The status of predictive biomarkers in metastatic colorectal cancer is currently underdeveloped. Our study aimed to investigate the predictive value of six circulating exosomal miRNAs derived from ...plasma (miR-92a-3p, miR-143-3p, miR-146a-5p, miR-221-3p, miR-484, and miR-486-5p) for chemosensitivity, resistance patterns, and survival. Thirty-one metastatic colorectal cancer patients were selected before receiving first-line irinotecan- or oxaliplatin-based chemotherapy. Blood samples were harvested at baseline and 4-6 months after the initiation of chemotherapy. The levels of exosomal expression for each miRNA were analyzed by qPCR. Our results for patients receiving first-line FOLFOX showed significantly higher baseline levels of miR-92a-3p (
= 0.007 **), miR-146a-5p (
= 0.036 *), miR-221-3p (
= 0.047 *), and miR-484 (
= 0.009 **) in non-responders (NR) vs. responders (R). Of these, miR-92a-3p (AUC = 0.735), miR-221-3p (AUC = 0.774), and miR-484 (AUC = 0.725) demonstrated a predictive ability to discriminate responses from non-responses, regardless of the therapy used. Moreover, Cox regression analysis indicated that higher expression levels of miR-92a-3p (
= 0.008 **), miR-143-3p (
= 0.009 **), miR-221-3p (
= 0.016 *), and miR-486-5p (
= 0.019 *) at baseline were associated with worse overall survival, while patients expressing higher baseline miR-92a-3p (
= 0.003 **) and miR-486-5p (
= 0.003 **) had lower rates of progression-free survival. No predictive values for candidate microRNAs were found for the post-chemotherapy period. In line with these findings, we conclude that the increased baseline exosomal expression of miR-92a-3p and miR-221-3p seems to predict a lack of response to chemotherapy and lower OS. However, further prospective studies on more patients are needed before drawing practice-changing conclusions.
MicroRNAs (miRNAs), a class of small non-coding RNAs represent potential biomarkers for colorectal cancer (CRC). The study hypothesized that miRNAs associated with liver metastases may also ...contribute to assessing treatment response when associated to plasma exosomes. In this study, we used two sets of biological samples, a collection of tumor tissues harvested from patients with CRC with and without liver metastases, and a collection of plasma from CRC patients with and without response to FOLFOX4/FOLFIRI regimens. We investigated 10 target miRNAs in the tissue of 28 CRC patients and identified miR-125b-5p, miR-17-5p, and miR-185-5p to be associated with liver metastasis. Further, we investigated the three miRNAs at the exosomal level in a plasma collection to test their association with chemotherapy response. Our data suggest that the elevated plasma levels of miR-17-5p and miR-185-5p could be predictive of treatment response. Overexpression of miR-17-5p and underexpression of miR-125b-5p and miR-185-5p in CRC tissue seem to be associated with metastatic potential. On the other hand, an increased expression of miR-125b-5p in plasma exosomes was potentially correlated with a more aggressive CRC phenotype.
Acute myocardial infarction (AMI) is considered as one of the main causes of death, threating human lives for decades. Currently, its diagnosis relies on electrocardiography (ECG), which has been ...proven to be insufficient. In this context, the efficient detection of cardiac biomarkers was proposed to overcome the limitations of ECG. In particular, the measurement of troponins, specifically cardiac troponin I (cTnI) and cardiac troponin T (cTnT), has proven to be superior in terms of sensitivity and specificity in the diagnosis of myocardial damage. As one of the most life-threatening conditions, specific and sensitive investigation methods that are fast, universally available, and cost-efficient to allow for early initiation of evidence-based, living-saving treatment are desired. In this review, we aim to present and discuss the major breakthroughs made in the development of cTnI and cTnT specific biosensor designs and analytical tools, highlighting the achieved progress as well as the remaining challenges to reach the technological goal of simple, specific, cheap, and portable testing chips for the rapid and efficient on-site detection of cardiac cTnI/cTnT biomarkers in order to diagnose and treat cardiovascular diseases at an incipient stage.
In late December 2019, the first cases of viral pneumonia caused by an unidentified pathogen were reported in China. Two years later, SARS-CoV-2 was responsible for almost 450 million cases, claiming ...more than 6 million lives. The COVID-19 pandemic strained the limits of healthcare systems all across the world. Identifying viral RNA through real-time reverse transcription-polymerase chain reaction remains the gold standard in diagnosing SARS-CoV-2 infection. However, equipment cost, availability, and the need for trained personnel limited testing capacity. Through an unprecedented research effort, new diagnostic techniques such as rapid diagnostic testing, isothermal amplification techniques, and next-generation sequencing were developed, enabling accurate and accessible diagnosis. Influenza viruses are responsible for seasonal outbreaks infecting up to a quarter of the human population worldwide. Influenza and SARS-CoV-2 present with flu-like symptoms, making the differential diagnosis challenging solely on clinical presentation. Healthcare systems are likely to be faced with overlapping SARS-CoV-2 and Influenza outbreaks. This review aims to present the similarities and differences of both infections while focusing on the diagnosis. We discuss the clinical presentation of Influenza and SARS-CoV-2 and techniques available for diagnosis. Furthermore, we summarize available data regarding the multiplex diagnostic assay of both viral infections.
Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a ...platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor prognosis and few treatment options with limited efficacy. Resistance to platinum compounds is a complex process involving multiple mechanisms pertaining not only to the tumoral cell but also to the tumoral microenvironment. In this review, we discuss the molecular mechanism involved in ovarian cancer cells' resistance to platinum-based chemotherapy, focusing on the alteration of drug influx and efflux pathways, DNA repair, the dysregulation of epigenetic modulation, and the involvement of the tumoral microenvironment in the acquisition of the platinum-resistant phenotype. Furthermore, we review promising alternative treatment approaches that may improve these patients' poor prognosis, discussing current strategies, novel combinations, and therapeutic agents.
Lung cancer is still one of the most commonly diagnosed cancers, and one of the deadliest. The high death rate is mainly due to the late stage of diagnosis and low response rate to therapy. Previous ...and ongoing research studies have tried to discover new reliable and useful cbiomarkers for the diagnosis and prognosis of lung cancer. Next generation sequencing has become an essential tool in cancer diagnosis, prognosis, and evaluation of the treatment response. This article aims to review the leading research and clinical applications in lung cancer diagnosis using next generation sequencing. In this scope, we identified the most relevant articles that present the successful use of next generation sequencing in identifying biomarkers for early diagnosis correlated to lung cancer diagnosis and treatment. This technique can be used to evaluate a high number of biomarkers in a short period of time and from small biological samples, which makes NGS the preferred technique to develop clinical tests for personalized medicine using liquid biopsy, the new trend in oncology.
Colorectal cancer remains one of the most frequent malignancies (third place at both genders) worldwide in the last decade, owing to significant changes in modern dietary habits. Approximately half ...of the patients develop metastases during the course of their disease. The available therapeutic armamentarium is constantly evolving, raising questions regarding the best approach for improving survival. Bevacizumab remains one of the most widely used therapies for treating metastatic colorectal cancer and can be used after progression. This study aimed to identify the best chemotherapy partner for bevacizumab after progression. We performed a retrospective analysis of patients with metastatic colorectal cancer who were treated with bevacizumab as first- and second-line chemotherapy. Data were collected for 151 patients, 40 of whom were treated with double-dose bevacizumab after the first progression. The two standard chemotherapy regimens combined with bevacizumab were FOLFIRI/CAPIRI and FOLFOX4/CAPEOX. The initiation of first-line treatment with irinotecan-based chemotherapy improved progression-free survival and time to treatment failure but not overall survival. After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively). No correlations were observed between the dose intensity of irinotecan, oxaliplatin, 5-fluorouracil, or bevacizumab and the overall survival, progression-free survival in the first-/second-line treatment, and time to treatment failure. Interaction between an irinotecan-based regimen as a second-line treatment and double-dose bevacizumab after progression was associated with an improved overall survival (p = 0.06). Initiating systemic treatment with an irinotecan-based regimen in combination with bevacizumab improved the progression-free survival in the first-line treatment and time to treatment failure. In terms of overall survival, bevacizumab treatment after the first progression is better partnered with the same regimen as that used in the induction phase.
It is a new and exciting time for acute lymphoblastic leukemia (ALL). While nearly 50 years ago, only one in nine children with ALL survived with chemotherapy, nowadays nearly 90% of children have a ...chance of long-term survival. Adults with ALL, as well as the special category of adolescents and young adult (AYA) patients, are catching up with the new developments seen in children, but still their prognosis is much worse. A plethora of factors are regarded as responsible for the differences in treatment response, such as age, ethnicity, disease biology, treatment regimens and toxicities, drug tolerance and resistance, minimal residual disease evaluation, hematopoietic stem cell transplantation timing and socio-economic factors. Taking these factors into account, bringing pediatric-like protocols to adult patient management and incorporating new agents into frontline treatment could be the key to improve the survival rates in adults and AYA.
Introduction: During the last three decades, there has been an excess weight epidemic due to changes in nutrition and lifestyle. Few data on the prevalence of overweight and obesity in children in ...Romania were published, without a single study representative at the national level. There are reports on the higher level of overweight and obesity in urban areas compared to rural ones. This study aimed to estimate the prevalence of underweight, overweight, obesity and severe obesity in children enrolled in schools from the urban area. Material and methods: For this cross-sectional study, children from 177 schools from the urban area of five counties from the northwestern part of Romania were included after the parents signed written informed consent. Anthropometric data were recorded (weight, height) based on World Health Organization (WHO) recommendations and Body-Mass-Index (BMI), and the z-score for BMI were calculated. The nutritional status was estimated using three reference criteria: WHO, International Obesity Task Force (IOTC) and the Center for Disease Control and Prevention (CDC). Results: We analyzed data of 21,650 children (48.19% boys) age between 7 and 18 years. The prevalence of overweight was 13.8%, 16.2% and 20.3%, of obesity was 10.7%, 10.0% and 5.7% and of severe obesity was 5.1%, 1.2% and 1.6% (using WHO, CDC and IOTF cut-offs). Underweight was present in 5.2% (WHO), 6% (CDC) and 2.6% (IOTF). The highest prevalence of overweight (including obesity) was found in children aged 10 years, and the lowest in adolescents at 18 years. Boys have a higher prevalence of excess weight than girls. Using IOTF cut-offs, the prevalence of obesity and severe obesity was lower than using WHO criteria. Conclusions: The prevalence of overweight (including obesity) in children from the urban area of Western Romania was recorded at alarming levels, higher in boys and at the pre-puberty ages. There are significant differences based on the reference system used. It is important to correctly choose the reference for the definition of overweight and obesity to have the correct estimation of the target for public health measures.
Catheter ablation is established as a treatment option for patients with high number Premature Ventricular Contractions (PVCs). However, complications can occur: cardiac tamponade, coronary artery ...injury or infectious endocarditis. Reversible causes such as hypocalcaemia, hypomagnesaemia and hypokalemia can be responsible for PVCs. Here, a case of nine years old boy, with vitamin D deficiency that presented high number PVCs which corrected using vitamin D dietary supplementation was described. A nine-year-old boy was hospitalised in the Cardiology Department for catheter ablation of PVCs. He presented short of breath during football matches and asthenia. Electrocardiography(ECG) and Holter ECG demonstrated high number PVCs with a morphology consistent of Right Ventricular Outflow Tract (RVOT) origin. Catheter ablation was postponed until Vitamin D came to normal values. Dietary supplementation was performed, together with Holter ECG monitoring. After vitamin D normalisation, PVC burden reduced significantly without the need of catheter ablation or anti-arrhythmic drugs. Catheter ablation and anti-arrhythmic drugs can be avoided in patients with frequent PVCs and vitamin D deficiency.
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