Exploring Biomarkers in Breast Cancer: Hallmarks of Diagnosis, Treatment, and Follow-Up in Clinical Practice.

Breast cancer is a prevalent malignancy in the present day, particularly affecting women as one of the most common forms of cancer. A significant portion of patients initially present with localized disease, for which curative treatments are pursued. Conversely, another substantial segment is diagnosed with metastatic disease, which has a worse prognosis. Recent years have witnessed a profound transformation in the prognosis for this latter group, primarily due to the discovery of various biomarkers and the emergence of targeted therapies. These biomarkers, encompassing serological, histological, and genetic indicators, have demonstrated their value across multiple aspects of breast cancer management. They play crucial roles in initial diagnosis, aiding in the detection of relapses during follow-up, guiding the application of targeted treatments, and offering valuable insights for prognostic stratification, especially for highly aggressive tumor types. Molecular markers have now become the keystone of metastatic breast cancer diagnosis, given the diverse array of chemotherapy options and treatment modalities available. These markers signify a transformative shift in the arsenal of therapeutic options against breast cancer. Their diagnostic precision enables the categorization of tumors with elevated risks of recurrence, increased aggressiveness, and heightened mortality. Furthermore, the existence of therapies tailored to target specific molecular anomalies triggers a cascade of changes in tumor behavior. Therefore, the primary objective of this article is to offer a comprehensive review of the clinical, diagnostic, prognostic, and therapeutic utility of the principal biomarkers currently in use, as well as of their clinical impact on metastatic breast cancer. In doing so, our goal is to contribute to a more profound comprehension of this complex disease and, ultimately, to enhance patient outcomes through more precise and effective treatment strategies.

Clinical and Translational Applications of Serological and Histopathological Biomarkers in Metastatic Breast Cancer: A Comprehensive Review.

Breast cancer is one of the most common malignancies worldwide and the most common form of cancer in women. A large proportion of patients begin with localized disease and undergo treatment with curative intent, while another large proportion of patients debuts with disseminated metastatic disease. In the last subgroup of patients, the prognosis in recent years has changed radically, given the existence of different targeted therapies thanks to the discovery of different biomarkers. Serological, histological, and genetic biomarkers have demonstrated their usefulness in the initial diagnosis, in the follow-up to detect relapses, to guide targeted treatment, and to stratify the prognosis of the most aggressive tumors in those with breast cancer. Molecular markers are currently the basis for the diagnosis of metastatic disease, given the wide variety of chemotherapy regions and existing therapies. These markers have been a real revolution in the therapeutic arsenal for breast cancer, and their diagnostic validity allows the classification of tumors with higher rates of relapse, aggressiveness, and mortality. In this sense, the existence of therapies targeting different molecular alterations causes a series of changes in tumor biology that can be assessed throughout the course of the disease to provide information on the underlying pathophysiology of metastatic disease, which allows us to broaden our knowledge of the different mechanisms of tissue invasion. Therefore, the aim of the present article is to review the clinical, diagnostic, predictive, prognostic utility and limitations of the main biomarkers available and under development in metastatic breast cancer.

Biological Responses in the Blood and Organs of Rats to Intraperitoneal Inoculation of Graphene and Graphene Oxide.

BACKGROUND: The discrepancy among the in vivo results found in the literature regarding graphene's side effects led us to conduct an in vivo study with graphene. METHODS: In vivo tests involving intraperitoneal inoculation of graphene and graphene oxide nanosheets in rats were carried out to assess potential changes in the blood and organs after 15 and 30 days. Graphene and graphene oxide nanosheets at a concentration of 4 mg per kilogram were suspended in an aqueous solution of 0.9% NaCl at a 1:1 proportion (graphene or graphene oxide), i.e., 1 mg/mL. RESULTS: Optical microscopy of liver, kidney, spleen, and lung tissues revealed no visible histological changes. However, particle traces were found in the peritoneal cavity. Thirty days after inoculation, blood samples were collected for hematological analysis. The blood analysis showed changes indicating a hepatic inflammatory process. Hematological changes after 30 days consisted of alterations to the red series, including microcytosis or higher mean hemoglobin concentrations. In addition, changes in prothrombin and thromboplastin caused longer coagulation times. CONCLUSION: This study contributes to further clarifying the possible toxicity of graphene and its potential biomedical applications.

Adiposity Is Related to Inflammatory Disease Activity in Juvenile Idiopathic Arthritis.

OBJECTIVE: To identify factors associated with the higher proportion of fatty tissue and overweight/obesity observed in patients with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: We performed a cross-sectional study of 80 JIA patients aged 4-15 years with 80 age- and sex-matched healthy controls. Body composition was assessed using dual-energy x-ray absorptiometry. The 27-joint Juvenile Arthritis Disease Activity score (JADAS27) was calculated. Two multivariate models were constructed to identify factors associated with overweight/obesity and fat mass index (FMI). RESULTS: No differences were found between cases and controls in body mass index (BMI) or body composition. However, compared with controls, patients with a high inflammatory activity (JADAS27 > 4.2 for oligoarticular JIA or >8.5 for polyarticular disease) had higher values for BMI (p = 0.006); total fat mass (p = 0.003); FMI (p = 0.001); and fat in the legs (p = 0.001), trunk (p = 0.001), and arms (p = 0.002). The factors associated with overweight/obesity in patients were the duration of therapy with biological drugs, measured in months (OR [95% CI] = 1.12 [1.02-1.04]; p = 0.037), and physical activity (OR [95% CI] = 0.214 [0.07-0.68]; p = 0.010), while the factors associated with FMI were age (ß [95% CI] = 0.30 [0.17-1.41]; p = 0.014), JADAS27 (ß [95% CI] = 0.45 [0.16-1.08]; p = 0.009), and physical activity (ß [95% CI] = -0.22 [-5.76 to 0.29]; p = 0.031). CONCLUSION: Our study revealed no differences between JIA patients with well-controlled disease and low disability and the healthy population in BMI or body composition. Furthermore, the association observed between inflammatory activity and adiposity could be responsible for poorer clinical course.

Study of human radius construction systematics: evaluation by DXA in dry bone.

This study has been undertaken in order to describe the bone mass distribution of the dry human radius via dual x-ray absorptiometry (DXA) with a Norland XR-800 densitometer machine. A sample of 39 dry radius bones was used. Two projections were made: antero-posterior and lateral, and five regions of interest were selected. The bone densities and the bone mineral contents of the various regions of the radius in the two projections were compared using Student's t tests for paired samples, with statistically significant differences being found in all of the values, except in the proximal extremity (P Ext). The area of greatest bone mineral content (BMC) was the medial diaphysis (M Diaph), followed by the distal extremity (D Ext), with the lowest value being found in the proximal extremity (P Ext). As for bone mineral density (BMD), a great symmetry is observed if we take the mean point of the longitudinal axis as a reference, with it being distributed from highest to lowest from the central part to the extremities. A correlation study of the BMD and BMC values between the segments themselves and with the total, in both positions, provides us with a high correlation (p ≤ 0.01), with the highest correlation value being found for the proximal diaphysis (P Diaph) region, indicating the heterogeneous nature of the distribution of the radius bone mass. Bone densitometry via DXA is useful in order to establish an overview of the structural construction of the human radius.

Isokinetic assessment of shoulder complex strength in adolescent elite synchronized swimmers.

Children and adolescent participation in sport has increased in recent years. Synchronized swimming requires correct muscle balance in the shoulder complex. The purpose of this study was to establish isokinetic strength profiles and peak torque ratios of shoulder internal and external rotator muscles in a female high-level synchronized swimming team. Twenty-six adolescent female high-level synchronized swimmers, aged 12-14, participated in this study. Maximal bilateral shoulder concentric external and internal rotation force was measured at 60°/s (5 repetitions) and 180°/s (15 repetitions). The isokinetic concentric strength generated by the internal rotator muscles was significantly higher (p < 0.05) than by the external rotators in both limbs and at both velocities. Significant bilateral differences in the external rotation (ER):internal rotation (IR) strength ratio were noted at 60°/s. Isokinetic assessment is essential in sports medicine, since it is the only test capable of diagnosing any shoulder strength deficit.

Osseoincorporation of Porous Tantalum Trabecular-Structured Metal: A Histologic and Histomorphometric Study in Humans.

Porous tantalum trabecular-structured metal (PTTM) has been applied to titanium orthopedic and dental implants. This study evaluated the healing pattern of bone growth into experimental PTTM cylinders (N = 24; 3.0 × 5.0 mm) implanted in the partially edentulous jaws of 23 healthy volunteers divided into four groups. Six PTTM cylinders per group were explanted, prepared, and analyzed histologically/metrically after 2, 3, 6, and 12 weeks of submerged healing. PTTM implant osseoincorporation resulted from the formation of an osteogenic tissue network that over the course of 12 weeks resulted in vascular bone volume levels in PTTM that are comparable to clinically observed mean trabecular volumes in edentulous posterior jaws.

Osseointegration of TI6Al4V dental implants modified by thermal oxidation in osteoporotic rabbits.

BACKGROUND: In this work, the effect of the heat treatment on Ti6Al4V implants and topical administration of growth hormone to address a better osseointegration in osteoporotic patients has been analysed. METHODS: The osseointegration process of Ti6Al4V implants modified by oxidation treatment at 700 °C for 1 h and the influence of local administration of growth hormone (GH) in osteoporotic female rabbits after 15 and 30 days of implantation have been studied. Bone response was analysed through densitometric and histomorphometric studies. Characterization of the surface was provided by scanning electron microscopy. RESULTS: The oxidation treatment promotes the formation of an oxide scale grown on the Ti6Al4V implants that alters the nanoroughness of the surface. Bone mineral density (BMD) increases from 0.347 ± 0.014 (commercial) to 0.383 ± 0.012 g cm-2 (modified), and bone-to-implant contact (BIC) goes from 48.01 ± 14.78 (commercial) to 55.37 ± 15.31 (modified) after 30 days of implantation. CONCLUSIONS: The oxidation treatment on the Ti6Al4V dental implants enhances the early bone formation at the longest periods of implantation. No significant differences in the BMD and BIC results in healthy and osteoporotic rabbits were revealed with respect to the local administration of GH in the implantation site.