ABSTRACT: Serum markers reflect a bone cell activity that regulate bone remodeling, bone alkaline phosphatase (PAO), Total Intact Procollagen Type I N- terminal propeptide (TP1NP) for training and tartrate-resistant acid phosphatase (TRAPB5), carboxy-terminal collagen crosslinks (Cross Laps) for bone resorption. These markers are sensitive and early tools, Elevated serum levels of these markers is a very good prognostic factor of primary bone tumors as well as monitoring and evaluation tools. We investigated whether biomarkers of bone formation (PAO, P1NP) and bone resorption (CTX and TRAPb5) were modified by chemotherapy. The aim of this study was to evaluate the impact of treatment on serum PAO and TP1NP and TP1NP and TRAPB5. Result: We found a significant correlation between serum levels of training biomarkers (PAO and TP1NP in the group of patients (p = 0.0042) and a strong correlation between PAO and TP1NP In the sick and control groups (p = 0.00027) and a strong correlation between TP1NP and TRAP5b in the groups of patients and controls (p = 0.033). Bone markers can be used in therapeutic monitoring of experimental bone disorders and to assess remodeling during chemotherapy for primary tumors .
The purpose of this study is to determine Magnetic Resonance Imaging (MRI) characteristics of different primary bone tumors and to evaluate the role of MRI in prediction of malignancy and delineation of anatomic extent of primary bone tumors. Fifty three patients either suspected or proven cases of bone tumors were first evaluated with radiograph, followed by MRI examination. In our study of 53 cases, MRI detected marrow involvement, soft tissue involvement (37%), joint involvement (23%) and cortical break (45%), thus helped in staging and management. MRI is the best modality to evaluate the osseous as well as extra-osseous component, marrow involvement, exact extent and neurovascular involvement. It is very helpful in staging of the tumor.
epigenetic regulation of TAp73β through miRNAs has already been described and interestingly, even if in silico analysis predicts that the miRs -125b, -486-3p and -34a could potentially target TAp73 , only the miR-193a- 5p was validated as a direct bona-fide TAp73β’s repressor . Through modulating the miR-193a-5p’s expression level, we highlighted its implication in the Cisplatin- chemoresistance of the Bone Sarcoma cells, as previously shown in a head and neck squamous cell carcinoma model . In contradiction with our results (Figure 4e, 5c, 6f and Supp. Figure 4e), it was interestingly previously reported that the miR-193 is an inducer of the caspase-3 activity, arguing here for its tumor-suppressive functions . In addition, beyond the fact that the miR-193a- 5p can probably inhibit multiple target-genes, it seems clear that its dual role in the apoptotic-processes’ control could be partially explained by its p73-targeting features. Obviously, the different functions of the isoforms of p73 are not yet fully elucidated and are undoubtedly modulated by the interactions of p73 itself with the other members of the p53 family, especially p63. In return, this gene-family also regulates the expression of this miRNA, as it was reported that the oncogenic transcription factor ΔNp63α is an inducer of the miR-193a-5p’s expression, thus contributing to the Cisplatin-chemoresistance . These data could explain a previous study reporting that a stable p73 knock-down in breast cancer cell lines induce a higher Cisplatin chemoresistance in the cells which express ΔNp63 compared with these which do not .
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ES is characterized by extensive bone destruction due to osteolysis. Ewing ' s sarcoma cells are unable to directly degrade the bone matrix and accordingly, osteoclast activation and sub- sequent bone resorption might be responsible for the clinical features of bone destruction . Indeed, as demonstrated for bone metastases , a vicious cycle between bone cells (osteo- clasts and osteoblasts) and tumor cells occurs during the devel- opment of tumor in bone site. Therefore, targeting the osteoclasts may represent a promising adjuvant strategy for the treatment of bone tumors. Among the factors involved in the regulation of bone remodeling, the molecular triad osteoprotegerin (OPG)/receptor activator of NF-kB (RANK)/RANK Ligand (RANKL) is strongly implicated [12,13]. Osteoclast differentiation and activation is mainly mediated by RANKL, a cytokine member of the tumor necrosis factor (TNF) superfamily (TNFSF11) that binds to its receptor RANK at the surface of osteoclasts . OPG (TNFRSF11B) is a soluble protein that acts as a decoy receptor for RANKL inhibiting osteoclast formation, function and survival by prevent- ing the binding of RANKL to RANK . Transgenic mice over- expressing OPG exhibit an osteopetrotic phenotype, whereas OPG- knockout mice have severe osteoporosis [16,17]. The OPG/RANKL/ RANK system is also involved in various pathologies associated with tumors in bone [18,19]. Therefore, OPG has demonstrated increased interest as a therapeutic strategy in malignant bone pathologies associated with osteolytic lesions [20,21]. Concerning primary bone tumors, the inhibition of RANKL activity by OPG induced a signi ﬁ cant therapeutic effect on bone lesion and tumor development in two preclinical models of osteosarcoma in mice (POS-1) and in rats (OSRGa) . This effect was also con ﬁ rmed by using the soluble form of the RANKL receptor, RANK-Fc  or by the RNA interference strategy targeting RANKL . In addition, OPG is also able to bind to the TNF Related Apoptosis Inducing Ligand (TRAIL), another member of the TNF superfamily (TNFSF10) , thereby limiting its ability to induce apoptosis in tumor cells. It has been even reported that OPG acts as a pro-tumoral factor in some cancer cell lines in vitro [24 – 26]. In addition, Taylor et al. previously reported that the expression of RANKL in Ewing ' s sarcoma cell lines and tissues could support osteoclast activation . Therefore, targeting this cytokine with OPG may represent a promising therapeutic option.
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The diagnosis of a bone tumor is dependent on an evaluation of clinical, radiologic, and pathologic features. In most cases, the pathologist can render an accurate diagnosis based on histopathologic features. In some cases, however, a variety of ancillary studies, especially immunohistochemistry (IHC), has proven to be more helpful in distinguishing between entities that share similar morphologic features or are of uncertain histogenesis. Immunohistochemistry (IHC) provides the histological identification of antigenic factors in cells not otherwise evident in routinely stained histological sections. It is more helpful in elucidating the histogenesis of the cell population, but less helpful in distinguishing between reactive, benign and malignant lesions. This review will focus on frequently used diagnostic immunomarkers in selected primary bone tumors based on the World Health Organization tumor classification of 2005.
Abstract: Micro ribonucleic acids (miRNAs) are small non-coding RNA segments that have a role in the regulation of normal cellular development and proliferation including normal osteogenesis. They exert their effects through inhibition of specific target genes at the post- transcriptional level. Many miRNAs have altered expression levels in cancer (either increased or decreased depending on the specific miRNA). Altered miRNA expression profiles have been identified in several malignancies including primary bone tumors such as osteosarcoma and Ewing’s sarcoma. It is thought that they may function as tumor suppressor genes or oncogenes and hence when dysregulated contribute to the initiation and progression of malignancy. miRNAs are also thought to have a role in the development of bone metastases in other malignancies. In addition, evidence increasingly suggests that miRNAs may play a part in determining the response to chemotherapy in the treatment of osteosarcoma. These molecules are readily detectable in tissues, both fresh and formalin fixed paraffin embedded and, more recently, in blood. Although there are fewer published studies regarding circulating miRNA profiles, they appear to reflect changes in tissue expression. Thus miRNAs may serve as potential indicators of disease presence but more importantly, may have a role in disease characterization or as potential therapeutic targets. This review gives a brief overview of miRNA biochemistry and explores the evidence to date implicating these small molecules in the pathogenesis of bone tumors.
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normal-looking skin. The plain radiograph (Fig. 1a, b) and the CT (Fig. 1d) showed a left frontal intraosseous lesion with osteolytic characteristics with moderate aggressiveness. The radiological differential diagnosis included bone metastasis or plasmacytoma. The sys- temic studies of tumor tracking (blood count, hematological smear, tumor markers, proteinogram, and cervical-thoraco-abdominal CT) were negative. The per- cutaneous puncture with fine needle of the tumor was inconclusive for the diagnosis; only blood fragments were obtained. Finally, it was decided to surgically inter- vene the patient based on the clinical progression of the lesion, with its esthetic implications, as well as to obtain a definitive histological diagnosis. During the surgery, a bone-dependent tumor was identified, with multiple di- lated vascular channels in its center, which expanded the external table. To avoid manipulation of the lesion, it was decided to include it in a piece of craniectomy with a circumferential margin of 1 cm of the seemingly healthy bone. The resulting bone defect was recon- structed by means of a cylindrical metametacrylate plasty, which was fixed to the surrounding bone with ti- tanium miniplates. The postoperative period was un- eventful. The definitive anatomopathological diagnosis was intraosseous cavernous hemangioma.
Chordoma is a rare low grade, primary malignant bone tumour arising from primitive notochord remnants. It accounts for 1- 4% of all primary skeletal tumours. Sacrum represents the more common anatomical site of origin followed by skull base region, cervical vertebrae and thoracolumbar vertebrae. Muller in 1858 was the first person to propose that the tumor was related to the notochord while as Ribbert was the first person to coin the term ‘chordoma’ in 1894. Data from Swedish registry (2009) found that annual incidence of chordoma was 0.5% per million individuals and that chordoma was responsible for 17.5% of all primary malignant bone tumors. A small number of families have been reported in which multiple relatives have been affected by chordoma. In four of these families duplication of the brachyury gene was found to be responsible for causing chordoma. A possible association with tuberous sclerosis complex (TSC1 or TSC2 has been suggested
I brachytherapy was carried out with the intent to narrow the resection scope of conventional surgery, re- duce recurrence rate, improve the completeness of tumor resection, and preserve organ function. Inclusion criteria were as follows: (1) the tumor proliferated and locally infiltrated the surrounding organs or tissues; (2) the tumor was not easily resectable, due to large major axis length (>6 cm), extension to adjacent vasculature and nerves, and/or no clear margin; (3) isolated recur- rent or metastatic bone tumor; (4) need to treat localized residual pelvic cancer after conventional surgery or ex- ternal radiation therapy; (5) the patient declined con- ventional surgery or was unfit for conventional surgery; (6) no history of radiotherapy to the pelvis; and (7) the patient accepted brachytherapy using 125 I seeds. The exclusion criteria were (1) active tumor bleeding, ne- crosis, or ulceration; (2) cancer infiltration into a large area or involving a large blood vessel; (3) non- suitability of the patient for radiotherapy, or contraindi- cation to anesthesia; or (4) closeness of large vessels to seed implantation site.
SCPs from MDA-MB-231 cells have a poor-prognosis gene expression signature. (A) Microarray expression data of 46 of the 70 poor-prognosis genes (7) that are present on the Affymetrix U133A GeneChip for the MCF10A normal breast epithelial cell line, parental MDA-MB-231 cell line, and various SCPs from MDA-MB-231. Each column represents a gene (denoted along the bottom) and each row represents a cell line (denoted along the right). Genes of the poor-prognosis signature that are expressed at higher levels in poor-prognosis tumors are above the red line, and those that are underexpressed are above the green line. Genes with low trust values due to low or absent expression are shaded in darker colors (Trust; wedge). (B) Microarray expression data of primary human breast carcinoma from 63 patients treated at our institution who had at least 5 years of clinical follow-up and/or developed metastatic disease. Hierarchical clustering of the patients’ data was performed with the 46 poor- prognosis genes. Each column represents a patient and each row, a gene. The MDA-MB-231 cell line was included and is denoted by a blue dot in the dendrogram. Those patients in the good-prognosis versus the poor-prognosis cluster are separated by the yellow line. (C) Five-year metastasis-free survival data for the 63 patients classified according to the hierarchical clustering described in B. The P value shown in the graph was calculated by the χ 2 test. (D) Dendrogram showing hierarchical clustering of the SCPs and MCF10A using the poor-prognosis genes. A scale
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The patella is defined as a sesamoid originating in the quadriceps tendon. It develops from a cartilaginous pre- cursor in the third month of gestation and ossifies about 3 years of age . Its ossification is similar to that of a long bone’s epiphysis or apophysis. This makes the pa- tella a possible location of bony lesions . Due to lim- ited published literatures, we still know a little about patellar neoplasms. As the patellar neoplasms are such a rare etiology as anterior knee pain, their determination is often postponed. However, a majority of primary pa- tellar neoplasms usually cause a dilemma in diagnosis. Therefore, physicians urgently need more evidences to distinguish primary patellar tumors from other kind of lesions through integrated analysis of epidemiology, pathogenesis, symptomatology, imageology, and histo- pathology and in reference to the reported treatments.
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Solid primary tumors of mesenteric origin are quite rare among the intraabdominal soft tissue tumors . The most frequent tumors are Gastrointestinal Stromal Tumors (GIST) and smooth muscle tumors. GISTs as the largest group of these tumors are usually seen in the wall of gastrointestinal tract and 25% of them are malignant  . They usually occur in adults and there is no sexual predominance. It may also cause intestinal obstruction. Fibromyoma is a benign mesenchymal tumor that can occur at visceral organs such as the heart, lung, liver, kidney, pancreas, gastrointestinal tract and central nervous system [2, 3]. As well as smooth muscle
: Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Their complex nature, unpredictable behaviour, prognosis and varying therapeutic strategies, necessitates an accurate diagnosis. Aims and The present study was undertaken to study the diverse histomorphological patterns of 2012. Results: Out of 119 neoplastic ed as benign, 1.7% (2) as borderline and. 42.0% (48) as malignant. Age of the patients ranged from 1 to 70 years. with maximum cases (42.8 %) seen in the 40 years. The commonest category of the ovarian tumors encountered in our series pithelial tumors (73.94%) followed by germ cell tumors (16.8%). Abdominal pain was the most Benign ovarian tumours were more common than malignant ones across all age groups. Surface epithelial tumours were the most common histopathological type of ovarian tumour. Due to vague symptoms, patients present late. Development of methods for early diagnosis of ovarian neoplasia is therefore, a pressing need today. The relative urs shows regional variations, highlighting the need
The primary tumor was evaluated on plain radio- graphs, computed tomography (CT) scans, and magnetic resonance imaging scans. The bone scintigraphy and CT scanning of the chest were performed to confirm that there were no metastases. All the patients received the 2–3 circles of standard three-course neoadjuvant chemotherapy with a 3-week interval between cycles. After receiving the full course of neoadjuvant chemo- therapy, all the patients were restaged using MRI and received surgery 2 weeks after the last course. Postop- erative chemotherapy (1 circle) was performed every month and lasted for 12 to 18 months.
The most important considerations of tumor implant device in orthopedic oncology surgery are to confirm strength of the part of bone replacing and to design the connection part between the implant and remaining bones so that the implant was easily and firmly attached to the bone. Moreover, anatomical reconstruction is common important issue for specific skeletons including both forearm bones to gain maximal function. For the designing step, cooperated with surgeon for his clinical knowledge or/else infor- mation of surgical approach and engineer owing to his knowledge of mechanical and structural property. The model created in Mimics was exported to 3-Matic (Materialize, Belgium) for further process- ing to isolate the forearm and to construct the final implant model. 3-Matic provides with a means of error corrections, where the DI- COM data model can be checked for issues such as multiples shells and inverted normal, such that any produced design would be fit for digital manipulation and the final 3D printing. For the patient with the bone tumor on the both forearm bones, the entire shaft of the implant was basically modeled to the same size as the original bone(Figure 3).
Conventional radiology plays a minimum role in identifying bone tumors of the sacrum in the initial stage since sacrum is a curved bone and often is obscured by overlying intestinal contents. Sacrum is composed of two distinct tissues, which include osseous and neural. This paper deals with osseous tumors only. Primary tumors of the sacrum may be benign or malignant. In malignant tumors soft tissue component is more prominent. As elsewhere, age is important in deciding whether the tumor is benign or malignant. Benign tumors include osteoid osteoma, osteoblastoma, osteochondroma, giant cell tumor and aneurysmal bone cyst. Malignant tumors include chordoma, osteosarcoma, Ewing sarcoma, chondrosarcoma, plasmacytoma and malignant fibrous histocytoma. Primary lymphoma of sacrum is very rare. Plain radiographs depict osteolysis, osteosclerosis and expansion of the bone with soft tissue swelling with mineralisation. Advanced imaging may be necessary in arriving at a final diagnosis. Imaging characteristics are described with the help of illustrations. Neurogenic tumors secondarily involving the sacrum are not included in this paper.
The cases used in this study were identified through a review of databases and from our center. Cases were retrieved from Chinese and foreign databases. The Chinese databases were China National Knowledge In- frastructure (CNKI) (seven cases), VIP (eight cases), WANFANG DATA (13 cases), while the foreign data- bases included PubMed (12 cases) and EMBASE (four cases). After data synthesis, 20 reports were filtered [8– 27], which included a total of 24 cases. One case of PAST that was identified during autopsy was excluded. From January 2009 to October 2017, our center reported only one case of PAST, a 59-year-old female patient, who received an exploratory laparotomy fol- lowing the identification of a mass in the right lower quadrant upon CT examination for cervical cancer. During the exploration, a 10-cm-sized tumor was found on the appendix, with the ileocecal valve violated, and the patient received a right hemicolectomy and append- ectomy. According to the National Institutes of Health (NIH) primary GIST standard [2, 28], this case was di- agnosed as a high-risk appendiceal stromal tumor. Modified NIH risk classification is divided into categor- ies according to tumor size and mitotic phase, as fol- lows: very low risk, low risk, intermediate risk, and high risk .
Echocardiography has a high sensitivity and specificity (90% and 95%, resp.) for the detection of cardiac tumors. Transthoracic echocardiography ( TTE ) can vi- sualize the shape, size, extent and relation of the tumor to adjacent cardiac structures. Hemodynamic consequences of the tumor can also be studied. Tran- sesophageal echocardiography ( TEE ) is superior to TTE in identifying small tu- mors ( < 5 mm) and tumors localized at the posterior cardiac segments . Contrast echocardiography helps in the differentiating tumors by examining tissue perfusion. Malignant tumors or tumors rich in vascularity, appear with an intense enhancement of the echocardiographic image. Benign cardiac tumors exhibit sparse vascularity. Three dimensional echocardiography (3 D Echo ) con- tributes mainly to an improved assessment of the shape, the size, the mobility of a tumor and its relationship regarding adjacent structures, by making use of the wider imaging range that this technique provides .
13-year-old boy presented with progressively increasing size of the swelling in the left parietal region over 3 years without any pain. Apart from the swelling the child was asymptomatic. There was no significant past history. On examination 8x8 cm swelling with diffuse borders, bony hard consistency, non-pulsatile, with absent cough impulse, without any venus hum or bruit noted over the left parietal region. Computed tomography of the skull and brain showed fusiform shaped expansile osteolytic intra diploic lesion which had typical soap bubble or honey comb like appearance with intra diploic trabeculae which was suggestive of aneurysmal bone cyst. Brain parenchyma was normal except for the minimal cortical buckling of the ipsilateral parietal cortex. Patient underwent surgical excision of the tumor en bloc with a margin of 1cm all around along with cranioplasty. Intra operatively, the involved bone was ballooned out with bluish hue on the surface with lot of branching vessels, outer and inner tables were thin and easily breakable, without any dural involvement. Histopathologically the tumor showed evidences of large blood filled spaces surrounded by stromal and scattered giant cells, which was suggestive of primary aneurysmal bone cyst.
The clinical survey for recurrence after com- plete resection of the primary tumor is focused on the liver or peritoneum and is usually per- formed using abdominal CT. Because it is unknown how much consideration should be given to delayed bone metastasis in the follow- up survey, we have evaluated the time relation- ship between bone and liver metastases. Bone metastasis preceded liver metastasis in four of the 23 cases (17%). Three of the four cases had bone metastasis as the primary or the only metastatic manifestation and one case had synchronous pulmonary metastasis. Although the optimal method or interval for the detection of bone metastasis requires clarification, bone metastasis can sometimes be the primary met- astatic manifestation.