Search Results (2,709)

Background: Invasive BC patients are at risk of loco-regional recurrence, distant MTS, and the development of second primary tumors. SPMs comprise the sixth most common group of malignancies. Material and methods: The records of 125 consecutive patients with primary invasive TCC of the bladder seen in the Oncology Department of Soroka University Medical Center were reviewed between January 2016 and December 2023. We recorded demographic details, the type of primary treatment, tumor site, time to diagnosis of MTS, and occurrence of SPMs. Results: The primary treatments included RC in 58 patients (median age 66 years, range 43–86), PC in 9 patients (median age 64 years, range 22–73), and XRT in 23 patients (median age 74 years, range 22–87). Five patients from the PC group were also treated by XRT. A total of 90 (72%) patients developed MTS or SPMs, with 66 of these developing MTS and 24 developing SPMs. The median age was 70 years (range 22–87). The most frequent site of MTS was in the pelvic LNs (34 patients), followed by bone (18 patients), liver (8 patients), and lung (6 patients), with 4 patients developing synchronous MTS in the pelvic LNs and liver. The median time from diagnosis to MTS was 14.3 months. The distribution of MTS varied according to primary treatment. After RC, 17 patients developed LN MTS, 7 liver, 6 bone, and 3 lung MTS. The average times for developing MTS were as follows: LNs, 14.8 months, liver, 59.7 months, bone, 6.8 months, and lung, 16 months. Following XRT, LN MTS developed in 17 patients: 12 bone, 3 lung, and 1 liver. The most frequent SPMs were prostate cancer with 11 patients and lung cancer with 6 patients, with the median time from TCC diagnosis of 54 months. Conclusion: A regular extended follow-up for invasive BC patients is vital to ensure the early detection of frequently occurring MTS and SPMs. Through the early diagnosis of local recurrences, MTS, and SPMs, treatment results and patient prognosis can be significantly improved. Full article

Background and Objectives: Non-small-cell lung cancer (NSCLC) often has epidermal growth factor receptor (EGFR) mutations, which are key targets for therapy. EGFR mutation subtypes, especially exon 19 deletions and exon 21 L858R mutations, influence responses to EGFR tyrosine kinase inhibitors (TKIs) and patient survival. Despite progress in TKI treatments, resistance and different responses remain challenges. This study explores the relationship between EGFR mutation subtypes, PD-L1 expression, and patient outcomes after anti-EGFR therapy. Materials and Methods: We studied 176 cases of EGFR mutation-positive NSCLC. Next-generation sequencing was used to analyze EGFR and other mutations, while PD-L1 expression was evaluated through immunohistochemistry. We analyzed EGFR mutation subtypes, PD-L1 status, treatments, and survival outcomes. Results: Among 176 cases, 88.6% were adenocarcinomas. Within the EGFR mutation spectrum, exon 19 deletions were the most common subtype, accounting for 40.9% of cases, followed by the point mutation in exon 21, which occurred in 35.8% of cases. Less frequent alterations, making up 23.3% of all detected mutations, included mutations in exon 18, insertions, and point mutations such as S768I and T790M in exon 20, as well as changes in exon 2, exon 7, and other less frequently affected regions. Exon 19 mutations were associated with older age, female sex, adenocarcinoma, and bone metastasis (p < 0.05). TP53 was the most common concurrent mutation (44.3%). PD-L1 positivity (TPS ≥ 1%) was observed in 48.3%, with high expression (TPS ≥ 50%) in 25.9%. Exon 21 mutations were significantly linked to PD-L1 negativity (p = 0.008). The median overall survival was longest with TKI therapy (51 months), and this was also observed in PD-L1-positive patients, although the difference was not statistically significant. The median progression-free survival for patients treated with TKIs and those with EGFR mutations was 14 months. PD-L1-positive patients receiving TKIs had significantly longer survival than those who did not (51 vs. 17 months, p = 0.003). Conclusions: EGFR mutation subtypes and PD-L1 expression seem to affect treatment outcomes and survival in NSCLC. The observed links emphasize the potential value of combining molecular and immunological markers to guide therapy choices. Full article

Background: Vitamin D deficiency is a worldwide health problem associated with various health complications. This study aimed to determine the prevalence of vitamin D supplementation in the Czech Republic, understand reasons for supplementation, and assess participants’ knowledge of vitamin D’s physiological effects. Methods: The study included 1812 participants representing the Czech population aged 15+, stratified by gender, age, and regional distribution. Data analysis was performed using SASD 1.5.8, using chi² independence tests and regression analysis. Results: The results revealed that only 13.5% of the participants maintained regular year-round vitamin D supplementation, while 51.5% never supplemented. A slight increase in supplementation was observed during the pandemic (2020–2021). Supplementation patterns were influenced by socioeconomic factors including age, gender, marital status, income, employment, and education (p > 0.001). Regarding vitamin D knowledge, 67.5% and 65.6% of participants recognized its role in immune system modulation and bone health, respectively. There were minor misconceptions, with 1.4% believing that it aggravates allergies and 1.8% linking it to cancer. Knowledge levels varied with education and residence size. Conclusions: Despite the high prevalence of vitamin D deficiency in the Czech population, regular supplementation remains low, indicating the need for enhanced prevention programs and awareness campaigns. Full article

Background: Currently, it is a priority to develop prognostic biomarkers that would allow the identification of patients with progressing prostate diseases with a low risk of progression, so that unnecessary treatment and patient burden can be avoided. Objectives: This study aimed to assess the clinical features and concentrations of selected mediators of apoptosis, markers of inflammation, and immunoexpression of Ki67 and selected mediators of inflammation in patients with PCa after prostatectomy procedures and who underwent palliative radiotherapy for bone metastases, as well as patients with benign prostatic hyperplasia (BPH). Methods: A total of 88 patients, including 54 cases with PCa and 34 with BPH, were included. Stage and tumor grades were determined according to Gleason’s grading system. Immunoenzymatic methods were used to determine apoptotic and inflammatory mediators in serum, as well as deoxynucleotidyl transferase-mediated dUTP Nick End Labeling (TUNEL) reaction, and immunohistochemistry to determine selected markers of inflammation and Ki67 expression. Results: Strong differentiating indicators were revealed, such as Ki67, and tumor necrosis factor receptor 2. Ki-67 expression was significantly associated with the Gleason score. In turn, the tumor necrosis factor receptor 2 (TNFRII) showed the highest expression in the inflammatory environment of cancer in the metastatic stage. Conclusions: Ki67 and TNFRII can be classified as high-value clinical markers. These factors may be treated as markers regarding future information about the implementation or withdrawal of more aggressive treatment to possibly avoid toxic complications associated with both increased doses in radiotherapy and prolonged hormonal therapy. Full article

Prostate cancer is a clinically heterogeneous disease. Since PSA is not cancer-specific, and due to the bone metastases seen in the advanced stage and bone deformations caused by hormone therapy, it is necessary to use new biomarkers. Formin-like-protein 1 (FMNL1), a member of the formin protein family, is of great importance in actin polymerization, cell attachment, and migration processes. p21-activated kinase 1 (PAK1) proteins, members of the PAK protein kinases, play a role in cytoskeletal organization, as well as regulating other cellular activities such as cell survival, mitosis, and transcription. In our study, plasma and urine samples of 60 prostate cancer patients and 20 healthy controls were studied using RT-PCR and ELISA methods. No statistical difference was found between FMNL1 mRNA and protein expression levels of patients and controls in both plasma and urine samples (p > 0.05). There was no statistical difference between PAK1 mRNA expression levels of patients and controls in plasma and urine samples (p > 0.05). While no significant difference was found in PAK1 protein levels in plasma samples (p > 0.05), it was found to be lower in urine samples of patients compared to the control group (p = 0.00). Both marker molecules have low expression levels in early-stage PCa. Full article

Background/Objectives: Gamma irradiation is a promising terminal sterilization method for nanoparticle-based biomedical systems. However, its potential effects on the physicochemical properties and biological performance of multifunctional nanomaterials must be carefully evaluated. This study aimed to assess the structural integrity, sterility, and cytocompatibility of magnetic nanoparticles (MNPs) and bioactive-glass-coated magnetic nanoparticles (MNPBGs), both based on magnetite (Fe₃O₄), after gamma irradiation. Methods: MNPs and MNPBGs were synthesized and subjected to gamma irradiation at 25 kGy, with additional doses explored in preliminary evaluations. Physicochemical characterizations were performed using XRD, TEM, SAED, and Raman spectroscopy. FTIR analyses were conducted on bioactive glass (BG) controls without magnetite. Sterility was evaluated via microbiological assays. Cytocompatibility and nitric oxide (NO) production were assessed using RAW 264.7 macrophages and Saos-2 osteosarcoma cells. Prussian blue staining was used to evaluate cellular uptake. Results: Gamma irradiation preserved the crystal structure, morphology, and size distribution of the nanoparticles. FTIR revealed only minor changes in the silicate network of BG, such as reduced intensity and slight shifting of Si-O-Si and Si-O-NBO bands, indicating limited radiation-induced structural rearrangement without affecting the material’s stability or cytocompatibility. Microbiological assays confirmed complete inhibition of microbial growth. All irradiated samples exhibited high cytocompatibility, with MNPBGs demonstrating enhanced biological responses. Notably, MNPBGs induced a more pronounced NO production in macrophages. Cellular uptake of nanoparticles by Saos-2 cells remained unaffected after irradiation. Conclusions: Gamma irradiation at 25 kGy is an effective sterilization strategy that maintains the structural and functional integrity of MNPs and MNPBGs. These findings support their safe use in sterile biomedical applications, particularly for bone-related therapies involving immunomodulation and drug delivery, with potential relevance for cancer treatment strategies such as osteosarcoma. Full article

Background/Objectives: Vitamin D plays an important role in a wide range of health outcomes, including immune regulation, bone metabolism, cardiovascular health, and cancer prevention. However, recent data on the prevalence and risk factors for elevated serum 25-hydroxyvitamin D [25(OH)D] concentrations—indicative of potential vitamin D toxicity—remain limited in Korea. Methods: We conducted a retrospective analysis of laboratory data from individuals who underwent serum 25(OH)D testing between 2020 and 2022. Potential vitamin D toxicity was defined as serum 25(OH)D levels exceeding 50, 100, or 150 ng/mL. The prevalence of potential toxicity was examined by age, sex, test month, and year. Results: A total of 1,198,947 individuals (mean age, 45.7 ± 19.4 years; 31.6% male) were included in the study. The prevalence of serum 25(OH)D > 50 ng/mL increased from 4.41% in 2020 to 6.21% in 2022, and that of >100 ng/mL rose from 0.09 to 0.12% over the same period. The proportions exceeding 50 and 100 ng/mL also rose significantly (p < 0.05), while >150 ng/mL remained rare (0.01%) and stable. Elevated 25(OH)D concentrations were more frequently observed among females, children aged 0–9 years, and adults aged ≥50 years (adjusted odds ratios for multivariable logistic regression > 1.0, p < 0.05). Conclusions: Although the prevalence of potential vitamin D toxicity remains low, its continuous upward trend highlights the need for increased public awareness, clinical monitoring, and guideline-based supplementation strategies to prevent inadvertent vitamin D intoxication, particularly in the aging population. Full article

Background/Objectives: In patients with metastatic castration-resistant prostate cancer (mCRPC) and osseous metastases only, ²²³Radium therapy represents a valuable therapeutic option. Bone scintigraphy (BS) is typically performed to assess metastasis load, with the BS-derived automated bone scan index (aBSI) used for response assessment. This study aimed to evaluate the prognostic value of aBSI in patients receiving three or six cycles of ²²³Ra therapy. Methods: We included patients that were diagnosed with extensive osseous tumor load on BS, had no visceral or nodal metastases, had undergone ²²³Ra therapy. The aBSI prior to and following three or six cycles of therapy, total tumor volume (TTV), SUV_max, and overall survival were analyzed. Results: This study included 49 mCRPC patients (mean age: 70 ± 9 years) with 42 (85.7%) receiving six and 7 (14.3%) receiving three cycles. After three cycles, the mean aBSI (p = 0.369), TTV (p = 0.902), and SUV_max (p = 0.149) remained unchanged. After six cycles, the mean aBSI (p = 0.247) and TTV (p = 0.784) were unchanged, while SUV_max decreased significantly (p = 0.001). The aBSI did not significantly correlate with the mean aBSI (six cycles: χ² = 1.823, p = 0.177; three cycles: χ² = 0.308, p = 0.579). Conclusions: Although quantitative changes in TTV and aBSI did not significantly correlate with each other, their respective absolute values consistently indicated stable disease burden under therapy. This highlights its potential as a useful tool for monitoring disease burden while indicating that aBSI alone is insufficient for predicting overall survival. Full article

The human Poly ADP-ribose Polymerase (PARP) family comprises 17 enzymes responsible for the transfer of ADP-ribose to proteins, forming poly- or mono-ADP-ribosylation. This post-translational modification regulates DNA repair and programmed cell death, processes affecting cancer biology. PARP inhibitors, including the FDA-approved olaparib, are used to treat BRCA-dependent breast and ovarian cancers. Although therapies with use of PARP inhibitors are showing clinical success, their effects on the immune system remain understudied. Prior work has shown that PARP inhibition can modulate inflammatory responses and alter innate immunity. In this study, we evaluated the immunomodulatory effects of olaparib on myeloid cells in vivo, focusing on bone marrow and spleen. Olaparib treatment altered the composition and activation state of dendritic cells, neutrophils, and macrophages. In the bone marrow, olaparib increased the proportion of cDC2 population, mature neutrophils and inflammatory macrophages expressing CD80. In contrast, splenic myeloid cells exhibited enhanced expression of markers associated with tolerogenic phenotypes, including CD206 and CD124 in neutrophils and macrophages. The spleen also showed an increase in immature monocyte-derived dendritic cells (CD206+) and a bias toward the cDC2 subset. These findings indicate that PARP inhibition can induce short-term phenotypic remodeling of myeloid cell populations, promoting a more immunoregulatory profile, especially in the spleen. These changes may contribute to an altered immune landscape with implications for anti-tumor immunity. Full article

STAT3 mutations are commonly observed in human pathology yet have no uniform patient presentation. Their effects range from cancer and autoimmunity to primary immunodeficiencies and bone deformity. Designing animal models of those mutations can help researchers identify their direct effects to better inform the clinical setting. In this manuscript, we report a mouse model harboring the same mutation as an autosomal-dominant hyper-IgE syndrome (AD-HIES) patient reported in the literature. Surprisingly, while the deletion of five amino acids in the SH2 domain of STAT3 did result in frequency changes in several immune populations as measured by complete blood count and flow cytometry analysis, it did not yield the expected phenotype of AD-HIES, with no increase in serum IgE or eosinophil count. We additionally provide structural analysis of the STAT3^G656_M660del deletion, visualizing changes in protein architecture and potential effects on the neighboring Y705 phosphorylation site. Our model showcases the sexually dimorphic immune dysregulation caused by a STAT3 mutation and highlights that predicted gain- and loss-of-function mutations can yield unexpected phenotypes. Full article

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the impact of the extraosseous margin width (margin at the soft tissue invasion)—which needs to be close sometimes due to neurovascular structures—needs to be assessed. This study aims to evaluate the influence of soft tissue surgical margins on local recurrence and overall survival in patients with high-grade osteosarcoma. Methods: We conducted a retrospective, single-center study including 75 patients treated for high-grade osteosarcoma. All patients underwent standardized neoadjuvant chemotherapy followed by complete surgical resection. Patients were stratified into three groups based on the histological margin width of the extraosseous parts: group 1 (<1 mm), group 2 (1–5 mm), and group 3 (≥5 mm). Primary endpoints were local recurrence and overall survival (OS), analyzed using Kaplan–Meier estimates, log-rank tests, and Cox regression. Results: Local recurrence occurred in seven patients (9%). Although the overall comparison between the three groups was not statistically significant (p = 0.074), a subgroup analysis revealed a significantly higher recurrence rate in patients with margins < 1 mm compared to those with wider margins (p = 0.024). No significant differences in overall survival (OS) were observed between the groups (p = 0.896). Tumor location, metastatic status, and UICC stage were significant predictors for both endpoints in univariate analysis. However, none of these association were confirmed in multivariate analyses. Conclusions: Very close surgical margins (<1 mm) may increase the risk of local recurrence in high-grade osteosarcoma; however, they do not appear to affect overall survival. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway. Methods: This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60. Results: PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease. Conclusions: Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control. Full article

Understanding the utilization patterns of nuclear medicine (NM) services is essential for optimizing resource allocation and service provision. This study aimed to address the regional evidence gap by reporting the demand for NM services by sex and age at a public hospital in Jamaica. This was a non-experimental, retrospective study of NM scans that were completed at the University Hospital of the West Indies from 1 June 2022 to 31 May 2024. While all scans were reported in the descriptive totals, for patients with multiple scans during the study period, only the data from the first visit was used in the inferential statistical analysis. This was performed with the IBM SPSS (version 29.0) software and involved the use of chi-square goodness of fit and multinomial logistic regression. A total of 1135 NM scans for 1098 patients were completed (37 patients had more than one scan); 596 (54.3%) were female and 502 (45.7%) were male, with the ages ranging from 3 days to 94 years old. Among the female patients, there was a greater demand in the ≥60 years age group for cardiac amyloid scans (χ² = 6.40, p < 0.05), while females 18–59 years had a greater demand for thyroid scans (χ² = 7.714, p < 0.05) and bone scans (χ² = 3.904, p < 0.05). On the other hand, significantly more males in the ≥60 age group presented for cardiac amyloid (χ² = 4.167; p < 0.05) and bone scans (χ² = 145.79, p < 0.01). Males were significantly less likely to undergo a thyroid scan than females (p < 0.01, OR = 0.072, 95% CI: 0.021, 0.243) while individuals aged 18–59 years were more likely to undergo this scan than patients aged 60 or older (p = 0.02, OR = 3.565, 95% CI: 1.258, 10.104). Males were more likely to do a cardiac amyloid scan (p < 0.05, OR = 2.237, 95% CI: 1.023, 4.891) but less likely to undergo a cardiac rest/stress test than females (p = 0.02, OR = 0.307, 95% CI: 0.114, 0.828). Prolonged life expectancy and an aging population have the potential to impact NM utilization, thus requiring planning for infrastructure, equipment, work force, and supplies. Cancer-related and cardiovascular indications are a top priority at this facility; hence, age- and sex-specific analysis are useful in establishing models for policy makers with regard to the allocation of economic and human resources for the sustainability of this specialized service. Full article

Despite significant advancements in understanding the pathogenesis and treatment of hematological malignancies, including leukemia and multiple myeloma, the majority of patients continue to experience poor long-term outcomes. This is partly due to the difficulty of accurately recapitulating the malignant microenvironment in vitro, particularly the bone marrow niche. The complexity of the bone marrow microenvironment poses a challenge for the in vitro examination of hematological malignancies. Traditionally, 2D culture and animal models have been utilized, but these representations are limited and have been criticized for their lack of human physiological relevance. In an attempt to overcome this, 3D models have been developed that more accurately recapitulate the in vivo microenvironment. Herein, we present an overview of recent developments in 2D and 3D models used for studying the bone marrow niche in hematological malignancies, highlighting their advantages and limitations. Full article