Search Results (203)

Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article

(1) Background: Quality of life (QoL) assessment is a crucial aspect for patients diagnosed with cancer. Over the years, different tools have been developed to measure QoL, both generic and pathology specific, but the inclusion of quality of life among other indicators of efficacy in randomized controlled trials (RCTs) remains a controversial issue. In this review, we aim to review the frequency and modality of QoL assessment in RCTs, enrolling patients diagnosed with mesenchymal tumors. (2) Methods: An electronic literature search of bone and soft tissue sarcoma and GIST-related RCTs published between January 2000 and December 2023 was performed by two independent reviewers using PubMed. English-language phase II and III clinical trials enrolling at least more than 15 patients were included, regardless of the disease stage. Studies involving patients under the age of 18 years or for which the full text was not available were excluded. For each study, data regarding the journal and year of publication, the study design, the primary objective, and the evaluation of quality of life as an endpoint with any type of patient-reported outcomes used were extracted. (3) Results: Among the 742 publications screened, 171 resulted eligible. QoL assessment was listed among the endpoints in 35 trials and QoL results were reported in 29 primary publications. In these trials, 16 included patients with soft tissue sarcomas, 8 Kaposi sarcomas, 6 GIST, and 3 desmoid tumors. Among all the trials included, 10.4% on an adjuvant/neoadjuvant setting and 24.4% on a metastatic setting included QoL as an endpoint. The proportion of trials, including QoL, was variable over time, as follows: 16.9% of trials in 2000–2014 vs. 23.4% in 2015–2023. In 35 trials, including QoL endpoints, 27 had a superiority design and 25 reported a positive result. In the majority of trials (80%), the tools for QoL assessment were generic and those mostly used were the EORTC QLQ-C30, the EQ-5D questionnaire, and the modified Brief Pain Inventory–Short Form. (4) Conclusions: Quality of life has not been assessed or published in many phase II and III trials, despite an improvement over time. QoL evaluation in RCTs should be considered even more carefully in patients with rare tumors, where the low number of patients who can be enrolled makes it difficult to draw statistically significant conclusions on the effectiveness of treatments. Full article

Background: Primary malignant bone tumors among adolescent patients are most commonly associated with burdensome surgeries that can severely affect young patients’ early life. To this day, despite available autologous tissue donor sites, cement spacers or endoprostheses are still most commonly used as a form of reconstruction of post-resection defects. Methods: The study group includes 20 adolescent patients diagnosed with Osteosarcoma or Ewing Sarcoma involving the upper limbs. The inclusion criteria were as follows: primary malignant bone tumors sensitive to neoadjuvant chemotherapy, tumors not infiltrating major blood vessels and nerves, and the appliance of the microsurgical free flap as a reconstructive method. Poor tumor response to neodajuvant chemotherapy or patients with incomplete follow-up were excluded from this study. To achieve the functional reconstruction of post-resection defects, fibula free flaps were applied. In cases of resection, including the metaphysis of a long bone, a modification of the flap harvest was applied in order to prevent arthrodesis. The MSTS (Musculoskeletal Tumor Society Scoring System) scale was used as a functional outcome measurement tool. Results: The reported outcomes of this study prove the efficiency of the treatment’s approach of combining the resection of the tumor with subsequent microsurgical restoration with the use of autologous tissues. The average score on the MSTS scale, which assesses the functional outcome, was 26.8/30 points, which indicates great motor outcomes. There were no reports of local recurrence during follow-up. Conclusions: Patients with primary malignant bone tumors in the upper limbs can benefit from microsurgical techniques, which are highly customized; effective; and give sufficient functionality following extensive resection. Full article

Solitary plasmacytoma refers to a neoplastic, clonal proliferation of plasma cells forming a single mass. They are divided based on their origin site; solitary bone plasmacytomas originate from the bones, and extramedullary plasmacytomas represent extraosseous tumors. These are rare tumors but carry a risk of transforming to multiple myeloma; thus, optimal management and meticulous follow-up are needed. Their rarity poses a major challenge in conducting large-scale clinical trials, leaving important gaps in evidence regarding best practices. Newer imaging techniques have improved the quality of staging, management decisions, and outcomes. Radiation still has a significant role in treatment algorithms, and adjuvant chemotherapy is gaining more importance; trials are underway in this area. Follow-up should contain biochemical tests as the proposed response definition criteria. We aimed to review the key studies and guidelines in this paper. Full article

Glioblastoma (GBM) is the most aggressive form of malignant gliomas, with the eicosanoid-synthesizing enzyme cyclooxygenase-2 (COX-2) playing a pivotal role in its progression via the COX-2/prostaglandin E2/4 axis. COX-2 upregulations in tumor cells induces a pro-inflammatory tumor microenvironment (TME), affecting the behavior of invading bone marrow-derived macrophages (Mϕ) and brain-resident microglia (MG) through unclear autocrine and paracrine mechanisms. Using CRISPR/Cas9 technology, we generated COX-2 knockout U87 glioblastoma cells. In spheroids and in vivo xenografts, this resulted in a significant inhibition of tumorigenic properties, while not observed in standard adherent monolayer culture. Here, the knockout induced a G1 cell cycle arrest in adherent cells, accompanied by increased ROS, mitochondrial activity, and cytochrome c-mediated apoptosis. In spheroids and xenograft models, COX-2 knockout led to notable growth delays and increased cell death, characterized by features of both apoptosis and autophagy. Interestingly, these effects were partially reversed in subcutaneous xenografts after co-culture with Mϕ, while co-culture with MG enhanced the growth-suppressive effects. In an orthotopic model, COX-2 knockout tumors displayed reduced proliferation (fewer Ki-67 positive cells), increased numbers of GFAP-positive astrocytes, and signs of membrane blebbing. These findings highlight the potential of COX-2 knockout and suppression as a therapeutic strategy in GBM, particularly when combined with suppression of infiltrating macrophages and stabilization of resident microglia populations to enhance anti-tumor effects. Full article

Osteosarcoma (OSA) is the most common primary bone malignancy in dogs, characterized by aggressive growth and high metastatic potential. Despite advances in treatment, the prognosis for affected animals remains poor, mainly due to metastatic disease. Metastasis is a complex process that involves forming new blood vessels in the primary tumor (angiogenesis), intravasation, the transport of cancer cells to other locations, extravasation, and the growth of cancer cells in the secondary site. Gold nanoparticles (AuNPs), due to their unique physicochemical properties, are considered promising tools in cancer therapy, both as drug delivery systems and potential anti-metastatic agents. Previously, it has been demonstrated that 500 µg/mL glutathione-stabilized gold nanoparticles (Au-GSH NPs) inhibit cancer cell extravasation—one of the steps of the metastatic cascade. This study aimed to evaluate the anti-metastatic properties of Au-GSH NPs through their influence on OSA cell migration, proliferation, and colony formation in vitro, as well as their antiangiogenic properties on the chick embryo chorioallantoic (CAM) model. Additionally, we investigated whether these effects are associated with changes in alpha-2-macroglobulin (A2M) expression, as it was previously demonstrated to play an essential role in the metastatic cascade. Au-GSH NPs significantly inhibited migration and colony formation in canine osteosarcoma cells (from OSCA-8, OSCA-32, and D-17 cell lines) at 200 µg/mL concentrations. Interestingly, at 500 µg/mL, Au-GSH NPs inhibited angiogenesis on the CAM model and cancer cell migration, but fewer colonies were formed. These results may be directly related to the higher efficiency of Au-GSH NPs uptake by OSA cells at the dose of 200 μg/mL than at the dose of 500 μg/mL, as demonstrated using Microwave Plasma Atomic Emission Spectroscopy (MP-AES). Moreover, this is the first study that demonstrates a significant increase in A2M expression in cancer cells after Au-GSH NPs treatment. This study provides new insight into the potential use of Au-GSH NPs as anti-metastatic agents in canine osteosarcoma, indicating that their anti-metastatic properties may be related to A2M. However, further in vitro and in vivo studies are needed to explore the molecular mechanism underlying these effects and to evaluate the clinical relevance of AuNPs in veterinary oncology. Full article

In this article, we present a case of a 49-year-old woman presenting with a recurrent metastatic neuroendocrine tumor. Background: Insulinomas are neuroendocrine tumors derived from beta cells of the pancreas that secrete insulin. Usually, they are benign tumors; however, metastatic insulinomas are an extremely rare malignant form of these tumors, carrying a significantly worse prognosis. Case Presentation: A 49-year-old woman, a patient in the University Hospital in Wroclaw in the Department of Endocrinology, Diabetes and Isotope Therapy, first presented with abdominal pain in 2009, when ultrasound and further examination led to the diagnosis of a tumor in the pancreas (a solid pseudopapillary tumor of the pancreas—meta NET G2), and the patient underwent distal pancreatectomy with splenectomy. For ten years, she was under observation, and her symptoms, such as abdominal pain, nausea, weight loss, and general weakness, reappeared in 2019. Then, magnetic resonance imaging (MRI) showed a lesion in the liver, and further histopathology revealed neuroendocrine tumor (NET) metastasis to the liver. In 2022, the patient presented with loss of consciousness and convulsion, loss of weight, and hypoglycemia after meals. In April 2022, the daily glycemic profile was recorded and a 72 h fasting test was performed; however, their results excluded insulinoma. Positron emission tomography–computed tomography (PET-CT) with 18F-fluorodeoxyglucose (18F-FDG) and PET with gallium-68-DOTA-(Tyr3)-octreotate (68Ga-DOTA-TATE) showed a metastatic proliferative process in the liver. Persistent hypoglycemia led to another hospitalization in May 2022, and repeated tests allowed for the diagnosis of insulinoma. Treatment with somatostatin analogs and diazoxide was started. A CT scan in November 2022 and a PET scan in January 2023 showed new metastases to the liver, bones, and cervical lymph nodes, and it was decided to intensify the treatment. In May 2023, the patient was qualified for Lutathera treatment for insulinoma at the University Clinical Hospital in Poznań. In June 2023, another disturbing symptom was reported by the patient, a painful lump in the breast. During diagnostics, metastases with high proliferation markers were found in both breasts. Two months later, in August 2023, the patient received another dose of Lutathera. In October 2023, significant progression of liver lesions, metastases to bones of the spine, ribs, and pelvis, and periaortic and pelvic lymphadenopathy were found as well as elevated values of neuron-specific enolase and calcitonin. The patient was also referred to the Palliative Medicine Home Hospice. In consultation with the Lower Silesian Cancer Center, the decision was made to forgo further treatment with PRRT and initiate systemic chemotherapy. Despite the chosen treatment, the patient died on 27/DEC/2023. Conclusions: This case report can serve clinicians, as it presents a case of an extremely rare and insidious tumor, metastatic insulinoma. Full article

Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as vaccine carriers to incorporate both adjuvants and peptides. One such nanoparticle is RNA origami (RNA-OG), a nucleic acid nanostructure that is programmed to form different sizes and shapes. Our designed RNA-OG can incorporate various biomolecules and has intrinsic adjuvant activity by acting as a toll-like receptor 3 agonist. We previously showed that the RNA-OG functions as an adjuvanted, carrier-free vaccine platform to assemble peptides. Although effective, only a fixed number of peptides (13) could be covalently linked to each RNA-OG. Methods: Here, we developed a simple physical assembly strategy to attach polylysine-linked neopeptides onto RNA-OG so that the number of peptides per RNA-OG could be readily tuned and tested for their immunogenicity. Results: Although the vaccines with a high number of peptides, i.e., 100–200 peptides/RNA-OG, led to greater peptide presentation by bone marrow-derived dendritic cells, they failed to mount effective CD8⁺ T cell responses against engrafted tumor cells, probably owing to an induction of early T cell exhaustion. Interestingly, the same vaccine format with a low number of peptides, i.e., 10–15 peptides/RNA-OG, enhanced CD8⁺ T cell responses without provoking T cell exhaustion in tumor-bearing mice, leading to strong protective anti-tumor immunity. In comparison, the covalently assembled RNA-OG-peptide vaccine, having a similarly low peptide dosage, offered the highest therapeutic efficacy. Thus, our RNA-OG nanostructure provides a simple and tunable platform for peptide loading to optimize vaccine efficacy. Conclusions: Our findings have significant implications for peptide vaccine design regarding peptide dosages and structural stability of RNA-OG complexed with peptides, which could guide the development of more effective peptide vaccines for cancer immunotherapy. Full article

Cancer remains a leading cause of death globally, characterized by uncontrolled cell proliferation, tumor growth and metastasis. Bone morphogenetic proteins (BMPs) and their growth differentiation factor (GDF) relatives are crucial regulators of developmental processes such as limb, kidney and lung formation, cell fate determination, cell proliferation, and apoptosis. Cancer stem cells (CSCs) are a subpopulation of self-renewing cells within tumors that possess stemness properties and a tumor cell-forming capability. The presence of CSCs in a tumor is linked to growth, metastasis, treatment resistance and cancer recurrence. The tumor microenvironment in which CSCs exist also plays a critical role in the onset, progression and treatment resistance in many cancers. Growth factors such as BMPs and GDFs counterbalance transforming growth factor-beta (TGF-β) in the maintenance of CSC pluripotency and cancer cell differentiation. BMP signaling typically functions in a tumor suppressor role in various cancers by inducing CSC differentiation and suppressing stemness characteristics. This differentiation process is vital, as it curtails the self-renewal capacity that characterizes CSCs, thereby limiting their ability to sustain tumor growth. The interplay between BMPs and their secreted antagonists, such as GREM1, Noggin and Chordin, adds another layer of complexity to CSC regulation. Human cancers such as gastric, colorectal, glioblastoma, and breast cancer are characterized by GREMLIN1 (GREM1) overexpression, leading to inhibition of BMP signaling, facilitating the maintenance of pluripotency in CSCs, thus promoting tumorigenesis. GREM1 overexpression may also contribute to CSC immune evasion, further exacerbating patient prognoses. In addition to BMP inhibition, GREM1 has been implicated as a target of fibroblast growth factor (FGF) → Sonic hedgehog (Shh) signaling, as well as the Wnt/Frizzled pathway, both of which may contribute to the maintenance of CSC stemness. The complex role of BMPs and their antagonists in regulating CSC behavior underscores the importance of a balanced BMP signaling pathway. This article will summarize current knowledge of BMP and GREM1 regulation of CSC function, as well as conflicting data on the exact role of GREM1 in modulating CSC biology, tumor formation and cancer. Targeting this pathway by inhibiting GREM1 using neutralizing antibodies or small molecules may hold early-stage promise for novel therapeutic strategies aimed at reducing CSC burden in cancers and improving patient outcomes. Full article

Basal cell carcinoma (BCC) is the most prevalent form of skin cancer, with infiltrative subtypes presenting significant clinical challenges due to their aggressive behavior and potential for deep tissue and bone invasion. This study aimed to evaluate factors associated with bone infiltration and surgical bone removal in patients with infiltrative BCC. A prospective cohort of 100 patients with histologically confirmed infiltrative BCC was analyzed retrospectively. Clinical, histopathological, and imaging data were assessed to identify predictors of tumor behavior. Tumor size, histological subtype, and disease duration emerged as significant factors associated with bone invasion and resection. Logistic regression analysis identified tumor length as the most significant predictor of both bone infiltration (OR = 1.102, p < 0.001) and surgical bone removal (OR = 1.105, p < 0.001). Aggressive subtypes, such as infiltrative and morpheaform BCC, were more likely to invade bone and exhibited higher recurrence rates. While these findings highlight the importance of early detection and individualized treatment strategies, the absence of data on sun exposure and urban-rural residency limits the broader applicability of the results. Future research addressing these variables will provide a more comprehensive understanding of BCC aggressiveness and improve clinical management of this malignancy. Full article

The term axial spondyloarthritis (axSpA) encompasses patients with both radiographic (r-axSpA) and non-radiographic (nr-axSpA) forms of the disease. These are two entities within the same family that share many genetic and pathogenic factors, but they also have significant differences. For example, the male-to-female ratio is 2:1 in r-axSpA and 1:1 in nr-axSpA. Additionally, the prevalence of the HLA-B27 gene is notably higher in r-axSpA. Early diagnosis remains an unmet need, with magnetic resonance imaging (MRI) being the most important tool for diagnosis and disease monitoring. Early detection is crucial, as it allows for timely treatment, increasing the chances of preventing new bone formation and long-term structural bone damage. Various cytokines, such as tumor necrosis factor (TNF)-α and interleukin-17, play active roles in the disease’s pathogenesis, although the exact mechanisms of interaction are not yet fully understood. Clarifying these mechanisms will be key to developing new classification criteria, screening methods, and more personalized, targeted therapies. Non-steroidal anti-inflammatory drugs (NSAIDs), TNF inhibitors, interleukin-17 blockers, and, more recently, Janus kinase (JAK) inhibitors, are the most effective treatments for both radiographic and non-radiographic axial spondyloarthritis. Full article

Background: Intracranial teratomas are very rare in adults, representing only 0.3–0.5% of all primary brain tumors. They originate from all three germ layers, and are classified as mature, immature, or malignant. Mature teratomas constitute the most prevalent type in the adult population, commonly originating from midline structures such as the pineal and suprasellar regions. However, the localization of these tumors within the cerebellum is exceedingly rare, with only a limited number of cases reported globally. In this manuscript, we describe, to the best of our knowledge, the first documented case of a young adult patient presenting with a mature teratoma situated between the cerebellar hemispheres. Notably, this tumor was accompanied by occipital bone loss, through which a tumor pedicle extended, forming an extracranial component. Methods: After analyzing the clinical picture and additional examinations, the patient was classified for surgery. The intracranial part of the tumor contained numerous cysts with yellow fluid, a tooth, and fat tissue. The tumor was removed radically, with its extracranial part. Results: On the fourth day after surgery, the patient was discharged from the clinic in a good general condition, walking, with marked cerebellar symptoms. In a follow-up at 6 months postoperatively, the neurological examination was normal, with no headaches. MRI at the 6 months follow-up did not show any residual or recurrent tumor. Conclusions: Histopathological examination confirmed the diagnosis of mature teratoma. Full article

Follicular lymphoma (FL) is an indolent, rarely curable B-cell malignancy with a heterogeneous clinical course. While generally treatable, FL is characterized by remissions and relapses, and its clinical presentation varies widely. Rituximab has revolutionized FL treatment, significantly improving overall survival over the past two decades. Risk assessment typically relies on histological grade, tumor burden, and the Follicular Lymphoma International Prognostic Index, which incorporates factors like age, hemoglobin level, and Ann Arbor stage. However, these indices have limitations in fully capturing the clinical variability of FL. Some patients experience indolent disease for extended periods without requiring treatment, while others present with aggressive forms resistant to standard therapies. This review examines various prognostic factors in FL, including the FLIPI, FLIPI2, PRIMA-PI, and m7-FLIPI. The FLIPI, based on five risk factors, stratifies patients into low-, intermediate-, and high-risk groups. The FLIPI2 incorporates beta2-microglobulin and the longest diameter of the largest involved node, offering improved prognostication. The PRIMA-PI, designed for patients receiving rituximab-containing regimens, uses beta2-microglobulin, bone marrow involvement, and the longest diameter of the largest involved node. The m7-FLIPI integrates mutational status with FLIPI2 parameters, further refining risk stratification. The review also discusses clinical parameters like maximum standardized uptake value on PET/CT and lymphocyte/monocyte ratio as prognostic factors. A high SUVmax and low lymphocyte/monocyte ratio identify high-risk patients. While FL remains incurable, advances in immunochemotherapy and targeted therapies have improved outcomes. This review provides a comprehensive overview of prognostic tools in FL, emphasizing the importance of risk stratification for personalized treatment strategies. Full article

Osteosarcoma is medically defined as a bone-forming tumor with associated bone-degrading activity. There is a lack of knowledge about the network that generates the overproduction of bone. We studied the early stage of osteosarcoma development with mice enduring a periosteum injection of osteosarcoma cells at the proximal third of the tibia. On day 7 (D7), tumor cells activate the over-synthesis of bone-like material inside the medulla. This overproduction of bone is quickly (D13) followed by degradation. Samples were characterized by microfocus small-angle X-ray scattering (SAXS), wide-angle X-ray scattering (WAXS), optical and electron microscopies, and micro-indentation. This intramedullary apatite–collagen composite synthesis highlights an unknown network of bone synthesis stimulation by extramedullary osteosarcoma cells. This synthesis activation mechanism, coupled with the well-known bone induced osteosarcoma growth activation, produces a rare synergy that may enlighten the final osteosarcoma morphology. With this aim, a 3D cellular automaton was developed that only included two rules. Simulations can accurately reproduce the bi-continuous sponge macroscopic structure that was analyzed from mice tumor micro-tomography. This unknown tumor activation pathway of bone synthesis, combined with the known bone activation of tumor growth, generates a positive feedback synergy explaining the unusual sponge-like morphology of this bone cancer. From a biomaterials point of view, how nature controls self-assembly processes remains an open question. Here, we show how the synergy between two biological growth processes is responsible for the complex morphology of a bone tumor. This highlights how hierarchical morphologies, accurately defined from the nanometer to the centimeter scale, can be controlled by positive feedback between the self-assembly of a scaffold and the deposition of solid material. Full article

Giant cell tumor of bone (GCTb), formerly also known as osteoclastoma, is a pathological entity that in veterinary medicine is still undefined and, probably, underdiagnosed. In humans, GCTb is recognized as a primary benign bone tumor, locally aggressive, with high local recurrence rates, with controversial histogenesis that can rarely progress or present as a malignant form. In pets, this tumor is still considered rare, though the possibility of underdiagnosis is significant. Hence, the aim of the present study is to provide a histological and immunohistochemical characterization of a small case series of presumptive feline GCTb, comparing our results to the data reported for the human counterpart. Searching our archive, we found, from 2010 to 2023, only three diagnosed cases of GCTb from domestic cats (felis catus). After diagnosis revision, the samples were submitted to immunohistochemistry for Iba1, TRAP, SATB2, RUNX2, RANK, karyopherin α2 (KPNA-2), and osteocalcin. Ki-67 index was also evaluated. Results showed that the multinucleated giant cells were positive for Iba1, TRAP, and RANK, accounting for their osteoclastic origin. On the other side, mononuclear cells were mostly positive for osteoblast markers such as RUNX2, SATB2, and KPNA-2, whereas tumor-associated macrophages showed positivity for Iba1. Hence, results on the cell types characterizing the feline GCTb were comparable to those described in the human form of the tumor. Currently, diagnostic criteria for GCTBs in cats and, in domestic animals more broadly, are still lacking. This study provides valuable data into the immunohistochemical characteristics of the cell populations in feline GCTBs, enhancing veterinarians’ and pathologists’ knowledge for its diagnosis, ultimately improving patient care. Larger case series, complete with follow-up information, molecular analyses for specific mutations, and imaging of both tumors and patients, are needed to improve identification and achieve greater sensitivity in diagnosing this unique tumor. Full article