proliferation, AZD-7648 induced apoptosis, cell cycle arrest, and DNA damage. In conclusion, these results suggest that AZD-7648 holds promise as a potential therapy for myeloid leukemias, however, with variations in drug sensitivity among tested cell lines, thus supporting further investigation to identify the specific factors influencing sensitivity to this DNA-PK inhibitor.

Acrocomia aculeata associated with doxorubicin: cardioprotection and anticancer activity.

Doxorubicin (Dox) is a chemotherapeutic agent widely used in the clinic, whose side effects include cardiotoxicity, associated with decreased antioxidant defenses and increased oxidative stress. The association of Dox with natural antioxidants can extend its use if not interfering with its pharmacological potential. In this study, we aimed to understand the effects and mechanisms of the aqueous extract of Acrocomia aculeata leaves (EA-Aa) in cancer cells and the co-treatment with Dox, in in vitro and in vivo models. It was found that EA-Aa showed a relevant decrease in the viability of cancer cells (K562 and MCF-7) and increased apoptosis and death. The Dox cytotoxic effect in co-treatment with EA-Aa was increased in cancer cells. The therapeutic association also promoted a change in cell death, leading to a higher rate of apoptosis compared to the Dox group, which induced necrosis. In addition, in non-cancer cells, EA-Aa enhanced red blood cell (RBC) redox state with lower hemolysis and malondialdehyde (MDA) content and had no in vitro nor in vivo toxicity. Furthermore, EA-Aa showed antioxidant protection against Dox-induced cytotoxicity in H9c2 cells (cardiomyoblast), partially mediated by the NRF2 pathway. In vivo, EA-Aa treatment showed a relevant decrease in MDA levels in the heart, kidney, and brain, evaluated in C57Bl/6 mice induced to cardiotoxicity by Dox. Together, our results proved the effectiveness of EA-Aa in potentiating Dox anticancer effects, with antioxidant and cardioprotective activity, suggesting EA-Aa as a potential Dox pharmacological adjuvant.

Anti-Algics in the Therapeutic Response of Breast and Urological Cancers.

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival (p < 0.05) and progression-free survival (p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients.

Magnetic-Based Human Tissue 3D Cell Culture: A Systematic Review.

Cell-based assays, conducted on monolayer (2D) cultured cells, are an unquestionably valuable tool for biomedical research. However, three-dimensional (3D) cell culture models have gained relevance over the last few years due to the advantages of better mimicking the microenvironment and tissue microarchitecture in vivo. Recent magnetic-based 3D (m3D) cell culture systems can be used for this purpose. These systems are based on exposing magnetized cells to magnetic fields by levitation, bioprinting, or ring formation to promote cell aggregation into 3D structures. However, the successful development of these structures is dependent on several methodological characteristics and can be applied to mimic different human tissues. Thus, a systematic review was performed using Medline (via Pubmed), Scopus, and Web of Science (until February 2022) databases to aggregate studies using m3D culture in which human tissues were mimicked. The search generated 3784 records, of which 25 met the inclusion criteria. The usability of these m3D systems for the development of homotypic or heterotypic spheroids with or without scaffolds was explored in these studies. We also explore methodological differences specifically related to the magnetic method. Generally, the development of m3D cultures has been increasing, with bioprinting and levitation systems being the most used to generate homotypic or heterotypic cultures, mainly to mimic the physiology of human tissues, but also to perform therapeutic screening. This systematic review showed that there are areas of research where the application of this method remains barely explored, such as cancer research.

GENES EXPRESSION AND SERUM BIOMARKERS FOR DIAGNOSIS OF HEPATOCELLULAR CARCINOMA, CIRRHOSIS AND HEPATITIS C.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Risk factors for HCC include hepatitis C (HCV) and B (HBV) virus infection, alcoholic cirrhosis and genetic alterations that can affect several cellular pathways. OBJECTIVE: This study purposed to analyze the gene and serum protein expression of vascular endothelial growth factor (VEGF), angiogenesis, alpha fetoprotein, cystatin B (CSTB), ß-catenin and glypican-3 (GPC3) in groups with HCC, cirrhosis or HCV and controls, and their relation with clinical staging in the HCC and cirrhosis groups, as well its sensitivity and specificity values. METHODS: A total of 230 individuals were distributed in Group 1 (G1) - 80 patients with HCC; Group 2 (G2) - 76 patients with cirrhosis due to any etiology; Group 3 (G3) - 33 patients with HCV; Group 4 (G4 - controls) - 41 individuals without clinical or biochemical signs of any liver disease. Gene expression was analyzed by qRT-PCR and serum proteins were performed using the ELISA method. RESULTS: Increased VEGF and angiogenesis, alpha fetoprotein expression could be observed in BCLC stage-D patients compared to stage-B patients, and stage-C patients showed higher expression of ß-catenin, compared to stage-B patients (P<0.05). For VEGF and GPC3, discriminatory power was observed between HCC patients and controls (AUC =0.71; 0.82, respectively). CSTB showed discriminatory power in the comparison between patients with HCV and controls (AUC =0.74). CONCLUSION: The present study confirms the sensitivity of serum CSTB in the diagnosis of hepatitis C, and gene expression of VEGF and serum GPC3, confer both sensitivity and specificity for the diagnosis of HCC.

Expressão gênica e biomarcadores séricos para diagnóstico de carcinoma hepatocelular, cirrose e hepatite C / Genes expression and serum biomarkers for diagnosis of hepatocellular carcinoma, cirrhosis and hepatitis c

ABSTRACT Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Risk factors for HCC include hepatitis C (HCV) and B (HBV) virus infection, alcoholic cirrhosis and genetic alterations that can affect several cellular pathways. Objective: This study purposed to analyze the gene and serum protein expression of vascular endothelial growth factor (VEGF), angiogenesis, alpha fetoprotein, cystatin B (CSTB), β-catenin and glypican-3 (GPC3) in groups with HCC, cirrhosis or HCV and controls, and their relation with clinical staging in the HCC and cirrhosis groups, as well its sensitivity and specificity values. Methods: A total of 230 individuals were distributed in Group 1 (G1) - 80 patients with HCC; Group 2 (G2) - 76 patients with cirrhosis due to any etiology; Group 3 (G3) - 33 patients with HCV; Group 4 (G4 - controls) - 41 individuals without clinical or biochemical signs of any liver disease. Gene expression was analyzed by qRT-PCR and serum proteins were performed using the ELISA method. Results: Increased VEGF and angiogenesis, alpha fetoprotein expression could be observed in BCLC stage-D patients compared to stage-B patients, and stage-C patients showed higher expression of β-catenin, compared to stage-B patients (P<0.05). For VEGF and GPC3, discriminatory power was observed between HCC patients and controls (AUC =0.71; 0.82, respectively). CSTB showed discriminatory power in the comparison between patients with HCV and controls (AUC =0.74). Conclusion The present study confirms the sensitivity of serum CSTB in the diagnosis of hepatitis C, and gene expression of VEGF and serum GPC3, confer both sensitivity and specificity for the diagnosis of HCC.

RESUMO Contexto: Carcinoma hepatocelular (CHC) é o tipo mais comum de câncer de fígado. Os fatores de risco para CHC incluem infecção pelo vírus da hepatite C (VHC) e B (VHB), cirrose alcoólica e alterações genéticas que podem afetar diversas vias celulares. Objetivo: Este estudo teve como objetivo analisar a expressão gênica e proteica sérica de VEGF, AFP, CSTB, β-catenina e GPC3 em grupos com CHC, cirrose ou VHC e controles, e sua relação com o estadiamento clínico nos grupos CHC e cirrose, bem como sua valores de sensibilidade e especificidade. Métodos: Duzentos e trinta indivíduos foram distribuídos no Grupo 1 (G1) - 80 pacientes com CHC; Grupo 2 (G2) - 76 pacientes com cirrose de qualquer etiologia; Grupo 3 (G3) - 33 pacientes com VHC; Grupo 4 (G4 - Controles) - 41 indivíduos sem sinais clínicos ou bioquímicos de qualquer doença hepática. A expressão gênica foi analisada por qRT-PCR e as proteínas séricas foram realizadas pelo método ELISA. Resultados: Aumento da expressão de VEGF e AFP pode ser observado em pacientes BCLC estágio D em comparação com pacientes estágio B, e pacientes estágio C apresentaram maior expressão de CTNNB1, em comparação com pacientes estágio B (P<0,05). Para VEGF e GPC3, foi observado poder discriminatório entre pacientes com CHC e controles (AUC = 0,71; 0,82, respectivamente). O CSTB mostrou poder discriminatório na comparação entre pacientes com VHC e controles (AUC =0,74). Conclusão: O presente estudo confirma a sensibilidade do CSTB sérico no diagnóstico da hepatite C, e a expressão gênica de VEGF e GPC3 sérica conferem sensibilidade e especificidade para o diagnóstico de CHC.

Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies.

The increasing cancer incidence has certified oncological management as one of the most critical challenges for the coming decades. New anticancer strategies are still needed, despite the significant advances brought to the forefront in the last decades. The most recent, promising therapeutic approaches have benefitted from the application of human perinatal derivatives (PnD), biological mediators with proven benefits in several fields beyond oncology. To elucidate preclinical results and clinic outcomes achieved in the oncological field, we present a narrative review of the studies resorting to animal models to assess specific outcomes of PnD products. Recent preclinical evidence points to promising anticancer effects offered by PnD mediators isolated from the placenta, amniotic membrane, amniotic fluid, and umbilical cord. Described effects include tumorigenesis prevention, uncontrolled growth or regrowth inhibition, tumor homing ability, and adequate cell-based delivery capacity. Furthermore, PnD treatments have been described as supportive of chemotherapy and radiological therapies, particularly when resistance has been reported. However, opposite effects of PnD products have also been observed, offering support and trophic effect to malignant cells. Such paradoxical and dichotomous roles need to be intensively investigated. Current hypotheses identify as explanatory some critical factors, such as the type of the PnD biological products used or the manufacturing procedure to prepare the tissue/cellular treatment, the experimental design (including human-relevant animal models), and intrinsic pathophysiological characteristics. The effective and safe translation of PnD treatments to clinical practice relies on the collaborative efforts of all researchers working with human-relevant oncological preclinical models. However, it requires proper guidelines and consensus compiled by experts and health workers who accurately describe the methodology of tissue collection, PnD isolation, manufacturing, preservation, and delivery to the final user.

Investigating VEGF. miR-145-3p, and miR-101-3p Expression in Patients with Cholangiocarcinoma.

INTRODUCTION: Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer. Several factors, such as epigenetic changes in promoter genes, gene expression, and microRNAs (miR), can contribute to genomic instability in cancer. This study aimed at evaluating the expression of VEGF, miRs 145-3p, and 101-3p in patients with CCA and their potential as biomarkers for diagnosis and prognosis of CCA. MATERIAL AND METHODS: Sixty two patients were studied. Out of these 62 patients, 41 cases had confirm CCA and 21 cases had hepatopathies complications. The RNA was extracted from a paraffined tissue block, and then the synthesis of cDNA was performed. The analysis of the expression of VEGF, miR-145-3p, and miR-101-3p was carried out by polymerase chain reaction in real time.  Results: The findings revealed that miRs 145-3p and 101-3p were under expressed in the case group compared to the control group (0.46; 0.17; P = 0.0001, respectively). VEGF was overexpressed in the case group compared to the control group (11.8; P = 0.0001). An increase in miR-145-3p expression level was observed in patients with perihilar CCA compared to those with distal CCA (0.51 ± 0.41; 0.17 ± 0.13; P = 0.0698). Survival rate analysis showed that 41.9% of patients with intrahepatic CCA and 31.5% of patients with extrahepatic CCA were free from death within 11 months, leading to a significant difference (P> 0.05). CONCLUSION: The underexpression of miRNAs, tumor suppressors, the overexpression of VEGF, smoking, and aging were associated with CCA based on our findings. It seems that the reduced expression of the studies miRNAs and increased expression of VEGF can contribute to a decrease in survival rate of patients with tumor in their intrahepatic bile ducts.

An Overview on Radiation Sensitivity in Hereditary Breast and Ovarian Cancer Syndrome.

Hereditary breast and ovarian cancer (HBOC) syndrome is a condition in which individuals have an increased risk of developing different types of cancer when compared to the general population. BRCA1 repair associated (BRCA1) and BRCA2 repair associated (BRCA2) genes are tumor suppressor genes that play a crucial role in cell, by repairing DNA damage. Mutations in these genes are responsible for 25% of HBOC cases. Individuals with this syndrome are often subjected to diagnostic imaging techniques, as well as therapeutic options, that use ionizing radiation, so it is crucial to understand whether these individuals may present higher radiosensitivity and, therefore, its consequences. Several studies have been carried out to understand if the exposure to different ionizing radiation doses can induce cancer in individuals with HBOC. Some of these studies have shown that individuals with HBOC are hypersensitive to the ionizing radiation and, therefore, have neoplasms resulting from mutations in genes that are important in maintaining genomic stability. When mutated, genes no longer guarantee this stability and promote the induction of carcinogenesis. Oppositely, other studies show that there is no association between exposure to ionizing radiation and an increased risk of developing cancer. Thus, the results are inconsistent, and there is a great need to clarify this relationship. In this review, we present the characteristics of HBOC syndrome and the effects that ionizing radiation can induce in individuals who have it. In addition, we review the studies that have already been carried out on this subject.

The Footprint of Exosomes in the Radiation-Induced Bystander Effects.

Radiation therapy is widely used as the primary treatment option for several cancer types. However, radiation therapy is a nonspecific method and associated with significant challenges such as radioresistance and non-targeted effects. The radiation-induced non-targeted effects on nonirradiated cells nearby are known as bystander effects, while effects far from the ionising radiation-exposed cells are known as abscopal effects. These effects are presented as a consequence of intercellular communications. Therefore, a better understanding of the involved intercellular signals may bring promising new strategies for radiation risk assessment and potential targets for developing novel radiotherapy strategies. Recent studies indicate that radiation-derived extracellular vesicles, particularly exosomes, play a vital role in intercellular communications and may result in radioresistance and non-targeted effects. This review describes exosome biology, intercellular interactions, and response to different environmental stressors and diseases, and focuses on their role as functional mediators in inducing radiation-induced bystander effect (RIBE).

Applications of Photodynamic Therapy in Endometrial Diseases.

Photodynamic therapy (PDT) is a medical procedure useful for several benign conditions (such as wound healing and infections) and cancer. PDT is minimally invasive, presents few side effects, good scaring, and is able to minimal tissue destruction maintaining organ anatomy and function. Endoscopic access to the uterus puts PDT in the spotlight for endometrial disease treatment. This work systematically reviews the current evidence of PDT's potential and usefulness in endometrial diseases. Thus, this narrative review focused on PDT applications for endometrial disease, including reports regarding in vitro, ex vivo, animal, and clinical studies. Cell lines and primary samples were used as in vitro models of cancer, adenomyosis and endometrioses, while most animal studies focused the PDT outcomes on endometrial ablation. A few clinical attempts are known using PDT for endometrial ablation and cancer lesions. This review emphasises PDT as a promising field of research. This therapeutic approach has the potential to become an effective conservative treatment method for endometrial benign and malignant lesions. Further investigations with improved photosensitisers are highly expected.

Cold Atmospheric Plasma Apoptotic and Oxidative Effects on MCF7 and HCC1806 Human Breast Cancer Cells.

Breast cancer (BC) is a malignant neoplasia with the highest incidence and mortality rates in women worldwide. Currently, therapies include surgery, radiotherapy, and chemotherapy, including targeted therapies in some cases. However, treatments are often associated with serious adverse effects. Looking for new options in BC treatment, we evaluated the therapeutic potential of cold atmospheric plasma (CAP) in two cell lines (MCF7 and HCC1806) with distinct histological features. Apoptosis seemed to be the most prevalent type of death, as corroborated by several biochemical features, including phosphatidylserine exposure, the disruption of mitochondrial membrane potential, an increase in BAX/BCL2 ratio and procaspase 3 loss. Moreover, the accumulation of cells in the G2/M phase of the cell cycle points to the loss of replication ability and decreased survival. Despite reported toxic concentrations of peroxides in culture media exposed to plasma, intracellular peroxide concentration was overall decreased accompanying a reduction in GSH levels shortly after plasma exposure in both cell lines. In HCC1806, elevated nitric oxide (NO) concentration accompanied by reduced superoxide levels suggests that these cells are capable of converting plasma-derived nitrites into NO that competes with superoxide dismutase (SOD) for superoxide to form peroxinitrite. The concomitant inhibition of the antioxidative activity of cells during CAP treatment, particularly the inhibition of cytochrome c oxidase with sodium azide, synergistically increased plasma toxicity. Thus, this in vitro research enlightens the therapeutic potential of CAP in the treatment of breast cancer, elucidating its possible mechanisms of action.