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Scientific Reports Jun 2024While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Identification of novel...
While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Identification of novel targetable pathways that contribute to tumor progression in PC could open new therapeutic options. The di-ganglioside GD2 is a target of FDA-approved antibody therapies in neuroblastoma, but the role of GD2 in PC is unexplored. Here, we show that GD2 is expressed in a small subpopulation of PC cells in a subset of patients and a higher proportion of metastatic tumors. Variable levels of cell surface GD2 expression were seen on many PC cell lines, and the expression was highly upregulated by experimental induction of lineage progression or enzalutamide resistance in CRPC cell models. GD2 cell fraction was enriched upon growth of PC cells as tumorspheres and GD2 fraction was enriched in tumorsphere-forming ability. CRISPR-Cas9 knockout (KO) of the rate-limiting GD2 biosynthetic enzyme GD3 Synthase (GD3S) in GD2 CRPC cell models markedly impaired the in vitro oncogenic traits and growth as bone-implanted xenograft tumors and reduced the cancer stem cell and epithelial-mesenchymal transition marker expression. Our results support the potential role of GD3S and its product GD2 in promoting PC tumorigenesis by maintaining cancer stem cells and suggest the potential for GD2 targeting in advanced PC.
Topics: Male; Humans; Neoplastic Stem Cells; Sialyltransferases; Animals; Cell Line, Tumor; Gangliosides; Mice; Carcinogenesis; Prostatic Neoplasms; Phenylthiohydantoin; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Benzamides; Nitriles
PubMed: 38866755
DOI: 10.1038/s41598-024-60052-3 -
International Journal of Surgery Case... Jul 2024Cystic lesions in long bones are the radiological presentation of various bone pathologies, they can easily be misdiagnosed and thus mistreated; treatment varies from...
INTRODUCTION
Cystic lesions in long bones are the radiological presentation of various bone pathologies, they can easily be misdiagnosed and thus mistreated; treatment varies from observation to aggressive surgical interventions based on the nature and characteristics of the lesion.
CASE PRESENTATION
A 25-year-old male had a twisting injury to his ankle and his radiographs showed a cystic lesion in the distal tibia that was asymptomatic until he injured his ankle. he had persistent pain since then. and after conservative methods failure, a two-stage surgical intervention was done; first, we curetted the lesion and filled it with antibiotics cement; then the cement was removed with autologous bone grafting. The patient eventually healed and returned to his normal activity level.
DISCUSSION
Brodie's abscess has a similar radiological appearance to other bone neoplasms and tumor-like lesions. Clinically, it is minimally symptomatic, and often initially misdiagnosed; surgical treatment is very effective, but it depends on the size, location, and aggressiveness of the lesion; the goal is to eliminate the infection, refill the residual gap, and restore the normal function, especially in weight-bearing bones.
CONCLUSION
Brodie's abscess is a hideous lesion that is hard to diagnose. It could mimic other tumor-like lesions. However, applying bone cement and a second stage of bone grafting might help maximize the treatment efficiency.
PubMed: 38865946
DOI: 10.1016/j.ijscr.2024.109865 -
Revista Da Associacao Medica Brasileira... 2024
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Diagnostic Pathology Jun 2024Osteosarcoma is a bone tumor that is characterized by high malignancy and a high mortality rate, and that originates from primitive osteoblastic mesenchymal cells and is...
BACKGROUND
Osteosarcoma is a bone tumor that is characterized by high malignancy and a high mortality rate, and that originates from primitive osteoblastic mesenchymal cells and is most common in rapidly growing long bones. PSMD14, also known as RPN11 or POH1, is a member of the JAMM isopeptidase family, which is able to remove the substrate protein ubiquitination label, thereby regulating the stability and function of the substrate protein. In this study, we explored the expression and potential biological significance of the PSMD14 deubiquitinating enzyme in osteosarcoma.
METHODS
Immunohistochemical methods were used to detect the expression of PSMD14 in biopsies of 91 osteosarcoma patients, and the specimens were classified into high and low PSMD14 expression groups. The correlation between PSMD14 expression and clinical indicators and prognosis was compared.SiRNA was used to downregulate PSMD14 in two osteosarcoma cell lines (HOS and SJSA-1), and the effects of downregulation of PSMD14 on the viability, proliferation, and invasion ability of osteosarcoma cells were analyzed.
RESULTS
We identified significant differences in recurrence, metastasis, and survival time of the osteosarcoma patients on the basis of PSMD14 expression. High expression of PSMD14 in osteosarcoma patients was associated with a low survival rate and high risk of metastasis and recurrence. Down-regulation of PSMD14 inhibited the viability, proliferation, and invasiveness of osteosarcoma cell lines.
CONCLUSIONS
PSMD14 may be a new prognostic marker and therapeutic target for osteosarcoma.
Topics: Osteosarcoma; Humans; Bone Neoplasms; Male; Biomarkers, Tumor; Female; Prognosis; Cell Line, Tumor; Adult; Cell Proliferation; Proteasome Endopeptidase Complex; Adolescent; Young Adult; Middle Aged; Neoplasm Invasiveness; Trans-Activators
PubMed: 38863002
DOI: 10.1186/s13000-024-01489-y -
Scientific Reports Jun 2024Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related...
Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9-43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93-11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01-0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13-11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68-15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.
Topics: Humans; Male; Prostatic Neoplasms; Risk Factors; Aged; Incidence; Bisphosphonate-Associated Osteonecrosis of the Jaw; Denosumab; Bone Neoplasms; Bone Density Conservation Agents; Middle Aged; Zoledronic Acid; Aged, 80 and over; Retrospective Studies
PubMed: 38862617
DOI: 10.1038/s41598-024-64440-7 -
Scientific Reports Jun 2024This study aimed to determine an immune-related RNA signature as a prognostic marker, in this study, we developed a risk score model for predicting the prognosis of...
This study aimed to determine an immune-related RNA signature as a prognostic marker, in this study, we developed a risk score model for predicting the prognosis of osteosarcoma metastasis. We first downloaded the clinical information and expression data of osteosarcoma samples from the UCSC Xena and GEO databases, of which the former was the training set and the latter was the validation set. Immune infiltration was assessed using the ssGSEA and ESTIMATE algorithms, and the osteosarcoma samples were divided into the Immunity_L and Immunity_H groups. Then, eleven RNAs were identified as the optimal prognostic RNA signatures using LASSO Cox regression analysis for establishing a risk score (RS) model. Kaplan-Meier approach indicated the high-risk group exhibited a shorter survival. Furthermore, we analyzed the tumor metastasis, age, and RS model status were determined to be independent clinical prognostic factors using Cox regression analysis. Decision curve analysis (DCA) indicated that the prognostic factor + RS model had the best net benefit. Finally, nine tumor-infiltrating immune cells (TIICs) showed significant differences in abundance between high- and low-risk groups via CIBERSORT deconvolution algorithm. In conclusion, the immune-related eleven-RNA signature be could served as a potential prognostic biomarker for osteosarcoma metastasis.
Topics: Osteosarcoma; Humans; Prognosis; Bone Neoplasms; Biomarkers, Tumor; Female; Male; Gene Expression Regulation, Neoplastic; Neoplasm Metastasis; Kaplan-Meier Estimate; Gene Expression Profiling; Transcriptome; Proportional Hazards Models; Risk Factors; Algorithms
PubMed: 38862526
DOI: 10.1038/s41598-024-54292-6 -
Acta Ortopedica Mexicana 2024different variables have been associated with a worse prognosis of patients with osteosarcoma (OS), highlighting tumor size, location in the axial skeleton and the...
INTRODUCTION
different variables have been associated with a worse prognosis of patients with osteosarcoma (OS), highlighting tumor size, location in the axial skeleton and the presence of metastases. The objective of this study is to analyze the prognostic impact of diagnostic delay in osteosarcoma in adults in the Mexican population in a center specialized in sarcomas.
MATERIAL AND METHODS
retrospective cohort study from January 1, 2005, to December 31, 2016, 96 patients over 21 years of age with a diagnosis of osteosarcoma were analyzed.
RESULTS
the median time to diagnosis from the onset of symptoms was six months (range: 2-36). This variable was dichotomized by applying the operator-dependent curve (ROC) analysis and we determined a cut-off value greater than five months, with an area under the curve (AUC) = 0.93 [95% CI 0.86-0.97], sensitivity 93.2% and specificity 94.6%.
CONCLUSION
time until diagnosis is a critical factor in the survival of adult patients with osteosarcoma, highlighting its influence on disease progression and the appearance of metastasis. The correlation between diagnostic delay and an unfavorable prognosis reinforces the need for rapid and efficient evaluation in suspected cases of osteosarcoma.
Topics: Humans; Osteosarcoma; Retrospective Studies; Male; Adult; Female; Bone Neoplasms; Delayed Diagnosis; Prognosis; Middle Aged; Young Adult; Aged; Mexico; Time Factors; Sensitivity and Specificity; Cohort Studies; Disease Progression; ROC Curve
PubMed: 38862146
DOI: 10.35366/115811 -
Journal of Nanobiotechnology Jun 2024Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited...
Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis.
Topics: Female; Animals; Breast Neoplasms; Mice; Bone Neoplasms; Cell Line, Tumor; Mice, Inbred BALB C; Bacterial Outer Membrane; Ultrasonic Therapy; Polylactic Acid-Polyglycolic Acid Copolymer; Humans; Nanoparticles; RAW 264.7 Cells; Cell Membrane; Multifunctional Nanoparticles
PubMed: 38858780
DOI: 10.1186/s12951-024-02619-w -
BMC Urology Jun 2024Wilms tumor (WT), also known as nephroblastoma, is rare in adults, accounting for merely 3% of all nephroblastomas or 0.2 cases per million individuals. Extrarenal Wilms... (Review)
Review
BACKGROUND
Wilms tumor (WT), also known as nephroblastoma, is rare in adults, accounting for merely 3% of all nephroblastomas or 0.2 cases per million individuals. Extrarenal Wilms tumor (ERWT) emerges outside the renal boundaries and comprises 0.5 to 1% of all WT cases, with even rarer incidences in adults. Oncogenic mutations associated with ectopic nephrogenic rests (NR) may contribute to ERWT development. Diagnosis involves surgical resection and pathology examination. Due to scarce cases, adults often rely on pediatric guidelines. We thoroughly searched PubMed, Scopus, and Web of Science databases to establish our case's uniqueness. To the best of our knowledge, this is the first documented incidence of extrarenal Wilms tumor within the spinal canal in the adult population.
CASE PRESENTATION
A 22-year-old woman with a history of congenital lipo-myelomeningocele surgery as an infant presented with a 6-month history of back pain. This pain gradually resulted in limb weakness, paraparesis, and loss of bladder and bowel control. An MRI showed a 6 × 5 × 3 cm spinal canal mass at the L4-S1 level. Consequently, a laminectomy was performed at the L4-L5 level to remove the intramedullary tumor. Post-surgery histopathology and immunohistochemistry confirmed the tumor as ERWT with favorable histology without any teratomatous component.
CONCLUSION
This report underscores the rarity of extrarenal Wilms tumor (ERWT) in adults, challenging conventional assumptions about its typical age of occurrence. It emphasizes the importance of clinical awareness regarding such uncommon cases. Moreover, the co-occurrence of spinal ERWTs and a history of spinal anomalies warrants further investigation.
Topics: Humans; Wilms Tumor; Female; Spinal Canal; Young Adult; Incidence; Kidney Neoplasms; Spinal Neoplasms
PubMed: 38858693
DOI: 10.1186/s12894-024-01508-6 -
International Journal of Implant... Jun 2024Prosthetics for patients after oncological resection of the upper jaw is a complex problem associated with the physiological and anatomical separation of the oral cavity...
PURPOSE
Prosthetics for patients after oncological resection of the upper jaw is a complex problem associated with the physiological and anatomical separation of the oral cavity and the nasal/paranasal region. This study reports the clinical results of the use of the zygomatic implants for prosthetic rehabilitation in patients with maxillectomy due to upper jaw tumors.
MATERIALS AND METHODS
The study included 16 patients who underwent prosthetic rehabilitation using a zygomatic implant after maxillectomy period from 2021 to 2023. After the tumor was removed, immediate surgical obturators were placed. Main prosthetic rehabilitation was performed 6-12 months after tumor removal, but before that, a temporary obturator was made and used. Six-twelve months after tumor resection, 1-4 zygomatic implants were inserted into the zygomatic bone unilaterally or bilaterally. A total of 42 zygomatic implants were installed, 2 of which were unsuccessful and were removed in 1 patient. The implants were placed using the surgical guide, which was planned and prepared digitally.
RESULTS
No postsurgical complications were seen, and the patients were discharged from the hospital after 7-10 days. The patients were able to return to a normal diet (hard food) after just 7 days following surgery, with no further complaints regarding function or pain, apart from the residual edema caused by the intervention.
CONCLUSIONS
The use of prostheses fixed on zygomatic implants in patients with maxillary defects is an effective method of prosthodontic rehabilitation in complex clinical cases after maxillectomy.
Topics: Humans; Zygoma; Male; Female; Maxillary Neoplasms; Middle Aged; Adult; Aged; Dental Implants; Maxilla; Palatal Obturators; Treatment Outcome; Dental Prosthesis, Implant-Supported
PubMed: 38856842
DOI: 10.1186/s40729-024-00545-y