Prognosis and Treatment of Gastric Cancer: A 2024 Update.

Due to the high death rate associated with gastric cancer, a great deal of research has been conducted on this disease. The goal of this paper was to start a trimestral review of 2024 for the year that had just started. The scientific literature from 1 January 2024 was chosen with consideration of the the guidelines of the European Society of Medical Oncology (ESMO), which are updated with new findings but not systematically reviewed annually. We used the search term "gastric cancer" to find the most current publications in the PubMed database related to the prognosis and treatment of gastric cancer. As previously said, the only articles that satisfied the inclusion criteria were those from 2024. Articles with case reports were eliminated since they had nothing to do with our research. The treatment of gastric cancer is the focus of the majority of articles from 2024. The primary research axes include surgery and immunonutrition, immunotherapy and Helicobacter pylori, and therapeutic targets. Patients with GC may experience less psychological, social, and financial hardship if the recently identified markers discovered in circulation are better assessed and validated. This could be achieved by either including the markers in an artificial intelligence-based diagnostic score or by using them in conjunction with traditional diagnostic methods. Due to the rising death rate associated with GC, funding for research into diagnosis, prognosis, therapy, and therapeutic targets is essential.

miRNA patterns in male LUSC patients - the 3-way mirror: Tissue, plasma and exosomes.

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. It is classified into two main histological groups: non-small cell lung cancer (NSCLC) and small cell lung cancer. Improving the outcome of cancer patients could be possible by enhancing the early diagnosis. In the current study, we evaluated the levels of three microRNAs - miR-21-5p, miR-155-5p, and miR-181a-5p in tumor (TT) vs adjacent normal tissue (NT), as well as their expression levels in plasma and extracellular vesicles (EVs) from plasma in lung squamous cell carcinoma (LUSC) male patients vs healthy individuals as means to identify a panel of miRNAs that could serve as novel biomarkers for the diagnosis of LUSC in male patients. Matched paired tissue samples from male LUSC (n=40) patients were used for miRNA expression analysis. MiR-21-5p and miR-155-5p in tumor tissue were overexpressed, while underexpression of miR-181a-5p was observed in LUSC TT vs NT. These results were further validated in the TCGA LUSC dataset, considering 279 male samples. These alterations of miR-21-5p, miR-181a-5p, and miR-155-5p in tumor tissue are also present in plasma and plasma extracellular vesicles in LUSC male patients. In addition, ROC curves were performed to assess the sensitivity and specificity of different combinations of these miRNAs, confirming a high diagnostic accuracy for LUSC of up to 88 % in male subjects. The expression levels in tissue samples and the abundance in plasma and plasma EVs of the three miRNAs combined - miR-21-5p, miR-155-5p and miR-181a-5p - could be considered for further studies on biomarkers for the early detection of LUSC in male subjects.

5-fluorouracil therapeutic drug monitoring and adverse events in a Romanian population.

Fluoropyrimidines represent the backbone of many chemotherapy protocols and the standard treatment for many types of tumors. Toxicity associated with fluoropyrimidines can occur in up to 40% of cases. Background and purpose: The objective of this study was to analyze the correlation between the plasma concentration of 5-fluorouracil and the adverse events that patients might experience during this therapy. Methods: A total of 58 patients received 5-fluorouracil-based chemotherapy. A blood sample was collected from each patient during the drug infusion, in order to assess the area under the curve for 5-fluorouracil. The occurring adverse events were evaluated through medical recordings of the patients' reported symptoms, clinical and paraclinical examinations. Results: In our study, the majority of patients experienced some type of toxicity. Moreover, we found a correlation between 5-FU plasma concentration (expressed as AUC) and adverse events, a stronger one with hematological adverse reactions and a weaker one with gastrointestinal and cardiovascular toxicity. Conclusion: Determining the plasma concentration of 5-FU in patients with severe toxicities could represent a method of individualizing the treatment and improving the safety profile.

Recurrent cardiotoxicity in a fluoropyrimidine treated cancer patient - case report and practical recommendations.

Fluoropyrimidines remain some of the most used chemotherapeutics, despite the appearance in the therapeutic arsenal of targeted therapy and immunotherapy. Fluropyrimidines related cardiotoxicity is an undesirable adverse event and affects almost 20% of patients. The mechanisms of fluoropyrimidine toxicity are closely related to deficient allelic variants of DPYD, but considering the low penetrance and interindividual variability, not all adverse reactions are explained by their presence. In this case, we report a patient with recurrent fluoropyrimidine toxicity without a deficient allelic variant and how this case was managed by the oncologist and cardiologist, considering the need to use fluoropyrimidine in the treatment.

Endoglin (CD105) as a putative prognostic biomarker for colorectal cancer: a systematic review.

The outcome of colorectal cancer (CRC) can be improved by the identification of prognostic biomarkers. This systematic review of observational cohort and case-control studies was conducted to investigate the role of Endoglin (CD105) in the prognosis of CRC. The databases PubMed, Web of Science, Scopus, and Cochrane CENTRAL were searched to identify the qualified studies using the relevant keywords. After the removal of duplicate articles, the screening was implemented on the titles, abstracts, and potential full-text articles. Afterward, the eligible cohort and case-control studies were identified, and the data were extracted into an Excel datasheet. In total, 11 observational cohort studies and 1 case-control study were identified to be eligible for this systematic review. The majority of the included studies achieved a moderate to high-degree quality according to the Newcastle-Ottawa Scale. Moreover, the eligible studies included a total of 1,400 patients with CRC and mean age of 60 years, the majority of whom were male. Endoglin was observed to be more upregulated in colorectal carcinomas and associated with poor survival outcomes, compared to healthy controls. The levels of Endoglin seem to reflect the degree of cancer invasiveness, therefore predicting dismal prognosis in patients with CRC. Larger and well-designed clinical studies with longer follow-up intervals are needed to investigate the role of Endoglin and its association with cancer metastasis.

Practical Considerations for the Use of Cannabis in Cancer Pain Management-What a Medical Oncologist Should Know.

Pain is a highly debilitating emotional and sensory experience that significantly affects quality of life (QoL). Numerous chronic conditions, including cancer, are associated with chronic pain. In the setting of malignancy, pain can be a consequence of the tumor itself or of life-saving interventions, including surgery, chemotherapy, and radiotherapy. Despite significant pharmacological advances and awareness campaigns, pain remains undertreated in one-third of patients. To date, opioids have been the mainstay of cancer pain management. The problematic side effects and unsatisfactory pain relief of opioids have revived patients' and physicians' interest in finding new solutions, including cannabis and cannabinoids. The medical use of cannabis has been prohibited for decades, and it remains in Schedule 1 of the Misuse of Drugs Regulations. Currently, the legal context for its usage has become more permissive. Various preclinical and observational studies have aimed to prove that cannabinoids could be effective in cancer pain management. However, their clinical utility must be further supported by high-quality clinical trials.

Long Term Administration of Nivolumab for Metastatic Melanoma: A Case Report.

The treatment of metastatic melanoma changed dramatically with the discovery of immune checkpoint inhibitors (ICIs). Patients face prolonged exposure to these agents, which can frequently generate a large spectrum of adverse reactions. It has been shown that a considerable number of patients treated with ICIs achieve a durable response to treatment that is maintained even after cessation. We present the case of a 75-year-old man with metastatic melanoma who underwent 95 cycles of nivolumab without significant treatment-related toxicities or progression. Future studies are needed to define more clearly the optimal duration of anti-programmed cell death protein 1 (PD-1) agents in patients with good tolerance and no progression. Patients could avoid discomfort caused by frequent physician visits, high additional costs, and possible adverse reactions that may occur after such a long period of exposure to immunotherapy.

Landscape of Immunotherapy Options for Colorectal Cancer: Current Knowledge and Future Perspectives beyond Immune Checkpoint Blockade.

Colorectal cancer is the third most prevalent malignancy in Western countries and a major cause of death despite recent improvements in screening programs and early detection methods. In the last decade, a growing effort has been put into better understanding how the immune system interacts with cancer cells. Even if treatments with immune checkpoint inhibitors (anti-PD1, anti-PD-L1, anti-CTLA4) were proven effective for several cancer types, the benefit for colorectal cancer patients is still limited. However, a subset of patients with deficient mismatch repair (dMMR)/microsatellite-instability-high (MSI-H) metastatic colorectal cancer has been observed to have a prolonged benefit to immune checkpoint inhibitors. As a result, pembrolizumab and nivolumab +/- ipilimumab recently obtained the Food and Drug Administration approval. This review aims to highlight the body of knowledge on immunotherapy in the colorectal cancer setting, discussing the potential mechanisms of resistance and future strategies to extend its use.

A Comprehensive Review of the Use of Antioxidants and Natural Products in Cancer Patients Receiving Anticancer Therapy.

Cancer is the leading cause of mortality and morbidity worldwide. The side effects of cancer treatment affect the quality of life. Cancer patients search for antioxidant dietary supplements and natural products during or after conventional cancer treatment for the alleviation of side effects, improvement of the benefits of treatment, and promotion of well-being. However, the efficacy and safety of these products remain controversial; moreover, previous data do not support the standardized use of those alternative treatments in clinics. The current study reviewed the manuscripts reporting the administration of antioxidants and natural products during cancer treatment and revised preclinical and clinical studies on various types of cancer. Most of the positive results were obtained from experimental animal models; however, human clinical studies are discouraging in this regard. Therefore, further precise and distinguishable studies are required regarding antioxidant dietary supplementation. Future studies are also needed to clarify dietary supplements' mechanism of action and pharmacokinetics in a suitable cancer patient population that will benefit the therapeutic regimens. Despite the popularity of dietary supplements, clinicians and patients should always consider their potential benefits and risks. Patients should discuss with their physician before taking any dietary antioxidant supplements or natural products.

Predictive Efficacy of MiR-125b-5p, MiR-17-5p, and MiR-185-5p in Liver Metastasis and Chemotherapy Response Among Advanced Stage Colorectal Cancer Patients.

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.

Highlights from the Romanian National Congress of Oncology: challenges in oncology in 2020, 15-17 October 2020 Poiana Brasov, Romania.

In a fast-moving world of change and adaptation, the first conference of the three oncology societies from Romania had as its main topic "The challenges in oncology in 2020". It proved to successfully replace a traditional conference by a virtually held event. Also, for the first time it united all oncology and radiotherapy societies under the same umbrella connected by the same aspirations of collaboration and sharing innovative ideas and progress for better cancer care and outcome in Romania.

ECG Markers of Cardiovascular Toxicity in Adult and Pediatric Cancer Treatment.

When a cardiologist is asked to evaluate the cardiac toxic effects of chemotherapy, he/she can use several tools: ECG, echocardiography, coronary angiography, ventriculography, and cardiac MRI. Of all these, the fastest and easiest to use is the ECG, which can provide information on the occurrence of cardiac toxic effects and can show early signs of subclinical cardiac damage. These warning signs are the most desired to be recognized by the cardiologist, because the dose of chemotherapeutics can be adjusted so that the clinical side effects do not occur, or the therapy can be stopped in time, before irreversible side effects. This review addresses the problem of early detection of cardiotoxicity in adult and pediatric cancer treatment, by using simple ECG recordings.

Interleukin 8 as predictive factor for response to chemotherapy in colorectal cancer patients.

Background: Colorectal cancer (CRC) represents a major public health problem owing to the fact that many patients are diagnosed in locally advanced or metastatic stage when chemotherapy is the only remaining option. However, treatment response is still unpredictable and depends upon a diversity of factors such as tumor inherited or acquired drug resistance and the host immune response to the malignant cells. The aim of this study was to evaluate the serum levels of interleukin 6, 8, 10 (IL-6, 8, 10) as possible predictive factors for response to chemotherapy and the correlation between the cytokines and the psychological distress.Methods: Forty-nine patients undergoing chemotherapy for locally advanced or metastatic CRC were included, for each patient IL-6, 8 and 10 were assessed through ELISA. Depression and anxiety were quantified through questionnaires. Statistical data were performed with GraphPad.Results: Patients with CRC had high serum levels of IL-8 and IL-6 compared to the healthy control group. High levels of IL-8 before treatment were correlated with progressive disease. There was a high incidence of psychological complication in CRC patients, especially in young male patients, from an urban area, with a positive correlation between serum levels of IL-8 and depression.Conclusions: These results indicate that high serum levels of IL-8 are predictive factors in CRC patients that undergo chemotherapy, but also could be useful in identifying psychological distress associated with this pathology.

A Critical Review of Second-Generation Anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer.

BACKGROUND: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. OBJECTIVE: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. CONCLUSION: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.

Multiple potential targets of opioids in the treatment of acute respiratory distress syndrome from COVID-19.

COVID-19 can present with a variety of clinical features, ranging from asymptomatic or mild respiratory symptoms to fulminant acute respiratory distress syndrome (ARDS) depending on the host's immune responses and the extent of the associated pathologies. This implies that several measures need to be taken to limit severely impairing symptoms caused by viral-induced pathology in vital organs. Opioids are most exploited for their analgesic effects but their usage in the palliation of dyspnoea, immunomodulation and lysosomotropism may represent potential usages of opioids in COVID-19. Here, we describe the mechanisms involved in each of these potential usages, highlighting the benefits of using opioids in the treatment of ARDS from SARS-CoV-2 infection.

Diagnostic and Prognostic Significance of MiR-150 in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Although treatment options have improved, the survival and quality of life of colorectal cancer (CRC) patients remain dismal. Therefore, significant biomarker prediction may help to improve colorectal cancer patient's prognosis profile. MiRNAs have come as an option because of their essential role in cancer initiation and progression by regulating several molecular processes. MiR-150 has different roles in cancer, but its function in CRC is still ambiguous. We undertook a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) research criteria by interrogating several databases in order to assess the diagnostic accuracy and prognostic value of miR-150. Additionally, clinicalgov.org was scanned for possible trials. The literature was screened from inception to February 2020. A total of 12 out of 70 full-text articles were included in the meta-analysis. Among these, nine studies were included for diagnostic accuracy, and the remaining three were considered for prognostic significance of miR-150. With our results, miR-150 is an appropriate diagnostic biomarker, especially in serum and plasma, while the prognostic value of miR-150 was not statistically significant. The present study findings suggest that miR-150 has high specificity and sensitivity values as a potential diagnostic biomarker in colorectal cancer patients.

A review on the importance of genotyping and phenotyping in fluoropyrimidine treatment.

Fluoropyrimidines, after more than 50 years from their discovery, are still the treatment of many types of cancer, and it is estimated that two million patients receive fluoropyrimidine therapy annually. The toxicity associated with fluoropyrimidines affects 30-40% of patients and some adverse effects can be lethal. Dihydroypyrimidine dehydrogenase is the main enzyme in the catabolism of 5-FU and DPD activity deficiency can cause important toxicity. This is an important reason to determine DPD activity in order to improve patient safety and to limit potential life-threating toxicity. At presentmultiple phenotypic and genotypic methods are available for the determination of DPD activity, some of these methods have proven their usefulness in practice, and yet they are not routinely recommended in clinical practice. This review is another statement of the importance of the determination of DPD status, the phenotypic and genotypic methods that are available and can be used.

Exosomal miRNAs in colorectal cancer: the carriers of useful news.

PURPOSE: In this review, we focused on presenting an up-to-date overview of exosomal miRNAs as biomarkers for diagnosis, prognosis, and their therapeutically perspectives in colorectal cancer (CRC). METHODS: A comprehensive literature search was conducted using the PUBMED database through February 2019 to identify all studies concerning the role of miRNAs and exosomes in CRC. RESULTS: Among the 77 studies identified, 43 articles were relevant for the collaboration of miRNAs and exosomes as therapeutic and diagnostic opportunities in CRC. CONCLUSIONS: This review reveals the role of exosomal miRNAs in CRC management and discusses the promises and challenges associated with the introduction of this combination into clinical practice.

Human Chorionic Gonadotropin Improves the Proliferation and Regenerative Potential of Bone Marrow Adherent Stem Cells and the Immune Tolerance of Fetal Microchimeric Stem Cells In Vitro.

Nongonadal tissues express luteinizing hormone-chorionic gonadotropin receptors (LHCG-R) which are essential for their growth during fetal development. Adult mesenchymal stem/stromal cells (MSCs) have been shown to express functional LHCG-R outside pregnancy conditions, making them susceptible to hCG stimulation. In the present study we tested the effect of hCG treatment on bone marrow (BM) derived adherent stem cells in vitro, isolated from a parous women, mother of male sons, in order to evaluate its effect on maternal MSCs and in the same time on fetal microchimeric stem cells (FMSCs), to better understand the outcomes of this safe and affordable treatment on cell proliferation and expression of pluripotency genes. Our study highlights the beneficial effects of hCG exposure on gene regulation in bone marrow adherent stem cells through the upregulation of pluripotency genes and selection of more primitive mesenchymal stem cells with a better differentiation potential. Validation of these effects on MSCs and FMSCs long after parturition in vivo represents a close perspective as it could set the premises of a new mobilization strategy for the stem cell transplantation procedures in the clinical setting.

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer.

Chimeric antigen receptor (CAR) T-cell therapy represents a new genetically engineered method of immunotherapy for cancer. The patient's T-cells are modified to express a specific receptor that sticks to the tumor antigen. This modified cell is then reintroduced into the patient's body to fight the resilient cancer cells. After exhibiting positive results in hematological malignancies, this therapy is being proposed for solid tumors like colorectal cancer. The clinical data of CAR T-cell therapy in colorectal cancer is rather scarce. In this review, we summarize the current state of knowledge, challenges, and future perspectives of CAR T-cell therapy in colorectal cancer. A total of 22 articles were included in this review. Eligible studies were selected and reviewed by two researchers from 49 articles found on Pubmed, Web of Science, and clinicaltrials.gov. This therapy, at the moment, provides modest benefits in solid tumors. Not taking into consideration the high manufacturing and retail prices, there are still limitations like increased toxicities, relapses, and unfavorable tumor microenvironment for CAR T-cell therapy in colorectal cancer.