A new updated prognostic index for patients with brain metastases (BMs) treated with palliative whole brain radiotherapy (WBRT) in the era of precision oncology. METASNCore project.

Introduction: Palliative WBRT is the main treatment for multiple BMs. Recent studies report no benefit in survival after WBRT compared to palliative supportive care in patients (pts) with poor prognosis. A new era of systemic treatment strategies based on targeted therapies are improving the prognosis of patients with BMs.

Basal VEGF-A and ACE Plasma Levels of Metastatic Colorectal Cancer Patients Have Prognostic Value for First-Line Treatment with Chemotherapy Plus Bevacizumab.

The identification of factors that respond to anti-angiogenic therapy would represent a significant advance in the therapeutic management of metastatic-colorectal-cancer (mCRC) patients. We previously reported the relevance of VEGF-A and some components of the renin-angiotensin-aldosterone system (RAAS) in the response to anti-angiogenic therapy in cancer patients. Therefore, this prospective study aims to evaluate the prognostic value of basal plasma levels of VEGF-A and angiotensin-converting enzyme (ACE) in 73 mCRC patients who were to receive bevacizumab-based therapies as a first-line treatment.

The Combination of Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly inflammatory microenvironment and liquid biopsy has emerged as a promising tool for the noninvasive analysis of this tumor. In this study, plasma was obtained from 58 metastatic PDAC patients, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), circulating cell-free DNA (cfDNA) concentration, and circulating RAS mutation were determined. We found that NLR was significantly associated with both overall survival (OS) and progression-free survival.

Nitric oxide-targeted therapy inhibits stemness and increases the efficacy of tamoxifen in estrogen receptor-positive breast cancer cells.

Cancer stem cells (CSCs) are involved in the resistance of estrogen (ER)-positive breast tumors against endocrine therapy. On the other hand, nitric oxide (NO) plays a relevant role in CSC biology, although there are no studies addressing how this important signaling molecule may contribute to resistance to antihormonal therapy in ER breast cancer. Therefore, we explored whether targeting NO in ER breast cancer cells impacts CSC subpopulation and sensitivity to hormonal therapy with tamoxifen.

Association of Tumor Budding With Immune Evasion Pathways in Primary Colorectal Cancer and Patient-Derived Xenografts.

Tumor budding has been found to be of prognostic significance for several cancers, including colorectal cancer (CRC). Additionally, the molecular classification of CRC has led to the identification of different immune microenvironments linked to distinct prognosis and therapeutic response. However, the association between tumor budding and the different molecular subtypes of CRC and distinct immune profiles have not been fully elucidated.

Circulating Cell-Free DNA-Based Liquid Biopsy Markers for the Non-Invasive Prognosis and Monitoring of Metastatic Pancreatic Cancer.

Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined.

SWATH-based proteomics reveals processes associated with immune evasion and metastasis in poor prognosis colorectal tumours.

Newly emerged proteomic methodologies, particularly data-independent acquisition (DIA) analysis-related approaches, would improve current gene expression-based classifications of colorectal cancer (CRC). Therefore, this study was aimed to identify protein expression signatures using SWATH-MS DIA and targeted data extraction, to aid in the classification of molecular subtypes of CRC and advance in the diagnosis and development of new drugs. For this purpose, 40 human CRC samples and 7 samples of healthy tissue were subjected to proteomic and bioinformatic analysis.

Altered S-nitrosothiol homeostasis provides a survival advantage to breast cancer cells in HER2 tumors and reduces their sensitivity to trastuzumab.

The monoclonal antibody trastuzumab against HER2/neu, which is overexpressed in 15-20% of breast cancers, has clinical efficacy but many patients do not respond to initial treatment or develop resistance during treatment. Nitric oxide (NO) regulates cell signaling by targeting specific cysteine residues in proteins, forming S-nitrosothiols (SNO) in a process known as S-nitrosylation. We previously reported that molecular characteristics in breast cancer may dictate the tumor response to impaired SNO homeostasis.

Genetic variants in the renin-angiotensin system predict response to bevacizumab in cancer patients.

Background: Currently, there are no predictive biomarkers for anti-angiogenic strategies in cancer, but response to anti-angiogenic drugs is associated with development of hypertension secondary to treatment. Therefore, this study explored the clinical relevance of genetic polymorphisms in some components of the renin-angiotensin system (RAS).

Material And Methods: Genomic DNA was isolated from peripheral blood from 95 metastatic breast or colorectal cancer patients treated with bevacizumab, and AGTR1-A1166C (rs5186), AGT-M235T (rs699) SNPs and ACE I/D (rs4646994) polymorphisms were genotyped using RT-PCR.

Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study.

Purpose: To test whether combining bevacizumab, an anti-vascular endothelial growth factor treatment, with endocrine therapy (ET) could potentially delay the emergence of resistance to ET.

Patients And Methods: A multicenter, randomized, open-label, phase III, binational (Spain and Germany) study added bevacizumab (15 mg/kg every 3 weeks) to ET (ET-B; letrozole or fulvestrant) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 (HER2) -negative and hormone receptor-positive advanced breast cancer. We compared progression-free survival (PFS), overall survival (OS), overall response rate (ORR), response duration (RD), time to treatment failure (TTF), clinical benefit rate (CBR), and safety.

CoCl2, a mimic of hypoxia, induces formation of polyploid giant cells with stem characteristics in colon cancer.

The induction of polyploidy is considered the reproductive end of cells, but there is evidence that polyploid giant cancer cells (PGCCs) contribute to cell repopulation during tumor relapse. However, the role of these cells in the development, progression and response to therapy in colon cancer remains undefined. Therefore, the main objective of this study was to investigate the generation of PGCCs in colon cancer cells and identify mechanisms of formation.

Maintenance of S-nitrosothiol homeostasis plays an important role in growth suppression of estrogen receptor-positive breast tumors.

Introduction: Protein denitrosylation by thioredoxin reductase (TrxR) is key for maintaining S-nitrosothiol (SNO) homeostasis, although its role in tumor progression is unknown. Therefore, the present study aimed to assess the role of altered SNO homeostasis in breast cancer cells.

Methods: The impairment of SNO homeostasis in breast cancer cells was achieved with the highly specific TrxR inhibitor auranofin and/or exposure to S-nitroso-L-cysteine.

Pseudomembranous colitis associated with chemotherapy with 5-fluorouracil.

Pseudomembranous colitis is frequently associated with antibiotics and more rarely with chemotherapeutic agents such as 5-fluorouracil. The objective of this study is to show that it is possible to confuse this infection with chemotherapy associated toxicity. We present a 54 year old woman who underwent surgery for colorectal cancer and in the first cycle of chemotherapy with 5-fluorouracil developed pseudomembranous colitis.

Comparative study of the immunohistochemical phenotype in breast cancer and its lymph node metastatic location.

At present, an important part of prognostic information, together with particular treatment strategies in breast cancer, take into account the immunohistochemical phenotype of the primary tumor location. However, the changing heterogeneity intrinsic to neoplastic cells in general leads us to consider the possibility that the expression of these proteins is modified during tumoral development and dissemination. With this hypothesis as a starting point, 60 patients with breast cancer were studied with immunohistochemistry, the expression of estrogen and progestagenic receptors, proliferation through the Ki-67 expression, and the overexpression of HER-2 and p53 in both the primary location and the lymph node metastases.

Adjuvant treatment in elderly patients with breast cancer: critical review of clinical practice.

Today the use of adjuvant treatment of breast cancer is unquestionable in the management of this disease. Both chemotherapy and hormonal therapy have proved to be beneficial, not only with respect to the reduction of the risk of recurrence, but also with respect to mortality. However, in elderly patients, this therapeutic approach is occasionally the subject of controversy, due to the undervaluing of the tumoral disease with respect to the multiple pathology frequently present in these patients.