Bosnian journal of basic medical sciences最新文献

This study aimed to investigate the programmed cell death-ligand 1 (PD-L1) expression in cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) and its relationship with prognostic factors in tumors that are not in the head and neck region and are therefore relatively less exposed to the sun. This retrospective cross-sectional study included 25 invasive cSCC and 42 BCC cases with a diameter ≥ 2 cm located outside the head and neck region from 2010 to 2018. The biopsy samples were examined based on the membranous PD-L1 (22C3 clone) staining. Staining results were scored as follows: 0, no staining (negative); 1, < 10% PD-L1 positivity of tumor cells; and 2, ≥ 10% PD-L1 positivity of tumor cells. PD-L1 positivity was not seen in any BCC cases, whereas 11 (44%) of cSCC cases were PD-L1 positive. No significant relationship was observed between PD-L1 expression and prognostic parameters, including tumor diameter, tumor depth, and lymphovascular or perineural invasion in the cSCC group. PD-L1 expression was not associated with prognostic factors in the early stages of BCC and SCC located outside the head and neck region. Therefore, investigating the PD-L1 expression seems to be more relevant in patients with advanced-stage disease.

Coronary artery disease (CAD) is uncommon in young adult patients. However, these patients have different risk factor profiles and high-risk coronary plaques are more common. The aim of this study was to examine the relations between the coronary plaque burden, plaque composition, serum non-high-density lipoprotein cholesterol (non-HDL-C) levels, and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio in young adults. We analyzed a total of 551 patients under age 45 who had undergone coronary computed tomography angiography (CCTA). Coronary plaque characteristics were analyzed using CCTA. Multivariate linear regression analysis was used to assess the predictors of non-calcified plaque (NCB) and calcified plaque (CB) burdens. Serum non-HDL-C levels and TG/HDL-C ratio were higher in the coronary atherosclerosis patient group. Serum non-HDL-C levels and the TG/HDL-C ratio were higher in the obstructive CAD patient group. The plaque burden was positively correlated with non-HDL-C (r = 0.30; p < 0.001), and TG/HDL-C ratio (r = 0.18; p < 0.001).  NCB was positively correlated with age, gender, smoking status, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, hbA1c, non-HDL-C, and TG/HDL-C ratio. Non-HDL-C (β coefficient = 0.13; p = 0.023) and TG/HDL-C ratio (β = 0.10;  p = 0.042) were independent predictors of NCB. Serum non-HDL-C levels and TG/HDL-C were significantly associated with the presence and burden of coronary plaques. Serum non-HDL-C and TG/HDL-C ratios were independently associated with NCB, suggesting their use as easy-to-compute markers for identifying high-risk groups in young adults.

Coronavirus disease 2019 (COVID-19) was declared a pandemic and has spread around the globe, unsparingly affecting vulnerable populations. Effective prevention measures for pregnant women, who are particularly affected, include early identification of those patients at risk of developing in-hospital complications, and the continuous improvement of maternal-fetal treatment strategies to ensure the efficient use of health resources. The objective of our retrospective study was to determine which patient biomarkers on hospital admission correlate with disease severity as measured by disease course classification, the need for oxygen supplementation and higher demand for oxygen, the need for mechanical ventilation, intensive care unit admission, and length of hospital stay. Analysis of 52 PCR SARS-CoV-2 positive pregnant women revealed that the median date of hospital admission was the 30th gestational week, with dyspnoea, cough, and fever as the leading symptoms. The presence of diabetes and hypertension predisposed pregnant women to the severe course of illness. Lung involvement shown by CT scans on admission correlated with the greater clinical severity. The main laboratory predictors of disease progression were lymphocytopenia, hypocalcemia, low total cholesterol, low total protein levels, and high serum levels of C-reactive protein, ferritin, interleukin-6, glucose, lactate dehydrogenase, procalcitonin, and troponin I. Further research with a larger cohort of pregnant women is needed to determine the utility of these results for everyday practice.

The neurofilament light chain (NfL) is a promising biomarker in the diagnosis, prognosis, and treatment response evaluation of neurological diseases. The aims of this study were to compare the cerebrospinal fluid (CSF) NfL levels in multiple sclerosis (MS) and certain non-demyelinating diseases of the central nervous system (NDCNS); to determine the relationship between clinical and radiological features and CSF NfL levels in patients with MS; and to compare the enzyme-linked immunosorbent assay (ELISA) and single molecule array (SIMOA) methods for NfL measurement using paired CSF and serum samples. We retrospectively analyzed the clinical data and performed NfL measurements in CSF and serum samples of newly diagnosed and treatment-naive patients with CNS diseases evaluated between 1 January 2019 and 1 January 2020. Eligible patients were divided into three groups: MS (n=23), differential diagnosis of MS (n=19), and NDCNS (n=42). First, we compared the CSF NfL levels among the three groups using the previously validated CSF ELISA assay. Next, we evaluated the relationship between CSF NfL levels and the clinical and radiological findings in MS group. Finally, we compared CSF and serum samples from patients of the MS groups (paired serum and CSF samples, n=19) using two different methods (ELISA and SIMOA). The CSF NfL level was the highest in the NDCNS group (1169.64 [535.92-5120.11] pg/mL, p=0.025). There was a strong positive correlation between the number of T2 lesions and CSF NfL level (r=0.786, p<0.001) in the MS group. There was excellent consistency between ELISA and SIMOA for CSF samples, but not for serum samples. Our results indicated that CSF NfL levels may also be used in the management of NDCNS and that SIMOA is the most reliable method for serum NfL determination.

c-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue.

Melanoma is a highly aggressive cancer originating from melanocytes. Its etiopathogenesis is strongly related to genetic, epigenetic, and environmental factors. Melanomas encountered in clinical practice are predominantly sporadic, whereas hereditary melanomas account for approximately 10% of the cases. Hereditary melanomas mainly develop due to mutations in the CDKN2A gene, which encodes two tumor suppressor proteins involved in the cell cycle regulation. CDKN2A, along with CDK4, TERT, and POT1 genes, is a high-risk gene for melanoma. Among the genes that carry a moderate risk are MC1R and MITF, whose protein products are involved in melanin synthesis. The environment also contributes to the development of melanoma. Patients at risk of melanoma should be offered genetic counseling to discuss genetic testing options and the importance of skin UV protection, avoidance of sun exposure, and regular preventive dermatological examinations. Although cancer screening cannot prevent the development of the disease, it allows for early diagnosis when the survival rate is the highest.

Malignancy is one of the major public health problems in Bosnia and Herzegovina. Along with breakthroughs in specific oncological therapy, improving the quality of life of cancer patients and management of therapy-induced side effects need to be recognized as a priority in the comprehensive cancer patient care. Fertility loss after cancer treatment is a field requiring special attention due to its various consequences on patients themselves.  Although oncofertility is well-recognized area of oncology, low- to middle-income countries are facing issues with its implementation in everyday practice. Increased awareness about fertility preservation is of high priority for all specialists who participate in the medical care of cancer patients. The absence of a systemic solution and lack of expertise led to the founding of Fertility Preservation Working Group of the Oncology Association of Bosnia and Herzegovina. We have made recommendationsas an expert consensus with the ultimate goal of making the first step towards enhancement of oncofertility implementation in Bosnia and Herzegovina.

The COVID-19 pandemic has caused a global public health emergency. Nutritional status is suggested to be related to the severity of COVID-19 infection. Herein, we aimed to explore the impact of using vitamin and mineral supplements prior to COVID-19 infection on disease severity and hospitalization. In addition, the prior use of aspirin as an anticoagulant on the disease severity was investigated. A cross-sectional, self-administered survey was conducted between March and July 2021. Recovered COVID-19 individuals (age ≥ 18 years, n = 2148) were recruited in the study. A multivariate logistic regression was used to evaluate the associations of supplements and aspirin use with COVID-19 disease severity and hospitalization status. Among the participants, 12.1% reported symptoms consistent with severe COVID-19, and 10.2% were hospitalized due to COVID-19. After adjustment for confounding variables (age, gender, BMI, cigarette smoking status, and the number of comorbidities), the multivariate logistic regression model showed that the consumption of vitamin D supplements prior to COVID-19 infection was associated with a significant decrease in disease severity (OR = 0.68, 95% CI 0.50 - 0.92; P = 0.01), and a lower risk of hospitalization (OR = 0.64, 95% CI 0.45 - 0.89; P = 0.01). On the other hand, there were no significant differences in the frequencies of severe illness and hospitalizations with the consumption of vitamin A, folic acid, vitamin B12, vitamin B complex, vitamin C, zinc, iron, selenium, calcium, magnesium, omega 3, and aspirin before COVID-19 infection. Among the investigated nutrients, the use of vitamin D prior to COVID-19 infection was associated with reduced disease severity and hospitalization. However, more studies are required to confirm this finding.

Preclinical models of tumors have the potential to become valuable tools for commercial drug research and development, and 3D culture systems are gaining traction in this area, particularly in prostate cancer (PCa) research. However, nearly all 3D drug design and screening assessments are based on 2D experiments, suggesting limitations of 3D drug testing. To simulate the natural response of human cells to the drug, we detected the half-maximal inhibitory concentration (IC50) changes of 2D/3D LNCaP cells in the drug docetaxel, as well as the sensitivity of different morphologies of 2D/3D LNCaP to docetaxel treatment. In contrast to 2D LNCaP cells, the evaluation of LNCaP spheroids' susceptibility to treatment was more complicated; the fitness of IC50 curves of 2D and 3D tumor cell preclinical models differs significantly. IC50 curves were unsuitable for large-sized LNCaP spheroids. More evaluation indexes (such as max inhibition) and experiments (such as spheroids formation) should be explored and performed to evaluate the susceptibility systematically.

The use of the biological medicines, also called "biologics," has contributed to the progress of the treatment of many chronic diseases, such as cancer, rheumatoid arthritis, Crohn's disease, multiple sclerosis, and psoriasis. However, biologicals are expensive for healthcare systems in several countries. Their availability has been a global issue, which has affected many patients that suffer from various diseases. A biosimilar medicine, also called "biosimilar," is a medicine with similar characteristics in terms of quality, biological activity, safety, and efficacy as the approved original biological medicine, known as "originator biologic." Biosimilars generate competition within the market because they lower the prices of biologics and thus allow for an increase in patient access. However, there are barriers when it comes to the acceptability rate of biosimilars and how interchangeable they are with the originator biologic. In this review, we present a national regulatory framework for biologics along with its limitations, a system of monitoring the safety profile of biologics, the guideline for interchangeability, and a list of approved and available biologics in Bosnia and Herzegovina. Additionally, recommendations were made here in order to provide opportunities for greater acceptance of biosimilars and better access to biologics. These recommendations include, but are not limited to, strengthening the national regulatory framework for biologics, capacity building, increasing awareness among healthcare providers for reporting adverse drug events and active pharmacovigilance, and better definitions of interchangeability. Finally, awareness among healthcare providers regarding biosimilars and biologics should be raised through continuous education and workshops, and by including this important topic in the graduate and postgraduate curriculum programs in the country.