Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in cN0 Breast Cancer: Impact of HER2-Positive Status on Survival.

Objective: High rates of negative sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) breast cancer (BC) after neoadjuvant chemotherapy (NAC) have been described. These results are associated with triple-negative (TNBC) and human epidermal growth factor receptor 2 (HER2+) subtypes achieving pathologic complete response (pCR). This study evaluates predictive variables and survival in order to assess the possible omission of SLNB after NAC. Materials and Methods: Prospective study of women with cN0 BC treated with NAC and subsequent surgery, between April 2010 and May 2021. SLNB technique included, performing axillary lymphadenectomy in the absence of detection or SLNB-positivity. Multivariable logistic regression was used for analysis of NAC-response and SLNB-results in molecular subtypes: HR-/HER2+, TNBC, HR+/HER2- and HR+/HER2+. Kaplan-Meyer and log-rank were used for survival analysis. Results: A total of 179 patients (50.5±10.1 years) were included. Of these, 39.7% achieved pCR (ypT0/Tis). HR-negative subtypes had higher pCR rates (HR-/HER2+: 59.4%; TNBC: 53.4%), with no cases of SLNB-positive. With residual disease, HR-/HER2+ and TNBC showed low rates of SLNB-positivity (6.7% and 10.3%) versus HR+ (HR+/HER2+: 20%; HR+/HER2-: 44%; p<0.001). Multivariable analysis identified independent predictors of SLNB-negativity (p<0.0001) to be: HR- [odds ratio (OR)=0.15; 95% confidence interval (CI): 0.06-0.37; p = 0.0001], HER2+ (OR=0.34; 95% CI: 0.14-0.81; p = 0.015) and high-grade Nottingham (OR=0.42; 95% CI: 0.18-0.99; p = 0.048). Disease-free survival showed worse outcomes with SLNB-positivity (p<0.0001), HR+/HER2- (p = 0.0277), larger tumor size (p = 0.002) and residual disease after NAC (p<0.0001). Conclusion: Patient selection based on NAC response, molecular subtype, and survival outcomes is a priority for establishing individualized therapeutic strategies after NAC. Molecular subtypes with higher pCR rates and lower rates of SLNB-positivity could benefit from non-invasive strategies that include omission of SLNB.

Molecular Mechanisms of Resistance to Ionizing Radiation in S. cerevisiae and Its Relationship with Aging, Oxidative Stress, and Antioxidant Activity.

The repair of the damage produced to the genome and proteome by the action of ionizing radiation, oxidizing agents, and during aging is important to maintain cellular homeostasis. Many of the metabolic pathways influence multiple processes. In this way, this work aims to study the relationship between resistance/response to ionizing radiation, cellular aging, and the response mechanisms to oxidative stress, free radicals, reactive oxygen species (ROS), and antioxidant activity in the yeast S. cerevisiae. Systems biology allows us to use tools that reveal the molecular mechanisms common to different cellular response phenomena. The results found indicate that homologous recombination, non-homologous end joining, and base excision repair pathways are the most important common processes necessary to maintain cellular homeostasis. The metabolic routes of longevity regulation are those that jointly contribute to the three phenomena studied. This study proposes eleven common biomarkers for response/resistance to ionizing radiation and aging (EXO1, MEC1, MRE11, RAD27, RAD50, RAD51, RAD52, RAD55, RAD9, SGS1, YKU70) and two biomarkers for response/resistance to radiation and oxidative stress, free radicals, ROS, and antioxidant activity (NTG1, OGG1). In addition, it is important to highlight that the HSP104 protein could be a good biomarker common to the three phenomena studied.

Pulsed magnetic field increases the effect of ultraviolet C radiation and thermal shock in aged yeasts.

The study of the effects of the magnetic field (MF) on living matter continues to be a dilemma. Until now, the interaction mechanisms of MF with living matter that explain the observed phenomena are unknown. Despite the existing literature and the multiple effects described to date, there are few published articles that study the combined effect of MF with other physical agents during the cellular aging process. In this sense, the aim of this work is to study whether low frequency and intensity pulsed and sinusoidal MF exposure produce alterations in the cell killing effect of ultraviolet C (UVC) radiation and thermal shock during the chronological aging of S. cerevisiae. Yeast cells were exposed to 2.45 mT (50 Hz) sinusoidal MF and 1.5 mT (25 Hz) pulsed MF, during 40 days of aging, in combination with UVC radiation (50 J/m2) and/or thermal shock (52°C). Cell survival was evaluated by clonogenic assay. The exposure of yeast to pulsed MF produces an acceleration of aging, which is not observed in cells exposed to sinusoidal MF. The pulsed MF modifies the cellular response to damaging agents only in aged S. cerevisiae cells. In this sense, the pulsed MF applied increases the damage induced by UVC radiation and by thermal shock. In contrast, the sinusoidal MF used has no effect.

Relationship between heat shock proteins and cellular resistance to drugs and ageing.

BACKGROUND AND AIMS: Ageing is a multifactorial degenerative process which causes a decrease in the cellular capacity for repair and adaptation to external stressors. In this way, it is important to maintain the proper balance of the proteome. Heat shock proteins (HSP) will intervene in this balance, which are responsible for the correct assembly, folding and translocation of other proteins when cells are subjected to stressors. This type of protein is overexpressed in human tumor cells, while its deficit, both in function and quantity, contributes to ageing processes. The present work aims to analyze the response of cells from studies carried out in normal and tumor cells that are subjected to stressors. METHODS AND RESULTS: A PubMed search was performed using the keywords "cell ageing, cell longevity, resistance, HSP, heat shock proteins, thermal shock proteins". This search generated 212 articles. Subsequently, a series of inclusion and exclusion criteria were applied to select the articles of interest to be evaluated. Normal cells subjected to external stressors at low doses increase the number of HSP, causing them to become more resistant. In addition, tumor cells expressing high levels of HSP show greater resistance to treatment and increased cell replication. HSP intervene in the cellular resistance of both normal and tumor cells. CONCLUSIONS: In the case of normal cells, the increase in HSP levels makes them respond effectively to an external stressor, increasing their resistance and not causing cell death. In the case of tumor cells, there is an increase in resistance to treatment.

Prevalence and Risk Factors Associated with Tumors and Other Structural Anomalies in Brain MRI Performed to Rule out Secondary Headache: A Multicenter Observational Study.

Headache disorders (HDs) are among the most common conditions of the central nervous system, with an estimated prevalence of 50% in adult population. The aim of this work is to analyze the prevalence of structural anomalies that may explain HDs in MRI exams performed to rule out secondary headache in real-world practice, as well as risk factors associated with these lesions. We conducted a retrospective observational study based on a consecutive case series of all patients that underwent brain MRI due to headache from 1 January 2019 to 31 May 2019. We included patients from six MRI diagnostic centers accounting for four provinces of Andalusia (southern Spain). Bivariate and multivariate logistical regression models were performed to identify risk factors associated with the outcomes (1) presence of a structural finding potentially explaining headache, (2) presence of intracranial space-occupying lesions (SOLs), and (3) presence of intracranial tumors (ITs). Of the analyzed sample (1041 patients), a structural finding that could explain headache was found in 224 (21.5%) patients. SOLs were found in 50 (6.8%) patients and ITs in 12 (1.5%) patients. The main factors associated with structural abnormalities were female sex (OR, 1.35; 95% CI, 1.02-1.85), accompanying symptoms (OR, 1.34; 95% CI, 1.05-1.89), use of gadolinium-based contrast agents (OR, 1.89; 95% CI, 1.31-2.72) and previously known conditions potentially explaining headache (OR, 2.44; 95% CI, 1.55-3.84). Female sex (p = 0.048) and accompanying symptoms (p = 0.033) were also associated with ITs in bivariate analyses. Our results may be relevant for different medical specialists involved in the diagnosis, management and prevention of headache. Moreover, the risk factors identified in our study might help the development of public health strategies aimed at early diagnosis of brain tumors. Future studies are warranted to corroborate our findings.

Factors and molecular mechanisms of radiation resistance in cancer cells.

PURPOSE: The aim of this work is to review the published studies on radiation resistance mechanisms and molecular markers involved in different tumors. The revision has been focused in the last 5 years (2016-2021). CONCLUSIONS: Radioresistance is a cause of concern as it causes failure of radiation therapy and subsequent tumor relapse. Combination chemotherapy and radiation therapy are clinically successful in treating many types of tumors. Despite continued improvements in cancer treatment, locoregional recurrence or metastatic spread continues to occur in a high proportion of patients after being treated with radiation therapy or combination treatments. There is strong evidence that cancer stem cells contribute to radiation resistance, contributing to treatment failure. The mechanisms of radiation resistance in different tumors are not fully understood. A better understanding of cancer stem cells and the associated signaling pathways that regulate radiation resistance will open up new strategies for treating cancer by radiation therapy. Radiation can damage malignant cells mainly by the induction of DNA double-strand breaks. However, in some tumors appear resistant cells that repopulate the tumor following therapy leading over time to the failure of the treatment. Native mechanisms and induced pathways are the cause of radiation resistance. It has been described that numerous molecular markers acting through numerous mechanisms of action involved in radiation resistance, such as apoptosis resistance, alterations of cell growth, proliferation and DNA repair, hypoxia, increase in invasiveness and migration capacity, cell cycle alterations, and expression of heat shock proteins, among others. Therefore, resistance to radiation is a multifactorial phenomenon that, in different cell types, occurs through different regulatory mechanisms in which different molecules intervene. Resistance can be acquired by altering different regulatory pathways in different tumors. The knowledge of radiation resistance markers could help in the classification and treatment of patients with more aggressive tumors.

Evidences of the (400 MHz - 3 GHz) radiofrequency electromagnetic field influence on brain tumor induction.

Due to the massive increase in non-ionizing radiation emitting devices, the social concern about the possible malignancy to its exposure has increased the research interest. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) included the radiofrequency electromagnetic field (RF-EMF) of mobile phones on the category 2B as 'possibly' carcinogenic to humans. Epidemiological studies noticed a causal association between the exposure to RF-EMF and the incidence of brain neoplasm in different populations, since this is the organ with the highest specific absorption rate. The fact that so many of the ipsilateral tumors found are statistically significant with RF-EMF exposure provides weight suggesting causality. In this way, the higher the exposure (ipsilateral vs contralateral), the longer the cumulative exposure (hours of exposure) and the longer the latency (beyond 10 years); the greater the risk. In addition, considering together all of these parameters suggest a strong causality.

The current role of radiologists in a multidisciplinary team treating breast cancer.

In the last decade, advances in the diagnosis and treatment of breast cancer have achieved a significant increase in the general and disease-free survival of affected women but have also increased the complexity of therapeutic decisions. The decision-making process requires agreement between the physicians involved in the management of these patients. Radiologists must understand what other physicians expect and inform them about the usefulness of imaging modalities. This review attempts to provide an update on these subjects.