Search Results (1,426)

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article

Pneumonitis is characterized as inflammation of the lung parenchyma, and a potential adverse effect of several anti-cancer therapies. Diagnosing pneumonitis can be particularly challenging in lung cancer patients due to inherent similarities in symptoms and radiological presentation associated with pneumonitis, as well as other common conditions such as infection or disease progression. Furthermore, many lung cancer patients have underlying pulmonary conditions that might render them more susceptible to severe or fatal outcomes from pneumonitis. Novel anti-cancer agents, such as antibody–drug conjugates (ADCs) and bispecific antibodies (BsAbs), are being incorporated into the treatment of lung cancer; therefore, understanding the risk and mechanisms underlying the potential development of pneumonitis with these new therapies is important to ensure continuous improvements in patient care. This narrative review provides an overview of the incidence of pneumonitis observed with novel anti-cancer agents, characterizes potential pathophysiological mechanisms underlying pneumonitis risk and emerging predictive biomarkers, highlights management strategies, and explores future directions for minimizing the risk of pneumonitis for lung cancer patients. Full article

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute lung injury seen in patients. In this study, we describe the predominance of the innate immune response in hamsters inoculated with four different SARS-CoV-2 variants, underscoring phenotypic differences among them. Severe inflammatory lung injury was chronologically associated with acute and significant weight loss, mainly in animals inoculated with A.2 and Delta variants. Omicron-infected animals had lower overall histopathology scores compared to other variants. We highlight the central role of endothelial injury and activation in the pathogenesis of experimental SARS-CoV-2 infection in hamsters, characterised by the presence of proliferative type I and type II pneumocytes with abundant surfactant expression, thereby maintaining hyperinflated alveolar fields. Additionally, there was evidence of intrapulmonary lymphatic vessel proliferation, which was accompanied by a lack of detectable microthrombosis in the lung parenchyma. However, white microthrombi were observed in lymphatic vessels. Our findings suggest that the physiological compensatory mechanisms that maintain respiratory homeostasis in Golden Syrian hamsters prevent severe respiratory distress and death after SARS-CoV-2 infection. Full article

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease predominantly of the small airways and parenchyma. COPD lungs exhibit an influx of circulating innate immune cells, which, when isolated, display impaired functions, including imbalanced protease secretion. In addition to immune cells, the extracellular matrix (ECM) plays a crucial role in COPD pathology. Remodeling of the ECM can generate ECM fragments, which can be released into circulation and subsequently induce pro-inflammatory responses. COPD is a heterogeneous disease, and serological biomarkers can be used to sub-categorize COPD patients for targeted treatments and optimal recruitment in clinical trials. This study evaluated fragments of calprotectin, collagen type VI, and versican, generated by neutrophil elastase and matrix metalloproteinases (MMP-) 2 and 12, respectively, as potential biomarkers of COPD disease, severity, and endotypes. Lower plasma levels of a neoepitope marker of calprotectin, indicative of activated neutrophils (nordicCPa9-HNETM), were detected in COPD donors compared to controls. CPa9-HNE was associated with milder disease, higher degree of air-trapping, and higher serum levels of MMP-2. Deposition of CPa9-HNE levels in lung tissue revealed no differences between groups. Taken together, CPa9-HNE was found to be a potential marker of mild COPD, but further studies are warranted to validate our findings. Full article

Radiation therapy serves as a fundamental treatment for primary and metastatic brain tumors, whether used alone or combined with surgery and chemotherapy. Despite its oncological efficacy, this treatment paradigm frequently induces radiation-induced brain injury (RBI), a progressive neuropathological condition characterized by structural and functional damage to healthy cerebral parenchyma. Patients with RBI frequently develop affective disorders, particularly major depressive disorder and generalized anxiety disorder, which profoundly impair psychosocial functioning and quality of life. The pathophysiology involves complex mechanisms such as neuroinflammation, oxidative stress, blood–brain barrier disruption, and white matter damage. Current management strategies include antidepressants, corticosteroids, and neuroprotective agents, while emerging therapies targeting neuroinflammation and neural repair show promise. This review comprehensively examines the pathogenesis of RBI-related affective disorders and evaluates both conventional and novel treatment approaches. By synthesizing current evidence, we aim to provide insights for developing more effective interventions to improve patient outcomes and quality of life. Full article

Introduction: Radiomics is the extraction of non-invasive and reproducible quantitative imaging features, which may yield mineable information for clinical practice implementation. Quantification of lung function through radiomics could play a role in the management of patients with pulmonary lesions. The aim of this study is to test the capability of radiomic features to predict pulmonary function parameters, focusing on the diffusing capacity of lungs to carbon monoxide (DL_CO). Methods: Retrospective data were retrieved from electronical medical records of patients treated with Stereotactic Body Radiation Therapy (SBRT) at a single institution. Inclusion criteria were as follows: (1) SBRT treatment performed for primary early-stage non-small cell lung cancer (ES-NSCLC) or oligometastatic lung nodules, (2) availability of simulation four-dimensional computed tomography (4DCT) scan, (3) baseline spirometry data availability, (4) availability of baseline clinical data, and (5) written informed consent for the anonymized use of data. The gross tumor volume (GTV) was segmented on 4DCT reconstructed phases representing the moment of maximum inhalation and maximum exhalation (Phase 0 and Phase 50, respectively), and radiomic features were extracted from the lung parenchyma subtracting the lesion/s. An iterative algorithm was clustered based on correlation, while keeping only those most associated with baseline and post-treatment DL_CO. Three models were built to predict DL_CO abnormality: the clinical model—containing clinical information; the radiomic model—containing the radiomic score; the clinical-radiomic model—containing clinical information and the radiomic score. For the models just described, the following were constructed: Model 1 based on the features in Phase 0; Model 2 based on the features in Phase 50; Model 3 based on the difference between the two phases. The AUC was used to compare their performances. Results: A total of 98 patients met the inclusion criteria. The Charlson Comorbidity Index (CCI) scored as the clinical variable most associated with baseline DL_CO (p = 0.014), while the most associated features were mainly texture features and similar among the two phases. Clinical-radiomic models were the best at predicting both baseline and post-treatment abnormal DL_CO. In particular, the performances for the three clinical-radiomic models at predicting baseline abnormal DL_CO were AUC₁ = 0.72, AUC₂ = 0.72, and AUC₃ = 0.75, for Model 1, Model 2, and Model 3, respectively. Regarding the prediction of post-treatment abnormal DL_CO, the performances of the three clinical-radiomic models were AUC₁ = 0.91, AUC₂ = 0.91, and AUC₃ = 0.95, for Model 1, Model 2, and Model 3, respectively. Conclusions: This study demonstrates that radiomic features extracted from healthy lung parenchyma on a 4DCT scan are associated with baseline pulmonary function parameters, showing that radiomics can add a layer of information in surrogate models for lung function assessment. Preliminary results suggest the potential applicability of these models for predicting post-SBRT lung function, warranting validation in larger, prospective cohorts. Full article

Central nervous system metastases involving the brain parenchyma and leptomeninges are common in non-small cell lung cancer, especially cases with EGFR mutations. Here, we examine treatment options for EGFR-mutated non-small cell lung cancer patients with central nervous system metastases, highlighting the efficacy of third-generation EGFR-targeted tyrosine kinase inhibitors. Furthermore, we examine the interplay of this modality with chemotherapy or radiation in resistant cases. Full article

Background/Objectives: One current cancer treatment is immunotherapy, in which tumor antigens (such as MAGE) or adjuvants (such as CpGs) can be used to induce the destruction of tumor cells by the immune system; however, the therapeutic response is generally weak. Therefore, it is necessary to develop a strategy that increases the immune response induced by tumor antigens and CpGs. We propose the coupling of tumor antigens and adjuvants to chitosan (Cs) microparticles to improve the immune response against cancer, as these microparticles can activate the innate immune response when recognized by macrophages and dendritic cells (DCs). Methods: Cs microparticles coupled with CpGs and tumor antigens were constructed with the emulsification method; then, their morphology, in vitro biological effect on DCs, and therapeutic effect in a murine melanoma model were analyzed. Results: The Cs microparticles showed a rounded morphology and a size of approximately 5 μ; in addition, they were not cytotoxic in in vitro assays and induced the production of IFNα. Finally, in the murine model of melanoma, treatment with Cs microparticles coupled to MAGE or CpGs reduced the tumor growth rate and increased both survival and the presence of cell death areas in the tumor parenchyma in contrast to the control group. Conclusions: The results suggest that treatment with Cs microparticles coupled to tumor antigen and/or CpGs can be considered a promising strategy in the field of immunotherapy based on the use of biomaterials. Full article

A young adult patient presented to the gastrointestinal outpatient department with a suspected hepatic tumor. The patient was in a traffic accident ten years ago and underwent splenectomy and distal pancreatectomy at another medical institution. The physical examination was unremarkable. The liver function tests and tumor markers were within normal limits, with the alpha-fetoprotein level at 1.38 ng/mL. Both hepatitis B surface antigen and anti-HCV were negative. Based on the clinical history, intrahepatic splenosis was suspected first. Dynamic computed tomography revealed a 2.3 cm lesion exhibiting suspicious early wash-in and early wash-out enhancement patterns. As previous studies have reported, this finding makes hepatocellular carcinoma and metastatic lesions the major differential diagnoses. For further evaluation, dynamic magnetic resonance imaging was performed, and similar enhancing features were observed, along with restricted diffusion. As hepatocellular carcinoma still could not be confidently ruled out, the patient underwent an ultrasound-guided biopsy. The diagnosis of intrahepatic splenosis was confirmed by the pathologic examination. Intrahepatic splenosis is a rare condition defined as an acquired autoimplantation of splenic tissue within the hepatic parenchyma. Diagnosis can be challenging due to its ability to mimic liver tumors in imaging studies. Therefore, in patients with a history of splenic trauma and/or splenectomy, a high index of suspicion and awareness is crucial for accurate diagnosis and for prevention of unnecessary surgeries or interventions. Full article

Cerebral edema is the abnormal accumulation of fluid in any of the tissue compartments of the cerebral parenchyma. It remains a significant challenge in neurotrauma care because it contributes to secondary brain injury, affecting prognosis. This review analyzes the recent literature, including foundational studies, to describe the mechanisms of distinct types of cerebral edema following traumatic brain injury (TBI). Emerging concepts, such as the role of the glymphatic system and heme-derived inflammasomes, offer new insights into new types of edemas, differentiated by pathogenesis and potential treatments. Recent advancements in understanding these molecular mechanisms can improve therapeutic strategies, facilitating a better approach in the era of precision and personalized medicine. Although there has been notable progress, a proposal to customize treatments for diverse types of edemas is necessary to improve outcomes following traumatic brain injury. In this review, we describe the current subtypes of post-traumatic brain edemas and link them to a specific management approach. Full article

Alzheimer’s disease (AD) is associated with an abnormal accumulation of amyloid β (Aβ) fibrils in the brain parenchyma and cerebrovasculature, which leads to cognitive impairment and cerebrovascular dysfunction. Cerebrovascular endothelial cells play a crucial role in regulating cerebral blood flow, vascular permeability, and neurovascular function. Reactive oxygen species (ROS), particularly those generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), contribute to vascular dysfunction and amyloid deposition in the Alzheimer’s disease (AD) brain. However, the role of the NOX4 isoform in AD pathogenesis remains to be examined. In the present study, we found that NOX4 among the NOX isoforms is predominantly expressed in bEnd.3 mouse brain endothelial cells. Treatment with Aβ₄₀ significantly enhanced the release of H₂O₂ and NO, and increased the endothelial cell viability. To test the involvement of NOX4 in Aβ₄₀-induced H₂O₂ production, we utilized pharmacological inhibitors of NOX isoforms. Aβ₄₀-induced H₂O₂ production was attenuated in the presence of the pan-NOX inhibitor, apocynin, or the NOX1/4-selective inhibitors, setanaxib and GKT136901. Since only the NOX4 isoform is expressed in bEnd.3 cells, these results indicate that NOX4 is responsible for the release of H₂O₂ stimulated by Aβ₄₀. Taken together, the present study demonstrated that Aβ₄₀ peptide exerts beneficial effects in bEnd.3 endothelial cells via the NOX4-dependent mechanism. Full article

Plants are continuously exposed to multiple environmental stressors throughout their lifecycle. Understanding their integrated physiological, biochemical, and anatomical responses under combined stress conditions is crucial for developing effective approaches to improve stress tolerance and maintain crop productivity. This study aimed to investigate the physiological, biochemical, and anatomical changes in photomorphogenic Micro-Tom plants exposed to high irradiance and water deficit—an abiotic stress combination that commonly co-occurs in natural environments but remains poorly understood in light-sensitive genotypes. We hypothesized that the high pigment 1 (hp1) mutant, due to its enhanced light responsiveness, would display improved stress acclimation compared to the wild-type when exposed to combined stress factors. This study was conducted in a controlled plant growth chamber, using a randomized block design with five replicates. Two Micro-Tom genotypes (wt and hp1) were exposed to control (soil at field capacity (FC) + 450 μmol m⁻² s⁻¹ PPFD) and combined stress (40% FC + 1800 μmol m⁻² s⁻¹ PPFD) conditions. Despite the higher concentration of chloroplast pigments in hp1, its photosynthetic performance under combined stress was not significantly improved, and its defense mechanisms did not effectively mitigate the stress impacts. Anatomically, wt exhibited greater structural adjustment, observed by adaptations in the spongy parenchyma and mesophyll. Overall, the wt genotype showed stronger defense mechanisms, while hp1 was more susceptible to combined abiotic stress. Full article

MET exon 14 skipping mutations have emerged as significant driver alterations in non-small-cell lung cancer (NSCLC), contributing to tumor progression. This study examines the immune microenvironment in NSCLC patients with these mutations and its prognostic implications. We performed multiplex immunofluorescence (mIF) staining on formalin-fixed paraffin-embedded (FFPE) tissue samples from nine NSCLC patients, including four recurrent/metastatic and five non-recurrent/non-metastatic patients. Two panels assessed immune cell markers (CD8, CD4, CD20, CD68, and FoxP3) and immune checkpoints (PD-L1, LAG3, and TIM3). Immune cell infiltration and checkpoint expression were analyzed using HALO^TM software (version 3.6.4134.464). Nearest neighbor analysis was conducted to assess the proximity of immune cells to tumor cells. Univariate Cox regression analysis assessed factors associated with disease-free survival (DFS). CD8+TIM3+ and CD8+LAG3+ cells were predominantly located in the tumor parenchyma of recurrent/metastatic patients but localized to the stroma in non-recurrent/non-metastatic patients. Non-recurrent/non-metastatic patients exhibited a higher density of tertiary lymphoid structures and closer proximity of CD20+ B cells, CD8+TIM3+, and CD8+LAG3+ cells to tumor cells compared to recurrent/metastatic patients, though the differences were not statistically significant. Cox regression analysis suggested a potential association between higher densities of CD8+TIM3+ cells and improved DFS (HR = 0.89), though these findings did not reach statistical significance. Our findings suggest that differences in immune microenvironmental factors, particularly those related to immune checkpoint expression (TIM3 and LAG3), may influence clinical outcomes in NSCLC patients with MET exon 14 skipping mutations. Further studies are needed to validate these observations and explore potential therapeutic implications. Full article

We aim to provide a translational model to investigate the reproductive consequences of pubertal delay using the GnRH agonist triptorelin in transgender girls, tested in particular on testicular maturation in peripubertal rats. A total of 30 Sprague Dawley rats were utilized, with 10 subjects assigned to each of three groups from day P30 postpartum (prepubertal) until day P95 (postpubertal), mimicking treatment timing in patients. Rats received triptorelin at three time points (P30, P50, and P71), or only at P30 and P50. Control rats were injected with vehicle. Plasma testosterone levels were determined using MRM analysis. Testes and epididymides were examined histologically. There were significantly lower testosterone levels at postnatal day 48 in treated rats, indicating delayed puberty, with further reductions by day 69. By day 93, testosterone levels had recovered in rats given vehicle at P71 but remained low in the triptorelin-continuous group, suggesting the reversibility of the treatment. Treated rats had smaller testes; however, the majority of the testicular parenchyma was unaffected, with most seminiferous tubules displaying complete spermatogenesis. However, focal atrophic changes were observed in 1–30% of the parenchyma. One-third of the short-term group and half of the long-term group were classified as atrophic. Despite these changes, all treated rats had mature sperm in the epididymis, ensuring their fertility. In conclusion, triptorelin treatment promotes a decline in testosterone levels accompanied by discrete atrophy of the seminiferous tubules, which is partially reversible and compatible with sperm production and fertility preservation. Triptorelin could be an appropriate treatment prior to estrogen therapy for patients seeking gender transition. Full article