Publications by authors named "Mariana-Ferreira Leal"

Article Synopsis
  • Fulvestrant, a selective estrogen receptor degrader (SERD), is limited in breast cancer treatment due to low oral bioavailability, while the investigational SERD elacestrant is more effective and can be taken orally.
  • Both drugs are shown to negatively affect tumor growth in ER+ patient-derived models, but elacestrant remains effective even after resistance develops against fulvestrant.
  • When used in conjunction with CDK4/6 inhibitors, elacestrant enhances anti-cancer effects and demonstrates potential against drug-resistant cells, signifying the need for further clinical testing.
View Article and Find Full Text PDF
Article Synopsis
  • This study investigates the impact of four specific genes (FAM49B, FAM84B, GSDMC, and miR-5194) located in the frequently altered 8q24.21 region on gastric cancer (GC), aiming to shed light on gene expression and copy number variations (CNV) related to GC.
  • Analysis involved comparing gene expression in tumoral and adjacent non-tumoral gastric tissues from 51 to 85 cancer patients against control samples from non-cancer individuals, revealing that three of the four genes were upregulated in cancerous tissues.
  • The findings suggest that higher expression levels of FAM49B, GSDMC, and miR-
View Article and Find Full Text PDF

Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines.

View Article and Find Full Text PDF
Article Synopsis
  • The text discusses the growing research on genetic factors influencing shoulder disorders like rotator cuff injuries, instability, and frozen shoulder.
  • It emphasizes the need to compile a comprehensive database of genetic markers to help predict disease risk and enhance diagnostic and treatment methods.
  • The article reviews current genetic studies, highlighting challenges such as difficulties in replication, statistical power issues, and a high occurrence of false positives in research findings.
View Article and Find Full Text PDF
Article Synopsis
  • The study aims to investigate the link between thyroid disorders and primary frozen shoulder by comparing patients with frozen shoulder to those with rotator cuff tears and healthy controls.
  • The analysis involved 166 frozen shoulder patients, 129 rotator cuff patients, and 251 controls, with all participants providing information on demographics and health factors, including thyroid disorders.
  • Findings indicate a significant association between thyroid disorders (especially hypothyroidism) and frozen shoulder, with individuals having thyroid issues being 2.69 times more likely to develop the condition, particularly among women.
View Article and Find Full Text PDF

A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Here we perform whole exome sequencing and gene expression analysis of matched primary breast tumours and bone metastasis-derived patient-derived xenografts (PDX). Transcriptomic analyses reveal enrichment of the G2/M checkpoint and up-regulation of Polo-like kinase 1 (PLK1) in PDX.

View Article and Find Full Text PDF

Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcome in advanced oestrogen receptor (ER)-positive breast cancer, however relapse is inevitable. Here, we show in model systems that other than loss of RB1 few gene-copy number (CN) alterations are associated with irreversible-resistance to endocrine therapy and subsequent secondary resistance to palbociclib. Resistance to palbociclib occurred as a result of tumour cell re-wiring leading to increased expression of EGFR, MAPK, CDK4, CDK2, CDK7, CCNE1 and CCNE2.

View Article and Find Full Text PDF

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Very few therapeutic options are currently available in this neoplasia. The use of 5-Aza-2'-deoxycytidine (5-AZAdC) was approved for the treatment of myelodysplastic syndromes, and this drug can treat solid tumours at low doses.

View Article and Find Full Text PDF

Despite the advancements in cancer treatments, gastric cancer is still one of the leading causes of death worldwide. In this context, it is of great interest to discover new and more effective ways of treating this disease. Accumulated evidences have demonstrated the amplification of 8q24.

View Article and Find Full Text PDF

After publication of the original article [1], we were notified that an author's surname has been erroneously spelled. Elisabetta Maragoni's family name should be replaced with Marangoni.

View Article and Find Full Text PDF

Background: Endocrine therapies are still the main strategy for the treatment of oestrogen receptor-positive (ER+) breast cancers (BC), but resistance remains problematic. Cross-talk between ER and PI3K/AKT/mTORC has been associated with ligand-independent transcription of ER. We have previously reported the anti-proliferative effects of the combination of everolimus (an mTORC1 inhibitor) with endocrine therapy in resistance models, but potential routes of escape via AKT signalling can lead to resistance; therefore, the use of dual mTORC1/2 inhibitors has met with significant interest.

View Article and Find Full Text PDF

Purpose: To investigate the presence of mutations in primary estrogen-receptor-positive (ER) breast cancer treated with extended (>4 weeks) neoadjuvant (presurgical) aromatase inhibitor (NAI) therapy and to identify patients who may gain less benefit from aromatase inhibition (AI) alone based upon on-treatment changes in gene expression.

Experimental Design: We evaluated ER, progesterone receptor, and Ki67 by immunostaining, mutations by droplet-digital PCR and expression of over 800 key breast cancer genes in paired pre- and post-NAI tumor samples from 87 ER breast cancer patients.

Results: Cell proliferation and estrogen-regulated genes (ERG) remained suppressed in most tumors indicative of persistent response to NAI.

View Article and Find Full Text PDF

Purpose: We evaluated whether multiplex protein quantification using antibody bar-coding with photocleavable oligonucleotides (NanoString) can be applied to evaluate protein expression in breast cancer FFPE specimens. We also assessed whether diagnostic core-cuts fixed immediately at time of procedures and surgical excision sections from routinely fixed breast cancers are affected by the same fixation related differences noted using immunohistochemistry (IHC).

Methods: The expression of 26 proteins was analysed using NanoString technology in 16 pairs of FFPE breast cancer core-cuts and surgical excisions.

View Article and Find Full Text PDF

Purpose: Previous research has provided evidence of a hereditary predisposition for anterior cruciate ligament (ACL) injury. The purpose of this study was to evaluate the association between ancestral population genetics and risk of non-contact ACL injuries.

Methods: Blood samples were collected from 177 individuals with a history of non-contact ACL injury and 556 non-injured control individuals for analysis of the genetic material through the use of a panel of 48 INDELs ancestry genetic markers from three ancestral origins.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the role of extracellular matrix (ECM) compounds in tendon degeneration, specifically in rotator cuff tears, by analyzing RNA and protein expression in both injured and healthy tendon samples.
  • Results indicated that several genes related to ECM were upregulated in torn tendons, and the duration of symptoms as well as smoking habits were correlated with specific changes in collagen fiber composition and gene expression.
  • The findings highlight how clinical factors, such as the duration of symptoms and smoking, influence the molecular changes in tendon degeneration, suggesting potential avenues for targeted treatments.
View Article and Find Full Text PDF

Rotator cuff tear is a common orthopedic condition. Metalloproteinases (MMP) and their inhibitors (TIMP) seem to play a role in the development of joint injuries and in the failure of tissue healing. However, the mechanisms of regulation of gene expression in tendons are still unknown.

View Article and Find Full Text PDF
Article Synopsis
  • - Cancer involves multiple factors and gastric cancer (GC) is the third most common cause of cancer-related deaths globally, showcasing its severity and complexity.
  • - GC exhibits a diverse range of molecular and genetic characteristics, making it a heterogeneous disease that varies from patient to patient.
  • - This review emphasizes the significance of chromosomal changes, genomic variants, H. pylori infection, and interleukin variants in the development of GC, and highlights the need to understand the mechanisms driving its progression.
View Article and Find Full Text PDF

The goal of our study was to evaluate the effect of kaurenoic acid, obtained from copaiba oil resin, in gastric cancer (GC) and a normal mucosa of stomach (MNP01) cell lines. The compound was tested at concentrations of 2.5, 5, 10, 30 and 60μg/mL.

View Article and Find Full Text PDF

Background: Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response.

Material And Methods: We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer.

View Article and Find Full Text PDF
Article Synopsis
  • The study aimed to identify common genetic alterations in four gastric cancer cell lines by using advanced genome analysis techniques.
  • All cell lines showed amplification of the 9p13.3 region, confirmed through multiple methods, indicating a consistent genetic change across samples.
  • The findings suggest that specific genes in the 9p13.3 region could be potential targets for understanding and treating gastric cancer.
View Article and Find Full Text PDF

We previously observed reduced YWHAE (14-3-3ε) protein expression in a small set of gastric cancer samples. YWHAE may act as a negative regulator of the cyclin CDC25B, which is a transcriptional target of MYC oncogene. The understanding of YWHAE role and its targets is important for the better knowledge of gastric carcinogenesis.

View Article and Find Full Text PDF

Different from genetic alterations, the reversible nature of epigenetic modifications provides an interesting opportunity for the development of clinically relevant therapeutics in different tumors. In this study, we aimed to screen and validate candidate genes regulated by the epigenetic marker associated with transcriptional activation, histone acetylation, in gastric cancer (GC). We first compared gene expression profile of trichostatin A-treated and control GC cell lines using microarray assay.

View Article and Find Full Text PDF

Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer.

View Article and Find Full Text PDF

Objectives: We evaluated mRNA expression levels of genes that encode TGF-β1; the TGF-β1 receptor; the collagen-modifying enzymes LOX, PLOD1, and PLOD2; and the extracellular matrix proteins COMP, FN1, TNC and TNXB in synovial/capsule specimens from patients with idiopathic adhesive capsulitis. Possible associations between the measured mRNA levels and clinical parameters were also investigated.

Methods: We obtained glenohumeral joint synovium/capsule specimens from 9 patients with idiopathic adhesive capsulitis who had not shown improvement in symptoms after 5 months of physiotherapy.

View Article and Find Full Text PDF