HDAC6 inhibitor WT161 performs antitumor effect on osteosarcoma and synergistically interacts with 5-FU

An imbalance between protein aggregation and protein degradation may induce “stress” in the functionality of the endoplasmic reticulum. There are quality control mechanisms to minimize misfolding and to eliminate misfolded proteins before aggregation becomes lethal for the cell. Proper protein folding and maturation is one of the crucial functions of the endoplasmic reticulum. Chaperones of the endoplasmic reticulum and folding enzymes guarantee correct conformational maturation of emerging secretory proteins. HDAC6 is a masterpiece coordinating the cell response to protein aggregate formation. The balance between HDAC6 and its partner Valosin-containing protein/p97 determines the fate of polyubiquitinated misfolded proteins. WT161 is a terrific, selective, and bioavailable HDAC6 inhibitor. WT161 selectively inhibits HDAC6 and adequately increases levels of acetylated α-tubulin. This compound induces accumulation of acetylated tubulin and cytotoxicity in multiple myeloma (MM) cells. In this Journal, Dr. Sun et al. identified that WT161 suppresses the cell growth of osteosarcoma cells. This discovery opens the door to future chemotherapeutic regimens of this bone neoplasm.

The Application of 3D-Printing and Nanotechnology for the Targeted Treatment of Osteosarcoma

Osteosarcoma is a malignant bone neoplasm prevalent in adolescents. Current therapies include chemotherapy and surgery. Surgical resection of osteosarcoma induces a large bone defect which may be overcome by employing scaffolds for bone tissue engineering. This review details the polymers and bioceramics that may be used to fabricate 3D printed scaffolds for bone regeneration and the nanotechnology strategies that may be incorporated into such scaffolds. Natural polymers discussed include chitosan, alginate, collagen, gelatin, and silk fibroin. Synthetic polymers discussed include polycaprolactone, polyurethane, poly(lactic)acid and poly(vinyl) alcohol. Bioceramics that are utilized in bone regeneration such as calcium phosphate, calcium silicate and bioglass are elaborated on. Furthermore, comparison data between different types of 3D printed scaffolds for bone regeneration are presented. A discussion on Photo-responsive and magneto-responsive 3D printed scaffolds that have been fabricated for bone regeneration is included. Research concerning drug-loaded scaffolds as well as the incorporation of nanocarriers into scaffolds for bone regeneration is provided. Chemotherapy utilized in osteosarcoma therapy has severe adverse effects due to being non-selective between healthy cells and tumor cells. A possible way to overcome this is to utilize nanotechnology. Therefore, research detailing other types of nanocarriers that have the potential to be incorporated into 3D printed scaffolds for localized adjuvant therapy is presented.

Case report of a female child with right nasal chondromyxoid fibroma

Chondromyxoid fibroma; a rarely found tumor, contributing <1% of all primary bone neoplasm. We reported a 4-year female child with a 1-year history of nasal obstruction and facial swelling. Large enhanced lesion with amorphous densities spreading into the right cribriform plate and floor of sphenoid sinus, laterallyinto right lamina papyracea, inferolaterally into medial wall of maxillary sinus, posteriorly into nasopharynx and superior aspect of oropharynx was appreciated in CT scan. Mass was excised by Caldwell Luc’s endoscopic medial maxillectomy via the sublabial approach. CMF was confirmed histologically in post-operative biopsy. Keywords: Chondromyxoid fibroma, benign neoplasm, lamina paprycea. Continuous...

Recent Advances in Nanotechnology-Based Diagnosis and Treatments of Human Osteosarcoma

Osteosarcoma (OSA) is a type of bone cancer that begins in the cells that form bones. OSA is a rare mesenchymal bone neoplasm derived from mesenchymal stem cells. Genome disorganization, chromosomal modifications, deregulation of tumor suppressor genes, and DNA repair defects are the factors most responsible for OSA development. Despite significant advances in the diagnosing and treatment of OSA, patients’ overall survival has not improved within the last twenty years. Lately, advances in modern nanotechnology have spurred development in OSA management and offered several advantages to overcome the drawbacks of conventional therapies. This technology has allowed the practical design of nanoscale devices combined with numerous functional molecules, including tumor-specific ligands, antibodies, anti-cancer drugs, and imaging probes. Thanks to their small sizes, desirable drug encapsulation efficiency, and good bioavailability, functionalized nanomaterials have found wide-spread applications for combating OSA progression. This review invokes the possible utility of engineered nanomaterials in OSA diagnosis and treatment, motivating the researchers to seek new strategies for tackling the challenges associated with it.

Metastatic Pelvic Osteosarcoma in a Dog

Background: Osteosarcomas are malignant neoplasms of bone tissue, with a high prevalence in dogs, especially in large and giant breeds. More commonly, such alterations affect the appendicular skeleton and, to a lesser extent, the axial skeleton. In order to obtain an accurate diagnosis, it is necessary to combine cytological and histopathological findings with clinical parameters, imaging exams and macroscopic findings. In the present study, we report a rare case of combined-type pelvic osteosarcoma with pulmonary metastasis in a dog.Case: A 5-year-old intact large male dog of mixed breed, was submitted to clinical care because of an increase in volume of the left perineal region. The cytological evaluation, performed without imaging exams, indicated that it was an undifferentiated sarcoma. An incisional biopsy defined the diagnosis as telangiectatic osteosarcoma, and with progressive clinical worsening, the patient died. Necroscopic examination revealed multiple nodules in the lungs and an irregular mass with a hard to friable consistency. The mass was intensely vascularised and extended craniodorsally from the left ischial tuberosity to the base of the renal fossa. Microscopically, the neoplasm was diagnosed as combined osteosarcoma, consisting of the osteoblastic, chondroblastic, and telangiectatic subtypes. Metastases with a predominance of the chondroblastic subtype were observed in the lungs.Discussion: This is the first report of combined-type canine osteosarcoma in the ischium. The case reported here is unusual, as there are few reports of canine osteosarcoma in the pelvic bones, and there is no concrete information regarding its histological appearance. Osteosarcoma is the most common bone neoplasm in dogs, representing up to 80% of the tumours found in such organs. In the present case, the dog was a large young adult with a higher probability of neoplasm development. A cytopathological examination is a diagnostic method with good sensitivity and specificity that can confirm osteosarcomas. However, in this case, the cytological diagnosis, performed without the information from the imaging exam, indicated that it was an undifferentiated sarcoma, given the impossibility of the architectural assessment of the lesion. Biopsy samples sent for histology may not be representative of the entire tumour, leading to misclassification of the histological type. Therefore, the evaluation of fragments from various sites of the lesions is recommended. Regarding the morphology of osteosarcomas, such neoplasms have the osteoblastic, chondroblastic, fibroblastic, telangiectatic, large cell, and poorly differentiated subtypes. With regard to tumours located in the axial skeleton, no studies have assessed the predominance of a particular morphological type, as well as the incidence of combined-type masses in dogs in this particular location. Such neoplasms are locally aggressive and have a high metastatic potential, with the lungs being the main location for implantation of neoplastic cells. There is no proven evidence of the correlation between morphological presentations and the presence of metastases from osteosarcomas in dogs. The histological type is not a predictive factor for the behaviour of the neoplasm. However, the anatomical location is considered as one of the factors with the greatest influence on the prognosis and metastatic potential. Rib masses are associated with a higher rate of metastases compared to others. The definitive diagnosis of osteosarcomas and its correct subclassification are of great importance in the prognosis of affected patients. These require an approach that considers the clinical findings, imaging examinations, and macroscopic and microscopic alterations. Keywords: bone, canine, cytopathology, histopathology, neoplasm.Título: Osteossarcoma pélvico metastático em cão Descritores: canino, citopatologia, histopatologia, neoplasia, osso.

Osteochondroma of the pubic symphysis causing hematuria: a case report and literature review

Background Osteochondroma is the most common benign bone neoplasm and is sometimes referred to as osteocartilaginous exostosis. The symptoms caused by osteochondroma are rare, especially the urogenital complications. Therefore, this tumour is sometimes misdiagnosed. Case presentation This report described a 70-year-old woman with hematuria who was initially misdiagnosed with a bladder tumour in the outpatient department by a urologist. However, during cystoscopy, we found that the mass did not resemble a bladder tumor. Multidisciplinary approach with careful analysis of the imaging data suggested the diagnosis of osteochondroma. Open surgical excision of the mass was done and histology confirmed the diagnosis of benign osteochondroma. After 6 months of follow-up, the patient was still asymptomatic. Conclusions This case illustrates that hematuria is caused by not only urogenital disease but also osteochondroma. We present this case to draw the attention of clinicians to osteochondroma of the pubic symphysis.

Chondroblastoma of mandibular condyle: Case report and literature review

Chondroblastoma is one of the uncommon benign bone tumors, particularly when located in the mandibular condyle. Such a location makes its diagnosis difficult when based on only its clinical presentation and radiographic features. Herein the current report presents a case of chondroblastoma of the mandibular condyle: its clinical presentation, radiographic features, and immediate condylar reconstruction after resection. Additionally, the relevant literature is discussed to provide clinical recommendations for its diagnosis and treatment. Chondroblastoma has been reported so infrequently in the temporomandibular joint (TMJ), more common entities should first be considered in the differential diagnosis of masses in this location. Osteochondroma is the most frequent bone neoplasm in the TMJ. Since a correct diagnosis is difficult, additional tools, such as magnetic resonance imaging (MRI) and immunohistochemical analyses, should be used for diagnostics and surgical planning.

Vitamin D Represses the Aggressive Potential of Osteosarcoma

Background: Osteosarcoma (OS) is the basic bone neoplasm with lower survival and poor prognosis. It is distinguished by its offensive nature and metastatic potential. The fundamental death source in OS patients is lung metastasis. In addition, the proliferation and cell migration are thus essential for cancer progression, especially for intrusion and transformation. Several studies have illustrated that 1,25-Dihydroxyvitamin D (1,25(OH)2D) has a critical role in the growth and differentiation of bone. However, knowledge about the outcome of 1,25(OH)2D on the progression and incursion of osteosarcoma cells is minimal. Objective: The present study aimed to analyze the effect of different concentrations of 1,25(OH)2D on the multiplication, progression, and intrusion of OS cells and verify the effective doses of 1,25(OH)2D that can decrease the intensity of the disease and improving the prognosis in OS patients. Methods: Saos-2 cells were treated with 1,25(OH)2D (0, 50, 100, and 200 nM) for 48, 72, and 96 hours. Proliferation, invasion, and migration were determined by MTT assay, Transwell assay, and Scratch test, respectively. The levels of c-Myc and FOXO1 proteins were determined by Western blotting. Results: The proliferation, invasiveness, and migration of Saos-2 cells that were treated with 1,25(OH)2D were significantly decreased compared with untreated cells. Although 1,25(OH)2D notably decreased c-Myc protein levels (after 48 and 72 hours), FOXO1 protein levels have been significantly increased after 48 and 72 hours. 1,25(OH)2D and the vitamin D receptor (VDR) suppress c-Myc function through regulating the c-Myc/MXD1 network and providing thus a molecular basis of 1,25(OH)2D related to the cancer-preventive actions. Conclusion: Based on the present results, 1,25(OH)2D by targeting c-Myc and FOXO1 expression displays anti-invasive, anti-migration and anti-proliferative effects on OS cells in vitro. Our findings suggest that effective doses of the 1,25(OH)2D may reduce of the aggressive potential of OS cell line. However, further investigation and clinical trials are needed.

Multilobular tumor of bone on the forehead of a guinea pig

Multilobular tumor of bone (MLTB) is an infrequent, slow-growing, bone neoplasm formed predominantly on the head. These tumors can behave as malignant neoplasms clinically and pathologically and can metastasize occasionally. No cases of MLTB in rodents have been reported, to our knowledge. We describe a novel case of an MLTB in a guinea pig. An adult guinea pig had an exophytic mass fixed on the frontal bone, maxilla, and nasal bone. On radiography, the mass had a spherical contour and variable density and was formed on the surface of the cranial bones. The mass was excised surgically. The cut surface was light-yellow to milky-white and had a granular texture with fine fibrous septa. Histologically, the neoplasm had a multilobular pattern, which consisted of many islands of bone and/or cartilage matrix surrounded by small cells and separated by fibrous septa, which closely resembles the equivalent neoplasm in dogs.