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Sample records for aggressive bone tumors

  1. May bone cement be used to treat benign aggressive bone tumors of the feet with confidence?

    PubMed

    Özer, Devrim; Er, Turgay; Aycan, Osman Emre; Öke, Ramadan; Coşkun, Mehmet; Kabukçuoğlu, Yavuz Selim

    2014-03-01

    Using bone cement for the reconstruction of defects created after curettage of benign aggressive bone tumors is among acceptable methods. The study aimed to assess the effect of bone cement used in aggressive bone tumors in the feet on the function of the feet. Five patients were reviewed. They were treated between 2004 and 2010. Three cases were female and two male. Their age ranged from 16 to 55 with an average of 34.8. Follow up period ranged from 14 to 86 months with an average of 34. Two cases were giant cell tumor of bone located in calcaneus and 3 were solid variant aneurysmal bone cyst located in talus, navicular and first proximal phalanx. None had any previous treatment. A biopsy was done in all cases. Treatment was curettage, high speed burring (except phalanx case), and filling the cavity with bone cement. The case located in talus recurred and re-operated 1 year later doing the same procedure. Final evaluation included physical examination, X-ray and Maryland Foot Score. No recurrence was present in the final evaluation. No problems were detected related to bone cement. Maryland Foot Scores ranged 84-100, average of 94. Cement integrity was not disturbed. The procedure is found not to effect foot functions adversely.

  2. Parotid gland solitary fibrous tumor with mandibular bone destruction and aggressive behavior

    PubMed Central

    González-Otero, Teresa; Castro-Calvo, Alejandro; Ruiz-Bravo, Elena; Burgueño, Miguel

    2014-01-01

    Introduction: Solitary fibrous tumor is associated with serosal surfaces. Location in the salivary glands is extremely unusual. Extrathoracic tumors have an excellent prognosis associated with their benign clinical behavior. We report an aggressive and recurrent case of this tumor. We review the clinical presentation, inmunohistochemical profiles and therapeutic approaches. Case Report: A 73-years-old woman presented a mass in her right parotid gland. She had a past history of right superficial parotidectomy due to a neurilemoma. FNAB and magnetic resonance were non-specific. After a tumor resection, microscopic findings were spindled tumor cells with reactivity to CD34, bcl-2 and CD99 and the tumor was diagnosed as Solitary Fibrous Tumor. The patient suffered two recurrences and the tumor had a histological aggressive behavior and a destruction of the cortical bone of the mandible adjacent to the mass. A marginal mandibulectomy with an alveolar inferior nerve lateralization was performed. Conclusions: Solitary fibrous tumor is a very rare tumor. Usually, they are benign, but occasionally they can be aggressive. Complete resection is the most important prognostic factor and no evidence supports the efficacy of any therapy different to surgery. Due to the unknown prognosis and to the small number of cases reported, a long-term follow-up is guaranteed. Key words:Solitary fibrous tumor, parotid mass, parotid gland, salivary gland, rare tumors. PMID:25136435

  3. 'Salvage Treatment' of Aggressive Giant Cell Tumor of Bones with Denosumab

    PubMed Central

    Vaishya, Raju; Vijay, Vipul

    2015-01-01

    Giant cell tumor of the bone (GCTB) presents as a lytic lesion of epiphyseometaphyseal regions of the long bones usually during the second to the fourth decade with female predilection. Histologically, they are formed of neoplastic mononuclear cells with a higher receptor activator of nuclear factor kappa-B ligand (RANKL) expression responsible for the aggressive osteolytic nature of the tumour. RANKL helps in the formation and functioning of osteoclasts. A newer molecule, Denosumab, is a monoclonal antibody directed against RANKL and thus prevents the formation and function of osteoclasts. Management of refractory, multicentric, recurrent, or metastatic GCTB remains challenging as achieving a tumor-free margin surgically is not always possible. Denosumab may play a crucial role, especially in the management of such difficult lesions. We present three cases of locally aggressive GCTB (involving proximal humerus, sacrum, and proximal femur) that were treated and responded very well to Denosumab therapy. PMID:26251767

  4. The interdisciplinary approach of an aggressive giant cell tumor of bone complicated with a fracture of the distal femur.

    PubMed

    Vîlcioiu, Iulian Daniel; Zamfirescu, Dragoş George; Cristescu, Ioan; Ursache, Andrei; Popescu, Şerban Arghir; Creangă, Cosmin Antoniu; Lascăr, Ioan

    2016-01-01

    Giant cell tumor of bone (GCTB) represents one of the commonest bone tumors encountered by an orthopedic surgeon. The giant-cell tumor is generally classified as benign but the fast growing rhythm and the aggressive soft-tissue invasion may in some cases demonstrate a malign potential of the tumor. We present the case of an aggressive giant cell tumor in a young patient that was first diagnosed in our emergency department with a fracture of the distal femur after a low energy trauma. With further examinations, we discovered that the tumor was invading the both femoral condyles and was vascularized by three major arterial pedicles. The onset of his problems was the femoral fracture and the changes on the major vessels, muscles and nerves. After an interdisciplinary approach of the patient and a meticulous preoperative planning, we decided to make an extensive total resection of the tumor followed by a complex reconstruction surgery for the bone. A very stable fixation of a vascularized graft allowed the bone to heal even if the surrounded soft-tissue was almost completely invaded by the tumor and removed during the excision. The follow-up of this case demonstrated that using an interdisciplinary approach of the patient with the Plastic Surgery team, we manage to remove the tumor within oncological limits and achieved bone healing with good stability of the distal femur. PMID:27516036

  5. Benign bone tumors.

    PubMed

    Steffner, Robert

    2014-01-01

    Benign bone lesions are a broad category that demonstrates a spectrum of activities from latent to aggressive. Differentiating the various tumors is important in order to properly determine necessary intervention. This chapter focuses on the presentation, imaging, diagnostic features, and treatment of the most common benign bone tumors in order to help guide diagnosis and management. PMID:25070230

  6. Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone

    PubMed Central

    Kawabata, Shigeru; Christine Hollander, M; Munasinghe, Jeeva P.; Brinster, Lauren R.; Mercado-Matos, José R.; Li, Jie; Regales, Lucia; Pao, William; Jänne, Pasi A.; Wong, Kwok-Kin; Butman, John A.; Lonser, Russell R.; Hansen, Marlan R.; Gurgel, Richard K.; Vortmeyer, Alexander O.; Dennis, Phillip A.

    2015-01-01

    Adenomatous tumors in the middle ear and temporal bone are rare but highly morbid because they are difficult to detect prior to the development of audiovestibular dysfunction. Complete resection is often disfiguring and difficult because of location and the late stage at diagnosis, so identification of molecular targets and effective therapies is needed. Here, we describe a new mouse model of aggressive papillary ear tumor that was serendipitously discovered during the generation of a mouse model for mutant EGFR-driven lung cancer. Although these mice did not develop lung tumors, 43% developed head tilt and circling behavior. Magnetic resonance imaging (MRI) scans showed bilateral ear tumors located in the tympanic cavity. These tumors expressed mutant EGFR as well as active downstream targets such as Akt, mTOR and ERK1/2. EGFR-directed therapies were highly effective in eradicating the tumors and correcting the vestibular defects, suggesting these tumors are addicted to EGFR. EGFR activation was also observed in human ear neoplasms, which provides clinical relevance for this mouse model and rationale to test EGFR-targeted therapies in these rare neoplasms. PMID:26027747

  7. Use of extended curettage with osteotomy and fenestration followed by reconstruction with conservation of muscle insertion in the treatment of Enneking stage II locally aggressive bone tumor of the proximal extremities: resection and treatment of bone tumors

    PubMed Central

    2013-01-01

    Background The purpose of this study was to investigate the clinical efficacy of extended resection with osteotomy, fenestration and conservation of muscle (tendon) insertion in the treatment of bone tumors. Methods A total of 15 patients with locally aggressive bone tumors (Enneking stage II) in the adjacent muscle (tendon) insertion of the proximal extremity were enrolled in the present study (mean age of 29 years). Extended curettage of lesions with osteotomy, fenestration and/or conservation of muscle (tendon) insertion and internal fixation with a bone graft or bone cement was performed at stage I. Postsurgical brace protection was used for 4 to 12 weeks and the patients were periodically followed-up by X-ray and functional assessment. Recurrence, postsurgical Enneking score and outcome rating were assessed. Results Treated cases included 15 patients aged 29 ±7.75 years (range, 18 to 42) with a male to female ratio of 8:7. Six had a femoral tumor and nine had a humeral tumor. These tumors comprised three chondroblastomas, five giant-cell tumors and seven aneurysmal bone cysts. Follow-up for 48 ±12.95 months (range, 25 to 72) revealed that 13 of 15 (87%) patients exhibited no recurrence. Local recurrence was observed in a patient with an aneurysmal bone cyst (nine months) and one with a giant-cell tumor (12 months). Mean Enneking scores were 27 ±4.07 (range, 18 to 29). Except for the patient with the recurrent giant-cell tumor, all patients reported good (13%, 2 out of 15) or very good (80%, 12 out of 15) outcomes. Very good outcomes were reported in 92% of patients (12 out of 13) without recurrence. Conclusions The procedures used in this study achieved high clinical efficacy, complete lesion removal, reduced recurrence and good restoration of joint function in patients with primary locally aggressive Enneking stage II bone tumors of the proximal extremities. PMID:23497479

  8. Bone Tumor

    MedlinePlus

    ... most common types of primary bone cancer are: • Multiple myeloma. Multiple myeloma is the most common primary bone cancer. It ... Any bone can be affected by this cancer. Multiple myeloma affects approximately six people per 100,000 each ...

  9. Cryosurgery and acrylic cementation as surgical adjuncts in the treatment of aggressive (benign) bone tumors. Analysis of 25 patients below the age of 21.

    PubMed

    Malawer, M M; Dunham, W

    1991-01-01

    This article reviews the clinical experience with cryosurgery (use of liquid nitrogen) and acrylic cementation (polymethylmethacrylate; PMMA) in the treatment of aggressive, benign bone sarcomas and the biologic basis of this technique. The results of 25 patients below the age of 21 treated by cryosurgery, with an average follow-up period of 60.8 months, are reported. Three approaches to surgical reconstruction were used: Group 1 (four patients) had cryosurgery with no reconstruction, Group 2 (13 patients) had bone graft reconstruction alone, and Group 3 (eight patients) had composite osteosynthesis with internal fixation, bone graft, and/or PMMA. The overall control rate was 96% (one recurrence). The tumor types were giant-cell tumor, chondroblastoma, aneurysmal bone cyst, and malignant giant-cell tumor. Nineteen lesions involved the lower extremity, and six lesions were located in the upper extremity. There were two secondary fractures (8%), one local flap necrosis, and one synovial fistula. There were no infections. Two epiphyseodeses were performed. The functional results were excellent (83%), good (13%), and fair (4%). The technique of composite osteosynthesis is recommended for all large tumors of the lower extremity. Cryosurgical results compare favorably with those obtained by en bloc resection and demonstrate the ability of cryosurgery to eradicate tumors while avoiding the need for extensive resections and reconstructive procedures. PMID:1984931

  10. Bone tumor

    MedlinePlus

    ... physical exam. Tests that may be done include: Alkaline phosphatase blood level Bone biopsy Bone scan Chest x- ... may also be ordered to monitor the disease: Alkaline phosphatase isoenzyme Blood calcium level Parathyroid hormone Blood phosphorus ...

  11. [Benign bone forming tumors].

    PubMed

    Caufourier, C; Leprovost, N; Guillou-Jamard, M-R; Compère, J-F; Bénateau, H

    2009-09-01

    Benign bone forming tumors typically produce dense bone (osteoma, enostosis) or osteoid tissue (osteoid osteoma, osteoblastoma). Even though these four lesions have distinct characteristics, it is sometimes difficult to tell them apart and to rule out malignant bone forming lesions such as osteosarcoma. The first line treatment is surgical exeresis.

  12. [New surgical treatment options for bone tumors].

    PubMed

    Andreou, D; Henrichs, M P; Gosheger, G; Nottrott, M; Streitbürger, A; Hardes, J

    2014-11-01

    Primary bone neoplasms can be classified into benign, locally/aggressive and rarely metastasizing and malignant tumors. Patients with benign tumors usually undergo surgical treatment in cases of local symptoms, mainly consisting of pain or functional deficits due to compression of important anatomical structures, such as nerves or blood vessels. Locally/aggressive and rarely metastasizing tumors exhibit an infiltrative growth pattern, so that surgical treatment is necessary to prevent further destruction of bone leading to local instability. Finally, the surgical treatment of malignant tumors is, with few exceptions, considered to be a prerequisite for long-term survival, either alone or in combination with systemic chemotherapy. Whereas the main objective of surgery in the treatment of benign tumors is relief of local symptoms with a minimum amount of damage to healthy tissue and minimizing the risk of local recurrence while ensuring bone stability in locally aggressive and rarely metastasizing tumors, the primary goal in the operative treatment of bone sarcomas is the resection of the tumor with clear surgical margins followed by defect reconstruction and the preservation of function. This review examines the current developments in the surgical treatment of primary bone neoplasms with respect to the management of the tumors and novel reconstructive options.

  13. Treatment of Bone Tumors

    PubMed Central

    Rajani, Rajiv; Gibbs, C. Parker

    2012-01-01

    Synopsis In this article, the authors summarize the state of the art and future potential in the management of Osteosarcoma, Ewing’s sarcoma, and Chondrosarcoma. They cover systemic therapy, surgical therapy, and radiotherapy, along with targeted therapies to inhibit signal transduction pathways. They discuss staging and the role of imaging evaluation to provide an overview of bone tumor treatment. Images presenting pathologic-radiologic correlations are included. PMID:22328909

  14. Bone Transport for Reconstruction in Benign Bone Tumors

    PubMed Central

    Oh, Chang Seon; Cho, Yong Jin; Ahn, Yeong Seub; Na, Bo Ram

    2015-01-01

    Background The aim of this study was to assess the results of using the Ilizarov apparatus to transport bones in the treatment of benign bone tumors. Methods Seven patients (six males and one female) with benign bone tumors were treated by bone transport with an Ilizarov apparatus at our institution. Their mean age at surgery was 14.4 years (range, 4.8 to 36.9 years). The histological diagnoses were osteofibrous dysplasia (4), giant-cell tumor (1), intraosseous cavernous hemangioma (1), and aneurysmal bone cyst (1). Three radiological indices were used for evaluating the results: an external fixation index, a distraction index, and a maturation index. The bone and functional results were evaluated according to the Association for the Study and Application of the Method of Ilizarov classification. Results Five patients had bone union at the reconstructed site, one patient had a local recurrence, and the other had a nonunion at the docking site. The mean length of distraction was 7.3 cm (range, 5.1 to 12.1 cm). The mean external fixation index was 26.0 day/cm (range, 19.8 to 32.5 day/cm), the distraction index was 9.6 day/cm (range, 6.8 to 12.0 day/cm), and the maturation index was 14.9 day/cm (range, 8.0 to 22.5 day/cm). Ultimately, the bone and the functional results were rated excellent in six cases and good in one case. Conclusions Bone transport using the Ilizarov apparatus is a good treatment option in patients with bone defects after the resection of an active or aggressive benign bone tumor. PMID:26217473

  15. Surgery for locally aggressive bone tumours.

    PubMed

    Devitt, A; O'Sullivan, T; Kavanagh, M; Hurson, B J

    1996-01-01

    Treatment of 16 patients with aggressive benign bone tumours and one patient with a low grade malignancy with a combined regimen of cryosurgery, phenolization and acrylic cementation is reported. Patients were aged between 9 and 51 years and were treated by this method between the years 1986 and 1993. Minimal follow up was 13 months. The commonest histological diagnosis was giant cell tumour (7), followed by aneurysmal bone cyst (6), chondromyxoidfibroma (3) and low grade chondrosarcoma (1). Patients were assessed for functional outcome and local recurrence. On average 86 per cent of premorbid function was restored at follow up and there was one local recurrence (6.29 per cent). We conclude that this is a satisfactory method of gaining local control of these tumours. PMID:8990655

  16. BENIGN BONE TUMORS AND TUMOR-LIKE BONE LESIONS: TREATMENT UPDATE AND NEW TRENDS

    PubMed Central

    Nogueira Drumond, José Marcos

    2015-01-01

    The treatment of benign bone tumors (BBT) and tumor-like bone lesions (TBL) has observed the introduction of new drugs, such as intravenous bisphosphonates, which have ossified bone lesions caused by fibrous dysplasia. Aneurismal bone cyst has been treated with sclerosing agents by percutaneous injection, yielding good results. Adjuvants allow joint salvage, maintenance of movements and function, with low rates of recurrence. Among them, the most used ones are bone cement (PMMA), phenol, nitrogen-based cryotherapy, hydrogen peroxide, ethanol and radiotherapy. New methods of treatment include thermal ablation with radiofrequency and laser, mainly utilized for treating osteoid osteoma. Arthroscopy allows resection of benign intra-joint lesions and assists the surgery of subchondral tumors. A great advance is the utilization of synthetic bone substitutes, which are a mixture of osteoinductive growth factors and osteoconductive ceramics, and have presented comparable results to autogenous bone grafts. There is a recent trend for closed treatments, with percutaneous injection of demineralized bone matrix (DBM) and calcium sulfate. Autogenous cancellous bone graft remains as the gold standard. Vascularized fibula graft, on the other hand, incorporates faster in the treatment of large destructive lesions. Also, allogenic cortical support allows structural augmentation for aggressive tumors. Freeze-dried allografts are used to fill contained defects and as expanders of autografts. Joint endoprosthesis may be used in large destructive lesions of the distal femur, hip and shoulder. PMID:27004184

  17. Giant Cell Tumor of Bone - An Overview

    PubMed Central

    Sobti, Anshul; Agrawal, Pranshu; Agarwala, Sanjay; Agarwal, Manish

    2016-01-01

    Giant Cell tumors (GCT) are benign tumors with potential for aggressive behavior and capacity to metastasize. Although rarely lethal, benign bone tumors may be associated with a substantial disturbance of the local bony architecture that can be particularly troublesome in peri-articular locations. Its histogenesis remains unclear. It is characterized by a proliferation of mononuclear stromal cells and the presence of many multi- nucleated giant cells with homogenous distribution. There is no widely held consensus regarding the ideal treatment method selection. There are advocates of varying surgical techniques ranging from intra-lesional curettage to wide resection. As most giant cell tumors are benign and are located near a joint in young adults, several authors favor an intralesional approach that preserves anatomy of bone in lieu of resection. Although GCT is classified as a benign lesion, few patients develop progressive lung metastases with poor outcomes. Treatment is mainly surgical. Options of chemotherapy and radiotherapy are reserved for selected cases. Recent advances in the understanding of pathogenesis are essential to develop new treatments for this locally destructive primary bone tumor. PMID:26894211

  18. Extracorporeal Irradiation in Malignant Bone Tumors.

    PubMed

    Bhandari, R B; Jha, A K; Neupane, P; Chaurasia, P P; Sigdel, A

    2015-01-01

    Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en block removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation and re implantation back in the body. PMID:27549504

  19. Aggressive Calcifying Epithelial Odontogenic Tumor of the Maxillary Sinus with Extraosseous Oral Mucosal Involvement: A Case Report

    PubMed Central

    Rani, Vidya; Masthan, Mahaboob Kadar; Aravindha, Babu; Leena, Sankari

    2016-01-01

    Calcifying epithelial odontogenic tumors are benign odontogenic neoplasms whose occurrence in the maxillary sinus is rare. Maxillary tumors tend to be locally aggressive and may rapidly involve the surrounding vital structures. We report a case of a large calcifying epithelial odontogenic tumor of the maxilla, involving the maxillary sinus in a 48-year-old woman. The tumor was largely intraosseous. In the canine and first premolar regions, the loss of bone could be palpated but the oral mucosa appeared normal. Histologically, the tumor tissue could be seen in the connective tissue below the oral epithelium. The most significant finding was the presence of an intraosseous tumor with an extraosseous involvement in a single tumor, indicating aggressive behavior and warranting aggressive treatment. In this article, we discuss the rare presentation of the tumor and its radiological appearance and histological features. We also highlight the importance of a detailed histopathological examination of the excised specimen. PMID:26989286

  20. Management of large aggressive nonfunctional pituitary tumors: experimental medical options when surgery and radiation fail.

    PubMed

    Miller, Brandon A; Rutledge, W Caleb; Ioachimescu, Adriana G; Oyesiku, Nelson M

    2012-10-01

    Pituitary adenomas are generally considered benign tumors; however, a subset of these tumors displays aggressive behavior and are not easily cured. The protocol for nonsurgical treatment of aggressive pituitary lesions is less standardized than that of other central nervous system tumors. Aggressive surgical treatment, radiation, dopamine agonists, antiangiogenic drugs, and other chemotherapeutics all have roles in the treatment of aggressive pituitary tumors. More studies are needed to improve outcomes for patients with aggressive pituitary tumors.

  1. Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness

    PubMed Central

    Adamo, Hanibal Hani; Strömvall, Kerstin; Nilsson, Maria; Halin Bergström, Sofia; Bergh, Anders

    2015-01-01

    In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues. PMID:26536349

  2. Bone tumor mimickers: A pictorial essay

    PubMed Central

    Mhuircheartaigh, Jennifer Ni; Lin, Yu-Ching; Wu, Jim S

    2014-01-01

    Focal lesions in bone are very common and many of these lesions are not bone tumors. These bone tumor mimickers can include numerous normal anatomic variants and non-neoplastic processes. Many of these tumor mimickers can be left alone, while others can be due to a significant disease process. It is important for the radiologist and clinician to be aware of these bone tumor mimickers and understand the characteristic features which allow discrimination between them and true neoplasms in order to avoid unnecessary additional workup. Knowing which lesions to leave alone or which ones require workup can prevent misdiagnosis and reduce patient anxiety. PMID:25114385

  3. Knee bone tumors: findings on conventional radiology.

    PubMed

    Andrade Neto, Francisco; Teixeira, Manuel Joaquim Diógenes; Araújo, Leonardo Heráclio do Carmo; Ponte, Carlos Eduardo Barbosa

    2016-01-01

    The knee is a common site for bone tumors, whether clinically painful or not. Conventional radiology has been established as the first line of investigation in patients with knee pain and can reveal lesions that often generate questions not only for the generalist physician but also for the radiologist or general orthopedist. History, image examination, and histopathological analysis compose the essential tripod of the diagnosis of bone tumors, and conventional radiology is an essential diagnostic tool in patients with knee pain. This pictorial essay proposes to depict the main conventional radiography findings of the most common bone tumors around the knee, including benign and malignant tumors, as well as pseudo-tumors.

  4. EFFICACY OF THE ENNEKING STAGING SYSTEM IN RELATION TO TREATING BENIGN BONE TUMORS AND TUMOR-LIKE BONE LESIONS

    PubMed Central

    Nogueira Drumond, José Marcos

    2015-01-01

    Objective: To evaluate the efficacy of the Enneking staging system for determining the prognosis, planning surgical treatment and indicating adjuvant therapy for benign bone tumors (BBT) and tumor-like bone lesions (TBL). Methods: A retrospective multicenter, descriptive, nonrandomized study was carried out on a representative sample comprising a large series of 165 patients with a total of 168 benign bone tumors and tumor-like bone lesions. The patient sample was typical, and matched the literature in all respects. All the patients were classified according to the Enneking staging system, and the initial staging of each lesion was correlated with its behavior after either conservative or surgical treatment, in order to determine the efficacy of the system. The treatment options and complications were described and analyzed. Results: The results from the treatment provided 95.2% agreement with the Enneking staging system, with a 95% confidence interval of between 90.8 and 97.9%. Of the 168 tumors treated, only eight (4.8%) could not be controlled in relation to the initial treatment indicated by the Enneking staging system. Tumors classified as active were the most prevalent, comprising 73.2% of the lesions. Tumor recurrence was significantly more frequent (p < 0.001) in the aggressive stage. All the patients staged as latent evolved to cure. The study suggested that surgery with wide margins, for aggressive lesions, could provide better lesion control, with a lower recurrence rate (p > 0.001). For latent and active lesions, the study demonstrated the efficacy of both expectant treatment and excision, with or without autogenous bone graft. Conclusion: The results confirm that the Enneking staging system was very efficient in determining the prognosis, enabling surgical planning and indicating adjuvant therapy for treatment of BBT and TBL. PMID:27019838

  5. Microwave Therapy for Bone Tumors

    NASA Astrophysics Data System (ADS)

    Takakuda, Kazuo; Inaoka, Shuken; Saito, Hirokazu; Hassan, Moinuddin; Koyama, Yoshikazu; Kuroda, Hiroshi; Kanaya, Tomohiro; Kosaka, Toshifumi; Tanaka, Shigeo; Miyairi, Hiroo; Shinomiya, Kenichi

    In vivo microwave treatments for bone tumor are designed, which enable us to conserve the activity and functionality of the matrix of living tissues. This treatment is composed of two steps. In the first step, the tumor was coagulated by the application of microwaves emitted from the antenna inserted into the tumor tissue, and then removed. In the second step, the surrounding tissue suspected to be invaded with transformed cells was covered with hydro gels and heated similarly. The tissue itself was heated by the conduction from the gels. The tissue temperature should be kept at 60°C for 30 minutes. This treatment should kill the whole cells within the tissues, but the mechanical strength and the biochemical activity of the matrix should be left intact. The matrix preserves the mechanical functions and ensures the maximum regeneration ability of the tissue. In this study, various hydro gels were examined and the most promising one was selected. Animal experiments were carried out and successful heating verified the applicability of the treatment.

  6. Malignant thyroid teratoma: report of an aggressive tumor in a 64-year-old man.

    PubMed

    Vilallonga, R; Zafon, C; Ruiz-Marcellan, C; Obiols, G; Fort, J M; Baena, J A; Villanueva, B; Garcia, A; Sobrinho-Simões, M

    2013-09-01

    Malignant teratoma of the thyroid is a rare and aggressive tumor, frequent in children than in adults. Histologically, thyroid teratomas usually show a predominance of a neuroectodermal component. Mature cartilage and bone may be present. We present the case of primary malignant teratoma of the thyroid in a 64-year-old man. Histologically, the tumor displayed a predominant neuroectodermal component. The diagnosis was confirmed by immunohistochemistry. The patient underwent a radical thyroidectomy with central neck dissection as primary treatment and radioiodine treatment afterwards. The patient had local and distant recurrence. A second surgery was performed with poor results and the patient died 3 months afterwards.

  7. Primary bone tumors of the spine.

    PubMed

    Cañete, A Navas; Bloem, H L; Kroon, H M

    2016-04-01

    Primary bone tumors of the spine are less common than metastases or multiple myeloma. Based on the patient's age and the radiologic pattern and topography of the tumor, a very approximate differential diagnosis can be established for an osseous vertebral lesion. This article shows the radiologic manifestations of the principal primary bone tumors of the spine from a practical point of view, based on our personal experience and a review of the literature. If bone metastases, multiple myeloma, lymphomas, hemangiomas, and enostoses are excluded, only eight types of tumors account for 80% of all vertebral tumors. These are chordomas, osteoblastomas, chondrosarcomas, giant-cell tumors, osteoid osteomas, Ewing's sarcomas, osteosarcomas, and aneurysmal bone cysts. PMID:26917429

  8. Primary bone tumors of the spine.

    PubMed

    Cañete, A Navas; Bloem, H L; Kroon, H M

    2016-04-01

    Primary bone tumors of the spine are less common than metastases or multiple myeloma. Based on the patient's age and the radiologic pattern and topography of the tumor, a very approximate differential diagnosis can be established for an osseous vertebral lesion. This article shows the radiologic manifestations of the principal primary bone tumors of the spine from a practical point of view, based on our personal experience and a review of the literature. If bone metastases, multiple myeloma, lymphomas, hemangiomas, and enostoses are excluded, only eight types of tumors account for 80% of all vertebral tumors. These are chordomas, osteoblastomas, chondrosarcomas, giant-cell tumors, osteoid osteomas, Ewing's sarcomas, osteosarcomas, and aneurysmal bone cysts.

  9. Bone Windows for Distinguishing Malignant from Benign Primary Bone Tumors on FDG PET/CT

    PubMed Central

    Costelloe, Colleen M.; Chuang, Hubert H.; Chasen, Beth A.; Pan, Tinsu; Fox, Patricia S.; Bassett, Roland L.; Madewell, John E.

    2013-01-01

    Objective. The default window setting on PET/CT workstations is soft tissue. This study investigates whether bone windowing and hybrid FDG PET/CT can help differentiate between malignant and benign primary bone tumors. Materials and methods. A database review included 98 patients with malignant (n=64) or benign primary bone (n=34) tumors. The reference standard was biopsy for malignancies and biopsy or >1 year imaging follow-up of benign tumors. Three radiologists and/or nuclear medicine physicians blinded to diagnosis and other imaging viewed the lesions on CT with bone windows (CT-BW) without and then with PET (PET/CT-BW), and separate PET-only images for malignancy or benignity. Three weeks later the tumors were viewed on CT with soft tissue windows (CT-STW) without and then with PET (PET/CT-STW). Results. Mean sensitivity and specificity for identifying malignancies included: CT-BW: 96%, 90%; CT-STW: 90%, 90%; PET/CT-BW: 95%, 85%, PET/CT-STW: 95%, 86% and PET-only: 96%, 75%, respectively. CT-BW demonstrated higher specificity than PET-only and PET/CT-BW (p=0.0005 and p=0.0103, respectively) and trended toward higher sensitivity than CT-STW (p=0.0759). Malignant primary bone tumors were more avid than benign lesions overall (p<0.0001) but the avidity of benign aggressive lesions (giant cell tumors and Langerhans Cell Histiocytosis) trended higher than the malignancies (p=0.08). Conclusion. Bone windows provided high specificity for distinguishing between malignant and benign primary bone tumors and are recommended when viewing FDG PET/CT. PMID:23983816

  10. Knee bone tumors: findings on conventional radiology*

    PubMed Central

    Andrade Neto, Francisco; Teixeira, Manuel Joaquim Diógenes; Araújo, Leonardo Heráclio do Carmo; Ponte, Carlos Eduardo Barbosa

    2016-01-01

    The knee is a common site for bone tumors, whether clinically painful or not. Conventional radiology has been established as the first line of investigation in patients with knee pain and can reveal lesions that often generate questions not only for the generalist physician but also for the radiologist or general orthopedist. History, image examination, and histopathological analysis compose the essential tripod of the diagnosis of bone tumors, and conventional radiology is an essential diagnostic tool in patients with knee pain. This pictorial essay proposes to depict the main conventional radiography findings of the most common bone tumors around the knee, including benign and malignant tumors, as well as pseudo-tumors. PMID:27403019

  11. Vaccination against strontium-90-induced bone tumors

    SciTech Connect

    Reif, A.E.; Triest, W.E.

    1983-09-01

    The thesis was tested that immunization against a murine osteosarcoma virus can reduce the incidence of bone tumors induced by /sup 90/Sr. C57BL/6J female mice (190) were divided into three sets of 2 groups. Each set consisted of a control group and an experimental group treated ip with 1.0 muCi /sup 90/Sr at 66 days of age. The three sets of groups received the following additional treatments: none (controls), 6 injections of Formalin-inactivated FBJ osteosarcoma virus (vaccinated group), or 6 injections of active FBJ virus (active virus controls). Only 1 bone tumor developed in a mouse not treated with /sup 90/Sr in the active virus controls. In /sup 90/Sr-treated mice, vaccination reduced bone tumor deaths during the first 600 days from 9 of 36 in controls to 1 of 33 in vaccinated mice (P less than .01), but bone tumor deaths during the entire life-span, 10 of 36 and 5 of 33, respectively, were not significantly different (P . .07). Thus the vaccination procedure delayed the development of bone tumors. In contrast, injection of active virus into /sup 90/Sr-treated mice increased the lifetime incidence of bone tumors from 10 of 36 in controls to 19 of 32 (P . .01).

  12. Copy Number Alterations in Prostate Tumors and Disease Aggressiveness

    PubMed Central

    Cheng, Iona; Levin, Albert M.; Tai, Yu Chuan; Plummer, Sarah; Chen, Gary K.; Neslund-Dudas, Christine; Casey, Graham; Rybicki, Benjamin A.; Witte, John S.

    2011-01-01

    Detecting genomic alterations that result in more aggressive prostate cancer may improve clinical treatment and our understanding of the biology underlying this common but complex disease. To this end, we undertook a genome-wide copy number alterations (CNAs) study of clinicopathological characteristics of 62 prostate tumors using the Illumina 1M SNP array. The highest overall frequencies of CNAs were on chromosomes 8q (gains), 8p (loss and copy-neutral) and 6q (copy-loss). Combined loss and copy-neutral events were associated with increasing disease grade (p=0.03), stage (p=0.01), and diagnostic PSA (p=0.01). Further evaluation of CNAs using gene ontology identified pathways involved with disease aggressiveness. The ‘regulation of apoptosis’ pathway was associated with stage of disease (p=0.004), while the ‘reproductive cellular process’ pathway was associated with diagnostic PSA (p=0.00038). Specific genes within these pathways exhibited strong associations with clinical characteristics; for example, in the apoptosis pathway BNIP3L was associated with increasing prostate tumor stage (p=0.007). These findings confirm known regions of CNAs in prostate cancer, and localize additional regions and possible genes (e.g., BNIP3L, WWOX, and GATM) that may help clarify the genetic basis of prostate cancer aggressiveness. PMID:21965145

  13. Response of an aggressive periosteal aneurysmal bone cyst (ABC) of the radius to denosumab therapy

    PubMed Central

    2014-01-01

    Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the bony containment, mostly located intracortically in the proximal radius. The diagnosis of a periosteal ABC was confirmed by FISH demonstrating USP6 gene rearrangement on the initial biopsy. Function conserving surgery could be performed, enabling reconstruction of the affected bone. Inhibition of RANKL with denosumab may offer therapeutic option for patients not only with giant cell tumors but also with ABCs. PMID:24438319

  14. Melanotic neuroectodermal tumor of infancy arising in the temporal bone.

    PubMed

    Zhang, Jian-guo; Zhao, Rui-jiao; Kong, Ling-fei

    2015-04-01

    Melanotic neuroectodermal tumor of infancy is a rare melanin-containing neoplasm with locally aggressive and rapid expansile growth, usually involving the maxilla, skull, and mandible of early infancy. Radical surgery is critical for a long-term outcome. We present a case of 14-month-old girl with rapid-growing subcutaneous mass arising in the right temporal bone and extending intracranially on computed tomographic scan. Radical surgery was performed. A brownish-black tumor composed of large pigmented epithelioid cells, positive for cytokeratins and HMB-45, and nests of small neuroblast-like cells positive for neuron-specific enolase and synaptophysin, was diagnosed as melanotic neuroectodermal tumor of infancy. The patient remained well without evidence of recurrence for 1 year after surgery. Clinicopathological features, management alternatives and outcome were discussed.

  15. Giant cell tumor of bone arising in long bones possibly originates from the metaphyseal region

    PubMed Central

    FUTAMURA, NAOHISA; URAKAWA, HIROSHI; TSUKUSHI, SATOSHI; ARAI, EISUKE; KOZAWA, EIJI; ISHIGURO, NAOKI; NISHIDA, YOSHIHIRO

    2016-01-01

    Giant cell tumor of bone (GCTB) is a primary benign bone tumor with a locally aggressive character. Definitive descriptions of the site of origin for this type of tumor are not available. The aim of the present study was to evaluate the site of origin of GCTB of long bones with regards to epiphyseal lines by means of radiographic examination. For that purpose, plain X-ray scans of 71 GCTBs arising in long bones were retrospectively reviewed. The tumor locations were the distal femur in 31 cases, proximal femur in 11 cases, proximal tibia in 13 cases, distal radius in 6 cases, proximal humerus in 5 cases and proximal fibula in 5 cases. The vertical center (VC) of the tumor was determined with X-ray anteroposterior view, and the correlation between the VC and the epiphyseal line, and between the distance from the epiphyseal line to the VC and tumor area or volume were analyzed using a regression model equation based on scatter plot diagrams. The VC of the tumor was located in the metaphyseal region in 57 cases, in the epiphyseal line in 11 cases and in the epiphyseal region in 3 cases. In cases of GCTB located in the distal femur or proximal tibia, significant correlations between the distance from the VC to the epiphyseal line and tumor area or volume were identified. The site of origin of GCTB was estimated to be located in the metaphyseal region. GCTB often occurs in mature patients, which renders it challenging to estimate the true site of origin of this lesion, since the metaphyseal line has disappeared in mature patients. The results of the present study suggest that GCTB possibly originates in the metaphyseal region. PMID:27073530

  16. Aggressively managing type 2 diabetes mellitus, hyperlipidemia, and bone loss.

    PubMed

    Spellman, Craig W

    2008-05-01

    Physicians have many options available for treating patients with type 2 diabetes mellitus (T2DM). Making decisions on types of pharmaceuticals to use and when to introduce them into the treatment regimen can be a complex process. In addition, nutrition and exercise must be considered in any comprehensive treatment plan. The author describes the case of an African American woman with uncontrolled T2DM, obesity, hyperlipidemia, low bone mass, menopausal symptoms, stage 3 chronic kidney disease, distal sensory neuropathy, and background retinopathy. An aggressive, comprehensive treatment plan developed for this patient included pharmaceuticals (triple oral therapy: metformin, pioglitazone hydrochloride, and sitagliptin phosphate), nutrition counseling (with a registered, licensed dietician), and exercise. Treatment led to substantial improvements in the patient's daytime glucose level, glycosylated hemoglobin level, and body weight at 3-month follow-up. Further interventions were needed to address the patient's hyperlipidemia and low bone mass. The author offers physician guidelines for making decisions on glycemic control for patients with T2DM and for managing hyperlipidemia. He also strongly recommends incorporating nutrition counseling by registered, licensed dietitians and exercise (preferably of a weight-bearing nature) into treatment plans for patients with T2DM, hyperlipidemia, and low bone mass.

  17. Plumbagin inhibits breast tumor bone metastasis and osteolysis by modulating the tumor-bone microenvironment.

    PubMed

    Li, Z; Xiao, J; Wu, X; Li, W; Yang, Z; Xie, J; Xu, L; Cai, X; Lin, Z; Guo, W; Luo, J; Liu, M

    2012-09-01

    Bone metastasis is a common and serious consequence of breast cancer. Bidirectional interaction between tumor cells and the bone marrow microenvironment drives a so-called 'vicious cycle' that promotes tumor cell malignancy and stimulates osteolysis. Targeting these interactions and pathways in the tumor-bone microenvironment has been an encouraging strategy for bone metastasis therapy. In the present study, we examined the effects of plumbagin on breast cancer bone metastasis. Our data indicated that plumbagin inhibited cancer cell migration and invasion, suppressed the expression of osteoclast-activating factors, altered the cancer cell induced RANKL/OPG ratio in osteoblasts, and blocked both cancer cell- and RANKL-stimulated osteoclastogenesis. In mouse model of bone metastasis, we further demonstrated that plumbagin significantly repressed breast cancer cell metastasis and osteolysis, inhibited cancer cell induced-osteoclastogenesis and the secretion of osteoclast-activating factors in vivo. At the molecular level, we found that plumbagin abrogated RANKL-induced NF-κB and MAPK pathways by blocking RANK association with TRAF6 in osteoclastogenesis, and by inhibiting the expression of osteoclast-activating factors through the suppression of NF-κB activity in breast cancer cells. Taken together, our data demonstrate that plumbagin inhibits breast tumor bone metastasis and osteolysis by modulating the tumor-bone microenvironment and that plumbagin may serve as a novel agent in the treatment of tumor bone metastasis.

  18. MMSET is overexpressed in cancers: Link with tumor aggressiveness

    SciTech Connect

    Kassambara, Alboukadel; Klein, Bernard Moreaux, Jerome

    2009-02-20

    MMSET is expressed ubiquitously in early development and its deletion is associated with the malformation syndrome called Wolf-Hirschhorn syndrome. It is involved in the t(4; 14) (p16; q32) chromosomal translocation, which is the second most common translocation in multiple myeloma (MM) and is associated with the worst prognosis. MMSET expression has been shown to promote cellular adhesion, clonogenic growth and tumorigenicity in multiple myeloma. MMSET expression has been recently shown to increase with ascending tumor proliferation activity in glioblastoma multiforme. These data demonstrate that MMSET could be implicated in tumor emergence and/or progression. Therefore, we compared the expression of MMSET in 40 human tumor types - brain, epithelial, lymphoid - to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. We found significant overexpression of MMSET in 15 cancers compared to their normal counterparts. Furthermore MMSET is associated with tumor aggressiveness or prognosis in many types of these aforementioned cancers. Taken together, these data suggest that MMSET potentially acts as a pathogenic agent in many cancers. The identification of the targets of MMSET and their role in cell growth and survival will be key to understand how MMSET is associated with tumor development.

  19. The Clinical Approach Toward Giant Cell Tumor of Bone

    PubMed Central

    van der Heijden, Lizz; Dijkstra, P.D. Sander; van de Sande, Michiel A.J.; Kroep, Judith R.; Nout, Remi A.; van Rijswijk, Carla S.P.; Bovée, Judith V.M.G.; Hogendoorn, Pancras C.W.

    2014-01-01

    We provide an overview of imaging, histopathology, genetics, and multidisciplinary treatment of giant cell tumor of bone (GCTB), an intermediate, locally aggressive but rarely metastasizing tumor. Overexpression of receptor activator of nuclear factor κB ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells. Conventional radiographs show a typical eccentric lytic lesion, mostly located in the meta-epiphyseal area of long bones. GCTB may also arise in the axial skeleton and very occasionally in the small bones of hands and feet. Magnetic resonance imaging is necessary to evaluate the extent of GCTB within bone and surrounding soft tissues to plan a surgical approach. Curettage with local adjuvants is the preferred treatment. Recurrence rates after curettage with phenol and polymethylmethacrylate (PMMA; 8%–27%) or cryosurgery and PMMA (0%–20%) are comparable. Resection is indicated when joint salvage is not feasible (e.g., intra-articular fracture with soft tissue component). Denosumab (RANKL inhibitor) blocks and bisphosphonates inhibit GCTB-derived osteoclast resorption. With bisphosphonates, stabilization of local and metastatic disease has been reported, although level of evidence was low. Denosumab has been studied to a larger extent and seems to be effective in facilitating intralesional surgery after therapy. Denosumab was recently registered for unresectable disease. Moderate-dose radiotherapy (40–55 Gy) is restricted to rare cases in which surgery would lead to unacceptable morbidity and RANKL inhibitors are contraindicated or unavailable. PMID:24718514

  20. Radionuclide bone scanning in giant cell tumor

    SciTech Connect

    Van Nostrand, D.; Madewell, J.E.; McNiesh, L.M.; Kyle, R.W.; Sweet, D.

    1986-03-01

    Radionuclide bone scan findings are described and correlated with pathology in 23 patients with giant cell tumor (GCT) of the bone. The degree of radionuclide activity was markedly increased in 20 (87%), minimally increased in three (13%), and decreased in none of the patients. Of the 23 patients with increased radioactivity, the pattern was diffuse in 11 (48%) and doughnut in 12 (52%). Extended patterns of radioactivity were present in 19 of 22 patients; however, none were associated with true tumor extension. Bone scanning did not aid in the detection of GCT, was nonspecific, and did not differentiate benign from malignant GCT. Although radioactivity extended beyond the radiographic abnormality in the majority of patients, this was most likely secondary to other bony abnormalities or local and/or regional hyperemia, and caution should be taken in ascribing this extension to either tumor or metastasis.

  1. [Palliative radiotherapy for metastatic bone tumor].

    PubMed

    Yoshida, Kenji; Hiratsuka, Junichi

    2006-04-01

    Bone metastases are one of the most common conditions requiring radiation therapy today. Its main aim is relief of bone pain, prevention of pathological bone fractures as well as its healing, with anticipated effect upon improving mobility, function, and quality of life. For localized bone pain, external beam radiation therapy (EBRT) will be successful in reducing pain in some 80% of patients. However, optimal fraction dose and total doses of EBRT required for pain relief have been unknown. According to the recent reports, carbon ion radiotherapy seems to be a safe and effective modality in the management of metastatic bone tumor not eligible for conventional EBRT. For scattered painful metastases, the systemic administration of radioisotopes is thought to be effective. PMID:16582516

  2. Symplastic/pseudoanaplastic giant cell tumor of the bone

    PubMed Central

    Agaram, Narasimhan; Hwang, Sinchun; Lu, Chao; Wang, Lu; Healey, John; Hameed, Meera

    2016-01-01

    Objective Giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor. Its malignant counterpart is quite rare. Rarely, a conventional GCTB shows marked nuclear atypia, referred to as symplastic/pseudoanaplastic change, which can mimic sarcomatous transformation. Recently, somatic driver mutations of histone H3.3 exclusively in H3F3A have been described in GCTB. We report a series of 9 cases of GCTB with symplastic/pseudoanaplastic change, along with analysis of H3F3A variants. Materials and methods Nine cases of GCTB with symplastic change were identified. Clinico-radiological features, morphological features, and immunohistochemical stain for Ki-67 stain were reviewed. H3F3A variants were also analyzed using Sanger sequencing. Results Histologically, conventional giant cell tumor areas with scattered foci of markedly atypical cells were seen in all of the cases and all showed rare if any Ki-67 labeling. One patient had received denosumab treatment and another radiation therapy. Radiological features were characteristic of conventional GCTB. Mutation in H3F3A (p.Gly34Trp [G34W]) was found in 6 of the 7 cases. Clinical follow-up ranged from 6 to 208 months. Local recurrences were seen in 4 cases (44 %). Conclusions GCTB with symplastic/pseudoanaplastic change is an uncommon variant of conventional GCTB, which can mimic primary sarcoma or sarcomatous transformation. These tumors possess the same missense mutation in histone H3.3 as conventional GCTB. PMID:27020452

  3. [Typical tumors of the petrous bone].

    PubMed

    Ahlhelm, F; Müller, U; Ulmer, S

    2014-04-01

    In the region of the petrous bone, inner acoustic canal and cerebellopontine angle, a variety of different tissues can be found, such as bony, epithelial, neural and vascular structures. Tumorous or tumor-like lesions, vascular or bony malformations or other pathologies can therefore be found in all of these areas. We discuss various frequently occurring tumorous or tumor-like pathologies including congential lesions, such as mucoceles, inflammatory disorders including osteomyelitis, pseudotumors and Wegener's granulomatosis. Benign non-neoplastic lesions, such as cholesteatoma, cholesterol granuloma, epidermoid and benign neoplastic tumors, such as the most commonly found vestibular schwannoma, meningeoma, paraganglioma, vascular pathologies and finally malignant lesions, such as metastasis, chordoma or chondrosarcoma and endolymphatic sac tumor (ELST) are also discussed. The emphasis of this article is on the appearance of these entities in computed tomography (CT) and more so magnetic resonance imaging (MRI), it provides key facts and typical images and discusses possibilities how to distinguish these pathologies. PMID:24692010

  4. [Intraoperative radiotherapy in malignant bone tumors].

    PubMed

    Yamamuro, T; Kotoura, Y

    1993-06-01

    When a bone tumor is confirmed to be malignant by biopsy and has not expanded into the soft tissue, intraoperative radiation therapy (IORT) is indicated for most parts of the four extremities. The irradiation area is exposed through an extensive skin incision, and the soft tissues are opened and retracted away from the irradiation area, leaving a layer of normal tissue directly covering the tumor. The irradiation is performed with 12-26 MeV electron beams from a betatron at a dose of 50-100 Gy, depending on the radiosensitivity of each tumor. The multifocal bilateral irradiation method is the best for minimizing complications of the soft tissues. Since 1978, we have performed IORT in combination with chemotherapy in 41 cases of malignant bone tumors and experienced only five cases of tumor recurrence one in the irradiated area and four in the non-irradiated area. Joint function in the irradiated limb was excellent. However, due to the high incidence of pathological fracture after IORT in osteolytic tumors, the limb eventually had to be replaced by a prosthesis. After 1984 when cisplatinum was introduced to our chemotherapy protocol, the cumulative 5 year survival rate increased to 81%, with the irradiated lesion preserved in situ in osteoblastic tumors and replaced with a prosthesis in osteolytic tumors.

  5. Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma

    PubMed Central

    Redini, Françoise; Heymann, Dominique

    2015-01-01

    Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the “vicious cycle” concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable “niche” for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma. PMID:26779435

  6. Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma.

    PubMed

    Redini, Françoise; Heymann, Dominique

    2015-01-01

    Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the "vicious cycle" concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable "niche" for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma. PMID:26779435

  7. Locally aggressive aneurysmal bone cyst of C4 vertebra treated by total en bloc excision and anterior plus posterior cervical instrumentation

    PubMed Central

    Parmar, Himanshu N.; Agrawal, Vinod A.; Shah, Munjal S.; Nanda, Saurav N.

    2015-01-01

    We are presenting a case of cervical (C4) aneurysmal bone cyst in a 13-year-old girl, came to the outpatient department with neck pain and stiffness since 6 months and normal neurology. We did an en bloc excision of locally aggressive tumor through anterior plus posterior approach and stabilization by lateral mass screw fixation and anterior cervical instrumentation. Involvement of several adjacent cervical vertebrae by an aneurysmal bone cyst is rare, and conventional treatment with curettage and bone grafting is most likely to carry a high rate of recurrence and spinal instability. We recommend complete excision of the tumor and instrumentation in a single stage to avoid instability. PMID:26288549

  8. Signaling between tumor cells and the host bone marrow microenvironment.

    PubMed

    Kovacic, Natasa; Croucher, Peter I; McDonald, Michelle M

    2014-01-01

    Tumor cells with high skeletal homing affinity express numerous cell surface receptors that bind ligands produced in bone. Upon arrival, these cells survive in the host environment, encompassed in close proximity to bone marrow cells. Interactions between tumor cells and cells of the host microenvironment are essential to not only tumor cell survival but also their activation and proliferation into environment-modifying tumors. Through the production of RANKL, PTHrP, cytokines, and integrins, activated tumor cells stimulate osteoclastogenesis, enhance bone resorption, and subsequently release matrix-bound proteins that further promote tumor growth and bone resorption. In addition, alterations in the TGF-β/BMP and Wnt signaling pathways via tumor cell growth can either stimulate or suppress osteoblastic bone formation and function, leading to sclerotic or lytic bone disease, respectively. Hence, the presence of tumor cells in bone dysregulates bone remodeling, dramatically impairing skeletal integrity. Furthermore, through complex mechanisms, cells of the immune system interact with tumor cells to further impact bone remodeling. Lastly, with alterations in bone cell activity, the environment is permissive to promoting tumor growth further, suggesting an interdependence between tumor cells and bone cells in metastatic bone disease and multiple myeloma.

  9. Deregulation of miR-183 and KIAA0101 in Aggressive and Malignant Pituitary Tumors

    PubMed Central

    Roche, Magali; Wierinckx, Anne; Croze, Séverine; Rey, Catherine; Legras-Lachuer, Catherine; Morel, Anne-Pierre; Fusco, Alfredo; Raverot, Gérald; Trouillas, Jacqueline; Lachuer, Joel

    2015-01-01

    Changes in microRNAs (miRNAs) expression in many types of cancer suggest that they may be involved in crucial steps during tumor progression. Indeed, miRNAs deregulation has been described in pituitary tumorigenesis, but few studies have described their role in pituitary tumor progression toward aggressiveness and malignancy. To assess the role of miRNAs within the hierarchical cascade of events in prolactin (PRL) tumors during progression, we used an integrative genomic approach to associate clinical–pathological features, global miRNA expression, and transcriptomic profiles of the same human tumors. We describe the specific down-regulation of one principal miRNA, miR-183, in the 8 aggressive (A, grade 2b) compared to the 18 non-aggressive (NA, grades 1a, 2a) PRL tumors. We demonstrate that it acts as an anti-proliferative gene by directly targeting KIAA0101, which is involved in cell cycle activation and inhibition of p53–p21-mediated cell cycle arrest. Moreover, we show that miR-183 and KIAA0101 expression significantly correlate with the main markers of pituitary tumors aggressiveness, Ki-67 and p53. These results confirm the activation of proliferation in aggressive and malignant PRL tumors compared to non-aggressive ones. Importantly, these data also demonstrate the ability of such an integrative genomic strategy, applied in the same human tumors, to identify the molecular mechanisms responsible for tumoral progression even from a small cohort of patients. PMID:26322309

  10. Radiation therapy in the treatment of aggressive fibromatoses (desmoid tumors).

    PubMed

    Kiel, K D; Suit, H D

    1984-11-15

    Twenty-five patients with aggressive fibromatoses (desmoid tumors) have been treated or followed in the Department of Radiation Medicine at the Massachusetts General Hospital between 1972 and 1982. Seventeen patients were treated by radiation, 4 for primary and 13 for recurrent disease. Seven patients were treated in conjunction with surgery. Partial or complete regression was achieved in 76%, and 59% are without evidence of disease (NED) at 9 to 94 months follow-up. Eight of ten patients treated primarily with radiation have achieved complete response without an attempt at resection (five) or have achieved stabilization (three) of their disease after some regression. Consistent complete control was seen with doses above 60 Gy. Periods to 27 months were required to observe complete responses. Only three failures within the radiation field were observed, two after low doses (22 and 24 Gy, respectively). Eight patients were seen after resection but with uncertain or histologically minimum positive margins, and were followed regularly and not treated. One patient has failed to date and is NED after resection. Radiation therapy is recommended in those situations where wide-field resection without significant morbidity is not possible for gross local disease. If minimally positive margins exist after resection in a patient who may be followed carefully, frequent follow-up and prompt treatment at recurrence may be an effective alternative to immediate radiation therapy.

  11. Fibroblasts Regulate Variable Aggressiveness of Syndromic Keratocystic and Non-syndromic Odontogenic Tumors

    PubMed Central

    Hong, Y.-Y.; Yu, F.-Y.; Qu, J.-F.; Chen, F.; Li, T.-J.

    2014-01-01

    Keratocystic odontogenic tumors (KCOTs) are jaw lesions that can be either sporadic or associated with nevoid basal cell carcinoma syndrome, which typically occurs as multiple, aggressive lesions that can lead to large areas of bone destruction and resorption and cause major impairment and even jaw fracture. To clarify the role of fibroblasts in the aggressivness of syndromic (S-) as compared with non-syndromic (NS-) KCOTs, we assessed fibroblasts derived from 16 S- and NS-KCOTs for differences in cell proliferation, multilineage differentiation potential, alkaline phosphatase activity, and osteoclastogenic potential. S-KCOT fibroblasts had proliferative and osteoclastogenic capacity higher than those from NS-KCOTs, as evidenced by higher numbers of tartrate-resistant acid-phosphatase-positive multinuclear cells, expression of cyclooxygenase 2, and ratio of receptor activator of nuclear factor–kappa B ligand to osteoprotegerin. The osteogenic potential was higher for S- than for NS-KCOT fibroblasts and was associated with lower mRNA expression of runt-related transcription factor 2, collagen type I α1, osteocalcin, and osteopontin as well as reduced alkaline phosphatase activity. These results suggest that the distinct characteristics of fibroblasts in KCOTs are responsible for the greater aggressiveness observed in the syndromic subtype. Abbreviations: AP, alkaline phosphatase; CK, cytokeratin; COL1A1, collagen type I α1; COX-2, cyclooxygenase-2; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-1α, interleukin 1α; KCOT, keratocystic odontogenic tumor; NBCCS, nevoid basal cell carcinoma syndrome; NS-KCOT, non-syndrome-associated KCOT; OCN, osteocalcin; OPG, osteoprotegerin; OPN, osteopontin; RANKL, receptor activator of nuclear factor-kappa B ligand; Runx2, runt-related transcription factor 2; S-KCOT, syndrome-associated KCOT; TAF, tumor-associated fibroblast; and TRAP, tartrate-resistant acid phosphatase. PMID:24972872

  12. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    PubMed Central

    Cannonier, Shellese A.; Sterling, Julie A.

    2015-01-01

    Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors. PMID:26343726

  13. Calvarial bone cavernous hemangioma with intradural invasion: An unusual aggressive course—Case report and literature review

    PubMed Central

    Nasi, Davide; Somma, Lucia di; Iacoangeli, Maurizio; Liverotti, Valentina; Zizzi, Antonio; Dobran, Mauro; Gladi, Maurizio; Scerrati, Massimo

    2016-01-01

    Introduction Cavernous hemangioma of the skull is a rare pathological diagnosis, accounting for 0.2% of bone tumors and 7% of skull tumors. Usually calvarial bone cavernous hemangioma are associated with a benign clinical course and, despite their enlargement and subsequent erosion of the surrounding bone, the inner table of the skull remains intact and the lesion is completely extracranial. Presentation of a case The authors present the unique case of a huge left frontal bone cavernous malformation with intradural extension and brain compression determining a right hemiparesis. Discussion Calvarial cavernous hemangiomas are benign tumors. They arise from vessels in the diploic space and tend to involve the outer table of the skull with relative sparing of the inner table. More extensive involvement of the inner table and extradural space is very unusual and few cases are reported in literature. To the best of our knowledge, intradural invasion of calvarial hemangioma has not been previously reported. Conclusion Our case highlights the possibility of an aggressive course of this rare benign pathology. PMID:27061482

  14. Locally administered zoledronic Acid therapy for giant cell tumor of bone.

    PubMed

    Nishisho, Toshihiko; Hanaoka, Naoyoshi; Endo, Kenji; Takahashi, Mitsuhiko; Yasui, Natsuo

    2011-07-07

    Giant cell tumor of bone is locally aggressive and occurs in the meta-epiphyseal region of long bones. Because of its high recurrence rate, local adjuvant therapies such as phenol or liquid nitrogen have been recommended. In the present study, zoledronic acid, a nitrogen-containing bisphosphonate, was administered locally as an adjuvant during a biopsy. An otherwise healthy 43-year-old man presented with pain and swelling in the right knee. Plain radiographs showed an osteolytic lesion of the right proximal tibia. An open biopsy was performed and the intraoperative pathologic diagnosis was giant cell tumor of bone. Following biopsy, the defect was filled with betatricalcium phosphate, and 4 mg of zoledronic acid was locally administered into the tumor lesion. Two months after the biopsy, curettage and bone grafting were performed. Sections were obtained during the curettage for histology to evaluate the response to bisphosphonate treatment. Histologic examination revealed massive tumor cell death in the lesion in which both stromal cells and osteoclast-like giant cells were necrotic. Curettage was performed and the defect was filled with a commercial preshaped hydroxyapatitetricalcium phosphate bone substitute. Eighteen months after curettage, the patient had regained full range of motion and good function of the knee, and radiographs at 18 months after curettage revealed no recurrence of giant cell tumor of bone.

  15. Differentiating giant cell tumor of bone from patellofemoral syndrome: a case study.

    PubMed

    Bonar, Jason; Carr, Shannon Clutton; De Carvalho, Diana; Wunder, Jay S

    2016-03-01

    Balancing the assessment of musculoskeletal dysfunctions with a high level of suspicion for non-mechanical origins can be a challenge for the clinician examining a sports injury. Without timely diagnosis, non-mechanical complaints could result in surgery or loss of limb. This case describes the discovery of a Giant Cell Tumor of Bone (GCTB) following the re-evaluation of an athlete who had undergone five years of conservative management for patellofemoral pain syndrome (PFPS). Knee injuries account for 32.6% of sports injuries with PFPS being the most common and most likely diagnosis for anterior knee pain. GCTB is a benign aggressive bone tumor with a predilection for the juxta-articular region of the knee, comprising up to 23% of all benign bone tumors, and commonly occurs in the second to fourth decades. This case report illustrates the difficulty in accurately diagnosing healthy athletes, reviews common differentials for knee complaints and explores helpful diagnostic procedures. PMID:27069267

  16. Differentiating giant cell tumor of bone from patellofemoral syndrome: a case study

    PubMed Central

    Bonar, Jason; Carr, Shannon Clutton; De Carvalho, Diana; Wunder, Jay S.

    2016-01-01

    Balancing the assessment of musculoskeletal dysfunctions with a high level of suspicion for non-mechanical origins can be a challenge for the clinician examining a sports injury. Without timely diagnosis, non-mechanical complaints could result in surgery or loss of limb. This case describes the discovery of a Giant Cell Tumor of Bone (GCTB) following the re-evaluation of an athlete who had undergone five years of conservative management for patellofemoral pain syndrome (PFPS). Knee injuries account for 32.6% of sports injuries with PFPS being the most common and most likely diagnosis for anterior knee pain. GCTB is a benign aggressive bone tumor with a predilection for the juxta-articular region of the knee, comprising up to 23% of all benign bone tumors, and commonly occurs in the second to fourth decades. This case report illustrates the difficulty in accurately diagnosing healthy athletes, reviews common differentials for knee complaints and explores helpful diagnostic procedures. PMID:27069267

  17. Mimicking biophysical stimuli within bone tumor microenvironment*

    PubMed Central

    Marturano-Kruik, A.; Yeager, K.; Bach, D.; Villasante, A.; Cimetta, E.; Vunjak-Novakovic, G.

    2016-01-01

    In vivo, cells reside in a complex environment regulating their fate and function. Most of this complexity is lacking in standard in vitro models, leading to readouts falling short of predicting the actual in vivo situation. The use of engineering tools, combined with deep biological knowledge, leads to the development and use of bioreactors providing biologically sound niches. Such bioreactors offer new tools for biological research, and are now also entering the field of cancer research. Here we present the development and validation of a modular bioreactor system providing: (i) high throughput analyses, (ii) a range of biological conditions, (iii) high degree of control, and (iv) application of physiological stimuli to the cultured samples. The bioreactor was used to engineer a three-dimensional (3D) tissue model of cancer, where the effects of mechanical stimulation on the tumor phenotype were evaluated. Mechanical stimuli applied to the engineered tumor model activated the mechanotransduction machinery and resulted in measurable changes of mRNA levels towards a more aggressive tumor phenotype. PMID:26737062

  18. Aggressive fibromatosis of anterior maxilla

    PubMed Central

    Shetty, Devi C; Urs, Aadithya B; Ahuja, Puneet; Sikka, Seema

    2011-01-01

    Aggressive fibromatosis is a comparitively rare tumor with unpredictable growth and varying local recurrence rates. It does not develop distant metastases but locally it shows an aggressive and infiltrative behavior. Clinically, aggressive fibromatosis manifests as a painless, firm, often rapidly enlarging mass, fixed to underlying bone or soft tissue. It is never encapsulated. Histologically, it is rich in collagen and fibroblastic cells that are devoid of hyperchromatic or atypical nuclei, but with more variable cellularity in different tumor sections. PMID:21731285

  19. A case of thoracic giant cell tumor of bone and discussion of radiological features and current management practices.

    PubMed

    Kelly, Deirdre; Mc Erlean, Sarah; Byrne, Danielle; Mahon, Peter Mac; Mc Caffrey, John

    2016-09-01

    Giant cell tumor of bone (GCTB) is a rare condition with distinct radiological features that aid diagnosis. We present the case of an adult female patient, with locally invasive GCTB and review important radiological and management principles. Specific radiological features include locally aggressive, lytic radiolucent lesions, which can demonstrate cortical thinning and expansile remodeling of bone and typically involve the epiphysis and metaphysis. Management is primarily surgical, and denosumab has a role in the advanced setting. PMID:27594954

  20. The Bone Microenvironment: a Fertile Soil for Tumor Growth.

    PubMed

    Buenrostro, Denise; Mulcrone, Patrick L; Owens, Philip; Sterling, Julie A

    2016-08-01

    Bone metastatic disease remains a significant and frequent problem for cancer patients that can lead to increased morbidity and mortality. Unfortunately, despite decades of research, bone metastases remain incurable. Current studies have demonstrated that many properties and cell types within the bone and bone marrow microenvironment contribute to tumor-induced bone disease. Furthermore, they have pointed to the importance of understanding how tumor cells interact with their microenvironment in order to help improve both the development of new therapeutics and the prediction of response to therapy. PMID:27255469

  1. Bone and Gallium scintigraphy in primary malignant and benign bone tumors of the extremities

    SciTech Connect

    Sepahdari, S.; Martin, W.B.; Ryan, J.; Simon, M.; Kirchner, P.

    1985-05-01

    A six yer prospective evaluation of 129 patients suspected of having a primary bone tumor included Tc-99m MDP bone scintigraphy followed by Ga-67 imaging at 48-72 hours. Blood pool images were part of bone scintigraphy in nearly half of the patients. Extent and intensity of tracer uptake in tumor and adjacent bone and joints were recorded for each tracer by two observers blind to the diagnosis. Tissue samples obtained in every patient by biopsy or tumor excision after scintigraphy, revealed 72 malignant and 57 benign bone tumors. The bone scan was positive in 95% (69/72) of malignancies. The scintigraphic intensity of benign and malignant lesions was comparable with both Tc-99m MDP and Ga-67. On the other hand, bone scintigraphy showed 72% (52/72) of bone malignancies to have abnormal proximal and distal bone/joint uptake whereas the Ga-67 images revealed this in only 6% (4/65) of malignancies. Benign lesions manifested this enhanced contiguous bone/joint uptake on only 8% (5/55) of bone and 0% of Ga-67 scans. This study concludes positive bone, blood pool, or Ga-67 images have less specificity for malignancy than the presence of increased Tc-99m MDP deposition in a contiguous bone/joint, but negative scintigraphic results strongly favor a benign lesion. Ga-67 was more accurate than Tc-99m MDP in portraying intraosseous extent of malignant tumors; however, this is now preferably done with C.T.

  2. Primary malignancy, secondary malignancy and semimalignancy of bone tumors.

    PubMed

    Uehlinger, E

    1976-01-01

    1. Bone tumors in contrast to tumors in soft tissue, show a wide variety of clinical behavior qualified by the expressions semimalignancy, low grade of malignancy, sarcomatous degeneration and primarily benign bone tumors and bone lesions. 2. The term semimalignancy is characterized by local invasive and destructive tumor growth with a tendency to recur locally but no hematogeneous spreading. Semimalignancy requires wide en-bloc resection of amputation. 3. The term low grade malignancy is used to describe a tumor of very slow growth and with very late metastasis. Low-grade malignancy requires resection with careful preservation of functional structures. 4. The term secondary malignancy means the sarcomatous degeneration of a primarily benign lesion or bone tumor. This transformation is enhanced by irradiation and probably by acceleration of the normal turnover of bone tissue. In Paget's disease sarcomatous degeneration is to be expected in 2 percent of cases and in fibrous dysplasia in 0.5 percent of cases. 5. Sarcomatous degeneration of bone infarcts is rare, but an increase is to be expected due to an increased frequency of bone infarcts caused by long-term treatment with cortisone. 6. Primary bone tumors and recurrences show the same structure and cytology. In a minority of cases the recurrences are less differentiated; in a very few cases the recurrences are more highly differentiated and have a better prognosis than the initial lesion. PMID:1070716

  3. Multilobular tumor of bone in the mandible of a dog.

    PubMed

    Eubanks, Diana L; Ray, Joel D; Bushby, Philip A; Anderson, Clay

    2010-01-01

    An 8-year-old Siberian husky dog was presented for a mass involving the rostral mandible. Intraoral radiographs demonstrated diffusely irregular bone and displacement of all mandibular incisor teeth. The mass was diagnosed as a grade I multilobular tumor of bone based on incisional biopsy. A bilateral rostral mandibulectomy was performed with tumor negative margins. Oral examination at 14-months following surgery indicated normal healing with minimal side effects and no evidence of tumor recurrence.

  4. Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor

    PubMed Central

    Thearle, Marie S.; Bruce, Jeffrey N.; Isaacson, Steven R.; Lee, Yoomi

    2010-01-01

    Only rarely do corticotroph pituitary tumors become invasive leading to symptoms caused by compression of cranial nerves and other local structures. When aggressive pituitary neuroendocrine tumors do develop, conventional treatment options are of limited success. A 50-year-old man developed a giant invasive corticotroph pituitary tumor 2 years after initial presentation. His tumor and symptoms failed to respond to maximal surgical, radio-surgical, radiation and medical therapy and a bilateral adrenalectomy was done. He subsequently developed rapid growth of his tumor leading to multiple cranial nerve deficits. He was administered salvage chemotherapy with capecitabine and temozolomide (CAPTEM), a novel oral chemotherapy regimen developed at our institution for treatment of neuroendocrine tumors. After two cycles of CAPTEM, his tumor markedly decreased in size and ACTH levels fell by almost 90%. Despite further decreases in ACTH levels, his tumor recurred after 5 months with increased avidity on PET scan suggesting a transformation to a more aggressive phenotype. Temozolomide had been reported to be effective against other pituitary tumors and this case adds to this literature demonstrating its use along with capecitabine (CAPTEM) against a corticotroph tumor. Further evaluation of the CAPTEM regimen in patients with pituitary neuroendocrine tumors which fail to respond to classic treatments is warranted. PMID:19960369

  5. Two Cases of Sarcoma Arising in Giant Cell Tumor of Bone Treated with Denosumab

    PubMed Central

    Broehm, Cory Julian; Garbrecht, Erika L.; Wood, Jeff; Bocklage, Therese

    2015-01-01

    Giant cell tumor (GCT) of bone is a generally benign, but often locally aggressive, neoplasm of bone, with a propensity for recurrence. Sarcomatous transformation is rare and typically occurs with a history of recurrences and radiation treatment. Denosumab, an inhibitor of the RANK ligand involved in bone resorption in GCT, is increasingly used in treatment of recurrent or unresectable giant cell tumor of bone. We report two cases of sarcomatous transformation of GCT to osteosarcoma in patients receiving denosumab. One was a 59-year-old male with a 12-year history of GCT and multiple recurrences taking denosumab for 2.5 years. The second case was in a 56-year-old male with a seven-year history of GCT taking denosumab for six months. Review of the literature shows one case report of malignant transformation of GCT in a patient being treated with denosumab. As the use of denosumab for treatment of GCT will likely increase, larger, controlled studies are needed to ascertain whether denosumab may play a role in malignant transformation of giant cell tumor of bone. PMID:26798348

  6. 3D Silicon Microstructures: A New Tool for Evaluating Biological Aggressiveness of Tumor Cells.

    PubMed

    Mazzini, Giuliano; Carpignano, Francesca; Surdo, Salvatore; Aredia, Francesca; Panini, Nicolò; Torchio, Martina; Erba, Eugenio; Danova, Marco; Scovassi, Anna Ivana; Barillaro, Giuseppe; Merlo, Sabina

    2015-10-01

    In this work, silicon micromachined structures (SMS), consisting of arrays of 3- μ m-thick silicon walls separated by 50- μm-deep, 5- μ m-wide gaps, were applied to investigate the behavior of eight tumor cell lines, with different origins and biological aggressiveness, in a three-dimensional (3D) microenvironment. Several cell culture experiments were performed on 3D-SMS and cells grown on silicon were stained for fluorescence microscopy analyses. Most of the tumor cell lines recognized in the literature as highly aggressive (OVCAR-5, A375, MDA-MB-231, and RPMI-7951) exhibited a great ability to enter and colonize the narrow deep gaps of the SMS, whereas less aggressive cell lines (OVCAR-3, Capan-1, MCF7, and NCI-H2126) demonstrated less penetration capability and tended to remain on top of the SMS. Quantitative image analyses of several fluorescence microscopy fields of silicon samples were performed for automatic cell recognition and count, in order to quantify the fraction of cells inside the gaps, with respect to the total number of cells in the examined field. Our results show that higher fractions of cells in the gaps are obtained with more aggressive cell lines, thus supporting in a quantitative way the observation that the behavior of tumor cells on the 3D-SMS depends on their aggressiveness level.

  7. Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009

    PubMed Central

    2010-01-01

    Objective To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children. Study design Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009. Results 21 cases were identified; 62% of the patients were boys. No familial cases were observed, and the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8-16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting signs were bone fracture (n = 4) and respiratory distress (n = 7), but more indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies and pleural effusion, was the most frequent form of extraosseous involvement (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as potentially curative treatments. High-dose radiotherapy appeared to be effective on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs like alpha interferon and zoledrenate have had a limited impact on the course of pulmonary complications. The impact of bisphosphonates and alpha interferon on bone lesions was also difficult to assess, owing to insufficient follow-up in most cases, but it was occasionally positive. Six deaths were observed and the overall 10-year mortality rate was about 30%. The prognosis depended mainly on pulmonary and spinal complications. Conclusion Aggressive vascular abnormalities of bone are extremely rare in childhood but are lifethreatening. The impact of anti-angiogenic drugs on pulmonary complications seems to be limited, but they may improve bone lesions. PMID:20128925

  8. Primary mixed malignant tumor of bone in an 18-year-old male: Report of a case with radiologic-pathologic correlation

    PubMed Central

    Courtier, Jesse; Robbins, Elizabeth; Soares, Bruno; Horvai, Andrew; Mackenzie, John D.

    2012-01-01

    We report a case of primary malignant mixed tumor (MMT) of bone in an 18-year-old boy with X-ray, CT, MR, scintigraphic, FDG PET, and pathologic correlation. Primary MMT of bone is a highly aggressive tumor and presents both a diagnostic and clinical treatment challenge. This tumor is extremely rare and to the best of our knowledge, this is the first report of the diagnostic imaging findings for primary MMT arising from bone in a patient of this age group. PMID:26909264

  9. Vascular patterns provide therapeutic targets in aggressive neuroblastic tumors

    PubMed Central

    Tadeo, Irene; Bueno, Gloria; Berbegall, Ana P.; Fernández-Carrobles, M. Milagro; Castel, Victoria; García-Rojo, Marcial; Navarro, Samuel; Noguera, Rosa

    2016-01-01

    Angiogenesis is essential for tumor growth and metastasis, nevertheless, in NB, results between different studies on angiogenesis have yielded contradictory results. An image analysis tool was developed to characterize the density, size and shape of total blood vessels and vascular segments in 458 primary neuroblastic tumors contained in tissue microarrays. The results were correlated with clinical and biological features of known prognostic value and with risk of progression to establish histological vascular patterns associated with different degrees of malignancy. Total blood vessels were larger, more abundant and more irregularly-shaped in tumors of patients with associated poor prognostic factors than in the favorable cohort. Tumor capillaries were less abundant and sinusoids more abundant in the patient cohort with unfavorable prognostic factors. Additionally, size of post-capillaries & metarterioles as well as higher sinusoid density can be included as predictive factors for survival. These patterns may therefore help to provide more accurate pre-treatment risk stratification, and could provide candidate targets for novel therapies. PMID:26918726

  10. High Potency VEGFRs/MET/FMS Triple Blockade by TAS-115 Concomitantly Suppresses Tumor Progression and Bone Destruction in Tumor-Induced Bone Disease Model with Lung Carcinoma Cells

    PubMed Central

    Fujioka, Yayoi; Kataoka, Yuki; Tanaka, Kenji; Hashimoto, Akihiro; Suzuki, Takamasa; Ito, Kenjiro; Haruma, Tomonori; Yamamoto-Yokoi, Hiromi; Harada, Naomoto; Sakuragi, Motomu; Oda, Nobuyuki; Matsuo, Kenichi; Inada, Masaki; Yonekura, Kazuhiko

    2016-01-01

    Approximately 25–40% of patients with lung cancer show bone metastasis. Bone modifying agents reduce skeletal-related events (SREs), but they do not significantly improve overall survival. Therefore, novel therapeutic approaches are urgently required. In this study, we investigated the anti-tumor effect of TAS-115, a VEGFRs and HGF receptor (MET)-targeted kinase inhibitor, in a tumor-induced bone disease model. A549-Luc-BM1 cells, an osteo-tropic clone of luciferase-transfected A549 human lung adenocarcinoma cells (A549-Luc), produced aggressive bone destruction associated with tumor progression after intra-tibial (IT) implantation into mice. TAS-115 significantly reduced IT tumor growth and bone destruction. Histopathological analysis showed a decrease in tumor vessels after TAS-115 treatment, which might be mediated through VEGFRs inhibition. Furthermore, the number of osteoclasts surrounding the tumor was decreased after TAS-115 treatment. In vitro studies demonstrated that TAS-115 inhibited HGF-, VEGF-, and macrophage-colony stimulating factor (M-CSF)-induced signaling pathways in osteoclasts. Moreover, TAS-115 inhibited Feline McDonough Sarcoma oncogene (FMS) kinase, as well as M-CSF and receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation. Thus, VEGFRs/MET/FMS-triple inhibition in osteoclasts might contribute to the potent efficacy of TAS-115. The fact that concomitant dosing of sunitinib (VEGFRs/FMS inhibition) with crizotinib (MET inhibition) exerted comparable inhibitory efficacy for bone destruction to TAS-115 also supports this notion. In conclusion, TAS-115 inhibited tumor growth via VEGFR-kinase blockade, and also suppressed bone destruction possibly through VEGFRs/MET/FMS-kinase inhibition, which resulted in potent efficacy of TAS-115 in an A549-Luc-BM1 bone disease model. Thus, TAS-115 shows promise as a novel therapy for lung cancer patients with bone metastasis. PMID:27736957

  11. Apoptosis triggered by pyropheophorbide-α methyl ester-mediated photodynamic therapy in a giant cell tumor in bone

    NASA Astrophysics Data System (ADS)

    Li, K.-T.; Zhang, J.; Duan, Q.-Q.; Bi, Y.; Bai, D.-Q.; Ou, Y.-S.

    2014-06-01

    A giant cell tumor in bone is the common primary bone tumor with aggressive features, occurring mainly in young adults. Photodynamic therapy is a new therapeutic technique for tumors. In this study, we investigated the effects of Pyropheophorbide-α methyl ester (MPPa)-mediated photodynamic therapy on the proliferation of giant cell tumor cells and its mechanism of action. Cell proliferation was evaluated using an MTT assay. Cellular apoptosis was detected by Hoechst nuclear staining, and flow cytometric assay. Mitochondrial membrane potential changes and cytochrome c, caspase-9, caspase-3, and Bcl-2 expression was assessed. Finally, we found that MPPa-mediated photodynamic therapy could effectively suppress the proliferation of human giant cell tumor cells and induce apoptosis. The mitochondrial pathway was involved in the MPPa-photodynamic therapy-induced apoptosis.

  12. Rheumatic manifestations of primary and metastatic bone tumors and paraneoplastic bone disease.

    PubMed

    Waimann, Christian A; Lu, Huifang; Suarez Almazor, Maria E

    2011-11-01

    Bone tumors can show a wide range of nonspecific rheumatic manifestations. The presence of unexplained or atypical chronic bone pain, an enlarging bone mass, neurovascular compression syndromes, or pathologic fractures should alert us to the possibility of a bone tumor causing these symptoms. These patients must undergo a complete physical examination; adequate imaging; and, if needed, a biopsy to confirm their diagnosis and offer them an opportune treatment. In addition, bone tumors and other malignancies can present remote clinical manifestations and unusual laboratory findings (eg, HOA, hypophosphatemia, hyperphosphaturia, and hypercalcemia) that may be the first and early manifestation of an occult cancer. These findings should motivate a cancer screening according to age, sex, and personal history. Cancer therapies also have a big impact on bone health, increasing the risk of osteoporosis, osteomalacia, and/or osteonecrosis. Rheumatologists should be aware of possible long-term adverse events of cancer treatment to avoid future complications.

  13. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  14. Nerve Fibers in Breast Cancer Tissues Indicate Aggressive Tumor Progression

    PubMed Central

    Huang, Di; Su, Shicheng; Cui, Xiuying; Shen, Ximing; Zeng, Yunjie; Wu, Wei; Chen, Jianing; Chen, Fei; He, Chonghua; Liu, Jiang; Huang, Wei; Liu, Qiang; Su, Fengxi; Song, Erwei; Ouyang, Nengtai

    2014-01-01

    Abstract Emerging evidence has indicated nerve fibers as a marker in the progression of various types of cancers, such as pancreatic cancer and prostate cancer. However, whether nerve fibers are associated with breast cancer progression remains unclear. In this study, we evaluated the presence of nerve fibers in 352 breast cancer specimens and 83 benign breast tissue specimens including 43 cases of cystic fibrosis and 40 cases of fibroadenoma from 2 independent breast tumor center using immunohistochemical staining for specific peripheral nerve fiber markers. In all, nerve fibers were present in 130 out of 352 breast cancer tissue specimens, while none were detected in normal breast tissue specimens. Among 352 cases, we defined 239 cases from Sun Yat-Sen Memorial Hospital, Guangzhou, China, as the training set, and 113 cases from the First Affiliated Hospital of Shantou University, Guangdong, China, as the validation set. The thickness of tumor-involving nerve fibers is significantly correlated with poor differentiation, lymph node metastasis, high clinical staging, and triple negative subtype in breast cancer. More importantly, Cox multifactor analysis indicates that the thickness of tumor-involving nerve fibers is a previously unappreciated independent prognostic factors associated with shorter disease-free survival of breast cancer patients. Our findings are further validated by online Oncomine database. In conclusion, our results show that nerve fiber involvement in breast cancer is associated with progression of the malignancy and warrant further studies in the future. PMID:25501061

  15. [Toxic effects of cisplatin in the treatment of malignant bone and soft tissue tumors].

    PubMed

    Umeda, T; Takada, N; Hodaka, E; Endoh, F; Ishii, T

    1986-05-01

    A total of 31 patients with malignant bone and soft tissue tumors were evaluated for toxic effects after receiving cisplatin (104 courses) at doses of 2.0-3.0 mg/kg with aggressive hydration. Nausea was common and in 86% of cisplatin courses severe vomiting was observed. Nephrotoxicity was observed in less than 10% of all courses but ototoxicity, especially tinnitis, developed in 5 of 6 patients whose total doses of cisplatin were over 500mg, and one of them showed hearing disorder in the upper frequency above 5,000 Hz. There were no other toxic effects such as severe myelosuppression, allergic reaction or peripheral neuropathy. PMID:3707148

  16. TUMOR CONTAMINATION IN THE BIOPSY PATH OF PRIMARY MALIGNANT BONE TUMORS

    PubMed Central

    Oliveira, Marcelo Parente; Lima, Pablo Moura de Andrade; de Mello, Roberto José Vieira

    2015-01-01

    Objective: To study factors possibly associated with tumor contamination in the biopsy path of primary malignant bone tumors. Method: Thirty-five patients who underwent surgical treatment with diagnoses of osteosarcoma, Ewing's tumor and chondrosarcoma were studied retrospectively. The sample was analyzed to characterize the biopsy technique used, histological type of the tumor, neoadjuvant chemotherapy used, local recurrences and tumor contamination in the biopsy path. Results: Among the 35 patients studied, four cases of contamination occurred (11.43%): one from osteosarcoma, two from Ewing's tumor and one from chondrosarcoma. There was no association between the type of tumor and presence of tumor contamination in the biopsy path (p = 0.65). There was also no association between the presence of tumor contamination and the biopsy technique (p = 0.06). On the other hand, there were associations between the presence of tumor contamination and local recurrence (p = 0.01) and between tumor contamination and absence of neoadjuvant chemotherapy (p = 0.02). Conclusion: Tumor contamination in the biopsy path of primary malignant bone tumors was associated with local recurrence. On the other hand, the histological type of the tumor and the type of biopsy did not have an influence on tumor contamination. Neoadjuvant chemotherapy had a protective effect against this complication. Despite these findings, tumor contamination is a complication that should always be taken into consideration, and removal of the biopsy path is recommended in tumor resection surgery. PMID:27047877

  17. Central nervous system recurrence of desmoplastic small round cell tumor following aggressive multimodal therapy: A case report

    PubMed Central

    UMEDA, KATSUTSUGU; SAIDA, SATOSHI; YAMAGUCHI, HIDEKI; OKAMOTO, SHINYA; OKAMOTO, TAKESHI; KATO, ITARU; HIRAMATSU, HIDEFUMI; IMAI, TSUYOSHI; KODAIRA, TAKESHI; HEIKE, TOSHIO; ADACHI, SOUICHI; WATANABE, KEN-ICHIRO

    2016-01-01

    Patients with desmoplastic small round cell tumors (DSRCTs) have an extremely poor outcome despite the use of aggressive therapy. The current study presents the case of 16-year-old male with metastatic DSRCT, in which multimodal therapy, including intensive chemotherapies using frequent autologous stem cell support, gross resection of primary and metastatic lesions, and whole abdominopelvic intensity-modulated radiation therapy, was administered. Subsequent to these treatments, there was no evidence of active disease. However, cerebellar and pineal body lesions, and bone metastasis to the left humerus were detected 1 year and 2 months after the initial diagnosis. Combination chemotherapy with irinotecan and temozolomide was initially effective against the central nervous system (CNS) metastatic lesions; however, the patient succumbed due to progressive CNS disease after seven courses of combination chemotherapy. Additional studies are required to accumulate information regarding CNS recurrence of DSRCT. PMID:26870296

  18. A metastatic glomus jugulare tumor. A temporal bone report

    SciTech Connect

    El Fiky, F.M.; Paparella, M.M.

    1984-01-01

    The clinicopathologic findings in the temporal bone of a patient with a highly malignant metastasizing glomus jugulare tumor are reported. The patient exhibited all the symptoms of primary malignant tumors of the ear, including facial paralysis, otorrhea, pain, hearing loss, tinnitus, dizziness, and vertigo. He was treated with cobalt irradiation followed by radium implant in the ear canal for a residual tumor; then a left-sided radical mastoidectomy was performed.

  19. Protein Expression Profiling of Giant Cell Tumors of Bone Treated with Denosumab

    PubMed Central

    Mukaihara, Kenta; Suehara, Yoshiyuki; Kohsaka, Shinji; Akaike, Keisuke; Tanabe, Yu; Kubota, Daisuke; Ishii, Midori; Fujimura, Tsutomu; Kazuno, Saiko; Okubo, Taketo; Takagi, Tatsuya; Yao, Takashi; Kaneko, Kazuo; Saito, Tsuyoshi

    2016-01-01

    Giant cell tumors of bone (GCTB) are locally aggressive osteolytic bone tumors. Recently, some clinical trials have shown that denosumab is a novel and effective therapeutic option for aggressive and recurrent GCTB. This study was performed to investigate the molecular mechanism underlying the therapeutic effect of denosumab. Comparative proteomic analyses were performed using GCTB samples which were taken before and after denosumab treatment. Each expression profile was analyzed using the software program to further understand the affected biological network. One of identified proteins was further evaluated by gelatin zymography and an immunohistochemical analysis. We identified 13 consistently upregulated proteins and 19 consistently downregulated proteins in the pre- and post-denosumab samples. Using these profiles, the software program identified molecular interactions between the differentially expressed proteins that were indirectly involved in the RANK/RANKL pathway and in several non-canonical subpathways including the Matrix metalloproteinase pathway. The data analysis also suggested that the identified proteins play a critical functional role in the osteolytic process of GCTB. Among the most downregulated proteins, the activity of MMP-9 was significantly decreased in the denosumab-treated samples, although the residual stromal cells were found to express MMP-9 by an immunohistochemical analysis. The expression level of MMP-9 in the primary GCTB samples was not correlated with any clinicopathological factors, including patient outcomes. Although the replacement of tumors by fibro-osseous tissue or the diminishment of osteoclast-like giant cells have been shown as therapeutic effects of denosumab, the residual tumor after denosumab treatment, which is composed of only stromal cells, might be capable of causing bone destruction; thus the therapeutic application of denosumab would be still necessary for these lesions. We believe that the protein expression

  20. Navigation Endoscopic Assisted Tumor (NEAT) surgery for benign bone tumors of the extremities.

    PubMed

    Wong, K C; Kumta, S M; Tse, L F; Ng, E W K; Lee, K S

    2010-01-01

    A novel technique of using both a navigation system and an endoscope in intra-lesional curettage of benign bone tumors enables safe and adequate tumor removal via a minimal access approach. We performed curettage of benign bone tumors in five consecutive patients (4 female, 1 male, mean age 31.4 years) using a commercial CT-based navigation system supplemented by visual guidance through a shoulder arthroscope. The bone defect was filled with bone cement in four patients and with artificial bone substitute in one patient. Mean follow-up time was 8.8 months (range: 7-12 months). Mean duration of surgery was 144 min (range: 120-165 min). Mean wound length of each portal site was 19.5 mm (range: 15-25 mm). All patients could achieve a full range of joint movement and walk unaided at 4 weeks post-surgery. No local recurrence was noted. PMID:20433316

  1. Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumor aggressiveness.

    PubMed

    Afonso, Julieta; Santos, Lúcio L; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2016-01-01

    Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells' compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance. PMID:26636903

  2. Depletion of plasmacytoid dendritic cells inhibits tumor growth and prevents bone metastasis of the breast cancer cells

    PubMed Central

    Sawant, Anandi; Hensel, Jonathan A.; Chanda, Diptiman; Harris, Brittney A.; Siegal, Gene P.; Maheshwari, Akhil; Ponnazhagan, Selvarangan

    2012-01-01

    Elevated levels of plasmacytoid dendritic cells (pDC) have been reported in breast cancer patients, the significance of which remains undefined. Using three different immunocompetent mouse models of BCa bone metastasis, we identified a key role for pDC in facilitating tumor growth through immunosuppression and aggressive osteolysis. Following infiltration of macrophages upon breast cancer dissemination, there was a steady increase of pDC within the bone, which resulted in a sustained Th2 response along with elevated levels of Treg and MDSC. Subsequently, pDC and CD4+ T cells, producing osteolytic cytokines, increased with tumor burden causing severe bone damage. Micro-CT and histology analyses of bone showed destruction of femur and tibia. Therapeutic significance of this finding was confirmed by depletion of pDC, which resulted in decreased tumor burden and bone loss by activating tumor-specific cytolytic CD8+ T cells and decreasing suppressor cell populations. Thus, pDC depletion may offer a novel adjuvant strategy to therapeutically influence breast cancer bone metastasis. PMID:23018462

  3. Giant cell tumor of bone in children and adolescents.

    PubMed

    Hoeffel, J C; Galloy, M A; Grignon, Y; Chastagner, P; Floquet, J; Mainard, L; Kadiri, R

    1996-10-01

    Giant cell tumor of bone rarely affects children, in whom it is usually located in a metaphysis in contrast to the predominantly epiphyseal localization in adults. Five cases are reported, two at the femur, two at the fibula and one at the tibia. Plain film radiography and computed tomography are the most informative imaging studies. The differential diagnosis is with aneurysmal bone cyst and, in metaphyseal-epiphyseal forms, with chondroblastoma. Treatment usually consists in curettage of the tumor followed by filling of the cavity; however, more extensive resection is required in some cases. PMID:8938873

  4. Preoperative embolization of primary bone tumors: A case control study

    PubMed Central

    Jha, Roushan; Sharma, Raju; Rastogi, Shishir; Khan, Shah Alam; Jayaswal, Arvind; Gamanagatti, Shivanand

    2016-01-01

    AIM: To study the safety and effectiveness of preoperative embolization of primary bone tumors in relation to intraoperative blood loss, intraoperative blood transfusion volume and surgical time. METHODS: Thirty-three patients underwent preoperative embolization of primary tumors of extremities, hip or vertebrae before resection and stabilization. The primary osseous tumors included giant cell tumors, aneurysmal bone cyst, osteoblastoma, chondroblastoma and chondrosarcoma. Twenty-six patients were included for the statistical analysis (embolization group) as they were operated within 0-48 h within preoperative embolization. A control group (non-embolization group, n = 28) with bone tumor having similar histological diagnosis and operated without embolization was retrieved from hospital record for statistical comparison. RESULTS: The mean intraoperative blood loss was 1300 mL (250-2900 mL), the mean intraoperative blood transfusion was 700 mL (0-1400 mL) and the mean surgical time was 221 ± 76.7 min for embolization group (group I, n = 26). Non-embolization group (group II, n = 28), the mean intraoperative blood loss was 1800 mL (800-6000 mL), the mean intraoperative blood transfusion was 1400 mL (700-8400 mL) and the mean surgical time was 250 ± 69.7 min. On comparison, statistically significant (P < 0.001) difference was found between embolisation group and non-embolisation group for the amount of blood loss and requirement of blood transfusion. There was no statistical difference between the two groups for the surgical time. No patients developed any angiography or embolization related complications. CONCLUSION: Preoperative embolization of bone tumors is a safe and effective adjunct to the surgical management of primary bone tumors that leads to reduction in intraoperative blood loss and blood transfusion volume. PMID:27158424

  5. Biallelic BRCA2 Mutations Shape the Somatic Mutational Landscape of Aggressive Prostate Tumors.

    PubMed

    Decker, Brennan; Karyadi, Danielle M; Davis, Brian W; Karlins, Eric; Tillmans, Lori S; Stanford, Janet L; Thibodeau, Stephen N; Ostrander, Elaine A

    2016-05-01

    To identify clinically important molecular subtypes of prostate cancer (PCa), we characterized the somatic landscape of aggressive tumors via deep, whole-genome sequencing. In our discovery set of ten tumor/normal subject pairs with Gleason scores of 8-10 at diagnosis, coordinated analysis of germline and somatic variants, including single-nucleotide variants, indels, and structural variants, revealed biallelic BRCA2 disruptions in a subset of samples. Compared to the other samples, the PCa BRCA2-deficient tumors exhibited a complex and highly specific mutation signature, featuring a 2.88-fold increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions, especially those longer than 10 bp. We next performed a BRCA2 deficiency-targeted reanalysis of 150 metastatic PCa tumors, and each of the 18 BRCA2-mutated samples recapitulated the BRCA2 deficiency-associated mutation signature, underscoring the potent influence of these lesions on somatic mutagenesis and tumor evolution. Among all 21 individuals with BRCA2-deficient tumors, only about half carried deleterious germline alleles. Importantly, the somatic mutation signature in tumors with one germline and one somatic risk allele was indistinguishable from those with purely somatic mutations. Our observations clearly demonstrate that BRCA2-disrupted tumors represent a unique and clinically relevant molecular subtype of aggressive PCa, highlighting both the promise and utility of this mutation signature as a prognostic and treatment-selection biomarker. Further, any test designed to leverage BRCA2 status as a biomarker for PCa must consider both germline and somatic mutations and all types of deleterious mutations.

  6. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors).

    PubMed

    Alman, B A; Li, C; Pajerski, M E; Diaz-Cano, S; Wolfe, H J

    1997-08-01

    Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues

  7. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors).

    PubMed Central

    Alman, B. A.; Li, C.; Pajerski, M. E.; Diaz-Cano, S.; Wolfe, H. J.

    1997-01-01

    Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues

  8. Rapidly growing giant cell tumor of bone in a skeletally immature girl.

    PubMed

    Akaike, Gensuke; Ueno, Teruko; Matsumoto, Seiichi; Motoi, Noriko; Matsueda, Kiyoshi

    2016-04-01

    Giant cell tumor of bone (GCTB) in skeletally immature patients is rare, and little is known regarding how fast GCTB can grow. We report a case of a 10-year-old skeletally immature girl with pathologically proven GCTB with obvious growth plate invasion that showed surprisingly rapid growth over only 14 days. A radiograph of the left knee revealed well-circumscribed, geographic bone destruction at the distal metaphysis of the femur with a focal cortical defect, suggesting a pathologic fracture. No abnormal mineralization or periosteal reaction was seen. A CT without contrast and an MRI demonstrated a homogeneous lesion with cortical disruption posteriorly and laterally with a slight soft tissue extension. Biopsy showed numerous multinucleated giant cells and spindle-shaped mononuclear cells without any sign of malignancy, suggesting GCTB. However, rapid lesion enlargement and destruction of the surrounding cortex were noted 14 days after biopsy. Considering the amount of bone destruction, traditional treatment of curettage and bone cement would not suffice to sustain structural strength. In addition, considering the patient's age, the tumor location, and the aggressive course, a malignant tumor, especially a giant cell-rich osteosarcoma, could not be excluded. Therefore, en bloc resection, including the growth plate and prosthetic replacement, were performed. Confirmation of GCTB was made from a pathologic evaluation, and a breach to the growth plate was identified. Since very little inflammatory reaction, degenerative change, or aneurysmal, bone, cyst-like change was found, the growth plate invasion was confirmed as due to GCTB extension, not due to the preoperative biopsy.

  9. External bone remodeling after injectable calcium-phosphate cement in benign bone tumor: two cases in the hand.

    PubMed

    Ichihara, S; Vaiss, L; Acciaro, A L; Facca, S; Liverneaux, P

    2015-12-01

    Bone remodeling commonly occurred after fracture and curettage benign bone tumor. A lot of previous articles reported "internal" trabecular bone remodeling. There were no previous clinical reports about "external" cortical bone remodeling. We present here 2 clinical cases of "external" bone remodeling after injectable calcium-phosphate in benign bone tumor in the hand. In two cases of benign bone tumor, we performed complete removal of the tumor and immediate filling of the metacarpal bone with injectable calcium-phosphate cement Arexbone(®) from the mechanical viewpoint. With respect to the shape of the calcium-phosphate, by using an injection-type, calcium-phosphate is adhered uniformly to the bone cortex by injecting, remodeling has been promoted. After 5 and 8years, both cases were no recurrences, and the shape of the metacarpal looked close to the contralateral side. These findings supposed to be concerned with potential self-healing and self-protection mechanism in human body.

  10. Laxative Related Primary Hyperphosphatemic Tumoral Calcinosis Identified by Bone Scintigraphy.

    PubMed

    Asokendaran, Marcus; Lenzo, Nat Patrick

    2016-09-01

    We describe a case of a 40-year-old female patient presenting with tumor calcinosis where hypertrophic pulmonary osteoarthropathy (HPOA) was suspected given her extensive history of malignancy. Plain X-rays did not show reveal the typical periarticular calcification but did show appearances consistent with HPOA. Bone scintigraphy with (99m)Tc-methylene diphosphonate (MDP) is a sensitive investigation in the detection of hypertrophic osteoarthopathy but did not show findings characteristics of HPOA like bilateral symmetrical increased uptake of the radiopharmaceutical along the cortical margins of the long bones. The final diagnosis of tumor calcinosis was only made after low dose computerized tomography chest showed a moderated sized amorphous calcified cluster in the apical segment of the right upper lobe consistent. In conclusion, bone scintigraphy continues to be a useful investigation for both common and rare conditions like tumor calcinosis. The unusual three phase bone scan finding of diffuse activity throughout both lung fields, which turned to out to be tumoral calcinosis is highlighted in this case. PMID:27651742

  11. Laxative Related Primary Hyperphosphatemic Tumoral Calcinosis Identified by Bone Scintigraphy

    PubMed Central

    Asokendaran, Marcus; Lenzo, Nat Patrick

    2016-01-01

    We describe a case of a 40-year-old female patient presenting with tumor calcinosis where hypertrophic pulmonary osteoarthropathy (HPOA) was suspected given her extensive history of malignancy. Plain X-rays did not show reveal the typical periarticular calcification but did show appearances consistent with HPOA. Bone scintigraphy with 99mTc-methylene diphosphonate (MDP) is a sensitive investigation in the detection of hypertrophic osteoarthopathy but did not show findings characteristics of HPOA like bilateral symmetrical increased uptake of the radiopharmaceutical along the cortical margins of the long bones. The final diagnosis of tumor calcinosis was only made after low dose computerized tomography chest showed a moderated sized amorphous calcified cluster in the apical segment of the right upper lobe consistent. In conclusion, bone scintigraphy continues to be a useful investigation for both common and rare conditions like tumor calcinosis. The unusual three phase bone scan finding of diffuse activity throughout both lung fields, which turned to out to be tumoral calcinosis is highlighted in this case. PMID:27651742

  12. Laxative Related Primary Hyperphosphatemic Tumoral Calcinosis Identified by Bone Scintigraphy

    PubMed Central

    Asokendaran, Marcus; Lenzo, Nat Patrick

    2016-01-01

    We describe a case of a 40-year-old female patient presenting with tumor calcinosis where hypertrophic pulmonary osteoarthropathy (HPOA) was suspected given her extensive history of malignancy. Plain X-rays did not show reveal the typical periarticular calcification but did show appearances consistent with HPOA. Bone scintigraphy with 99mTc-methylene diphosphonate (MDP) is a sensitive investigation in the detection of hypertrophic osteoarthopathy but did not show findings characteristics of HPOA like bilateral symmetrical increased uptake of the radiopharmaceutical along the cortical margins of the long bones. The final diagnosis of tumor calcinosis was only made after low dose computerized tomography chest showed a moderated sized amorphous calcified cluster in the apical segment of the right upper lobe consistent. In conclusion, bone scintigraphy continues to be a useful investigation for both common and rare conditions like tumor calcinosis. The unusual three phase bone scan finding of diffuse activity throughout both lung fields, which turned to out to be tumoral calcinosis is highlighted in this case.

  13. Image-guided ablation therapy of bone tumors.

    PubMed

    Sabharwal, Tarun; Katsanos, Konstantinos; Buy, Xavier; Gangi, Afshin

    2009-04-01

    A wide range of thermal and cryoablation methods is currently available for the curative eradication or palliative treatment of a variety of bone and soft-tissue tumors. Radiofrequency ablation has been developed as a multipurpose tool for the skeletal system. Cryoablation has the added advantages of direct computed tomography or magnetic resonance visualization and monitoring of treatment outcome with less peri- and postoperative pain. Use of appropriate thermo-sensors and insulation techniques, like carbon dioxide insufflation, results in enhanced safety and efficacy. Ablation of weight-bearing bones has to be supplemented with cement consolidation. The authors present an overview of the current status of percutaneous image-guided ablation therapy of bone and soft-tissue tumors, analyze the merits and limitations of the various systems available, and discuss possible new applications for the future.

  14. Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

    PubMed Central

    Ford, Catriona A.; Petrova, Sofia; Pound, John D.; Voss, Jorine J.L.P.; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L.; Gallimore, Awen M.; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E.; Dunbar, Donald R.; Murray, Paul G.; Ruckerl, Dominik; Allen, Judith E.; Hume, David A.; van Rooijen, Nico; Goodlad, John R.; Freeman, Tom C.; Gregory, Christopher D.

    2015-01-01

    Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. PMID:25702581

  15. Radiation therapy for aggressive fibromatosis (desmoid tumors): Results of a national Patterns of Care Study

    SciTech Connect

    Micke, Oliver . E-mail: omicke@benign-news.de; Seegenschmiedt, M. Heinrich

    2005-03-01

    Purpose: After a general Patterns of Care Study (PCS) the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) initiated a multicenter cohort study to analyze the radiation therapy practice for aggressive fibromatosis. Methods and materials: In 2002 a PCS was conducted in all German radiotherapy (RT) institutions by mailing a standardized structured questionnaire, to assess patients accrual, number, pretreatment, treatment indications, RT, and target volume concepts for irradiation in aggressive fibromatosis. In addition, the treatment outcome of individual patients was evaluated. The PCS was structured and analyzed according to the model for quality assessment by Donabedian in three major components: structure, process, and outcome evaluation. Results: A total of 101 institutions returned the questionnaire: 52.7% reported satisfactory clinical data and experience for inclusion in this analysis. A total accrual rate of 278 patients per year was reported with median number of 2 cases (1-7 cases) per institution. Satisfactory data for a long-term clinical evaluation was reported for 345 patients from 19 different institutions. The applied total doses ranged between 36 and 65 Gy (median, 60 Gy). The local control rate was 81.4% in primary RT for unresectable tumors and 79.6% in postoperative RT. No acute or late radiation toxicities > Grade 2 (RTOG) were observed. No clear dose-response relationship could be established, but there was a tendency toward a lower local control rate in patients with a higher number of operative procedures before RT and patients treated for recurrent aggressive fibromatosis. Conclusions: This study comprises the largest database of cases reported for RT in aggressive fibromatosis. Radiotherapy provides a high local control rate in the postoperative setting and in unresectable tumors. This PCS may serve as a starting point for a national or international prospective multicenter study or registry, or both.

  16. Pattern of primary tumors and tumor-like lesions of bone in children: retrospective survey of biopsy results

    PubMed Central

    Özkan, Esra Akyüz; Göret, Ceren Canbey; Özdemir, Zeynep Tuğba; Yanık, Serdar; Doğan, Meryem; Gönültaş, Aylin; Akkoca, Ayşe Neslin

    2015-01-01

    Background: Although primary bone tumors are relatively uncommon, they constitute the most important tumors in patients less than 20 years. We aimed to determine the frequencies of primary bone tumors and tumor-like lesions of bone and the anatomical sites of their occurrence. Methods: A retrospective review of histopathology reports of all bone specimens received in a private pathology laboratory in Istanbul between 2009 and 2015. Results: A total of 57 patients (aged 5 to 18 years) with a mean of 13.12 years were studied. Thirty five patients (61.4%) were males and 22 (38.6%) were females. Fifty five (94.4%) of the tumors were benign. Osteochondroma was the commonest tumor accounting for 31 cases (54.3%) followed by osteoid osteoma, 9 cases (15.7%). Chondrosarcoma observed in two patients and Ewing sarcoma in one patient as malignant tumors. Of the 57 bone tumors 13 (22.8%) occurred in the upper extremities, while 44 (77.2%) were in the lower extremities. Proximal humerus was the most commonly involved site in upper extremity tumors, with osteochondromas representing the most frequent type of tumor (4 patients; 7%). In the lower extremities again osteochondromas were the most common type of tumor (8 cases, 14%), with the femur being the most common site of involvement (18 patients, 31.5%). Of the patients with tumor-like lesions; four patients had fibrous dysplasia, 4 patients had non-ossified fibromas, 4 patients had simple bone cysts and 3 had aneurismal bone cyst. Conclusion: This study showed that primary bone tumors were mainly benign, settled predominantly in the lower extremities mostly in the femur with a male preponderance. Osteochondroma was the most common benign bone tumor. We didn’t observed osteosarcoma, which is the most frequent malignant bone tumor. PMID:26617888

  17. Clinically aggressive primary solid pseudopapillary tumor of the ovary in a 45-year-old woman

    PubMed Central

    Syriac, Susanna; Kesterson, Joshua; Izevbaye, Iyare; de Mesy Bentley, Karen L.; Lele, Shashikant; Mhawech-Fauceglia, Paulette

    2016-01-01

    We report the first case of primary solid pseudopapillary tumor of the ovary with aggressive behavior and fatal outcome in a 45-year-old woman. The patient presented with weight loss, decrease of appetite, and abdominal bloating for the last several weeks. Computed tomography scan revealed an ovarian mass, omental caking, complex ascites, and 2 hepatic lesions. The pancreas was unremarkable. Grossly, the ovarian mass showed severe capsular adhesion, and the cut surface was cystic and solid. On histologic examination, the tumor was composed of diffuse solid pseudopapillary and pseudocystic patterns. The neoplastic cells were uniform and round with very dispersed chromatin. The cytoplasm was faintly pink. There was mild atypia, but the mitotic rate was as high as 62 per 50 high-power field, and the Ki-67 was elevated at 20%. The tumor exhibited severe necrosis. Numerous foci of lymphovascular invasion were also seen. The tumor cells were positive for cytokeratin (focal) and for β-catenin (cytoplasmic and nuclear patterns). They were negative for chromogranin, synaptophysin, thyroglobulin, calcitonin, hepatocyte-paraffin 1, epithelial membrane antigen, calretinin, and α-inhibin. Electron microscopic study revealed nests of tumor cells with oval nuclei. The cytoplasm contained numerous pleomorphic mitochondria interspersed among short strands of rough endoplasmic reticulum. The tumor involved the fallopian tube, omentum, cul-de-sac, and abdominal wall. The pelvic washing was also positive for tumor cells. Despite chemotherapy, the patient's condition had worsened, and she died of her disease 8 months after the initial diagnosis. We discuss the differential diagnosis of this tumor and the hypothesis of its origin. PMID:21778097

  18. Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance

    SciTech Connect

    Hoogsteen, Ilse J.; Marres, Henri A.M.; Hoogen, Franciscus J.A. van den

    2012-11-01

    Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.

  19. Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma.

    PubMed

    Shigeoka, Manabu; Urakawa, Naoki; Nakamura, Tetsu; Nishio, Mari; Watajima, Taketo; Kuroda, Daisuke; Komori, Takahide; Kakeji, Yoshihiro; Semba, Shuho; Yokozaki, Hiroshi

    2013-08-01

    Tumor associated macrophages (TAMs) are the most abundant cancer stromal cells educated by tumor microenvironment to acquire trophic functions facilitating angiogenesis, matrix breakdown and cancer cell motility. Tumor associated macrophages have anti-inflammatory properties or "alternatively" activated (M2) phenotype expressing CD204 and/or CD163. To know the role of TAMs in the growth and progression of esophageal squamous cell carcinomas (ESCCs), we calculated intratumoral CD204, CD163 or CD68 expressing macrophage count (MϕC) and CD34-positive microvessel density (MVD) by immunohistochemistry in 70 cases of surgically resected ESCCs and compared them with the clinicopathological factors and prognosis of patients. MϕC had positive linear association with MVD. High CD204(+) MϕC were significantly correlated with more malignant phenotypes including depth of tumor invasion, lymph and blood vessel invasion, lymph node metastasis as well as clinical stages. On the other hand, CD163(+) MϕC did not associate with these clinicopathological factors with the exception of depth of tumor invasion and blood vessel invasion. Patients with high CD204(+) MϕC ESCCs showed poor disease-free survival (P = 0.021). Conditioned media of five ESCC cell lines (TE-8, -9, -10, -11 and -15) induced mRNA as well as protein expression of CD204 but not of CD163 with upregulation of vascular endothelial growth factor-A mRNA in TPA treated human acute monocytic leukemia cell line THP-1. These results overall indicate that CD204 is a useful marker for TAMs contributing to the angiogenesis, progression and prognosis of ESCCs whose specific tumor microenvironment may educate macrophages to be CD204(+) M2 TAMs.

  20. An aggressive solitary fibrous tumor with evidence of malignancy: a rare case report.

    PubMed

    Vimi, S; Punnya, V A; Kaveri, H; Rekha, K

    2008-09-01

    Solitary fibrous tumor (SFT) is rare mesenchymal neoplasm that has been originally and most often documented in the pleura. Recently, the ubiquitous nature of the SFT has been recognized with reports of involvement of numerous sites all over the body, i.e, upper respiratory tract, breast, somatic tissue, mediastinum, head, and neck, etc. The diagnosis of SFT still remains an enigma in our field. Furthermore, malignant SFT is extremely rare and only two cases have been reported in the oral cavity till date. Here, we present a rare case report of an aggressive solitary fibrous tumor which presented as a palatal mass and extended throughout the middle cranial fossa and exhibited features of malignancy.

  1. Molecular changes in bone marrow, tumor and serum after conductive ablation of murine 4T1 breast carcinoma.

    PubMed

    Przybyla, Beata D; Shafirstein, Gal; Vishal, Sagar J; Dennis, Richard A; Griffin, Robert J

    2014-02-01

    Thermal ablation of solid tumors using conductive interstitial thermal therapy (CITT) produces coagulative necrosis in the center of ablation. Local changes in homeostasis for surviving tumor and systemic changes in circulation and distant organs must be understood and monitored in order to prevent tumor re-growth and metastasis. The purpose of this study was to use a mouse carcinoma model to evaluate molecular changes in the bone marrow and surviving tumor after CITT treatment by quantification of transcripts associated with cancer progression and hyperthermia, serum cytokines, stress proteins and the marrow/tumor cross-talk regulator stromal-derived factor 1. Analysis of 27 genes and 22 proteins with quantitative PCR, ELISA, immunoblotting and multiplex antibody assays revealed that the gene and protein expression in tissue and serum was significantly different between ablated and control mice. The transcripts of four genes (Cxcl12, Sele, Fgf2, Lifr) were significantly higher in the bone marrow of treated mice. Tumors surviving ablation showed significantly lower levels of the Lifr and Sele transcripts. Similarly, the majority of transcripts measured in tumors decreased with treatment. Surviving tumors also contained lower levels of SDF-1α and HIF-1α proteins whereas HSP27 and HSP70 were higher. Of 16 serum chemokines, IFNγ and GM-CSF levels were lower with treatment. These results indicate that CITT ablation causes molecular changes which may slow cancer cell proliferation. However, inhibition of HSP27 may be necessary to control aggressiveness of surviving cancer stem cells. The changes in bone marrow are suggestive of possible increased recruitment of circulatory cancer cells. Therefore, the possibility of heightened bone metastasis after thermal ablation needs to be further investigated and inhibition strategies developed, if warranted.

  2. The Impact of Immune System in Regulating Bone Metastasis Formation by Osteotropic Tumors.

    PubMed

    D'Amico, Lucia; Roato, Ilaria

    2015-01-01

    Bone metastases are frequent and debilitating consequence for many tumors, such as breast, lung, prostate, and kidney cancer. Many studies report the importance of the immune system in the pathogenesis of bone metastasis. Indeed, bone and immune system are strictly linked to each other because bone regulates the hematopoietic stem cells from which all cells of the immune system derive, and many immunoregulatory cytokines influence the fate of bone cells. Furthermore, both cytokines and factors produced by immune and bone cells promote the growth of tumor cells in bone, contributing to supporting the vicious cycle of bone metastasis. This review summarizes the current knowledge on the interactions among bone, immune, and tumor cells aiming to provide an overview of the osteoimmunology field in bone metastasis from solid tumors.

  3. Tumor-induced pressure in the bone microenvironment causes osteocytes to promote the growth of prostate cancer bone metastases

    PubMed Central

    Sottnik, Joseph L.; Dai, Jinlu; Zhang, Honglai; Campbell, Brittany; Keller, Evan T.

    2015-01-01

    Crosstalk between tumor cells and their microenvironment is critical for malignant progression. Crosstalk mediators including soluble factors and direct cell contact have been identified, but roles for the interaction of physical forces between tumor cells and the bone microenvironment have not been described. Here we report preclinical evidence that tumor-generated pressure acts to modify the bone microenvironment to promote the growth of prostate cancer bone metastases. Tumors growing in mouse tibiae increased intraosseous pressure. Application of pressure to osteocytes, the main mechanotransducing cells in bone, induced PCa growth and invasion. Mechanistic investigations revealed that this process was mediated in part by upregulation of CCL5 and matrix metalloproteinases in osteocytes. Our results defined the critical contribution of physical forces to tumor cell growth in the tumor microenvironment, and they identified osteocytes as a critical mediator in the bone metastatic niche. PMID:25855383

  4. Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina

    PubMed Central

    Bruno, Oscar D.; Juárez-Allen, Lea; Christiansen, Silvia B.; Manavela, Marcos; Danilowicz, Karina; Vigovich, Carlos; Gómez, Reynaldo M.

    2015-01-01

    We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34–78 years, presenting aggressive pituitary tumors. In all the patients tested O6-methylguanine-DNA methyltransferase (MGMT) immunoexpression in surgical specimens was absent. Patients received temozolomide 140–320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson's syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing's disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on—until now—incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration. PMID:26106414

  5. Modern Interpretation of Giant Cell Tumor of Bone: Predominantly Osteoclastogenic Stromal Tumor

    PubMed Central

    Kim, Yuhree; Nizami, Saqib; Goto, Hana

    2012-01-01

    Owing to striking features of numerous multinucleated cells and bone destruction, giant cell tumor (GCT) of bone, often called as osteoclastoma, has drawn major attractions from orthopaedic surgeons, pathologists, and radiologists. The name GCT or osteoclastoma gives a false impression of a tumor comprising of proliferating osteoclasts or osteoclast precursors. The underlying mechanisms for excessive osteoclastogenesis are intriguing and GCT has served as an exciting disease model representing a paradigm of osteoclastogenesis for bone biologists. The modern interpretation of GCT is predominantly osteoclastogenic stromal cell tumors of mesenchymal origin. A diverse array of inflammatory cytokines and chemokines disrupts osteoblastic differentiation and promotes the formation of excessive multi-nucleated osteoclastic cells. Pro-osteoclastogenic cytokines such as receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin (IL)-6, and tumor necrosis factor (TNF) as well as monocyte-recruiting chemokines such as stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein (MCP)-1 participate in unfavorable osteoclastogenesis and bone destruction. This model represents a self-sufficient osteoclastogenic paracrine loop in a localized area. Consistent with this paradigm, a recombinant RANK-Fc protein and bisphosphonates are currently being tried for GCT treatment in addition to surgical excision and conventional topical adjuvant therapies. PMID:22662295

  6. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.

    PubMed

    Cooper, Odelia; Mamelak, Adam; Bannykh, Serguei; Carmichael, John; Bonert, Vivien; Lim, Stephen; Cook-Wiens, Galen; Ben-Shlomo, Anat

    2014-06-01

    As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92 %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas.

  7. Multi-Detector Computed Tomography in Evaluating Locally Aggressive and Malignant Bone Tumours

    PubMed Central

    Ramavathu, Kumar Venu Madhav; Garga, U.C.

    2015-01-01

    Objective: To evaluate the ability of Multi-Detector Computed Tomography in preoperative evaluation of locally aggressive and malignant bone tumours in correlation with histopathological findings. Materials and Methods: Twenty patients suspected of malignant bone tumours on the basis of their clinical profile were selected. Following a plain radiograph evaluation, all of them were subjected to CT scan examination. Multi Planar Reconstruction (MPR) was done in sagittal and coronal planes and also three-dimensional Volume Rendering (VR) and Maximum Intensity Projection (MIP) images were obtained. Results: Of the 20 patients, 18 underwent surgery, and their histopathological findings were compared and correlated with MDCT findings. MDCT was 92.8% sensitive and 100% specific in determining the vascularity of the tumour and also can detect displacement/ encasement/ involvement of adjacent vessels. It has a sensitivity and specificity of 100% in determining cortical break, calcification and periosteal reaction. However, it is less sensitive in detecting joint involvement. Post contrast enhancement gives details of the extent of the soft tissue component. Conclusion: Although MRI is a preferred modality in preoperative evaluation of bone tumours, CT may be used an alternative in case of non-availability of MRI, which has faster acquisition time and better resolution. Using three dimensional MPR imaging, the location and extent of the tumour can be studied. It is also useful in determining cortical discontinuity, periosteal reaction, and calcification. By virtue of MIP and VR imaging, vascularity of the tumour and its relationship with the adjacent vasculature can be established. However, it is inferior to MRI in soft tissue characterization and has poor sensitivity in detecting marrow and joint involvement. PMID:26023618

  8. Treatment Challenges with Benign Bone Tumors of the Orbit

    PubMed Central

    Merritt, Helen; Yin, Vivian T.; Pfeiffer, Margaret L.; Wang, Wei-Lien; Sniegowski, Matthew C.; Esmaeli, Bita

    2015-01-01

    Benign mesenchymal tumors of the craniofacial complex present unique challenges for orbital surgeons because of their potential for orbital compartment syndrome, ocular morbidity, and facial disfigurement and because definitive surgical management may be associated with significant morbidity. While the precise classification of such lesions depends on radiologic as well as histologic evaluations and remains controversial, benign tumors involving the bony walls of the orbit share features of bony expansion, facial deformity, and the potential to cause significant orbital and ophthalmic morbidity. We herein present 2 cases of benign mesenchymal tumors with bony involvement in the orbitofacial region (1 juvenile ossifying fibroma and 1 central giant cell granuloma) and review the current management of similar benign fibro-osseous and reactive bone lesions of the orbit. These rare entities presented share common orbital and ophthalmic manifestations and remain without any effective definitive treatment options. PMID:27171013

  9. Pulmonary metastasis of giant cell tumor of bones.

    PubMed

    Muheremu, Aikeremujiang; Niu, Xiaohui

    2014-08-20

    Giant cell tumor of bone (GCTB) accounts for 5% of primary skeletal tumors. Although it is considered to be a benign lesion, there are still incidences of pulmonary metastasis. Pulmonary metastasis of GCTB may be affected by tumor grading and localization as well as the age, gender and overall health status of the patient. Patients with local recurrence are more likely to develop pulmonary metastasis of GCTB. High expression of some genes, cytokines and chemokines may also be closely related to the metastatic potential and prognosis of GCTB. The treatment of the primary GCTB is key to the final outcome of the disease, as intralesional curettage has a significantly higher local recurrence and pulmonary metastasis rate than wide resection. However, even patients with pulmonary metastasis seem to have a good prognosis after timely and appropriate surgical resection. It is hoped that with the development of novel surgical methods and drugs, pulmonary metastasis of GCTB can be prevented and treated more effectively.

  10. [Aggressive fibromatoses in orthopedics].

    PubMed

    Adler, C P; Stock, D

    1986-01-01

    Aggressive fibromatoses which may develop either in soft tissue or in the bone present considerable problems for the pathologist trying to establish a diagnosis as well as for the radiologist and surgeon. In radiographs, a destruction of the soft and osseous tissue is seen which suggests a malignant tumor. Histologically a monomorphic connective tissue prevails in the biopsy showing no essential signs of malignancy. Under pathoanatomical aspects often a benign proliferation of the connective tissue is assumed. Surgically the tumor may either be removed in a too radical and mutilating way, or the excision may remain incomplete. Two cases of desmoplastic bone fibroma (aggressive fibromatosis in the ulna and in the sacrum) are described in which the complete tumor removal led to healing, whereas the incomplete excision of the tumor resulted in recurrences. Aggressive fibromatosis represents a semimalignant tumor which has a locally destructive and invasive growth tendency but does not metastasize. The various fibromatoses are defined with regard to their biological growth tendency and the therapeutic consequences are discussed.

  11. Integrins and bone metastasis: integrating tumor cell and stromal cell interactions.

    PubMed

    Schneider, Jochen G; Amend, Sarah R; Weilbaecher, Katherine N

    2011-01-01

    Integrins on both tumor cells and the supporting host stromal cells in bone (osteoclasts, new blood vessels, inflammatory cells, platelets and bone marrow stromal cells) play key roles in enhancing bone metastasis. Tumor cells localize to specific tissues through integrin-mediated contacts with extracellular matrix and stromal cells. Integrin expression and signaling are perturbed in cancer cells, allowing them to "escape" from cell-cell and cell-matrix tethers, invade, migrate and colonize within new tissues and matrices. Integrin signaling through αvβ3 and VLA-4 on tumor cells can promote tumor metastasis to and proliferation in the bone microenvironment. Osteoclast (OC) mediated bone resorption is a critical component of bone metastasis and can promote tumor growth in bone and αvβ3 integrins are critical to OC function and development. Tumors in the bone microenvironment can recruit new blood vessel formation, platelets, pro-tumor immune cells and bone marrow stromal cells that promote tumor growth and invasion in bone. Integrins and their ligands play critical roles in platelet aggregation (αvβ3 and αIIbβ3), hematopoietic cell mobilization (VLA-4 and osteopontin), neoangiogenesis (αvβ3, αvβ5, α6β4, and β1 integrin) and stromal function (osteopontin and VLA-4). Integrins are involved in the pathogenesis of bone metastasis at many levels and further study to define integrin dysregulation by cancer will yield new therapeutic targets for the prevention and treatment of bone metastasis.

  12. Benign Brenner tumor of the ovary detected on Tc-99m methylene diphosphonate bone scan

    SciTech Connect

    Renner, J.B.; McCartney, W.H.

    1984-11-01

    Many disease states, including neoplasia, have been detected by bone scanning. Among the neoplastic processes detected by bone imaging agents are ovarian tumors, both benign and malignant. This report is concerned with the visualization of a benign Brenner tumor during routine Tc-99m MDP bone scanning.

  13. Effects of an exercise intervention on bone mass in pediatric bone tumor patients.

    PubMed

    Müller, C; Winter, C; Boos, J; Gosheger, G; Hardes, J; Vieth, V; Rosenbaum, D

    2014-07-01

    The aim was to evaluate the effects of additional exercises during inpatient stays on bone mass in pediatric bone tumor patients. 21 patients were non-randomly allocated either to the exercise group (n = 10) or the control group (n = 11). DXA of the lumbar spine, the non-affected femur and both calcanei was performed after completion of neoadjuvant chemotherapy (baseline), as well as 6 and 12 months after baseline. Bone mineral content (BMC), bone mineral density (BMD) and height-corrected lumbar spine Z-scores were determined. Group changes after 6 and 12 months were compared by covariance analyses. Additionally, daily physical activities (PA) were assessed by means of accelerometry. After adjusting for initial age, height and weight, mean reductions in lumbar spine and femoral BMC were lower in the exercise group (not significant). Effect sizes during the observational period for lumbar spine and femur BMC were generally small (partial η² = 0.03). The exercise group demonstrated substantially higher PA levels in terms of gait cycles per day, per hour and moderate PA (activities above 40 gait cycles per minute). Additional exercises for bone tumor patients are feasible during hospitalization. Though the intervention did not influence BMC, it appeared beneficial regarding PA promotion with respect to volume and intensity.

  14. Aggressive CD34-positive fibrous scalp lesion of childhood: extrapulmonary solitary fibrous tumor.

    PubMed

    Ramdial, P K; Madaree, A

    2001-01-01

    Although solitary fibrous tumor (SFT) was originally described as a pleural tumor, an increasing number of extrapleural sites of SFTs have been documented. This has been attributed not only to the heightened awareness of the spectrum of histopathological features that characterizes SFTs but also to the recognition of the role of CD34 immunostaining in soft tissue tumors in general, and in SFTs in particular. Despite the large number of documented extrapleural SFTs in adults, cranial SFTs are rare, having been documented in the meninges, scalp, and infratemporal fossa. Extrapleural SFTs are, to date, an unrecognized entity in children. We document an aggressive fibrous scalp lesion in a 30-month-old female child that demonstrated features common to benign cranial fasciitis and SFT. However, based on bright, diffuse CD34 antigen immunopositivity, a diagnosis of SFT was made. The need to include the CD34 antigen stain in a panel of immunohistochemical markers used to assess spindle cell lesions of childhood is emphasized.

  15. Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion

    PubMed Central

    Roselli, Séverine; Pundavela, Jay; Demont, Yohann; Faulkner, Sam; Keene, Sheridan; Attia, John; Jiang, Chen Chen; Zhang, Xu Dong; Walker, Marjorie M.; Hondermarck, Hubert

    2015-01-01

    The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion. PMID:25871389

  16. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  17. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers

    PubMed Central

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-01-01

    Abstract A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414–13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674–18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292–13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097–14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects. GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new

  18. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  19. Tumor-host cell interactions in the bone disease of myeloma

    PubMed Central

    Fowler, Jessica A.; Edwards, Claire M.; Croucher, Peter I.

    2010-01-01

    Multiple myeloma is a hematological malignancy that is associated with the development of a destructive osteolytic bone disease, which is a major cause of morbidity for patients with myeloma. Interactions between myeloma cells and cells of the bone marrow microenvironment promote both tumor growth and survival and bone destruction, and the osteolytic bone disease is now recognized as a contributing component to tumor progression. Since myeloma bone disease is associated with both an increase in osteoclastic bone resorption and a suppression of osteoblastic bone formation, research to date has largely focused upon the role of the osteoclast and osteoblast. However, it is now clear that other cell types within the bone marrow, including cells of the immune system, mesenchymal stem cells and bone marrow stromal cells, can contribute to the development of myeloma bone disease. This review discusses the cellular mechanisms and potential therapeutic targets that have been implicated in myeloma bone disease. PMID:20615487

  20. AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas.

    PubMed

    Qi, Wenqing; Liu, Xiaobing; Cooke, Laurence S; Persky, Daniel O; Miller, Thomas P; Squires, Matthew; Mahadevan, Daruka

    2012-06-15

    Aurora kinases are oncogenic serine/threonine kinases that play key roles in regulating the mitotic phase of the eukaryotic cell cycle. Auroras are overexpressed in numerous tumors including B-cell non-Hodgkin's lymphomas and are validated oncology targets. AT9283, a pan-aurora inhibitor inhibited growth and survival of multiple solid tumors in vitro and in vivo. In this study, we demonstrated that AT9283 had potent activity against Aurora B in a variety of aggressive B-(non-Hodgkin lymphoma) B-NHL cell lines. Cells treated with AT9283 exhibited endoreduplication confirming the mechanism of action of an Aurora B inhibitor. Also, treatment of B-NHL cell lines with AT9283 induced apoptosis in a dose and time dependent manner and inhibited cell proliferation with an IC(50) < 1 μM. It is well known that inhibition of auroras (A or B) synergistically enhances the effects of microtubule targeting agents such as taxanes and vinca alkaloids to induce antiproliferation and apoptosis. We evaluated whether AT9283 in combination with docetaxel is more efficient in inducing apoptosis than AT9283 or docetaxel alone. At very low doses (5 nM) apoptosis was doubled in the combination (23%) compared to AT9283 or docetaxel alone (10%). A mouse xenograft model of mantle cell lymphoma demonstrated that AT9283 at 15 mg/kg and docetaxel (10 mg/kg) alone had modest anti-tumor activity. However, AT9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrated a statistically significant tumor growth inhibition and enhanced survival. Together, our results suggest that AT9283 plus docetaxel may represent a novel therapeutic strategy in B-cell NHL and warrant early phase clinical trial evaluation. PMID:21796626

  1. AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas.

    PubMed

    Qi, Wenqing; Liu, Xiaobing; Cooke, Laurence S; Persky, Daniel O; Miller, Thomas P; Squires, Matthew; Mahadevan, Daruka

    2012-06-15

    Aurora kinases are oncogenic serine/threonine kinases that play key roles in regulating the mitotic phase of the eukaryotic cell cycle. Auroras are overexpressed in numerous tumors including B-cell non-Hodgkin's lymphomas and are validated oncology targets. AT9283, a pan-aurora inhibitor inhibited growth and survival of multiple solid tumors in vitro and in vivo. In this study, we demonstrated that AT9283 had potent activity against Aurora B in a variety of aggressive B-(non-Hodgkin lymphoma) B-NHL cell lines. Cells treated with AT9283 exhibited endoreduplication confirming the mechanism of action of an Aurora B inhibitor. Also, treatment of B-NHL cell lines with AT9283 induced apoptosis in a dose and time dependent manner and inhibited cell proliferation with an IC(50) < 1 μM. It is well known that inhibition of auroras (A or B) synergistically enhances the effects of microtubule targeting agents such as taxanes and vinca alkaloids to induce antiproliferation and apoptosis. We evaluated whether AT9283 in combination with docetaxel is more efficient in inducing apoptosis than AT9283 or docetaxel alone. At very low doses (5 nM) apoptosis was doubled in the combination (23%) compared to AT9283 or docetaxel alone (10%). A mouse xenograft model of mantle cell lymphoma demonstrated that AT9283 at 15 mg/kg and docetaxel (10 mg/kg) alone had modest anti-tumor activity. However, AT9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrated a statistically significant tumor growth inhibition and enhanced survival. Together, our results suggest that AT9283 plus docetaxel may represent a novel therapeutic strategy in B-cell NHL and warrant early phase clinical trial evaluation.

  2. Epiphyseal Sparing and Reconstruction by Frozen Bone Autograft after Malignant Bone Tumor Resection in Children

    PubMed Central

    Hamed Kassem Abdelaal, Ahmed; Yamamoto, Norio; Hayashi, Katsuhiro; Takeuchi, Akihiko; Miwa, Shinji; Tsuchiya, Hiroyuki

    2015-01-01

    Limb salvage surgery has become the standard treatment for malignant primary bone tumors in the extremities. Limb salvage represents a challenge in skeletally immature patients. Several treatment options are available for limb reconstruction after tumor resection in children. We report our results using the technique of epiphyseal sparing and reconstruction with frozen autograft bone in 18 children. The mean follow-up period for the all patients included in this study is 72 ± 26 m. Eight patients remained disease-free, seven patients lived with no evidence of disease, two were alive but with disease, and one patient died of the disease. Five- and ten-year rates of survival were 94.4%. Graft survival at 5 and 10 years was 94.4%. Functional outcome using the Enneking scale was excellent in 17 patients (94.4%) and poor in one patient (5.5%). Complications include 2 nonunions, 2 fractures, 2 deep infections, 1 soft tissue recurrence, and leg length discrepancy in 7 cases. This technique is a good reconstructive choice in a child with a nonosteolytic primary or secondary bone tumor, responsive to chemotherapy, without involvement of the articular cartilage. It is a straight forward, effective, and biological technique, which affords immediate mobilization of joints and possible cryoimmune effects, with excellent long term functional outcome and less complication. PMID:27034614

  3. Image-Guided Percutaneous Ablation of Bone and Soft Tissue Tumors

    PubMed Central

    Kurup, A. Nicholas; Callstrom, Matthew R.

    2010-01-01

    Image-guided percutaneous ablation of bone and soft tissue tumors is an effective minimally invasive alternative to conventional therapies, such as surgery and external beam radiotherapy. Proven applications include treatment of benign primary bone tumors, particularly osteoid osteoma, as well as palliation of painful bone metastases. Use of percutaneous ablation in combination with cementoplasty can provide stabilization of metastases at risk for fracture. Local control of oligometastatic disease and treatment of desmoid tumors are emerging applications. PMID:22550367

  4. [Genetic Aberration and Pathological Diagnosis in Bone and Soft-Tissue Tumors].

    PubMed

    Iura, Kunio; Oda, Yoshinao

    2016-03-01

    Bone and soft-tissue sarcomas comprise a rare, complex, and heterogeneous group of tumors for which it is difficult for even experienced pathologists to provide a conclusive diagnosis. The number of diagnoses made using genetic analysis has increased since the detection of fusion genes in several soft-tissue tumors in the 1990s. Moreover, other specific genetic aberrations have been reported in various bone and soft-tissue tumors. In addition, molecular therapeutic targets have been sought in advanced cases of soft-tissue and bone tumors similar to other organ malignancies. To enable the pathological diagnosis of bone and soft-tissue tumors, it is necessary to combine histological diagnosis with immunohistochemistry and gene analysis findings including fusion gene or other genetic aberrations. In this review, we describe the fusion genes recently reported in bone and soft-tissue tumors such as solitary fibrous tumor, aneurysmal bone cyst, nodular fasciitis, CIC-DUX4 fusion gene-positive small round cell tumors, or BCOR-CCNB3-positive sarcoma as well as other genetic aberrations in dedifferentiated liposarcoma, malignant rhabdoid tumor, cartilaginous tumor, Langerhans cell histiocytosis chondroblastoma, or giant cell tumor of the bone. We also demonstrate their association with pathological diagnosis. PMID:27067846

  5. An unusually large aggressive adenomatoid odontogenic tumor of maxilla involving the third molar: A clinical case report

    PubMed Central

    Dhupar, Vikas; Akkara, Francis; Khandelwal, Pulkit

    2016-01-01

    Adenomatoid odontogenic tumor (AOT) is a rare tumor comprising only 3% of all odontogenic tumors. It is a benign, encapsulated, noninvasive, nonaggressive, slowly growing odontogenic lesion associated with an impacted tooth. These lesions may go unnoticed for years. The usual treatment is enucleation and curettage, and the lesion does not recur. Here, we present a rare case of an unusually large aggressive AOT of maxilla associated with impacted third molar. The authors also discuss clinical, radiographic, histopathologic, and therapeutic features of the case. Subtotal maxillectomy with simultaneous reconstruction of the surgical defect with temporalis myofascial flap was planned and carried out. PMID:27095910

  6. Advantages of Pressurized-Spray Cryosurgery in Giant Cell Tumors of the Bone

    PubMed Central

    Dabak, Nevzat; Göçer, Hasan; Çıraklı, Alper

    2016-01-01

    Background: Giant Cell Tumor is considered a benign, local and aggressive tumor. Although considered a benign bone tumor, it is still the subject of discussion and research because of the associated local bone destruction, as well as high rates of recurrence and distant metastases. Options are being developed for both surgical techniques and adjuvant therapies. Aims: The present study evaluated the administration of cryotherapy via a pressurized-spray technique in giant cell tumors of the bone. Study Design: Cross-sectional study. Methods: The study included 40 patients who were treated with extensive curettage and cryotherapy at various locations during the period from February 2006 to December 2013. Informed consent forms were obtained from the participants and ethics committee approval was taken from the local ethics committee of Ondokuz Mayıs University. The pressurized-spray technique was performed using liquid nitrogen. The patients were evaluated with respect to age, gender, radiological appearance, treatment modality, duration of follow-up, skin problems and recurrence. Results: Twenty-one patients were female; 19 were male. The average age of the patients was 33 years (range: 16–72 years), and the average duration of follow-up was 43 months (range: 12–80 months). The average time from the onset of the complaints to the diagnosis was 6 months (range: 2–12 months). Based on the Campanacci classification: 9 patients were Grade I; 25 patients were Grade II; six patients were Grade III. The lesion was located in the femur in 14 patients, in the tibia in 11 patients, in the radius in 5 patients, in the pelvis in 4 patients, in the fibula in 3 patients, in the metatarsal in 2 patients and in the phalanges of the hand in one patient. One patient had postoperative early fracture. None of the patients had skin problems and infection. Three (7.5%) of the patients had recurrence. Conclusion: It was found that cryotherapy was highly effective in the lesions

  7. Miscellaneous cancers (lung, thyroid, renal cancer, myeloma, and neuroendocrine tumors): role of SPECT and PET in imaging bone metastases.

    PubMed

    Chua, Sue; Gnanasegaran, Gopinath; Cook, Gary J R

    2009-11-01

    In this review, we assess the current role of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) in the imaging of skeletal metastatic disease from a miscellaneous group of malignancies, including lung, thyroid, and renal carcinomas; multiple myeloma; and neuroendocrine tumors, and consider how recent advances may enhance their effectiveness in this area. Bone scintigraphy using technetium-labeled diphosphonates has long been the mainstay of functional imaging of bony metastases, but is of limited value in myeloma and aggressive osteolytic metastases, and has the limitation of relatively poor specificity. SPECT, as a tomographic imaging technique, produces three-dimensional images of tracer distribution from multiplanar images. Its application to bone scintigrams greatly aids accurate anatomic localization and sensitivity in detection of foci of tracer uptake. SPECT can equally be applied to scintigrams using radiotracers, which are specific for particular groups of tumors, such as somatostatin analogs for neuroendocrine tumors. The advent of combined SPECT/computed tomography (CT) systems has further enhanced the accuracy of SPECT in all these malignancies. PET uses positron-emitting radiotracers and achieves a higher spatial resolution than single-photon imaging. Its high resolution and coverage of the entire body have made it a highly effective technique for the evaluation of skeletal metastatic disease, particularly when combined with CT. (18)F-fluorodeoxyglucose ((18)F-FDG)-PET/CT now forms part of routine staging for many carcinomas, such as non-small-cell lung carcinomas, and may obviate the need for routine staging scintigraphy in these patients. As uptake of the most common PET radiotracer, (18)F-FDG, is dependent on the increased cellular metabolism of most tumors, it may enable earlier detection of metastatic foci than bone scintigraphy, which relies on detecting an osteoblastic response. Another significant

  8. [Metaloosteosynthesis in the pathological fracture of the bone with benign and malignant tumors].

    PubMed

    Protsenko, V V

    2004-01-01

    Metaloosteosynthesis of pathological fractures of bone on the background of bone tumors was carried out in 56 patients in the department of tumors of locomotion system. The good results of the treatment were obtained. In 42% of the cases it was possible to reconstruct the function of extremities. 53% of patients succeeded to avoid amputation or exarticulation of an extremity.

  9. Histological Regression of Giant Cell Tumor of Bone Following RANK Ligand Inhibition

    PubMed Central

    Dietrich, Martin F.; Cavuoti, Dominick; Landay, Michael

    2014-01-01

    Lung metastases are a rare complication of giant cell tumors of bone. We herein describe an interesting case of histological regression and size reduction of lung metastases originating from a primary giant cell tumor of bone in response to the RANK ligand inhibitor denosumab. PMID:26425630

  10. p63 as a prognostic marker for giant cell tumor of bone

    PubMed Central

    kakizaki, Hiroshi; Okada, Kyoji; Torigoe, Tomoaki; Kusumi, Tomomi

    2013-01-01

    Background and purpose Giant cell tumor of bone (GCT) is sometimes difficult to distinguish from other giant-cell-rich tumors such as chondroblastoma (CHB) and aneurysmal bone cyst (ABC). The usefulness of p63 as a diagnostic marker for GCT is controversial. While there have been no reports about p63 as a prognostic marker for local recurrence, various p63-positive rates in GCT have been reported. The purpose of this study was to investigate retrospectively whether p63 is useful as a diagnostic marker and/or a prognostic marker for local recurrence of GCT. Methods This study included 36 patients diagnosed with either GCT (n = 16), CHB (n = 9), ABC (n = 7), or non-ossifying fibroma (NOF) (n = 4). p63 immunostaining was performed for all specimens. The mean p63-positive rate was compared with the four diseases and between the recurrent and non-recurrent cases of GCT. Results Although the mean p63-positive rate for GCT (36.3%) was statistically higher than that of all other diseases examined (CHB: 15.2%; ABC: 5.8%; NOF: 3.4%), p63 was not specific for GCT. The mean p63-positive rate for recurrent GCT cases (73.6%) was statistically higher than that for non-recurrent cases (29.1%). Conclusion In the diagnosis of GCT, p63 is a useful but not a conclusive marker. However, p63 did appear to indicate the biological aggressiveness of GCT. Therefore, p63 may help surgeons to estimate the risk of recurrence after surgery and help them to choose the best treatment for each GCT case. PMID:23033898

  11. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken’s embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

  12. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas.

    PubMed

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken's embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

  13. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    PubMed Central

    2011-01-01

    Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra

  14. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis.

    PubMed

    Karamurzin, Yevgeniy S; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R; Patel, Prusha; Pike, Malcolm C; Soslow, Robert A; Park, Kay J

    2015-11-01

    Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon.

  15. Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness.

    PubMed

    Gong, X; Yi, J; Carmon, K S; Crumbley, C A; Xiong, W; Thomas, A; Fan, X; Guo, S; An, Z; Chang, J T; Liu, Q J

    2015-09-01

    The four R-spondins (RSPO1-4) and their three related receptors LGR4, 5 and 6 (LGR4-6) have emerged as a major ligand-receptor system with critical roles in development and stem cell survival through modulation of Wnt signaling. Recurrent, gain-of-expression gene fusions of RSPO2 (to EIF3E) and RSPO3 (to PTPRK) occur in a subset of human colorectal cancer. However, the exact roles and mechanisms of the RSPO-LGR system in oncogenesis remain largely unknown. We found that RSPO3 is aberrantly expressed at high levels in approximately half of Keap1-mutated lung adenocarcinomas (ADs). This high RSPO3 expression is driven by a combination of demethylation of its own promoter region and deficiency in Keap1 instead of gene fusion as in colon cancer. Patients with RSPO3-high tumors (~9%, 36/412) displayed much poorer survival than the rest of the cohort (median survival of 28 vs 163 months, log-rank test P<0.0001). Knockdown (KD) of RSPO3, LGR4 or their signaling mediator IQGAP1 in lung cancer cell lines with Keap1 deficiency and high RSPO3-LGR4 expression led to reduction in cell proliferation and migration in vitro, and KD of LGR4 or IQGAP1 resulted in decrease in tumor growth and metastasis in vivo. These findings suggest that aberrant RSPO3-LGR4 signaling potentially acts as a driving mechanism in the aggressiveness of Keap1-deficient lung ADs.

  16. Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness

    PubMed Central

    Gong, Xing; Yi, Jing; Carmon, Kendra S.; Crumbley, Christine A.; Xiong, Wei; Thomas, Anthony; Fan, Xuejun; Guo, Shan; An, Zhiqiang; Chang, Jeffrey T.; Liu, Qingyun J.

    2015-01-01

    The four R-spondins (RSPO1-4) and their three related receptors LGR4, 5 and 6 (LGR4-6) have emerged as a major ligand-receptor system with critical roles in development and stem cell survival through modulation of Wnt signaling. Recurrent, gain-of-expression gene fusions of RSPO2 (to EIF3E) and RSPO3 (to PTPRK) occur in a subset of human colorectal cancer. However, the exact roles and mechanisms of the RSPO-LGR system in oncogenesis remain largely unknown. We found that RSPO3 is aberrantly expressed at high levels in approximately half of the Keap1-mutated lung adenocarcinomas. This high RSPO3 expression is driven by a combination of demethylation of its own promoter region and deficiency in Keap1 instead of gene fusion as in colon cancer. Patients with RSPO3-high tumors (~9%, 36/412) displayed much poorer survival than the rest of the cohorts (median survival of 28 vs. 163 months, logrank test p < 0.0001). Knockdown of RSPO3, LGR4, or their signaling mediator IQGAP1 in lung cancer cell lines with Keap1 deficiency and high RSPO3-LGR4 expression led to reduction in cell proliferation and migration in vitro, and knockdown of LGR4 or IQGAP1 resulted in decrease in tumor growth and metastasis in vivo. These findings suggest that aberrant RSPO3-LGR4 signaling potentially acts as a driving mechanism in the aggressiveness of Keap1-deficient lung adenocarcinomas. PMID:25531322

  17. Xanthogranulomatous Osteomyelitis of Proximal Femur Masquerading as Benign Bone Tumor.

    PubMed

    Singh, Shailendra; Batra, Sahil; Maini, Lalit; Gautam, Virender Kumar

    2015-08-01

    We describe a case of xanthogranulomatous osteomyelitis (XO) of the proximal femur in a 65-year-old woman who presented with pain of 6 months' duration in the right hip. Plain radiographs showed a lytic well-defined lesion in the right peritrochanteric region suggestive of a benign neoplastic etiology. The gross and histopathologic examination of the curettage specimen was consistent with XO. Xanthogranulomatous osteomyelitis is a rare chronic inflammatory process that is characterized by the presence of a large number of lipid-containing macrophages with an admixture of lymphocytes, plasma cells, and neutrophils. Gross and radiologic examination of this entity can mimic malignancy, and differentiation should be confirmed by histopathologic evaluation. To the best of our knowledge, XO of the femur has not been reported in the English-language literature. The rarity of this condition and its resemblance to bone tumors form the basis of this case report. PMID:26251942

  18. Interstitial ultrasound ablation of tumors within or adjacent to bone: Contributions of preferential heating at the bone surface

    NASA Astrophysics Data System (ADS)

    Scott, Serena J.; Prakash, Punit; Salgaonkar, Vasant; Jones, Peter D.; Cam, Richard N.; Han, Misung; Rieke, Viola; Burdette, E. Clif; Diederich, Chris J.

    2013-02-01

    Preferential heating of bone due to high ultrasound attenuation may enhance thermal ablation performed with cathetercooled interstitial ultrasound applicators in or near bone. At the same time, thermally and acoustically insulating cortical bone may protect sensitive structures nearby. 3D acoustic and biothermal transient finite element models were developed to simulate temperature and thermal dose distributions during catheter-cooled interstitial ultrasound ablation near bone. Experiments in ex vivo tissues and tissue-mimicking phantoms were performed to validate the models and to quantify the temperature profiles and ablated volumes for various distances between the interstitial applicator and the bone surface. 3D patient-specific models selected to bracket the range of clinical usage were developed to investigate what types of tumors could be treated, applicator configurations, insertion paths, safety margins, and other parameters. Experiments show that preferential heating at the bone surface decreases treatment times compared to when bone is absent and that all tissue between an applicator and bone can be ablated when they are up to 2 cm apart. Simulations indicate that a 5-7 mm safety margin of normal bone is needed to protect (thermal dose < 6 CEM43°C and T < 45°C) sensitive structures behind ablated bone. In 3D patient-specific simulations, tumors 1.0-3.8 cm (L) and 1.3-3.0 cm (D) near or within bone were ablated (thermal dose > 240 CEM43°C) within 10 min without damaging the nearby spinal cord, lungs, esophagus, trachea, or major vasculature. Preferential absorption of ultrasound by bone may provide improved localization, faster treatment times, and larger treatment zones in tumors in and near bone compared to other heating modalities.

  19. Interleukin-27 Gene Delivery for Modifying Malignant Interactions Between Prostate Tumor and Bone

    PubMed Central

    Zolochevska, Olga; Ellis, Jayne; Parelkar, Sangram; Chan-Seng, Delphine; Emrick, Todd; Wei, Jingna; Patrikeev, Igor; Motamedi, Massoud

    2013-01-01

    Abstract We have examined the role of a novel cytokine, interleukin-27 (IL-27), in mediating interactions between prostate cancer and bone. IL-27 is the most recently characterized member of the family of heterodimeric IL-12-related cytokines and has shown promise in halting tumor growth and mediating tumor regression in several cancer models, including prostate cancer. Prostate cancer is frequently associated with metastases to the bone, where the tumor induces a vicious cycle of communication with osteoblasts and osteoclasts to induce bone lesions, which are a significant cause of pain and skeletal-related events for patients, including a high fracture risk. We describe our findings in the effects of IL-27 gene delivery on prostate cancer cells, osteoblasts, and osteoclasts at different stages of differentiation. We applied the IL-27 gene delivery protocol in vivo utilizing sonoporation (sonodelivery) with the goal of treating and reducing the growth of prostate cancer at a bone metastatic site in vivo. We used a new model of immune-competent prostate adenocarcinoma and characterized the tumor growth reduction, gene expression, and effector cellular profiles. Our results suggest that IL-27 can be effective in reducing tumor growth, can help normalize bone structure, and can promote enhanced accumulation of effector cells in prostate tumors. These results are promising, because they are relevant to developing a novel IL-27-based strategy that can treat both the tumor and the bone, by using this simple and effective sonodelivery method for treating prostate tumor bone metastases. PMID:24028178

  20. Tumoral calcinosis associated with sarcoidosis and positive bone and gallium imaging

    SciTech Connect

    Wolpe, F.M.; Khedkar, N.Y.; Gordon, D.; Werner, P.; Shirazi, P.; Al-Sabban, M.H.

    1987-07-01

    A 63-year-old female with biopsy proven tumoral calcinosis presented with progressive and recurrent swelling and tenderness of the right hip, thigh, elbow, and wrist. Both gallium and bone imaging demonstrated intense, congruent uptake in these areas. This is the third case of tumoral calcinosis with sarcoidosis documented in the literature. However, these are the first published bone and gallium scans in a patient with a history of sarcoidosis and tumoral calcinosis.

  1. Development of bone-targeted catalase derivatives for inhibition of bone metastasis of tumor cells in mice.

    PubMed

    Zheng, Yunlong; Nishikawa, Makiya; Ikemura, Mai; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2012-02-01

    Removal of hydrogen peroxide by delivering catalase to the vicinity of metastasizing tumor cells is a promising approach for inhibiting tumor metastasis. To inhibit bone metastasis, catalase was conjugated with 3,5-di(ethylamino-2,2-bisphosphono)benzoic acid (Bip), a derivative of bone-seeking bisphosphonates, polyethylene glycol (PEG), or both. Bip-conjugated catalase derivatives, that is, catalase-Bip and PEG-catalase-Bip, exhibited a higher affinity for bone matrix as compared with their counterparts without Bip. The tissue distribution of (111) In-labeled catalase derivatives indicated that the accumulation of radioactivity in bones was increased by conjugation of either Bip or PEG with catalase. An experimental bone metastasis model was developed by injecting male C57BL/6 mice with murine melanoma B16-BL6/Luc cells, which stably express firefly luciferase into left ventricle. Repeated injections of catalase to tumor-bearing mice had no significant effect on the number of melanoma cells in tibiae and femurs, whereas injections of catalase-Bip, PEG-catalase, or PEG-catalase-Bip significantly reduced the number. These results indicate that targeted delivery of catalase to the bones can be achieved by conjugating the enzyme with either Bip or PEG, and this delivery is effective in inhibiting the bone metastasis of tumor cells. PMID:21953593

  2. A reappraisal of hemangiopericytoma of bone; analysis of cases reclassified as synovial sarcoma and solitary fibrous tumor of bone.

    PubMed

    Verbeke, Sofie L J; Fletcher, Christopher D M; Alberghini, Marco; Daugaard, Søren; Flanagan, Adrienne M; Parratt, Tim; Kroon, Herman M; Hogendoorn, Pancras C W; Bovée, Judith V M G

    2010-06-01

    Hemangiopericytoma (HPC) was first described as a neoplasm with distinct morphologic features, presumably composed of pericytes. In soft tissue, it is accepted that most such lesions are solitary fibrous tumors (SFTs), monophasic synovial sarcomas (SSs), or myofibromatoses. It is unclear whether HPC of bone exists. We reviewed 9 primary "HPC" of bone from 4 institutions diagnosed between 1952 and 2002. Immunohistochemistry was performed for CD31, CD34, von Willebrand factor, smooth muscle actin, keratin AE1/AE3, and epithelial membrane antigen. There were 4 male and 5 female patients between 21 and 73 years. All tumors were located within bone, either sited within spine or extremities. All tumors showed thin-walled branching vessels surrounded by undifferentiated spindle or round cells. These cells showed variation in their morphologic pattern: 6 tumors showed a pattern-less architecture and varying cellularity, consistent with SFT; 3 of 5 cases examined were CD34-positive. Three tumors showed more densely packed sheets and fascicles of poorly differentiated cells, resembling SS, of which 2 showed focal staining for keratin AE1/AE3 or epithelial membrane antigen. Fluorescent in-situ hybridization confirmed the presence of SS18 rearrangement in 1 of 2 tumors examined. In conclusion, similar to their soft-tissue counterpart, HPC-like features in bone are a nonspecific growth pattern rather than a true diagnosis. We confirm the existence of 2 entities: SFT and SS of bone. Both are characterized by distinct morphology and immunohistochemical profile. SFT of bone is located within spine and has a better prognosis, whereas SS of bone is located within long bones having a poor prognosis.

  3. Sub-100 nm Gold Nanomatryoshkas Improve Photo-thermal Therapy Efficacy in Large and Highly Aggressive Triple Negative Breast Tumors

    PubMed Central

    Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-01-01

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or nectrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising of concentric gold-silica-gold layers compared to conventional ~150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5X accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  4. Galectin-3 in bone tumor microenvironment: a beacon for individual skeletal metastasis management.

    PubMed

    Nakajima, Kosei; Kho, Dong Hyo; Yanagawa, Takashi; Zimel, Melissa; Heath, Elisabeth; Hogan, Victor; Raz, Avraham

    2016-06-01

    The skeleton is frequently a secondary growth site of disseminated cancers, often leading to painful and devastating clinical outcomes. Metastatic cancer distorts bone marrow homeostasis through tumor-derived factors, which shapes different bone tumor microenvironments depending on the tumor cells' origin. Here, we propose a novel insight on tumor-secreted Galectin-3 (Gal-3) that controls the induction of an inflammatory cascade, differentiation of osteoblasts, osteoclasts, and bone marrow cells, resulting in bone destruction and therapeutic failure. In the approaching era of personalized medicine, the current treatment modalities targeting bone metastatic environments are provided to the patient with limited consideration of the cancer cells' origin. Our new outlook suggests delivering individual tumor microenvironment treatments based on the expression level/activity/functionality of tumor-derived factors, rather than utilizing a commonly shared therapeutic umbrella. The notion of "Gal-3-associated bone remodeling" could be the first step toward a specific personalized therapy for each cancer type generating a different bone niche in patients afflicted with non-curable bone metastasis.

  5. Galectin-3 in bone tumor microenvironment: a beacon for individual skeletal metastasis management.

    PubMed

    Nakajima, Kosei; Kho, Dong Hyo; Yanagawa, Takashi; Zimel, Melissa; Heath, Elisabeth; Hogan, Victor; Raz, Avraham

    2016-06-01

    The skeleton is frequently a secondary growth site of disseminated cancers, often leading to painful and devastating clinical outcomes. Metastatic cancer distorts bone marrow homeostasis through tumor-derived factors, which shapes different bone tumor microenvironments depending on the tumor cells' origin. Here, we propose a novel insight on tumor-secreted Galectin-3 (Gal-3) that controls the induction of an inflammatory cascade, differentiation of osteoblasts, osteoclasts, and bone marrow cells, resulting in bone destruction and therapeutic failure. In the approaching era of personalized medicine, the current treatment modalities targeting bone metastatic environments are provided to the patient with limited consideration of the cancer cells' origin. Our new outlook suggests delivering individual tumor microenvironment treatments based on the expression level/activity/functionality of tumor-derived factors, rather than utilizing a commonly shared therapeutic umbrella. The notion of "Gal-3-associated bone remodeling" could be the first step toward a specific personalized therapy for each cancer type generating a different bone niche in patients afflicted with non-curable bone metastasis. PMID:27067726

  6. [Microsurgical transplantation of bone tumors of uncertain prognosis in athymic nude mice].

    PubMed

    Duprez, A; Féry, A; Sommelet, J

    1986-01-01

    Eight cases of human bone or soft tissue tumours were transplanted to nude mice. After such transplants to nude mice which are immunologically deficient, the malignant tumors developed like benign tumours, but maintaining malignant cytological characteristics. The transplants of normal human tissues or of benign tumours decreased in size or remained stable. The technique allowed a change of an original diagnosis of osteosarcoma to a final diagnosis of chondrosarcoma. It made it possible to diagnose a benign osteoblastoma, the diagnosis of which was doubtful before the transplant between osteosarcoma and chondroblastoma. It was possible to diagnose the malignancy of a haemangiopericytoma of muscle. Two aggressive tumours--a non-ossifying fibroma and a giant-cell tumour--were rated as benign after transplantation. This technique also allowed a more precise diagnosis of the grade of one chondrosarcoma and one osteosarcoma. Finally, transplantation also made it possible to test the efficacy of chemotherapy. In a patient so treated, the extreme cell proliferation after transplantation to the nude mouse led to a change in the drugs administered.

  7. Advances in the biology of bone metastasis: how the skeleton affects tumor behavior.

    PubMed

    Sterling, Julie A; Edwards, James R; Martin, T John; Mundy, Gregory R

    2011-01-01

    It is increasingly evident that the microenvironment of bone can influence the cancer phenotype in many ways that favor growth in bone. The ability of cancer cells to adhere to bone matrix and to promote osteoclast formation are key requirements for the establishment and growth of bone metastases. Several cytokine products of breast cancers (e.g. PTHrP, IL-11, IL-8) have been shown to act upon host cells of the bone microenvironment to promote osteoclast formation, allowing for excessive bone resorption. The increased release of matrix-derived growth factors, especially TGF-β, acts back upon the tumor to facilitate further tumor expansion and enhance cytokine production, and also upon osteoblasts to suppress bone formation. This provides a self-perpetuating cycle of bone loss and tumor growth within the skeleton. Other contributing factors favoring tumor metastasis and colonization in bone include the unique structure and stiffness of skeletal tissue, along with the diverse cellular composition of the marrow environment (e.g. bone cells, stromal fibroblasts, immune cells), any of which can contribute to the phenotypic changes that can take place in metastatic deposits that favor their survival. Additionally, it is also apparent that breast cancer cells begin to express different bone specific proteins as well as proteins important for normal breast development and lactation that allow them to grow in bone and stimulate bone destruction. Taken together, these continually emerging areas of study suggest new potential pathways important in the pathogenesis of bone metastasis and potential areas for targeting therapeutics.

  8. Multilobular tumor of bone in an African wild dog (Lycaon pictus).

    PubMed

    McAloose, Denise; Raske, Matthew; Moore, Robert; Rodriguez, Carlos E

    2012-12-01

    A 13-mo-old, captive-born, female African wild dog (Lycaon pictus) was presented with a progressively enlarging, firm mass on the dorsum of the head. Due to rapid tumor growth and the development of neurologic signs, elective euthanasia and a complete postmortem were performed 2 months after initial presentation. Histologic findings were similar in both antemortem biopsy and postmortem samples from the tumor and consisted of nodules of cartilage and/or bone separated by thin interconnected trabeculae that contained spindle-shaped cells, consistent with multilobular tumor of bone. Very few reports of tumors in the endangered African wild dog have been published to date. To the authors' knowledge, this is the first report of an osseous tumor in an African wild dog and the first report of a multilobular tumor of bone in a nondomestic canid. PMID:23272370

  9. Multilobular tumor of bone in an African wild dog (Lycaon pictus).

    PubMed

    McAloose, Denise; Raske, Matthew; Moore, Robert; Rodriguez, Carlos E

    2012-12-01

    A 13-mo-old, captive-born, female African wild dog (Lycaon pictus) was presented with a progressively enlarging, firm mass on the dorsum of the head. Due to rapid tumor growth and the development of neurologic signs, elective euthanasia and a complete postmortem were performed 2 months after initial presentation. Histologic findings were similar in both antemortem biopsy and postmortem samples from the tumor and consisted of nodules of cartilage and/or bone separated by thin interconnected trabeculae that contained spindle-shaped cells, consistent with multilobular tumor of bone. Very few reports of tumors in the endangered African wild dog have been published to date. To the authors' knowledge, this is the first report of an osseous tumor in an African wild dog and the first report of a multilobular tumor of bone in a nondomestic canid.

  10. Imaging of bone tumors using a monoclonal antibody raised against human osteosarcoma

    SciTech Connect

    Armitage, N.C.; Perkins, A.C.; Pimm, M.V.; Wastie, M.; Hopkins, J.S.; Dowling, F.; Baldwin, R.W.; Hardcastle, J.D.

    1986-07-01

    The radiolabeled monoclonal antibody 791T/36 raised against a human osteosarcoma was injected into 20 patients with known or suspected bone tumors. Gamma camera images were acquired at 48 or 72 hours after injection, and assessed for antibody localization. Positive images were obtained in all five osteosarcomas and four other primary malignant sarcomas. Two of the four other primary bone tumors gave positive images. Three patients with trauma had negative images as did one patient with Paget's disease. Two patients with suppurative disease gave positive images. The antibody localized in the majority of malignant sarcomas tested. In one tumor where tissue was available, a tumor:non-tumor ratio of 2.8:1 was measured. Repeat imaging was performed in five patients. Immunoscintigraphy using the monoclonal antibody 791T/36 has shown tumor localization in patients with bone and soft tissue sarcomas.

  11. [Chondromyxoid fibroma of bone: a rare benign bone tumor in children].

    PubMed

    Rouas, L; Malihy, A; Cherradi, N; Lamalmi, N; Alhamany, Z

    2004-12-01

    Chondromyxoid fibroma is a rare benign tumor that is typically found in the metaphyseal ends of long tubular bones, such as the tibia. The radiographic appearances are those of a single, lytic lesion with lobulated margins, septations, cortical expansion and a sclerotic rim. The classic histological feature of a chondromyxoid fibroma is stellate or spindle-shaped cells arranged in lobules in a myxoid or chondroid background. Two cases are presented here: 8, and 12-year-old patients, both with lesions in the proximal tibia. The first case showed an unusual feature: it was diaphyseal chondromyxoid fibroma. In the second case, the lesion was metaphyso-diaphyseal. The differential diagnosis includes chondroblastoma, myxoma, aneurysmal cyst as well as chondrosarcoma. A surgical conservative treatment with complete excision is recommended even in case of recurrence. PMID:15688891

  12. Retrieval of Disseminated Tumor Cells Colonizing the Bone in Murine Breast Cancer Metastasis Models

    PubMed Central

    Welte, Thomas; Yu, Cuijuan

    2016-01-01

    In breast cancer, the most frequent site of metastasis is bone. Disseminated tumor cells (DTCs) can be detected in the bone marrow of patients by their expression of epithelial or oncogenic markers [1], and the presence and frequency of these DTCs are associated with poor prognosis. However, many of the details behind this process remain elusive, including the biological properties and fates of these apparently indolent cancer cells. To provide pre-clinical models of DTCs, we have developed a procedure that allows for controlled and enhanced delivery of tumor cells to the bone in animal experiments via injection into the iliac artery of the hind limb [2]. To our surprise, we found that most cancer cells became integrated into the solid bone matrix shortly after arriving in the bone, and only a minority can be flushed out with the bone marrow. Here we describe a method that helps to retrieve DTCs homing to the bone in which we achieve an improved recovery of those tumor cells closely associated with the bone microenvironment. In our view it is especially important to analyze these tumor cell subpopulations, as they may take full advantage of growth-, survival- and immune-protective signals provided by neighbor cells. We also show a pilot study on how this approach may be applied to the analysis of cancer dormancy. Our study suggests that the detection and retrieval of DTCs in clinical studies are incomplete because they are conducted exclusively with bone marrow aspirates. PMID:26490041

  13. Histogenetic Characterization of Giant Cell Tumor of Bone

    PubMed Central

    Salerno, Manuela; Avnet, Sofia; Alberghini, Marco; Giunti, Armando

    2008-01-01

    The unpredictable behavior of giant cell tumor (GCT) parallels its controversial histogenesis. Multinucleated giant cells, stromal cells, and CD68+ monocytes/macrophages are the three elements that interact in GCT. We compared the ability of stromal cells and normal mesenchymal stromal cells to differentiate into osteoblasts. Stromal cells and mesenchymal cells had similar proliferation rates and lifespans. Although stromal cells expressed early osteogenic markers, they were unable to differentiate into osteoblasts but they did express intracellular adhesion molecule-1, a marker of bone-lining cells. They were unable to form clones in a semisolid medium and unable to promote osteoclast differentiation, although they exerted a strong chemotactic effect on osteoclast precursors. Stromal cells may be either immature proliferating osteogenic elements or specialized osteoblast-like cells that fail to show neoplastic features but can induce the differentiation of osteoclast precursors. They might be secondarily induced to proliferate by a paracrine effect induced by monocyte-macrophages and/or giant cells. The increased number of giant cells in GCT may be secondary to an autocrine circuit mediated by the receptor activator of nuclear factor kB. PMID:18543051

  14. Osteochondroma of maxillofacial region: Tumor arising from two different developmental bones

    PubMed Central

    Mohanty, Sujata; Gupta, Himanshu; Dabas, Jitender; Kumar, Priyadarshan

    2016-01-01

    Osteochondromas are benign bony tumors which are commonly believed to originate by the proliferation of epiphyseal cartilage into the surrounding tissues. However, this hypothesis cannot explain the occurrence of this tumor in the intramembranous bones and soft tissue. Since most of the craniofacial bones have intramembranous origin, the occurrence of this lesion in this territory is considered rare. Contrary to the above hypothesis, Lichtenstein proposed that this entity arises from the metaplastic changes in the periosteum which explains the occurrence of this tumor in endochondral as well as intramembranous bones and also in soft tissues. Complying with Lichtenstein's hypothesis, the authors are presenting two cases of osteochondromas with one arising from the endochondral bone (the coronoid process of the mandible) and the other from an intramembranous bone (lateral pterygoid plate of the sphenoid). PMID:27601834

  15. Osteochondroma of maxillofacial region: Tumor arising from two different developmental bones.

    PubMed

    Mohanty, Sujata; Gupta, Himanshu; Dabas, Jitender; Kumar, Priyadarshan

    2016-01-01

    Osteochondromas are benign bony tumors which are commonly believed to originate by the proliferation of epiphyseal cartilage into the surrounding tissues. However, this hypothesis cannot explain the occurrence of this tumor in the intramembranous bones and soft tissue. Since most of the craniofacial bones have intramembranous origin, the occurrence of this lesion in this territory is considered rare. Contrary to the above hypothesis, Lichtenstein proposed that this entity arises from the metaplastic changes in the periosteum which explains the occurrence of this tumor in endochondral as well as intramembranous bones and also in soft tissues. Complying with Lichtenstein's hypothesis, the authors are presenting two cases of osteochondromas with one arising from the endochondral bone (the coronoid process of the mandible) and the other from an intramembranous bone (lateral pterygoid plate of the sphenoid). PMID:27601834

  16. Osteochondroma of maxillofacial region: Tumor arising from two different developmental bones

    PubMed Central

    Mohanty, Sujata; Gupta, Himanshu; Dabas, Jitender; Kumar, Priyadarshan

    2016-01-01

    Osteochondromas are benign bony tumors which are commonly believed to originate by the proliferation of epiphyseal cartilage into the surrounding tissues. However, this hypothesis cannot explain the occurrence of this tumor in the intramembranous bones and soft tissue. Since most of the craniofacial bones have intramembranous origin, the occurrence of this lesion in this territory is considered rare. Contrary to the above hypothesis, Lichtenstein proposed that this entity arises from the metaplastic changes in the periosteum which explains the occurrence of this tumor in endochondral as well as intramembranous bones and also in soft tissues. Complying with Lichtenstein's hypothesis, the authors are presenting two cases of osteochondromas with one arising from the endochondral bone (the coronoid process of the mandible) and the other from an intramembranous bone (lateral pterygoid plate of the sphenoid).

  17. Outcome of bone defect reconstruction with clavicle bone cement prosthesis after tumor resection: a case series study

    PubMed Central

    2014-01-01

    Background To investigate the short and medium term outcomes of bone defect reconstruction with bone cement prosthesis after clavicle malignancies resection. Methods A total of 5 clavicular malignancy patients experienced bone cement prosthesis reconstruction after subtotal claviculectomy were enrolled the study from January 2005 to May 2012. Musculoskeletal Tumor Society score (MSTS), Visual Analogue scale (VAS) and American Shoulder and Elbow Surgeons shoulder outcome score (ASES) were adopted for assessment. Results The mean follow-up period was 25.8 months. All patients were performed bone cement defect reconstruction after claviculectomy. In which, 3 cases showed disease-free and other 2 cases were alive with sickness. The average Musculoskeletal Tumor Society score was 85.40% ± 5.68%(77%-90%), Visual Analogue Scale was 1.40 ± 0.55 (1–2) and American Shoulder and Elbow Surgeons Shoulder Outcome Score was 92.40 ± 3.29(87–96). Conclusions Adoption of clavicle bone cement prosthesis for bone defect reconstruction after tumor resection can maintain the contour of shoulder and reduce the complications ascribe to the claviculectomy. It is an effective and feasible therapeutic procedure in clinical setting. PMID:24885109

  18. Histological and clinical characteristics of malignant giant cell tumor of bone.

    PubMed

    Gong, Lihua; Liu, Weifeng; Sun, Xiaoqi; Sajdik, Constantin; Tian, Xinxia; Niu, Xiaohui; Huang, Xiaoyuan

    2012-03-01

    Malignant giant cell tumors of bone (MGCTB) are rare, and the diagnosis can be difficult due to the occurrence of a variety of malignant tumors containing giant cells. To better understand its clinicopathological features, we have reviewed our experience with 17 cases of MGCTB. Five cases were primary malignant giant cell tumor of bone (PMGCTB), and 12 cases were giant cell tumors of bone initially diagnosed as benign but malignant in a recurrent lesion (secondary MGCTB, SMGCTB). The patients included six women and 11 men (age ranged from 17 to 52 years; mean, 30.5 years). The tumor arose in the femur (six cases), the tibia (seven cases), the humerus (three cases), and the fibula (one case). Microscopically, PMGCTB showed both conventional giant cell tumor and malignant sarcoma features. SMGCTB were initially diagnosed as conventional giant cell tumor of bone, the recurrent lesion showing malignant features. Histologically, the malignant components included osteosarcoma (11 cases), undifferentiated high-grade pleomorphic sarcoma (two cases), and fibrosarcoma (four cases). SMGCTB cases showed strong expression of p53. Follow-up information revealed that four patients died of lung metastasis, two patients are alive with lung metastases, and 11 patients are alive without tumor. MGCTB should be considered as a high-grade sarcoma. It must be distinguished from GCTB and other malignant tumors containing giant cells. p53 might play a role in the malignant transformation of GCTB. PMID:22350004

  19. A deep penetrating facial congenital melanocytic tumor with bone involvement and ipsilateral eye blindness.

    PubMed

    Bergman, Reuven; Ben-Arush, Miriam W; Bar-Shalom, Rachel; Gilboa, Michael; Simon, Einav; Hershkovitz, Dov; Sabo, Edmond; Maly, Alexander; Gerami, Pedram; Goldsher, Dorith

    2015-01-01

    Bone involvement has been described in tumors with melanocytic differentiation such as melanotic neuroectodermal tumor of infancy, and very rarely in cellular blue nevi and neurocristic cutaneous hamartoma. We present an unusual case of facial congenital melanocytic tumor that involved the underlying bones and maxillary sinus and led to unilateral blindness. A newborn with a large red bluish patch with peripheral brown and black macules overlying marked swelling on the left side of his face was presented. The tumor was shown by magnetic resonance imaging, scintigraphy, and histopathology to invade the underlying bones and maxillary sinus and to compress the left eyeball resulting in blindness. Histopathology, immunohistochemistry, morphometric computerized microscopy, molecular genetic mutation analysis, and fluorescent in situ hybridization studies were more congruent with a melanocytic nevus. An 8.5-year follow-up was uneventful, with spontaneous partial shrinkage of the tumor. PMID:25222197

  20. VEGF-A/VEGFR Inhibition Restores Hematopoietic Homeostasis in the Bone Marrow and Attenuates Tumor Growth.

    PubMed

    O'Donnell, Rebekah K; Falcon, Beverly; Hanson, Jeff; Goldstein, Whitney E; Perruzzi, Carole; Rafii, Shahin; Aird, William C; Benjamin, Laura E

    2016-02-01

    Antiangiogenesis-based cancer therapies, specifically those targeting the VEGF-A/VEGFR2 pathway, have been approved for subsets of solid tumors. However, these therapies result in an increase in hematologic adverse events. We surmised that both the bone marrow vasculature and VEGF receptor-positive hematopoietic cells could be impacted by VEGF pathway-targeted therapies. We used a mouse model of spontaneous breast cancer to decipher the mechanism by which VEGF pathway inhibition alters hematopoiesis. Tumor-bearing animals, while exhibiting increased angiogenesis at the primary tumor site, showed signs of shrinkage in the sinusoidal bone marrow vasculature accompanied by an increase in the hematopoietic stem cell-containing Lin-cKit(+)Sca1(+) (LKS) progenitor population. Therapeutic intervention by targeting VEGF-A, VEGFR2, and VEGFR3 inhibited tumor growth, consistent with observed alterations in the primary tumor vascular bed. These treatments also displayed systemic effects, including reversal of the tumor-induced shrinkage of sinusoidal vessels and altered population balance of hematopoietic stem cells in the bone marrow, manifested by the restoration of sinusoidal vessel morphology and hematopoietic homeostasis. These data indicate that tumor cells exert an aberrant systemic effect on the bone marrow microenvironment and VEGF-A/VEGFR targeting restores bone marrow function.

  1. Immunization against strontium-90 induction of bone tumors with inactivated FBJ virus and irradiated syngeneic strontium-90-induced tumor cells

    SciTech Connect

    Reif, A.E.; Triest, W.E.

    1981-01-01

    Three hundred six C57BL/6J female mice were subdivided into a control group left untreated and an experimental group treated intraperitoneally with 1.0 ..mu..Ci strontium-90/g of body weight at an age of 66 days. Treatments for the groups were as follows: none, 6 injections of formalin-inactivated FBJ viral preparation, 6 injections of active FBJ viral preparation, and 2 injections of 10,000 rad irradiated transplantable osteosarcoma previously induced in C57BL/6J mice by strontium-90. In addition to the above groups, two other groups were treated with respectively 0.032 and 0.10 ..mu..Ci strontium-90/g body weight in order to obtain information on the dose-response relationship between the injection of strontium-90 and the yield of bone tumors. In the groups not treated with strontium-90, only 1 bone tumor developed; this occurred in the group injected with FBJ virus. The incidence of bone tumors in the groups treated with 1.0 ..mu..Ci strontium-90 was significantly lower (18.5% or 18.2%) in the two groups that had received injections of inactivated FBJ virus or irradiated isogenic osteosarcoma when compared to the group left uninjected, which developed 43.5% tumors. In contrast, the strontium-90-treated group that also received injections of active FBJ virus developed 63.0% tumors. Only a single bone tumor developed in the groups treated solely with intermediate doses of strontium-90. The results indicate that immunization with inactivated FBJ virus or with irradiated syngeneic strontium-90-induced tumor cells can significantly decrease the development of strontium-90-induced tumors.

  2. A massive chondroblastoma in the proximal humerus simulating malignant bone tumors.

    PubMed

    Tonogai, Ichiro; Takahashi, Mitsuhiko; Manabe, Hiroaki; Nishisho, Toshihiko; Iwamoto, Seiji; Takao, Shoichiro; Kagawa, Seiko; Kudo, Eiji; Yasui, Natsuo

    2013-01-01

    Chondroblastoma is a mostly benign bone neoplasm that typically affects the second decade of life and exhibits a lytic lesion in the epiphysis of long bones. We report an extreme case of massive, destructive chondroblastoma of the proximal humerus in a 9-year-old girl. It was difficult to differentiate using imaging information the lesion from malignant bone tumors such as osteosarcoma. Histopathological examination from biopsy proved chondroblastoma. The tumor was resected after preoperative transcatheter embolization. Reconstructive procedure for the proximal humerus was not performed due to the local destruction. The present case demonstrates clinical and radiological differentiations of the massive chondroblastoma from the other lesions and histopathological understandings for this lesion.

  3. Successful treatment of a Musculoskeletal Tumor Society grade 3 aneurysmal bone cyst with N-butyl cyanoacrylate embolization and percutaneous cryoablation.

    PubMed

    Griauzde, Julius; Gemmete, Joseph J; Farley, Frances

    2015-06-01

    This report presents a 13-year-old girl with an aggressive skeletal lesion involving the posterior elements of the cervicothoracic junction. The lesion was determined to be a Musculoskeletal Tumor Society grade 3 aneurysmal bone cyst based on imaging and pathologic findings. The cyst was treated with endovascular n-butyl cyanoacrylate embolization and percutaneous cryoablation with sensory and motor-evoked potential monitoring. Follow-up imaging at 16 months demonstrated significant reduction in the size of the lesion, with no evidence of recurrence.

  4. Comparative value of bone scintigraphy and radiography in monitoring tumor response in systemially treated prostatic carcinoma

    SciTech Connect

    Levenson, R.M.; Sauerbrunn, B.J.; Bates, H.R.; Newman, R.D.; Eddy, J.L.; Ihde, D.C.

    1983-02-01

    Radionuclide bone scans and skeletal radiographs were obtained before and during combination chemotherapy or initial hormonal treatment in 46 patients with disseminated adenocarcinoma of the prostate. The purpose of the study was to determine the usefulness of these two modalities in evaluating tumor response to therapy. Prior to treatment, bone scans were positive in 44 patients (96%). In all but one patient either bone radiographs or bone marrow biopsy revealed evidence of osseous metastases. In 22 patients partial response to therapy was documented by a variety of other staging tests.Eleven of these patients showed concurrent or later improvement on bone scans; one showed improvement on a radiograph. ''Flare phenomena'' were observed relatively frequently since 23% of the scans and 50% of the radiographs showed worsening at the time of response. Bone scans revealed worsening in 79% of 33 patients with disease progression of extraosseous tumor; radiographs were equally sensitive (82% worsening). It is concluded that bone scans in particular are ueful for monitoring tumor status in systemically treated patients with prostate cancer. However, because of the lack of sensitivity for response and paradoxical worsening with tumor regression in some patients, scans are not accurate enough to be employed as the sole test in following these patients.

  5. Comparative value of bone scintigraphy and radiography in monitoring tumor response in systemically treated prostatic carcinoma

    SciTech Connect

    Levenson, R.M.; Sauerbrunn, B.J.; Bates, H.R.; Newman, R.D.; Eddy, J.L.; Ihde, DC

    1983-02-01

    Radionuclide bone scans and skeletal radiographs were obtained before and during combination chemotherapy or initial hormonal treatment in 46 patients with disseminated adenocarcinoma of the prostate. The purpose of the study was to determine the usefulness of these two modalities in evaluating tumor response to therapy. Prior to treatment, bone scans were positive in 44 patients (96%). In all but one patient either bone radiographs or bone marrow biopsy revealed evidence of osseous metastases. In 22 patients partial response to therapy was documented by a variety of other staging tests. Eleven of these patients showed concurrent or later improvement on bone scans; one showed improvement on a radiograph. Flare phenomena were observed relatively frequently since 23% of the scans and 50% of the radiographs showed worsening at the time of response. Bone scans revealed worsening in 79% of 33 patients with disease progression of extraosseous tumor; radiographs were equally sensitive (82% worsening). It is concluded that bone scans in particular are useful for monitoring tumor status in systemically treated patients with prostate cancer. However, because of the lack of sensitivity for response and paradoxical worsening with tumor regression in some patients, scans are not accurate enough to be employed as the sole test in following these patients.

  6. Bone tumors in pre-modern skulls from human skeletal series of Joseon Dynasty

    PubMed Central

    Shin, Dong Hoon; Oh, Chang Seok; Kim, Yi-Suk; Kim, Yusu; Oh, Seung Whan; Park, Jun Bum; Lee, In Sun

    2015-01-01

    To date, there are still very few reports on benign-tumor cases based on East Asian skeletal series, even though other regions and continents have been well represented. In our study on the Joseon Human Skeletal Series, we identified benign bone tumors in two skeletons (cases Nos. 75 and 96). Our radiological analyses showed both cases to be homogeneous sclerotic bone masses aligned with the cranial vault suture. In a subsequent series of differential diagnoses, we determined both cases to be osteoma, the most common bone-tumor type reported for archaeological samples. Our study is the osteoarchaeological basis for this, the first-ever report on benign bone neoplasm in a pre-modern East Asian population. PMID:26417482

  7. Treatment of the benign bone tumors including femoral neck lesion using compression hip screw and synthetic bone graft

    PubMed Central

    Nakamura, Tomoki; Matsumine, Akihiko; Asanuma, Kunihiro; Matsubara, Takao; Sudo, Akihiro

    2015-01-01

    Purpose: The proximal femur is one of the most common locations for benign bone tumors and tumor like conditions. We describe the clinical outcomes of the surgical treatment of benign lesions of the proximal femur including femoral neck using compression hip screw and synthetic bone graft. Methods: Thirteen patients with benign bone tumors or tumor like conditions of the proximal femur including femoral neck were surgically treated. Their average age at the time of presentation was 35 years and the average follow-up time was 76 months. Results: The average intraoperative blood loss was 1088 mL and intraoperative blood transfusion was required in eight patients. The average operative time was 167 minutes. All patients required one week and 12 weeks after surgery before full weight-bearing was allowed. All patients had regained full physical function without pain by the final follow-up. No patient sustained a pathological fracture of the femur following the procedure. All patients achieved partial or complete radiographic consolidation of the lesion within one year except one patient who developed a local tumor recurrence in 11 months. Post-operative superficial wound infection was observed in one patient, which resolved with intravenous antibiotics. Chronic hip pain was observed in one patient due to the irritation of tensor fascia lata muscle by the tube plate. Conclusion: We suggest that the treatment of benign bone lesion of the proximal femur using compression hip screw and synthetic bone graft is a safe and effective method. PMID:27163071

  8. Nuclear maspin expression correlates with the CpG island methylator phenotype and tumor aggressiveness in colorectal cancer.

    PubMed

    Kim, Jung Ho; Cho, Nam-Yun; Bae, Jeong Mo; Kim, Kyung-Ju; Rhee, Ye-Young; Lee, Hye Seung; Kang, Gyeong Hoon

    2015-01-01

    It has been suggested that nuclear expression of maspin (mammary serine protease inhibitor; also known as SERPINB5) in colorectal cancer (CRC) is associated with proximal colonic tumor location, mucinous and poorly differentiated histology, microsatellite instability-high (MSI-H), and poor prognosis. Based on these findings, there may be a potential association between nuclear maspin expression and the CpG island methylator phenotype (CIMP) in CRC, but no study has elucidated this issue. Here, we evaluated maspin protein expression status by immunohistochemistry in 216 MSI-H CRCs. CIMP status was also determined by methylation-specific quantitative PCR method (MethyLight) using eight CIMP markers (MLH1, NEUROG1, CRABP1, CACNA1G, CDKN2A (p16), IGF2, SOCS1, and RUNX3) in 216 MSI-H CRCs. Associations between maspin expression status and various pathological, molecular, and survival data were statistically analyzed. Among the 216 MSI-H CRCs, 111 (51%) cases presented nuclear maspin-positive tumors. Nuclear maspin-positive MSI-H CRCs were significantly associated with proximal tumor location (P = 0.003), tumor budding (P < 0.001), lymphovascular invasion (P = 0.001), perineural invasion (P = 0.008), absence of peritumoral lymphoid reaction (P = 0.045), lymph node metastasis (P = 0.003), distant metastasis (P = 0.005), advanced AJCC/UICC stage (stage III/IV) (P = 0.001), and CIMP-high (CIMP-H) status (P < 0.001). Patients with nuclear maspin-positive tumors showed worse disease-free survival than patients with nuclear maspin-negative tumors (log-rank P = 0.025). In conclusion, nuclear maspin expression is molecularly associated with CIMP-H rather than MSI-H, and clinicopathologically correlates with tumor aggressiveness in CRC.

  9. Biomarkers for Bone Tumors: Discovery from Genomics and Proteomics Studies and Their Challenges

    PubMed Central

    Wan-Ibrahim, Wan I; Singh, Vivek A; Hashim, Onn H; Abdul-Rahman, Puteri S

    2015-01-01

    Diagnosis of bone tumor currently relies on imaging and biopsy, and hence, the need to find less invasive ways for its accurate detection. More recently, numerous promising deoxyribonucleic acid (DNA) and protein biomarkers with significant prognostic, diagnostic and/or predictive abilities for various types of bone tumors have been identified from genomics and proteomics studies. This article reviewed the putative biomarkers for the more common types of bone tumors (that is, osteosarcoma, Ewing sarcoma, chondrosarcoma [malignant] and giant cell tumor [benign]) that were unveiled from the studies. The benefits and drawbacks of these biomarkers, as well as the technology platforms involved in the research, were also discussed. Challenges faced in the biomarker discovery studies and the problems in their translation from the bench to the clinical settings were also addressed. PMID:26581086

  10. Passive Entrapment of Tumor Cells Determines Metastatic Dissemination to Spinal Bone and Other Osseous Tissues

    PubMed Central

    Piffko, Andras; Hoffmann, Christian J.; Harms, Christoph; Vajkoczy, Peter; Czabanka, Marcus

    2016-01-01

    During the metastatic process tumor cells circulate in the blood stream and are carried to various organs. In order to spread to different organs tumor cell—endothelial cell interactions are crucial for extravasation mechanisms. It remains unclear if tumor cell dissemination to the spinal bone occurs by passive entrapment of circulating tumor cells or by active cellular mechanisms mediated by cell surface molecules or secreted factors. We investigated the seeding of three different tumor cell lines (melanoma, lung and prostate carcinoma) to the microvasculature of different organs. Their dissemination was compared to biologically passive microbeads. The spine and other organs were resected three hours after intraarterial injection of tumor cells or microbeads. Ex vivo homogenization and fluorescence analysis allowed quantification of tumor cells or microbeads in different organs. Interestingly, tumor cell distribution to the spinal bone was comparable to dissemination of microbeads independent of the tumor cell type (melanoma: 5.646% ± 7.614%, lung: 6.007% ± 1.785%, prostate: 3.469% ± 0.602%, 7 μm beads: 9.884% ± 7.379%, 16 μm beads: 7.23% ± 1.488%). Tumor cell seeding differed significantly between tumor cells and microbeads in all soft tissue organs. Moreover, there were significant differences between the different tumor cell lines in their dissemination behaviour to soft tissue organs only. These findings demonstrate that metastatic dissemination of tumor cells to spinal bone and other osseous organs is mediated by passive entrapment of tumor cells similar to passive plugging of microvasculature observed after intraarterial microbeads injection. PMID:27603673

  11. Passive Entrapment of Tumor Cells Determines Metastatic Dissemination to Spinal Bone and Other Osseous Tissues.

    PubMed

    Broggini, Thomas; Piffko, Andras; Hoffmann, Christian J; Harms, Christoph; Vajkoczy, Peter; Czabanka, Marcus

    2016-01-01

    During the metastatic process tumor cells circulate in the blood stream and are carried to various organs. In order to spread to different organs tumor cell-endothelial cell interactions are crucial for extravasation mechanisms. It remains unclear if tumor cell dissemination to the spinal bone occurs by passive entrapment of circulating tumor cells or by active cellular mechanisms mediated by cell surface molecules or secreted factors. We investigated the seeding of three different tumor cell lines (melanoma, lung and prostate carcinoma) to the microvasculature of different organs. Their dissemination was compared to biologically passive microbeads. The spine and other organs were resected three hours after intraarterial injection of tumor cells or microbeads. Ex vivo homogenization and fluorescence analysis allowed quantification of tumor cells or microbeads in different organs. Interestingly, tumor cell distribution to the spinal bone was comparable to dissemination of microbeads independent of the tumor cell type (melanoma: 5.646% ± 7.614%, lung: 6.007% ± 1.785%, prostate: 3.469% ± 0.602%, 7 μm beads: 9.884% ± 7.379%, 16 μm beads: 7.23% ± 1.488%). Tumor cell seeding differed significantly between tumor cells and microbeads in all soft tissue organs. Moreover, there were significant differences between the different tumor cell lines in their dissemination behaviour to soft tissue organs only. These findings demonstrate that metastatic dissemination of tumor cells to spinal bone and other osseous organs is mediated by passive entrapment of tumor cells similar to passive plugging of microvasculature observed after intraarterial microbeads injection. PMID:27603673

  12. Altered PTEN, ATRX, CHGA, CHGB, and TP53 expression are associated with aggressive VHL-associated pancreatic neuroendocrine tumors.

    PubMed

    Weisbrod, Allison B; Zhang, Lisa; Jain, Meenu; Barak, Stephanie; Quezado, Martha M; Kebebew, Electron

    2013-06-01

    Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome in which 8-17 % of germline mutation carriers develop pancreatic neuroendocrine tumors (PNETs). There is limited data on prognostic markers for PNETs other than Ki-67, which is included in the World Health Organization classification system. Recently, specific genes and pathways have been identified by whole exome sequencing which may be involved in the tumorigenesis of PNETs and may be markers of disease aggressiveness. The objective of this study was to identify molecular markers of aggressive disease in VHL-associated PNETs. The protein expression of eight genes (PTEN, CHGA, CHGB, ATRX, DAXX, CC-3, VEGF, and TP53) was analyzed in PNETs by immunohistochemistry and compared to clinical data, VHL genotype, functional imaging results, and pathologic findings. Subcellular distribution of phosphatase and tensin (PTEN), chromogranin A (CHGA), and alpha thalassemia/mental retardation syndrome X-linked (ATRX) were significantly different by WHO classifications (p ≤ 0.05). There was decreased PTEN nuclear to cytoplasmic ratio (p < 0.01) and decreased CHGA nuclear expression (p = 0.03) in malignant samples as compared to benign. Lower cytoplasmic chromogranin B (CHGB) expression (p = 0.03) was associated with malignant tumors and metastasis. Higher nuclear expression of PTEN was associated with VHL mutations in exon 3 (p = 0.04). Higher PTEN and CHGB expression was associated with higher FDG-PET avidity (p < 0.05). Cytoplasmic expression of CC-3 was associated with higher serum chromogranin A levels (ρ = 0.72, p = 0.02). Lastly, greater cytoplasmic expression of p53 was associated with metastasis. Our findings suggest that altered PTEN, ATRX, CHGA, and CHGB expression are associated with aggressive PNET phenotype in VHL and may serve as useful adjunct prognostic markers to Ki-67 in PNETs.

  13. Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients

    SciTech Connect

    Rock, M.G.; Sim, F.H.; Unni, K.K.; Witrak, G.A.; Frassica, F.J.; Schray, M.F.; Beabout, J.W.; Dahlin, D.C.

    1986-09-01

    Twenty-six patients who had a malignant giant-cell tumor of bone--a sarcoma either juxtaposed to a zone of typical benign giant-cell tumor or occurring at the site of a previously documented benign giant-cell tumor--have been seen at the Mayo Clinic. Of the twenty-six tumors, nineteen were secondary to a previous attempt at local control of a benign giant-cell tumor. All but one of these nineteen patients with a secondary tumor had received therapeutic irradiation four to thirty-nine years earlier. The nature and duration of the symptoms and the sites of predilection of the malignant giant-cell tumors were the same as for benign giant-cell tumor. Fibrosarcoma occurred three times as frequently as osteosarcoma. The best results of treatment of the secondary sarcoma were obtained with early ablation.

  14. Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer.

    PubMed

    Wang, Haiying; Molina, Julian; Jiang, John; Ferber, Matthew; Pruthi, Sandhya; Jatkoe, Timothy; Derecho, Carlo; Rajpurohit, Yashoda; Zheng, Jian; Wang, Yixin

    2013-11-01

    Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and

  15. Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer

    PubMed Central

    WANG, HAIYING; MOLINA, JULIAN; JIANG, JOHN; FERBER, MATTHEW; PRUTHI, SANDHYA; JATKOE, TIMOTHY; DERECHO, CARLO; RAJPUROHIT, YASHODA; ZHENG, JIAN; WANG, YIXIN

    2013-01-01

    Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and

  16. T1-201 chloride scintigraphy for bone tumors and soft part sarcomas

    SciTech Connect

    Terui, S.; Oyamada, H.; Nishikawa, K.; Beppu, Y.; Fukuma, H.

    1984-01-01

    The author investigated T1-201 chloride as a tumor scanning agent of both tumors and soft part sarcomas. Six bone tumors (2 with Ewing sarcoma, 3 with osteosarcoma and 1 with giant cell tumor) and 3 soft part sarcoma (1 with liposarcoma and 2 with malignant fibrous histiocytoma (MFH)) were examined. All but one MFH were untreated primary cases. The diagnosis was determined from biopsy specimen. One patient with Ewing sarcoma had bone metastases. All cases were subsequently received chemotherpeutic agents. Surgery or local irradiation were also used in treatment. T1-201 scintigraphy were performed with intravenous administration of 2 mCi of T1-201 chloride before initiation of therapy. In addition, follow-up examinations were done in 4 patients (2 with Ewing sarcoma and 2 with osteosarcoma) to study the effect of chemotherapy on T1-201 uptake by the tumor. Tc-99m bone scans were available for comparison in 6 tumor. Ga-67 citrate scans were also examined for the 3 soft part sarcomas. The untreated tumors even in the metastatic lesions of Ewing sarcoma were distinctly visualized with T1-201 in all cases. The distribution of T1-201 in the tumors was sometimes different from that of Tc-99m and similar to that of Ga-67. Of 3 out of the 4 follow-up patients, the post-therapy scan showed reduction in T1-201 uptake more markedly than Tc-99m uptake during effective chemotherapy. The other one patient had not responded to the treatment so that the scan showed no changes in T1-201 uptake. These findings indicate that the tumor imaging with T1-201 is useful in the diagnosis of these malignant tumors and may be of value in assessing the response of bone tumors to chemotherapy.

  17. The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness

    PubMed Central

    Bao, Bin; Azmi, Asfar S.; Ali, Shadan; Ahmad, Aamir; Li, Yiwei; Banerjee, Sanjeev; Kong, Dejuan; Sarkar, Fazlul H.

    2013-01-01

    Hypoxia is one of the fundamental biological phenomena that are intricately associated with the development and aggressiveness of a variety of solid tumors. Hypoxia-inducible factors (HIF) function as a master transcription factor, which regulates hypoxia responsive genes and has been recognized to play critical roles in tumor invasion, metastasis, and chemo-radiation resistance, and contributes to increased cell proliferation, survival, angiogenesis and metastasis. Therefore, tumor hypoxia with deregulated expression of HIF and its biological consequence lead to poor prognosis of patients diagnosed with solid tumors, resulting in higher mortality, suggesting that understanding of the molecular relationship of hypoxia with other cellular features of tumor aggressiveness would be invaluable for developing newer targeted therapy for solid tumors. It has been well recognized that cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT) phenotypic cells are associated with therapeutic resistance and contribute to aggressive tumor growth, invasion, metastasis and believed to be the cause of tumor recurrence. Interestingly, hypoxia and HIF signaling pathway are known to play an important role in the regulation and sustenance of CSCs and EMT phenotype. However, the molecular relationship between HIF signaling pathway with the biology of CSCs and EMT remains unclear although NF-κB, PI3K/Akt/mTOR, Notch, Wnt/β-catenin, and Hedgehog signaling pathways have been recognized as important regulators of CSCs and EMT. In this article, we will discuss the state of our knowledge on the role of HIF-hypoxia signaling pathway and its kinship with CSCs and EMT within the tumor microenvironment. We will also discuss the potential role of hypoxia-induced microRNAs (miRNAs) in tumor development and aggressiveness, and finally discuss the potential effects of nutraceuticals on the biology of CSCs and EMT in the context of tumor hypoxia. PMID:22579961

  18. Preliminary report on treatment of bone tumors with microwave-induced hyperthermia

    SciTech Connect

    Fan, Q.Y.; Ma, B.A.; Qiu, X.C.; Li, Y.L.; Ye, J.; Zhou, Y.

    1996-12-01

    Between July, 1992, and February, 1995, 62 patients with various bone tumors were treated with microwave-induced hyperthermia. The series had 47 cases of malignant tumors and 15 cases with benign tumors; most of the tumors occurred at or near knee joints (53/62 = 85.4%). The surgical procedure consisted of separating the tumorous segment from surrounding normal tissues with a safe margin, cooling the normal tissues (including the vital neurovascular bundle and the intrajoint structures) with a water circulation system while heating the tumor simultaneously with the microwave antenna array, and providing an adequate soft-tissue cover for the dead bone. The tumor core temperature and the surface temperature reached 108 and 65 C, respectively. The duration of microwave irradiation was usually 40--50 minutes. Meanwhile, the temperature of the normal tissues was kept under 39 C. The minimal and maximal periods of clinical observation were 3 months and 36 months, respectively, and the mean follow-up period was 17 months. The 62 cases were evaluated from both oncological and orthopedic points of view. Five cases had local recurrence and required amputation. The 57 other cases had excellent local control. Six malignancy cases die of lung metastasis during a period of 1--2 years. Pathological fracture occurred at devitalized bone in five cases. In most of the cases, the knee joints functioned well, were stable and painless, and had almost full range of motion. Single-photon emission-computed tomography study in 16 cases revealed that revascularization of the devitalized tumorous bone segment could be accomplished in 1 year or more. These results show that the use of microwave hyperthermia for the treatment of bone tumors can be considered to be a definitive operation procedure that is safe and is well tolerated by patients. The oncological and orthopedic results are very encouraging.

  19. Dermatofibrosarcoma protuberans, a rare but locally aggressive tumor on finger: clinical and aeromedical considerations

    PubMed Central

    Chiang, Kwo-Tsao; Lee, Shih-Yu; Chu, Hsin

    2015-01-01

    Abstract Dermatofibrosarcoma protuberans (DFSP) is a rare, slow growing, locally infiltrative tumor of intermediate malignancy. It is mostly found on the trunk and head, rarely on hands. The course of evaluation and treatment of a young pilot with DFSP on left middle finger is reported. The clinical issues and aeromedical considerations of this rare tumor is discussed. PMID:27252960

  20. Treatment of bone defect with calcium phosphate cement subsequent to tumor curettage in pediatric patients

    PubMed Central

    NAKAMURA, TOMOKI; MATSUMINE, AKIHIKO; ASANUMA, KUNIHIRO; MATSUBARA, TAKAO; SUDO, AKIHIRO

    2016-01-01

    The aim of the present study was to investigate the mid- to long-term clinical performance of calcium phosphate cement (CPC) in the treatment of benign bone tumors in pediatric patients with a follow-up of at least 2-years. The cases of 33 patients with benign bone tumors treated by curettage and subsequent implantation of CPC were retrospectively reviewed. The patients consisted of 13 males and 20 females, with a median age of 13 years and median follow-up time of 79 months. All patients were alive at the time of review. No toxicity was detected in routine blood tests. Radiography was used to confirm that CPC was well adapted to the surrounding host bone, although the resorbability of CPC was not obtained for all patients at the final follow-up. Local tumor recurrence occurred in 4 patients. None of the patients reported post-operative fractures. In total, 6 patients required a second surgical procedure, as follows: 4 patients in whom local tumor recurrence occurred; 1 patient with post-operative superficial wound infection, who underwent wound debridement; and 1 patient that required the removal of CPC due to deep infection at the proximal humerus. All patients had regained full physical function without any pain at the final follow-up. The present study recommends that the properties of CPC should be taken into consideration and applied to the reconstruction of bone defects subsequent to curettage of bone tumors. PMID:26870197

  1. Methods of reconstruction for bone defect after tumor excision: a review of alternatives.

    PubMed

    Nishida, Jun; Shimamura, Tadashi

    2008-08-01

    Bone defect is a common problem encountered in the treatment of musculoskeletal tumor surgery. Allograft is a commonly used technique to reconstruct a large osseous defect following tumor excision in the United States and some European countries, and relatively good results have been reported because of its biologic nature. However, with the use of an allograft, there are concerns of transmission of infectious diseases, immunological reactions, and social or religious refusal in some regions in the world. Under these circumstances, vascularized autogenous fibular or iliac bone grafts are commonly used techniques and bone lengthening techniques using external fixation have been reported recently. These procedures utilize viable bone. In addition to these procedures, some biological reconstructive techniques utilizing nonviable bone have been performed as surgical alternatives for allografts using treated recycling bone including irradiated or pasteurized resected bone graft and reconstruction using an autograft containing tumor treated by liquid nitrogen. Although each technique has its proper advantages and disadvantages, the clinical results are similar to the allograft, and numerous techniques are now available as reasonable alternatives for allografts.

  2. Treatment of intrabony defects with anorganic bone matrix/p-15 or guided tissue regeneration in patients with aggressive periodontitis.

    PubMed

    Queiroz, Adriana C; Nóbrega, Priscila Brasil da; Oliveira, Fabíola S; Novaes, Arthur B; Taba, Mário; Palioto, Daniela B; Grisi, Márcio F M; Souza, Sergio L S

    2013-01-01

    Intrabony periodontal defects present a particular treatment problem, especially in patients with generalized aggressive periodontitis (G-AgP). Regenerative procedures have been indicated for this clinical situation. The aim of this study was to compare treatment outcomes of intrabony periodontal defects with either anorganic bone matrix/cell binding peptide (ABM/P-15) or guided tissue regeneration (GTR) in patients with G-AgP. Fifteen patients, with two intrabony defects ≥3 mm deep, were selected. Patients were randomly allocated to be treated with ABM/P-15 or GTR. At baseline and at 3 and 6 months after surgery, clinical and radiographic parameters and IL-1β and IL-6 gingival fluid concentrations were recorded. There was a significant probing pocket depth reduction (p<0.001) for both groups (2.27 ± 0.96 mm for ABM/P-15 group and 2.57 ± 1.06 mm for GTR group). Clinical attachment level gain (1.87 ± 0.94 mm for ABM/P-15 group and 2.09 ± 0.88 mm for GTR group) was also observed. There were no statistically significant differences in clinical parameters between the groups. The radiographic bone fill was more expressive in ABM/P-15 group (2.49 mm) than in GTR group (0.73 mm). In subtraction radiographs, the areas representing gain in density were 93.16% of the baseline defect for ABM/P-15 group versus 62.03% in GRT group. There were no statistically significant differences in inter-group and intra-group comparisons with regards to IL-1β and IL-6 quantification. Treatment of intrabony periodontal defects in patients with G-AgP with ABM/P-15 and GTR improved significantly the clinical outcomes. The use of ABM/P-15 promoted a better radiographic bone fill. PMID:23969907

  3. Bone- and cartilage-forming tumors and ewing sarcoma: an update with a gnathic emphasis.

    PubMed

    Stewart, Brian D; Reith, John D; Knapik, Jacquelyn A; Chi, Angela C

    2014-12-01

    Over the past decade, there have been remarkable advances in bone tumor pathology. Insights into the genetic basis and pathobiology of many tumor types have impacted diagnosis, classification, and treatment. However, because gnathic lesions may comprise only a small proportion of cases overall for many tumors, clinicopathologic features and management considerations specific to this subset may be overlooked. Here we provide a summary of recent developments in the following tumor types: osteosarcoma (OS), chondrosarcoma (CS), osteoid osteoma (OO), osteoblastoma (OB), and Ewing sarcoma (ES). In particular, we will give special consideration to cases arising in the jaws.

  4. [Clinical perspectives of the study of RANK/RANKL/OPG system components in primary and metastatic bone tumor].

    PubMed

    Kushlinskiĭ, N E; Timofeev, Iu S; Gershteĭn, E S; Solov'ev, Iu N

    2014-01-01

    Disbalance of bone homeostasis, associated with malfunctioning of RANK/RANKL/OPG system underlies the oncological processes such as the destruction of bone, metastasis development, tumor progression. Pathological activity of system was described in such conditions, as breast cancer, prostate cancer, multiple myeloma, squamous cell carcinoma, Hodgkin's disease, and also metastasis in bones from lung cancer and other malignant diseases. In the literature, there is evidence of involvement of RANK/RANKL/OPG system in the pathogenesis of bone tumors (osteosarcoma, giant cell tumor of bone, chondroblastoma). Experimental data show that RANKL inhibitors can play a role in reducing tumor-induced lesions of bone in multiple myeloma, breast cancer, prostate cancer and lung cancer. Also this review presents data from clinical studies of the drug efficacy targeted on RANK/RANKL/OPG system and results of authors' study of the levels of this system's components and proinflammatory cytokines in blood serum of primary bone sarcoma patients. PMID:25552059

  5. Clinical value of digital image analysis in the diagnosis of urinary bladder cancer, particularly in aggressive tumors: a preliminary report.

    PubMed

    Borkowski, T; Monika Dulewicz, A; Borkowski, A; Piętka, D; Radziszewski, P

    2016-06-01

    The aim of the project was to evaluate the clinical value of a computer analysis of cytological specimen images obtained from urine and bladder washing samples. Three sample types (voided urine, catheterized urine and bladder washing) from 59 patients with primary or recurrent tumor were analyzed. All patients underwent cystoscopy and biopsy or resection. The histological results were compared with the results of the image analyzing computer system of collected urine samples. The consistency between the computer diagnosis and the clinical or histological diagnosis both in the presence and absence of cancer was as follows: 77% for voided urine samples, 72.5% for catheterized urine samples and 78% for bladder washing samples. The specificity of the method at the standard pathology level was 71%, and the sensitivity was 83%. The positive and negative predictive values (PPV and NPV) were 87.5% and 63% respectively. The sensitivity for G3 or CIS or T2 or T3 tumors reached nearly 100%. Computer analysis of urine provided correct diagnoses in cancer and control patients with the sensitivity of 83% and specificity of 71% and gave excellent results in aggressive tumors such as T2, T3, G3 and in CIS. PMID:27543866

  6. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    PubMed Central

    Chenevert, Thomas L.; Jacobson, Jon A.; Boes, Jennifer L.; Galbán, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D.; Pienta, Kenneth J.; Galbán, Craig J.; Meyer, Charles R.; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S.; Hussain, Maha; Ross, Brian D.

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05). These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease. Trial Registration ClinicalTrials.gov NCT02064283 PMID:25859981

  7. Malignant and benign bone tumors that you are likely to see.

    PubMed

    Lewis, Valerae O; Morris, Carol D; Parsons, Theodore W

    2013-01-01

    Although primary malignancies of bone are rare, thousands of benign bone tumors are diagnosed annually. It is important to be able to distinguish benign lesions from malignant lesions and differentiate those lesions that can be watched versus lesions that require further treatment and referral to an orthopaedic oncologist. Learning to distinguish these entities and their appropriate treatment or triage will positively affect the patient and the surgeon's practice. PMID:23395056

  8. Receptor-Activator of Nuclear KappaB Ligand Expression as a New Therapeutic Target in Primary Bone Tumors

    PubMed Central

    Yamagishi, Tetsuro; Kawashima, Hiroyuki; Ogose, Akira; Ariizumi, Takashi; Sasaki, Taro; Hatano, Hiroshi; Hotta, Tetsuo; Endo, Naoto

    2016-01-01

    The receptor-activator of nuclear kappaB ligand (RANKL) signaling pathway plays an important role in the regulation of bone growth and mediates the formation and activation of osteoclasts. Osteoclasts are involved in significant bone resorption and destruction. Denosumab is a fully human monoclonal antibody against RANKL that specifically inhibits osteoclast differentiation and bone resorption. It has been approved for use for multiple myeloma and bone metastases, as well as for giant cell tumor of bone. However, there is no previous report quantitatively, comparing RANKL expression in histologically varied bone tumors. Therefore, we analyzed the mRNA level of various bone tumors and investigated the possibility of these tumors as a new therapeutic target for denosumab. We examined RANKL mRNA expression in 135 clinical specimens of primary and metastatic bone tumors using real-time PCR. The relative quantification of mRNA expression levels was performed via normalization with RPMI8226, a human multiple myeloma cell line that is recognized to express RANKL. Of 135 cases, 64 were also evaluated for RANKL expression by using immunohistochemistry. Among all of the tumors investigated, RANKL expression and the RANKL/osteoprotegerin ratio were highest in giant cell tumor of bone. High RANKL mRNA expression was observed in cases of aneurysmal bone cyst, fibrous dysplasia, osteosarcoma, chondrosarcoma, and enchondroma, as compared to cases of multiple myeloma and bone lesions from metastatic carcinoma. RANKL-positive stromal cells were detected in six cases: five cases of GCTB and one case of fibrous dysplasia. The current study findings indicate that some primary bone tumors present new therapeutic targets for denosumab, particularly those tumors expressing RANKL and those involving bone resorption by osteoclasts. PMID:27163152

  9. Receptor-Activator of Nuclear KappaB Ligand Expression as a New Therapeutic Target in Primary Bone Tumors.

    PubMed

    Yamagishi, Tetsuro; Kawashima, Hiroyuki; Ogose, Akira; Ariizumi, Takashi; Sasaki, Taro; Hatano, Hiroshi; Hotta, Tetsuo; Endo, Naoto

    2016-01-01

    The receptor-activator of nuclear kappaB ligand (RANKL) signaling pathway plays an important role in the regulation of bone growth and mediates the formation and activation of osteoclasts. Osteoclasts are involved in significant bone resorption and destruction. Denosumab is a fully human monoclonal antibody against RANKL that specifically inhibits osteoclast differentiation and bone resorption. It has been approved for use for multiple myeloma and bone metastases, as well as for giant cell tumor of bone. However, there is no previous report quantitatively, comparing RANKL expression in histologically varied bone tumors. Therefore, we analyzed the mRNA level of various bone tumors and investigated the possibility of these tumors as a new therapeutic target for denosumab. We examined RANKL mRNA expression in 135 clinical specimens of primary and metastatic bone tumors using real-time PCR. The relative quantification of mRNA expression levels was performed via normalization with RPMI8226, a human multiple myeloma cell line that is recognized to express RANKL. Of 135 cases, 64 were also evaluated for RANKL expression by using immunohistochemistry. Among all of the tumors investigated, RANKL expression and the RANKL/osteoprotegerin ratio were highest in giant cell tumor of bone. High RANKL mRNA expression was observed in cases of aneurysmal bone cyst, fibrous dysplasia, osteosarcoma, chondrosarcoma, and enchondroma, as compared to cases of multiple myeloma and bone lesions from metastatic carcinoma. RANKL-positive stromal cells were detected in six cases: five cases of GCTB and one case of fibrous dysplasia. The current study findings indicate that some primary bone tumors present new therapeutic targets for denosumab, particularly those tumors expressing RANKL and those involving bone resorption by osteoclasts. PMID:27163152

  10. Tumor lysis syndrome during radiotherapy for prostate cancer with bone and bone marrow metastases without visceral metastasis.

    PubMed

    Kaplan, Muhammet Ali; Kucukoner, Mehmet; Alpagat, Gulistan; Isikdogan, Abdurrahman

    2012-01-01

    A 60-year-old male patient presented to our clinic with metastatic (bone and bone marrow) prostate cancer. Radiotherapy (RT) with a total of 30 Gy was planned in 10 fractions for the painful left shoulder region. On the 6th day of RT, urinary output decreased suddenly and dyspnea developed. Laboratory findings suggested tumor lysis syndrome (TLS). The patient, who showed improvement in overall status and had no requirement for hemodialysis up to this time, developed sudden impairment in overall status, dyspnea, and hypotension on the 11th day of follow-up. Thirty minutes after the development of these symptoms, the patient had a cardiopulmonary arrest and died. At the time of writing this was the fourth case of TLS during RT for solid tumors in adults, the first case of TLS during RT for prostate cancer and the fifth among total cases of prostate cancer in published reports.

  11. Enrichment of c-Met+ tumorigenic stromal cells of giant cell tumor of bone and targeting by cabozantinib.

    PubMed

    Liu, L; Aleksandrowicz, E; Fan, P; Schönsiegel, F; Zhang, Y; Sähr, H; Gladkich, J; Mattern, J; Depeweg, D; Lehner, B; Fellenberg, J; Herr, I

    2014-10-16

    Giant cell tumor of bone (GCTB) is a very rare tumor entity, which is little examined owing to the lack of established cell lines and mouse models and the restriction of available primary cell lines. The stromal cells of GCTB have been made responsible for the aggressive growth and metastasis, emphasizing the presence of a cancer stem cell population. To identify and target such tumor-initiating cells, stromal cells were isolated from eight freshly resected GCTB tissues. Tumorigenic properties were examined by colony and spheroid formation, differentiation, migration, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, immunohistochemistry, antibody protein array, Alu in situ hybridization, FACS analysis and xenotransplantation into fertilized chicken eggs and mice. A sub-population of the neoplastic stromal cells formed spheroids and colonies, differentiated to osteoblasts, migrated to wounded regions and expressed the metastasis marker CXC-chemokine receptor type 4, indicating self-renewal, invasion and differentiation potential. Compared with adherent-growing cells, markers for pluripotency, stemness and cancer progression, including the CSC surface marker c-Met, were enhanced in spheroidal cells. This c-Met-enriched sub-population formed xenograft tumors in fertilized chicken eggs and mice. Cabozantinib, an inhibitor of c-Met in phase II trials, eliminated CSC features with a higher therapeutic effect than standard chemotherapy. This study identifies a c-Met(+) tumorigenic sub-population within stromal GCTB cells and suggests the c-Met inhibitor cabozantinib as a new therapeutic option for targeted elimination of unresectable or recurrent GCTB.

  12. In vitro assessment of poly(methylmethacrylate)-based bone cement containing magnetite nanoparticles for hyperthermia treatment of bone tumor.

    PubMed

    Li, Zhixia; Kawamura, Koki; Kawashita, Masakazu; Kudo, Tada-aki; Kanetaka, Hiroyasu; Hiraoka, Masahiro

    2012-10-01

    Poly(methylmethacrylate) (PMMA)-based cements containing magnetite (C-PMMA/Fe(3)O(4)) is useful in hyperthermia treatment for bone tumor. We have prepared C-PMMA/Fe(3)O(4) by incorporating Fe(3) O(4) powders of different diameters (means of 300, 35, and 11 nm) into the polymerization reaction of methyl methacrylate monomer to develop a new bone cement with high heating efficiencies in alternating current (AC) magnetic fields. Further, we have investigated the in vitro heating capability of the cements in different AC magnetic fields. The mechanical strength and biocompatibility of the resultant cements were also assessed. Their heat generation strongly depends on the magnetite nanoparticle sizes and applied magnetic fields. The cement containing Fe(3)O(4) with mean diameter around 35 nm exhibited the highest heating capability in AC magnetic fields of 120 and 300 Oe at 100 kHz while that with mean diameter around 11 nm exhibited optimum heating capability in AC magnetic fields of 40 Oe at 600 kHz. The incorporation of Fe(3)O(4) into cement-30 wt % of the total amount of cement-did not significantly change the compressive strength of cement, and the proliferation of rat fibroblast Rat-1 cells on cement discs was not inhibited. Our investigations are useful for designing new PMMA/Fe(3)O(4) bone cement with high heating efficiencies and biocompatibilities for bone tumor treatments.

  13. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

    PubMed

    Naves, Luciana A; Daly, Adrian F; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Júnior, Armindo Jreige; Neto, Florêncio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S; Stratakis, Constantine A; Lupski, James R; Beckers, Albert

    2016-02-01

    X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome. PMID:26607152

  14. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

    PubMed

    Naves, Luciana A; Daly, Adrian F; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Júnior, Armindo Jreige; Neto, Florêncio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S; Stratakis, Constantine A; Lupski, James R; Beckers, Albert

    2016-02-01

    X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.

  15. Intraoperative /sup 99m/Tc bone imaging in the treatment of benign osteoblastic tumors

    SciTech Connect

    Sty, J.; Simons, G.

    1982-05-01

    Benign bone tumors can be successfully treated by local resection with the use of intraoperative bone imaging. Intraoperative bone imaging provided accurate localization of an osteoid osteoma in a patella of a 16-year-old girl when standard radiographs failed to demonstrate the lesion. In a case of osteoblastoma of the sacrum in a 12-year old girl, intraoperative scanning was used repeatedly to guide completeness of resection. In these cases in which routine intraoperative radiographs would have failed, intraoperative scanning proved to be essential for success.

  16. [Rare malignant tumors of the ovaries in adolescents--clinical aspects in deciding therapeutic aggressiveness].

    PubMed

    Schröder, W; Bau, O

    1990-01-01

    4 patients below the age of 20 years have been treated for a malignant tumor of the ovary during the period November 1, 1984 until April 30, 1988. Dysgerminoma was the diagnosis in two cases, as the third patient suffered from a bilateral malignant teratoma. Burkitt's Lymphoma involved both ovaries primarily in an 17-year-old girl. Retrospectively we analyzed diagnosis, therapy and clinical course of these young patients. Regarding the different histological types of the tumors that have been found we discuss critically current recommendations in therapeutic managements referring chemotherapy and/or radiotherapy. Defined conditions provided surgical treatment, that preserves fertility in early stages of malignant germ cell tumors of adolescent women, may be justified, especially for dysgerminomas. A real benefit relate to survival and quality of life by using chemotherapeutic agents can only be expected, if all prognostic factors are regarded.

  17. Circulating tumor cells exhibit a biologically aggressive cancer phenotype accompanied by selective resistance to chemotherapy.

    PubMed

    Pavese, Janet M; Bergan, Raymond C

    2014-10-01

    With prostate cancer (PCa), circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) portend a poor clinical prognosis. Their unknown biology precludes rational therapeutic design. We demonstrate that CTC and DTC cell lines, established from mice bearing human PCa orthotopic implants, exhibit increased cellular invasion in vitro, increased metastasis in mice, and express increased epithelial to mesenchymal transition biomarkers. Further, they are selectively resistant to growth inhibition by mitoxantrone-like agents. These findings demonstrate that CTC formation is accompanied by phenotypic progression without obligate reversion. Their increased metastatic potential, selective therapeutic resistance, and differential expression of potential therapeutic targets provide a rational basis to test further interventions.

  18. Giant Cell Tumor of the Temporal Bone with Direct Invasion into the Middle Ear and Skull Base: A Case Report

    PubMed Central

    Iizuka, Takashi; Furukawa, Masayuki; Ishii, Hisato; Kasai, Misato; Hayashi, Chieri; Arai, Hajime; Ikeda, Katsuhisa

    2012-01-01

    Giant cell tumor (GCT) is classified as a benign bone tumor, and it is frequently identified at the epiphysis of long bones and relatively rare in the temporal bone. For orthopedists expert at recognizing bone and soft tissue tumors, the diagnosis of GCT is relatively easy; however, since head and neck surgeons experience few cases of GCT, it may be difficult to diagnose when it occurs in the temporal bone. A 32-year-old man complained of left hearing loss, aural fullness, and tinnitus. Examination of the ear revealed a bulging tumor. Audiologic examination demonstrated conductive hearing loss of the left ear. Computer tomograph of the temporal bone showed a soft-tissue-density specification indicating bone destruction at the left temporal bone. The tumor invaded the skull base. Imaging examinations using magnetic resonance imaging revealed a nonhomogenous isosignal intensity area on T1 at the left temporal bone. After intravenous gadolinium, the mass showed unequal enhancement. This patient subsequently underwent surgery to remove the lesion using transmastoid and middle fossa approach. Pathological examinations from specimens of the tumor revealed characteristic of GCT. No clinical or radiological evidence of tumor recurrence was detected for 4 years. PMID:22953120

  19. Glycoproteomic Analysis of Prostate Cancer Tissues by SWATH Mass Spectrometry Discovers N-acylethanolamine Acid Amidase and Protein Tyrosine Kinase 7 as Signatures for Tumor Aggressiveness*

    PubMed Central

    Liu, Yansheng; Chen, Jing; Sethi, Atul; Li, Qing K.; Chen, Lijun; Collins, Ben; Gillet, Ludovic C. J.; Wollscheid, Bernd; Zhang, Hui; Aebersold, Ruedi

    2014-01-01

    The identification of biomarkers indicating the level of aggressiveness of prostate cancer (PCa) will address the urgent clinical need to minimize the general overtreatment of patients with non-aggressive PCa, who account for the majority of PCa cases. Here, we isolated formerly N-linked glycopeptides from normal prostate (n = 10) and from non-aggressive (n = 24), aggressive (n = 16), and metastatic (n = 25) PCa tumor tissues and analyzed the samples using SWATH mass spectrometry, an emerging data-independent acquisition method that generates a single file containing fragment ion spectra of all ionized species of a sample. The resulting datasets were searched using a targeted data analysis strategy in which an a priori spectral reference library representing known N-glycosites of the human proteome was used to identify groups of signals in the SWATH mass spectrometry data. On average we identified 1430 N-glycosites from each sample. Out of those, 220 glycoproteins showed significant quantitative changes associated with diverse biological processes involved in PCa aggressiveness and metastasis and indicated functional relationships. Two glycoproteins, N-acylethanolamine acid amidase and protein tyrosine kinase 7, that were significantly associated with aggressive PCa in the initial sample cohort were further validated in an independent set of patient tissues using tissue microarray analysis. The results suggest that N-acylethanolamine acid amidase and protein tyrosine kinase 7 may be used as potential tissue biomarkers to avoid overtreatment of non-aggressive PCa. PMID:24741114

  20. Liposomal delivery of dexamethasone attenuates prostate cancer bone metastatic tumor growth In Vivo

    PubMed Central

    Buijs, Jeroen T.; van der Horst, Geertje; Cheung, Henry; van der Mark, Maaike; van Bloois, Louis; Rizzo, Larissa Y.; Lammers, Twan; Pelger, Rob C.; Storm, Gert; van der Pluijm, Gabri; Metselaar, Josbert M.

    2015-01-01

    Background The inflammatory tumor microenvironment, and more specifically the tumor‐associated macrophages, plays an essential role in the development and progression of prostate cancer towards metastatic bone disease. Tumors are often characterized by a leaky vasculature, which ‐ combined with the prolonged circulation kinetics of liposomes ‐ leads to efficient tumor localization of these drug carriers, via the so‐called enhanced permeability and retention (EPR) ‐effect. In this study, we evaluated the utility of targeted, liposomal drug delivery of the glucocorticoid dexamethasone in a model of prostate cancer bone metastases. Methods Tumor‐bearing Balb‐c nu/nu mice were treated intravenously with 0.2–1.0–5.0 mg/kg/week free‐ and liposomal DEX for 3–4 weeks and tumor growth was monitored by bioluminescent imaging. Results Intravenously administered liposomes localize efficiently to bone metastases in vivo and treatment of established bone metastases with (liposomal) dexamethasone resulted in a significant inhibition of tumor growth up to 26 days after initiation of treatment. Furthermore, 1.0 mg/kg liposomal dexamethasone significantly outperformed 1.0 mg/kg free dexamethasone, and was found to be well‐tolerated at clinically‐relevant dosages that display potent anti‐tumor efficacy. Conclusions Liposomal delivery of the glucocorticoid dexamethasone inhibits the growth of malignant bone lesions. We believe that liposomal encapsulation of dexamethasone offers a promising new treatment option for advanced, metastatic prostate cancer which supports further clinical evaluation. Prostate 75: 815–824, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. PMID:25663076

  1. Bone cysts: unicameral and aneurysmal bone cyst.

    PubMed

    Mascard, E; Gomez-Brouchet, A; Lambot, K

    2015-02-01

    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy.

  2. (1) H NMR spectroscopy of glioblastoma stem-like cells identifies alpha-aminoadipate as a marker of tumor aggressiveness.

    PubMed

    Rosi, Antonella; Ricci-Vitiani, Lucia; Biffoni, Mauro; Grande, Sveva; Luciani, Anna Maria; Palma, Alessandra; Runci, Daniele; Cappellari, Marianna; De Maria, Ruggero; Guidoni, Laura; Pallini, Roberto; Viti, Vincenza

    2015-03-01

    Patients suffering from glioblastoma multiforme (GBM) face a poor prognosis with median survival of about 14 months. High recurrence rate and failure of conventional treatments are attributed to the presence of GBM cells with stem-like properties (GSCs). Metabolite profiles of 42 GSC lines established from the tumor tissue of adult GBM patients were screened with (1) H NMR spectroscopy and compared with human neural progenitor cells from human adult olfactory bulb (OB-NPCs) and from the developing human brain (HNPCs). A first subset (n=12) of GSCs exhibited a dramatic accumulation of the metabolite α-aminoadipate (αAAD), product of the oxidation of α-aminoadipic semialdehyde catalyzed by the ALDH7A1 aldehyde dehydrogenase (ALDH) family in lysine catabolism. αAAD was low/not detectable in a second GSC subset (n=13) with the same neural metabolic profile as well as in a third GSC subset (n=17) characterized by intense lipid signals. Likewise, αAAD was not detected in the spectra of OB-NPCs or HNPCs. Inhibition of mitochondrial ATP synthase by oligomycin treatment revealed that the lysine degradative pathway leading to αAAD formation proceeds through saccharopine, as usually observed in developing brain. Survival curves indicated that high αAAD levels in GSCs significantly correlated with poor patient survival, similarly to prostate and non-small-cell-lung cancers, where activity of ALDH7A1 correlates with tumor aggressiveness. PMID:25581615

  3. Diffusion-weighted Magnetic Resonance Imaging in the Diagnosis of Bone Tumors: Preliminary Results

    PubMed Central

    Pekcevik, Yeliz; Kahya, Mehmet Onur; Kaya, Ahmet

    2013-01-01

    Objective: The study aims to determine whether apparent diffusion coefficient (ADC) can help differentiate benign and malignant bone tumors. Materials and Methods: From January 2012 to February 2013, we prospectively included 26 patients. Of these 15 patients were male and 11 were female; ranging in age from 8 to 76 years (mean age, 34.5 years). Diffusion-weighted magnetic resonance (MR) imaging was obtained with a single-shot echo-planar imaging sequence using a 1.5T MR scanner. We grouped malignant lesions as primary, secondary, and primary tumor with chondroid matrix. The minimum ADC was measured in the tumors and mean minimum ADC values were selected for statistical analysis. ADC values were compared between malignant and benign tumors using the Mann-Whitney U-test and receiver operating curve analysis were done to determine optimal cut-off values. Results: The mean ADC values from the area with lowest ADC values of benign and malignant tumors were 1.99 ± 0.57 × 10−3 mm2/s and 1.02 ± 1.0 × 10−3 mm2/s, respectively. The mean minimum ADC values of benign and malignant tumors were statistically different (P = 0.029). With cut-off value of 1.37 (10−3 mm2/s), sensitivity was 77.8% and specificity was 82.4%, for distinguishing benign and malignant lesion. Benign and secondary malignant tumors showed statistically significant difference (P = 0.002). There was some overlap in ADC values between benign and malignant tumors. The mean minimum ADC values of benign and malignant chondroid tumors were high. Giant cell tumor, non-ossifying fibroma and fibrous dysplasia showed lower ADC values. Conclusion: Although there is some overlap, ADC values of benign and malignant bone tumors seem to be different. Further studies with larger patient groups are needed to find an optimal cut-off ADC value. PMID:24605258

  4. Giant cell tumor of the patella with a secondary aneurysmal bone cyst: A case report

    PubMed Central

    SONG, MINGZHI; DAI, WEI; SUN, RAN; LIANG, HONGFENG; LIU, BINGWU; WU, YUXUAN; MA, KAI; LU, MING

    2016-01-01

    The substance of the patella is an uncommon location for tumor occurrence and development. The present study reports a case of giant cell tumor (GCT) of the patella, combined with an aneurysmal bone cyst (ABC). To the best of our knowledge, this is the second report of GCT with ABC published in English. GCT is the most common type of benign tumor. Secondary ABC is frequently associated with GCT, but this symbiotic tumor rarely occurs in the patella. A 27-year-old male patient was examined at the outpatient clinic, and clinicopathological characteristics of the tumor were observed. X-ray and computed tomography (CT) scans revealed a lytic lesion located in the center of the right patella. Curettage, followed by autogenic and allograft bone grafting, was performed. Histopathologically, the lesion was diagnosed as a GCT with secondary ABC. No recurrence or metastasis was identified during the 1-year follow-up period. The present study reports a case of GCT with secondary ABC, and discusses the rare location and histopathological type of this tumor, in order to improve diagnosis and treatment of patellar tumors in general. PMID:27313738

  5. ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling

    PubMed Central

    Wang, Jun; Rouse, Clay; Jasper, Jeff S.; Pendergast, Ann Marie

    2016-01-01

    Bone metastases occur in up to 70% of advanced breast cancer. For most patients with breast cancer, bone metastases are predominantly osteolytic. Interactions between tumor cells and stromal cells in the bone microenvironment drive osteolytic bone metastasis, a process that requires the activation of osteoclasts, cells that break down bone. Here, we report that ABL kinases promoted metastasis of breast cancer cells to bone by regulating the crosstalk between tumor and the bone microenvironment. ABL kinases protected tumor cells from apoptosis induced by TRAIL (TNF-related apoptosis-inducing ligand), activated the transcription factor STAT5, and promoted osteolysis through the STAT5-dependent expression of genes encoding the osteoclast activating factors interleukin 6 (IL6) and matrix metalloproteinase-1 (MMP1). Furthermore, ABL kinases increased the abundance of the Hippo pathway mediator TAZ and the expression of TAZ-dependent target genes that promote bone metastasis. Knockdown of ABL kinases or treatment with ABL-specific allosteric inhibitor impaired osteolytic metastasis of breast cancer cells in mice. These findings revealed a role for ABL kinases in regulating tumor-bone interactions and provide a rationale for targeting both tumor and the bone microenvironment with ABL-specific inhibitors. PMID:26838548

  6. Myelopotentiating effect of curcumin in tumor-bearing host: Role of bone marrow resident macrophages

    SciTech Connect

    Vishvakarma, Naveen Kumar; Kumar, Anjani; Kumar, Ajay; Kant, Shiva; Bharti, Alok Chandra; Singh, Sukh Mahendra

    2012-08-15

    The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) accompanied by an up-regulated BMC survival and a declined induction of apoptosis. Curcumin administration modulated expression of cell survival regulatory molecules: Bcl2, p53, caspase-activated DNase (CAD) and p53-upregulated modulator of apoptosis (PUMA) along with enhanced expression of genes of receptors for M-CSF and GM-CSF in BMC. The BMC harvested from curcumin-administered hosts showed an up-regulated colony forming ability with predominant differentiation into bone marrow-derived macrophages (BMDM), responsive for activation to tumoricidal state. The number of F4/80 positive bone marrow resident macrophages (BMM), showing an augmented expression of M-CSF, was also augmented in the bone marrow of curcumin-administered host. In vitro reconstitution experiments indicated that only BMM of curcumin-administered hosts, but not in vitro curcumin-exposed BMM, augmented BMC survival. It suggests that curcumin-dependent modulation of BMM is of indirect nature. Such prosurvival action of curcumin is associated with altered T{sub H1}/T{sub H2} cytokine balance in serum. Augmented level of serum-borne IFN-γ was found to mediate modulation of BMM to produce enhanced amount of monokines (IL-1, IL-6, TNF-α), which are suggested to augment the BMC survival. Taken together the present investigation indicates that curcumin can potentiate myelopoiesis in a tumor-bearing host, which may have implications in its therapeutic utility. Highlights: ► Curcumin augments myelopoiesis in tumor-bearing host. ► Bone marrow resident macrophages mediate curcumin-dependent augmented myelopoiesis. ► Serum borne cytokine are implicated in modulation of bone marrow resident

  7. Differential Expression of ADAM23, CDKN2A (P16), MMP14 and VIM Associated with Giant Cell Tumor of Bone

    PubMed Central

    Conceição, André Luis Giacometti; Babeto, Erica; Candido, Natalia Maria; Franco, Fernanda Craveiro; de Campos Zuccari, Débora Aparecida Pires; Bonilha, Jane Lopes; Cordeiro, José Antônio; Calmon, Marilia Freitas; Rahal, Paula

    2015-01-01

    Though benign, giant cell tumor of bone (GCTB) can become aggressive and can exhibit a high mitotic rate, necrosis and rarely vascular invasion and metastasis. GCTB has unique histologic characteristics, a high rate of multinucleated cells, a variable and unpredictable growth potential and uncertain biological behavior. In this study, we sought to identify genes differentially expressed in GCTB, thus building a molecular profile of this tumor. We performed quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry and analyses of methylation to identify genes that are putatively associated with GCTB. The expression of the ADAM23 and CDKN2A genes was decreased in GCTB samples compared to normal bone tissue, measured by qPCR. Additionally, a high hypermethylation frequency of the promoter regions of ADAM23 and CDKN2A in GCTB was observed. The expression of the MAP2K3, MMP14, TIMP2 and VIM genes was significantly higher in GCTB than in normal bone tissue, a fact that was confirmed by qPCR and immunohistochemistry. The set of genes identified here furthers our understanding of the molecular basis of GCTB. PMID:26078788

  8. Nano-Scaled Particles of Titanium Dioxide Convert Benign Mouse Fibrosarcoma Cells into Aggressive Tumor Cells

    PubMed Central

    Onuma, Kunishige; Sato, Yu; Ogawara, Satomi; Shirasawa, Nobuyuki; Kobayashi, Masanobu; Yoshitake, Jun; Yoshimura, Tetsuhiko; Iigo, Masaaki; Fujii, Junichi; Okada, Futoshi

    2009-01-01

    Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO2) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO2, either uncoated (TiO2−1, hydrophilic) or coated with stearic acid (TiO2−2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO2−1, but not TiO2−2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO2−1 and TiO2−2 treatments. However, TiO2−2, but not TiO2−1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO2−1 and TiO2−2 resulted in intracellular ROS formation, TiO2−2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO2−2, but not TiO2−1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO2 toxicity acquired a tumorigenic phenotype. TiO2-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO2 has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells. PMID:19815711

  9. P15, MDM2, NF-κB, and Bcl-2 expression in primary bone tumor and correlation with tumor formation and metastasis

    PubMed Central

    Qian, Guibin; Hao, Songnan; Yang, Dawei; Meng, Qinggang

    2015-01-01

    Primary bone tumor is one of the most common malignant tumors in skeletal system. It seriously affected bone movement and development with unclear pathogenesis. In this paper, rabbit VX-2 malignant bone tumor model was applied to explore apoptotic genes P15, MDM2, NF-κB and Bcl-2 correlation with primary bone tumor occurrence and metastasis. 0.3 ml rabbit VX-2 tumor cell suspension (1×106/ml) was injected to the marrow cavity of the right tibia condyle to establish the rabbit malignant bone tumor model, while equal amount of the saline was injected to the left tibia as control. Real-time PCR was applied to determine P15, MDM2, NF-κB and Bcl-2 expression level. Immunohistochemistry was performed to detect the abovementioned genes expression in lung, stomach, kidney and bladder. Compared with control, P15 expression level in the inoculation site surrounding tissues decreased obviously following the inoculate time elongation (P<0.05), while Bcl-2, MDM2 and NF-κB expression significantly increased (P<0.05). Bcl-2 showed significant correlation with MDM2 and NF-κB (P<0.05). At the 2, 4, 6 weeks, Bcl-2, MDM2 and NF-κB in lung, Bcl-2 in kidney, and Bcl-2 and MDM2 in bladder positively expressed (P<0.05), whereas P15 gene exhibited no significant positive expression in these tissues (P>0.05). P15, MDM2, NF-κB, and Bcl-2 genes expression levels can effectively reflect malignant bone tumor growth of rabbit tibia. MDM2, NF-κB and Bcl-2 genes involved in primary bone tumors metastasis directly. It has important clinical significance for early diagnosis and treatment of primary bone tumor. PMID:26823818

  10. Total Humeral Endoprosthetic Replacement following Excision of Malignant Bone Tumors

    PubMed Central

    Kotwal, Suhel; Moon, Bryan; Lin, Patrick; Satcher, Robert; Lewis, Valerae

    2016-01-01

    Humerus is a common site for malignant tumors. Advances in adjuvant therapies and reconstructive methods provide salvage of the upper limb with improved outcomes. Reports of limb salvage with total humeral replacement in extensive humeral tumors are sparse. We undertook a retrospective study of 20 patients who underwent total humeral endoprosthetic replacement as limb salvage following excision of extensile malignant tumor from 1990 to 2011. With an average followup of 42.9, functional and oncological outcomes were analyzed. Ten patients were still alive at the time of review. Mean estimated blood loss was 1131 mL and duration of surgery was 314 minutes. Deep infection was encountered in one patient requiring debridement while mechanical loosening of ulnar component was identified in one patient. Subluxation of prosthetic humeral head was noted in 3 patients. Mean active shoulder abduction was 12.5° and active flexion was 15°. Incompetence of abduction mechanism was the major determinant of poor active functional outcome. Mean elbow flexion was 103.5° with 30.5° flexion contracture in 10 patients with good and useful hand function. Average MSTS score was 71.5%. Total humeral replacement is a reliable treatment option in restoring mechanical stability and reasonable functional results without compromising patient survival, with low complication rate. PMID:27042158

  11. Can Neutrophil/Lymphocyte Ratio be a Predictor for Bone Metastases of Solid Tumors?

    PubMed Central

    Caliskan, Billur; Korkmaz, Ayşe Nurdan

    2016-01-01

    Cancer-associated inflammation has been receiving increased attention due to its role in cancer development. It is known that tumors can cause an inflammatory reaction and inflammatory cells play an important role in neoplastic growth. In this study, we aimed to investigate any relationship between bone metastases and the neutrophil-to-lymphocyte ratio (NLR). Patients who were referred for bone scintigraphy to investigate bone metastasis were enrolled in the study. Patients’ hematological parameters were obtained from the hospital database retrospectively. Patients with a nonmetastatic bone scan were categorized as Group A (N = 171), patients who had metastatic bone disease without any other organ metastases were categorized as group B (N = 25), and patients who had metastatic bone disease with the other organ metastases were categorized as Group C (N = 48). The median NLR of the patients in Group A was 2.55 (range: 0.38–20.7), in Group B was 2.83 (range: 1.56–31.8), and in Group C was 4.12 (range: 1.79–38). NLR was significantly higher in Group C patients compared to Group A and B patients (P < 0.001). In conclusion, the NLR is significantly associated with the other organ metastases but has no significant correlation with bone metastases. PMID:27651741

  12. Can Neutrophil/Lymphocyte Ratio be a Predictor for Bone Metastases of Solid Tumors?

    PubMed

    Caliskan, Billur; Korkmaz, Ayşe Nurdan

    2016-09-01

    Cancer-associated inflammation has been receiving increased attention due to its role in cancer development. It is known that tumors can cause an inflammatory reaction and inflammatory cells play an important role in neoplastic growth. In this study, we aimed to investigate any relationship between bone metastases and the neutrophil-to-lymphocyte ratio (NLR). Patients who were referred for bone scintigraphy to investigate bone metastasis were enrolled in the study. Patients' hematological parameters were obtained from the hospital database retrospectively. Patients with a nonmetastatic bone scan were categorized as Group A (N = 171), patients who had metastatic bone disease without any other organ metastases were categorized as group B (N = 25), and patients who had metastatic bone disease with the other organ metastases were categorized as Group C (N = 48). The median NLR of the patients in Group A was 2.55 (range: 0.38-20.7), in Group B was 2.83 (range: 1.56-31.8), and in Group C was 4.12 (range: 1.79-38). NLR was significantly higher in Group C patients compared to Group A and B patients (P < 0.001). In conclusion, the NLR is significantly associated with the other organ metastases but has no significant correlation with bone metastases. PMID:27651741

  13. Can Neutrophil/Lymphocyte Ratio be a Predictor for Bone Metastases of Solid Tumors?

    PubMed Central

    Caliskan, Billur; Korkmaz, Ayşe Nurdan

    2016-01-01

    Cancer-associated inflammation has been receiving increased attention due to its role in cancer development. It is known that tumors can cause an inflammatory reaction and inflammatory cells play an important role in neoplastic growth. In this study, we aimed to investigate any relationship between bone metastases and the neutrophil-to-lymphocyte ratio (NLR). Patients who were referred for bone scintigraphy to investigate bone metastasis were enrolled in the study. Patients’ hematological parameters were obtained from the hospital database retrospectively. Patients with a nonmetastatic bone scan were categorized as Group A (N = 171), patients who had metastatic bone disease without any other organ metastases were categorized as group B (N = 25), and patients who had metastatic bone disease with the other organ metastases were categorized as Group C (N = 48). The median NLR of the patients in Group A was 2.55 (range: 0.38–20.7), in Group B was 2.83 (range: 1.56–31.8), and in Group C was 4.12 (range: 1.79–38). NLR was significantly higher in Group C patients compared to Group A and B patients (P < 0.001). In conclusion, the NLR is significantly associated with the other organ metastases but has no significant correlation with bone metastases.

  14. Risk factors for lymphatic metastasis of malignant bone and soft-tissue tumors: a retrospective cohort study of 242 patients.

    PubMed

    Yanagawa, Takashi; Saito, Kenichi; Takagishi, Kenji

    2014-12-01

    Metastasis to the lymph nodes is relatively rare in malignant bone and soft-tissue tumors, and its risk factors remains unknown, except for tumors of the lymphogenous histotype, including rhabdomyosarcoma, epithelioid sarcoma, and clear cell sarcoma. The purpose of this study was to identify the risk factors for lymph node metastasis of malignant bone and soft-tissue tumors. We retrospectively reviewed 242 patients with malignant bone and soft-tissue tumors. The predictors of interest for the risk of lymph node metastasis included age, sex, histopathological diagnosis, location(s) of the primary tumor(s), local recurrence, residual tumor(s), and the size of the primary tumors. To identify the risk factors for lymph node metastasis, Cox regression analyses were performed. Among the 242 patients with malignant bone and soft-tissue tumors in the current study, 60, 29, and 28 were detected to have lung, lymph node, and bone metastases, respectively. In the univariate analyses, the lymphogenous histotype and a primary tumor invading the subcutis were the risk factors for lymph node metastasis. In the multivariate analysis, the lymphogenous histotype (P < 0.01) and a primary tumor in the subcutis (P < 0.01) remained significantly associated with a higher risk of lymph node metastasis with 5.15 and 3.48 of hazard ratios, respectively. Lymph node metastasis was detected in malignant bone and soft-tissue tumors more frequently than that has been previously reported, and the risk factors for lymph node metastasis were the lymphogenous histotype and primary tumors invading the subcutis.

  15. Aneurysmal bone cyst secondary to a giant cell tumor of the patella: A case report

    PubMed Central

    YU, XIAOLONG; GUO, RUNSHENG; FAN, CONGLIANG; LIU, HUCHENG; ZHANG, BIN; NIE, TAO; TU, YI; DAI, MIN

    2016-01-01

    The patella is an unusual location for primary and metastatic bone tumors to develop. The most frequently encountered primary osteolytic lesions at the patella include giant cell tumors of the bone (GCT), chondroblastoma and aneurysmal bone cysts (ABC). However, the presentation of an ABC originating secondary to a GCT at the patella is rare. The present study describes such a case in a 46-year-old female. The differential diagnosis of the condition was extensive. The patient underwent curettage and the addition of bone cement to fill the defect. Pathological analysis of the resected tissue demonstrated that the lesion was consistent with an ABC forming secondary to a GCT. A 3-month follow-up was completed subsequent to the surgery, with a computed tomography scan demonstrating no evidence of recurrence. However, frequent and continuous observations of the patient following diagnosis are planned in order to evaluate the long-term efficacy of the surgical treatment. To the best of our knowledge, the present study describes the third reported case in the literature of this rare, double synchronous, benign tumor located at the patella. PMID:26893764

  16. ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling.

    PubMed

    Wang, Jun; Rouse, Clay; Jasper, Jeff S; Pendergast, Ann Marie

    2016-02-01

    Bone metastases occur in up to 70% of advanced breast cancer. For most patients with breast cancer, bone metastases are predominantly osteolytic. Interactions between tumor cells and stromal cells in the bone microenvironment drive osteolytic bone metastasis, a process that requires the activation of osteoclasts, cells that break down bone. We report that ABL kinases promoted metastasis of breast cancer cells to bone by regulating the crosstalk between tumor cells and the bone microenvironment. ABL kinases protected tumor cells from apoptosis induced by TRAIL (TNF-related apoptosis-inducing ligand), activated the transcription factor STAT5, and promoted osteolysis through the STAT5-dependent expression of genes encoding the osteoclast-activating factors interleukin-6 (IL-6) and matrix metalloproteinase 1 (MMP1). Furthermore, in breast cancer cells, ABL kinases increased the abundance of the Hippo pathway mediator TAZ and the expression of TAZ-dependent target genes that promote bone metastasis. Knockdown of ABL kinases or treatment with ABL-specific allosteric inhibitor impaired osteolytic metastasis of breast cancer cells in mice. These findings revealed a role for ABL kinases in regulating tumor-bone interactions and provide a rationale for using ABL-specific inhibitors to limit breast cancer metastasis to bone. PMID:26838548

  17. Lowering bone mineral affinity of bisphosphonates as a therapeutic strategy to optimize skeletal tumor growth inhibition in vivo.

    PubMed

    Fournier, Pierrick G J; Daubiné, Florence; Lundy, Mark W; Rogers, Michael J; Ebetino, Frank H; Clézardin, Philippe

    2008-11-01

    Bisphosphonates bind avidly to bone mineral and are potent inhibitors of osteoclast-mediated bone destruction. They also exhibit antitumor activity in vitro. Here, we used a mouse model of human breast cancer bone metastasis to examine the effects of risedronate and NE-10790, a phosphonocarboxylate analogue of the bisphosphonate risedronate, on osteolysis and tumor growth. Osteolysis was measured by radiography and histomorphometry. Tumor burden was measured by fluorescence imaging and histomorphometry. NE-10790 had a 70-fold lower bone mineral affinity compared with risedronate. It was 7-fold and 8,800-fold less potent than risedronate at reducing, respectively, breast cancer cell viability in vitro and bone loss in ovariectomized animals. We next showed that risedronate given at a low dosage in animals bearing human B02-GFP breast tumors reduced osteolysis by inhibiting bone resorption, whereas therapy with higher doses also inhibited skeletal tumor burden. Conversely, therapy with NE-10790 substantially reduced skeletal tumor growth at a dosage that did not inhibit osteolysis, a higher dosage being able to also reduce bone destruction. The in vivo antitumor activity of NE-10790 was restricted to bone because it did not inhibit the growth of subcutaneous B02-GFP tumor xenografts nor the formation of B16-F10 melanoma lung metastases. Moreover, NE-10790, in combination with risedronate, reduced both osteolysis and skeletal tumor burden, whereas NE-10790 or risedronate alone only decreased either tumor burden or osteolysis, respectively. In conclusion, our study shows that decreasing the bone mineral affinity of bisphosphonates is an effective therapeutic strategy to inhibit skeletal tumor growth in vivo.

  18. [Unusual bone tumor in a hemophiliac patient. Diagnosis using aspiration biopsy of the lesion].

    PubMed

    Magallón, M; Rodríguez Merchán, C; López Barea, F; Vicandi, B; Atienza, M; Lamas, M; Sanjurjo, M J

    1990-08-01

    Bone tumors due to repeated haemorrhages in haemophiliacs (haemophilic pseudotumours) usually are no diagnostic trouble. However, when x-ray findings are not conclusive, the differential diagnosis with malignant tumours may be difficult as bleeding complications hinder invasive diagnostic procedures. A fifteen year-old patient with severe haemophilia A is presented, who had a tumor in his left fibula with no previous traumatism. X-ray and CT scan images showed a broken cortical substance with reactive sclerosis and no alteration of the soft tissues. In order to establish the diagnosis and choose the adequate surgical management, aspiration with thin needle was performed through the cortical hole, under visual control with CT scan. A benign lesion was found upon study of the aspirate. No haemorrhagic or infectious complications developed after tumor dissection and filling with heterologous lyophilized bone. The final diagnosis was "giant cell reparative granuloma", an uncommon lesion in the fibula not previously reported in haemophiliacs. It was concluded that aspiration, when appropriately applied, may be a useful diagnostic procedure which should be borne in mind for the diagnosis of bone tumors in haemophiliacs.

  19. Inflammatory myofibroblastic tumor of the temporal bone presenting with pulsatile tinnitus: a case report

    PubMed Central

    2013-01-01

    Introduction Inflammatory myofibroblastic tumor of the temporal bone is an unusual but distinct disease entity. The most common presenting symptoms are otalgia, otorrhea, hearing loss, facial palsy, and vertigo. We describe here what we believe to be the first reported case of a patient presenting with persistent pulsatile tinnitus. The clinical features, radiological and histopathologic findings, and treatment outcomes of the patient are presented. Case presentation A 59-year-old woman of Chinese Han origin presented with complaints of left-sided pulsatile tinnitus and progressive hearing loss for several years. Clinical evaluations revealed a reddish mass behind the intact tympanic membrane, and a moderately severe conductive hearing loss in the left ear. The computed tomographic imaging of the temporal bone demonstrated a slightly ill-defined left middle ear soft tissue mass involving the posterior portion of the mesotympanum and epitympanum, and the mastoid antrum. The patient underwent surgical excision of the lesion which subsequently resolved her symptoms. Postoperative pathology was consistent with an inflammatory myofibroblastic tumor. Conclusions An inflammatory myofibroblastic tumor of the temporal bone can present clinically with pulsatile tinnitus and masquerade as venous hum or vascular tumors of the middle ear; therefore, it should be included in the differential diagnosis of pulsatile tinnitus. PMID:23787119

  20. Protein Kinase A Effects of an Expressed PRKAR1A Mutation Associated with Aggressive Tumors

    PubMed Central

    Meoli, Elise; Bossis, Ioannis; Cazabat, Laure; Mavrakis, Manos; Horvath, Anelia; Stergiopoulos, Sotiris; Shiferaw, Miriam L.; Fumey, Glawdys; Perlemoine, Karine; Muchow, Michael; Robinson-White, Audrey; Weinberg, Frank; Nesterova, Maria; Patronas, Yianna; Groussin, Lionel; Bertherat, Jérôme; Stratakis, Constantine A.

    2011-01-01

    Most PRKAR1A tumorigenic mutations lead to nonsense mRNA that is decayed; tumor formation has been associated with an increase in type II protein kinase A (PKA) subunits. The IVS6+1G>T PRKAR1A mutation leads to a protein lacking exon 6 sequences [R1αΔ184-236 (R1αΔ6)]. We compared in vitro R1αΔ6 with wild-type (wt) R1α. We assessed PKA activity and subunit expression, phosphorylation of target molecules, and properties of wt-R1α and mutant (mt) R1α; we observed by confocal microscopy R1α tagged with green fluorescent protein and its interactions with Cerulean-tagged catalytic subunit (Cα). Introduction of the R1αΔ6 led to aberrant cellular morphology and higher PKA activity but no increase in type II PKA subunits. There was diffuse, cytoplasmic localization of R1α protein in wt-R1α– and R1αΔ6-transfected cells but the former also exhibited discrete aggregates of R1α that bound Cα; these were absent in R1αΔ6-transfected cells and did not bind Cα at baseline or in response to cyclic AMP. Other changes induced by R1αΔ6 included decreased nuclear Cα. We conclude that R1αΔ6 leads to increased PKA activity through the mt-R1α decreased binding to Cα and does not involve changes in other PKA subunits, suggesting that a switch to type II PKA activity is not necessary for increased kinase activity or tumorigenesis. PMID:18451138

  1. Automated segmentation of tumors on bone scans using anatomy-specific thresholding

    NASA Astrophysics Data System (ADS)

    Chu, Gregory H.; Lo, Pechin; Kim, Hyun J.; Lu, Peiyun; Ramakrishna, Bharath; Gjertson, David; Poon, Cheryce; Auerbach, Martin; Goldin, Jonathan; Brown, Matthew S.

    2012-03-01

    Quantification of overall tumor area on bone scans may be a potential biomarker for treatment response assessment and has, to date, not been investigated. Segmentation of bone metastases on bone scans is a fundamental step for this response marker. In this paper, we propose a fully automated computerized method for the segmentation of bone metastases on bone scans, taking into account characteristics of different anatomic regions. A scan is first segmented into anatomic regions via an atlas-based segmentation procedure, which involves non-rigidly registering a labeled atlas scan to the patient scan. Next, an intensity normalization method is applied to account for varying levels of radiotracer dosing levels and scan timing. Lastly, lesions are segmented via anatomic regionspecific intensity thresholding. Thresholds are chosen by receiver operating characteristic (ROC) curve analysis against manual contouring by board certified nuclear medicine physicians. A leave-one-out cross validation of our method on a set of 39 bone scans with metastases marked by 2 board-certified nuclear medicine physicians yielded a median sensitivity of 95.5%, and specificity of 93.9%. Our method was compared with a global intensity thresholding method. The results show a comparable sensitivity and significantly improved overall specificity, with a p-value of 0.0069.

  2. [Giant cell tumor of the 4th metacarpal bone of the left hand. Apropos of a case].

    PubMed

    Kamel, E J; Pinto, J A; Potenza, L; Michelena, A; Perez Signini, F; Fuenmayor, A

    1983-01-01

    He is a 46 year old patient that consults on a tumor that deforms the back of his left hand. The X-ray examination shows a bone osteolytic tumor with complete dis appearance of the 4th metacarpal. Surgical removal of the tumor was practiced with immediate reconstruction of the 4th metacarpal by an oseo-iliac graft. Anatomopathological examination. It is an ovoid tumor 6.5 long and irregular surface.

  3. Primary hyperparathyroidism diagnosed after surgical ablation of a costal mass mistaken for giant-cell bone tumor: a case report

    PubMed Central

    2011-01-01

    Introduction Primary hyperparathyroidism is a common endocrine disorder characterized by elevated parathyroid hormone levels, which cause continuous osteoclastic bone resorption. Giant cell tumor of bone is an expansile osteolytic tumor that contains numerous osteoclast-like giant cells. There are many similarities in the radiological and histological features of giant cell tumor of bone and brown tumor. This is a rare benign focal osteolytic process most commonly caused by hyperparathyroidism. Case presentation We report the unusual case of a 40-year-old Caucasian woman in which primary hyperparathyroidism was diagnosed after surgical ablation of a costal mass. The mass was suspected of being neoplastic and histopathology was compatible with a giant cell tumor of bone. On the basis of the biochemical results (including serum calcium, phosphorous and intact parathyroid hormone levels) primary hyperparathyroidism was suspected and a brown tumor secondary to refractory hyperparathyroidism was diagnosed. Conclusions Since giant cell tumor is a bone neoplasm that has major implications for the patient, the standard laboratory tests in patients with bone lesions are important for a correct diagnosis. PMID:22204520

  4. Efficacy of bisphosphonates and other bone-targeted agents in metastatic bone disease from solid tumors other than breast and prostate cancers.

    PubMed

    Karim, Syed Mustafa; Brown, Janet; Zekri, Jamal

    2013-05-01

    Metastatic bone disease complicates the course of malignancy in a substantial proportion of patients with advanced cancer. Bisphosphonates are now widely used to improve skeleton-related outcomes of patients with metastatic cancer to the bone. Most studies evaluating the efficacy of bisphosphonates and other bone-targeted agents have been performed in patients with metastatic breast and prostate cancer. Only a few studies have evaluated the role of bisphosphonates in other tumor types involving the skeletal system. We present a review of the clinical literature focusing on the current and potential roles of bisphosphonates (particularly zoledronic acid) and newer bone-targeted therapies in patients with metastasis to bone arising from solid tumors other than breast and prostate cancer.

  5. Histopathological, immunohistochemical, and image analytic parameters characterizing the stromal component in primary and recurrent giant cell tumor of bone.

    PubMed

    Saxena, Charu Chandra; Safaya, Rajni; Kawatra Madan, Neha; Khan, Shah Alam; Iyer, Venkateswaran K

    2016-01-01

    Giant cell tumor (GCT) of bone is a benign locally aggressive tumor whose biological behavior is unpredictable. Currently, there are no definitive clinical, histological, biochemical, or immunological parameters that can predict its behavior. This study was undertaken to examine whether delineation of reactive and neoplastic stromal component of GCT can help in this regard. 55 cases of GCT (30 primary, 25 recurrent) were subjected to histopathological grading, immunohistochemistry, and image analysis. Spindling of stroma was more frequent in recurrent GCT with 64% cases having more than 50% spindled stroma (p < 0.001). Number of mitosis/10 HPF and higher grade were more in recurrent GCT. Mean percentage positivity for CD68 (38.36%) and α1-ACT (70.86%) was higher in primary than recurrent GCT. PCNA and MiB-1 labeling indices were higher in recurrent (42.62% and 9.18%, respectively) than in primary group (24.75% and 7.7%, respectively). A single numerical parameter encompassing stromal cell population and its proliferation was derived as ratio of PCNA/CD68 and PCNA/α1-ACT. Both ratios were higher in recurrent (0.81 ± 0.38; 1.58 ± 1.50) than in primary GCT (0.58 ± 0.62; 0.34 ± 0.29) (p = 0.002; 0.01). On image analysis, parameters significantly different between the two groups were nuclear area and nuclear integrated optical density. It was thus concluded that recurrent GCT shows higher grade, increased mitosis, more spindling, fewer reactive components, and higher proliferation than primary GCT. Delineation of reactive component (α1-ACT positive) and proliferating component (PCNA positive cells) using immunohistochemistry with calculation of the PCNA/ACT ratio delivers more information than image analysis.

  6. ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor

    PubMed Central

    Divisato, Giuseppina; Formicola, Daniela; Esposito, Teresa; Merlotti, Daniela; Pazzaglia, Laura; Del Fattore, Andrea; Siris, Ethel; Orcel, Philippe; Brown, Jacques P.; Nuti, Ranuccio; Strazzullo, Pasquale; Benassi, Maria Serena; Cancela, M. Leonor; Michou, Laetitia; Rendina, Domenico; Gennari, Luigi; Gianfrancesco, Fernando

    2016-01-01

    Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone (GCT). We performed whole-exome sequencing in a large family with 14 PDB-affected members, four of whom developed GCT at multiple pagetic skeletal sites, and we identified the c.2810C>G (p.Pro937Arg) missense mutation in the zinc finger protein 687 gene (ZNF687). The mutation precisely co-segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated individuals with GCT associated with PDB (GCT/PDB) identified the same mutation in all individuals, unravelling a founder effect. ZNF687 is highly expressed during osteoclastogenesis and osteoblastogenesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB. Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk. PMID:26849110

  7. MicroRNA function and dysregulation in bone tumors: the evidence to date

    PubMed Central

    Nugent, Mary

    2014-01-01

    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. PMID:24426787

  8. Prognostic Impact of Reduced Connexin43 Expression and Gap Junction Coupling of Neoplastic Stromal Cells in Giant Cell Tumor of Bone

    PubMed Central

    Balla, Peter; Maros, Mate Elod; Barna, Gabor; Antal, Imre; Papp, Gergo; Sapi, Zoltan; Athanasou, Nicholas Anthony; Benassi, Maria Serena; Picci, Pierro; Krenacs, Tibor

    2015-01-01

    Missense mutations of the GJA1 gene encoding the gap junction channel protein connexin43 (Cx43) cause bone malformations resulting in oculodentodigital dysplasia (ODDD), while GJA1 null and ODDD mutant mice develop osteopenia. In this study we investigated Cx43 expression and channel functions in giant cell tumor of bone (GCTB), a locally aggressive osteolytic lesion with uncertain progression. Cx43 protein levels assessed by immunohistochemistry were correlated with GCTB cell types, clinico-radiological stages and progression free survival in tissue microarrays of 89 primary and 34 recurrent GCTB cases. Cx43 expression, phosphorylation, subcellular distribution and gap junction coupling was also investigated and compared between cultured neoplastic GCTB stromal cells and bone marow stromal cells or HDFa fibroblasts as a control. In GCTB tissues, most Cx43 was produced by CD163 negative neoplastic stromal cells and less by CD163 positive reactive monocytes/macrophages or by giant cells. Significantly less Cx43 was detected in α-smooth muscle actin positive than α-smooth muscle actin negative stromal cells and in osteoclast-rich tumor nests than in the adjacent reactive stroma. Progressively reduced Cx43 production in GCTB was significantly linked to advanced clinico-radiological stages and worse progression free survival. In neoplastic GCTB stromal cell cultures most Cx43 protein was localized in the paranuclear-Golgi region, while it was concentrated in the cell membranes both in bone marrow stromal cells and HDFa fibroblasts. In Western blots, alkaline phosphatase sensitive bands, linked to serine residues (Ser369, Ser372 or Ser373) detected in control cells, were missing in GCTB stromal cells. Defective cell membrane localization of Cx43 channels was in line with the significantly reduced transfer of the 622 Da fluorescing calcein dye between GCTB stromal cells. Our results show that significant downregulation of Cx43 expression and gap junction coupling in

  9. [Aggressive fibromatoses].

    PubMed

    Döhler, J R; Hamelmann, H; Lasson, U

    1984-03-01

    Benign by nature, aggressive fibromatoses (desmoid fibromas) may represent as difficult therapeutic problems as malignant tumours. When subtotally resected they tend to recur. But spontaneous regression is possible. Expense and limits of their surgical treatment are discussed with reference to seven patients. In five cases primary affliction of bone was evident. There are three reports given in detail: In the first, malignant transformation may be due to radiation therapy and hemipelvectomy could not prevent recurrence. In the second, spontaneous regression of untreated pelvic affection may have occurred. In the third, several resections and amputation of the leg failed to cure congenital infantile fibromatosis.

  10. Detection of N-glycolyl GM3 ganglioside in neuroectodermal tumors by immunohistochemistry: an attractive vaccine target for aggressive pediatric cancer.

    PubMed

    Scursoni, Alejandra M; Galluzzo, Laura; Camarero, Sandra; Lopez, Jessica; Lubieniecki, Fabiana; Sampor, Claudia; Segatori, Valeria I; Gabri, Mariano R; Alonso, Daniel F; Chantada, Guillermo; de Dávila, María Teresa G

    2011-01-01

    The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5 μm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an average of about 70% of positive tumors cells. Immunoreactivity was moderate to intense in most tumors, showing a diffuse cytoplasmic and membranous staining, although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No significant differences were observed between neuroblastoma with and without NMYC oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in more aggressive cancers. Until now, the expression of N-glycolylated gangliosides in pediatric neuroectodermal tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal tumors, suggesting its potential utility as a specific target of immunotherapy.

  11. Tumor-induced osteomalacia. Kinetics of calcium, phosphorus, and vitamin D metabolism and characteristics of bone histomorphometry.

    PubMed

    Siris, E S; Clemens, T L; Dempster, D W; Shane, E; Segre, G V; Lindsay, R; Bilezikian, J P

    1987-02-01

    A patient with a mesenchymal tumor and hypophosphatemic osteomalacia was studied before and after tumor excision. Initial laboratory values included normal serum calcium, decreased serum phosphorus and tubular reabsorption of phosphate, undetectable 1,25-dihydroxyvitamin D, and normal parathyroid hormone. Histomorphometry of a bone biopsy specimen showed evidence of increased osteoclastic bone resorption. By 16 hours after tumor removal, 1,25-dihydroxyvitamin D level had normalized, but serum phosphorus level was unchanged; at 28 hours, both serum phosphorus value and tubular reabsorption of phosphate were within normal limits. It is concluded that tumor removal is associated with rapid correction both of 1,25-dihydroxyvitamin D production and of renal phosphate wasting. Increased bone resorption suggests the production of an osteoclast activator by the tumor and may explain the typically normal serum calcium value in this disorder. PMID:3812526

  12. Radionuclide bone scanning in neuroblastoma: skeletal metastases and primary tumor localization of /sup 99m/Tc-MDP

    SciTech Connect

    Podrasky, A.E.; Stark, D.D.; Hattner, R.S.; Gooding, C.A.; Moss, A.A.

    1983-09-01

    Of 42 radionuclide bone scans in 35 children with neuroblastoma, 21 were abnormal for the presence of skeletal metastases. Of the 21 abnormal scans, 16 were corroborated by positive bone-marrow biopsy or clinical data. The false-negative and false-positive rates for bone scanning were 4.8% and 9.5%, respectively. Calcification of the primary tumor was seen on pretreatment computed tomographic (CT) scans in 24 (89%) of 27 cases, while only 13 (48%) of 27 were detectable by plain radiographs. Uptake of /sup 99m/Tc methylene diphosphate /sup 99m/Tc-MDP) by the primary tumor occurred in 20 of 27 cases, but correlation between tumor uptake and calcification was not statistically significant. All children with markedly elevated urinary vanillylmandelic acid exhibited primary tumor uptake. Survival was not affected independently by primary tumor uptake.

  13. Surgical treatment of multifocal giant cell tumor of carpal bones with preservation of wrist function: case report.

    PubMed

    Tarng, Yih-Wen; Yang, Shan-Wei; Hsu, Chien-Jen

    2009-02-01

    We report a rare case of multifocal giant cell tumor of bone involving the trapezium, trapezoid, capitate, and scaphoid with soft tissue extension. Following intralesional resection, an autogenous corticocancellous iliac crest bone graft was used to fill the resultant defect and preserve carpal height and radiocarpal motion. Successful union with no recurrence was noted at 1-year follow-up.

  14. Interleukin-1 and tumor necrosis factor-alpha gene polymorphisms in Turkish patients with localized aggressive periodontitis.

    PubMed

    Guzeldemir, Esra; Gunhan, Meral; Ozcelik, Onur; Tastan, Hakki

    2008-06-01

    Localized aggressive periodontitis (LAgP) is a complex multifactorial periodontal disease to which genetic factors are thought to predispose individuals. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are potent immunomodulators and proinflammatory cytokines that have been implicated in the pathogenesis of autoimmune and infectious diseases and proposed to be risk factors for LAgP. Our aim was to investigate IL-1 alpha (+4845), IL-1 beta (+3954), and TNF-alpha (-308) gene polymorphisms in Turkish LAgP patients. We genotyped 31 LAgP patients and 31 healthy controls for IL-1alpha(+4845), IL-1beta(+3954), and TNF-alpha(-308) using standard PCR amplification followed by restriction enzyme digestion and gel electrophoresis. Higher prevalence of heterozygosity for IL-1alpha(+4845) was found in cases (65%) when compared to controls (35%) (P < 0.05). While homozygous allele 1 of IL-1beta(+3954) was the most frequent genotype in cases (62%), no controls were homozygous for this allele (P < 0.001). Homozygous allele 1 was the most common TNF-alpha genotype in both groups, however no significant difference in TNF-alpha genotypes was found between groups. In conclusion, in this Turkish population, susceptibility to LAgP is increased by heterozygosity for allele 1 of IL-1alpha(+4845) or homozygosity for allele 1 of IL-1beta(R+3954). Moreover, IL-1 gene polymorphisms appear to have a role in susceptibility to LAgP, and the above-mentioned genotypes could be an important risk factor for LAgP in the Turkish population.

  15. Warburg Effect’s Manifestation in Aggressive Pheochromocytomas and Paragangliomas: Insights from a Mouse Cell Model Applied to Human Tumor Tissue

    PubMed Central

    Fliedner, Stephanie M. J.; Kaludercic, Nina; Jiang, Xiao-Sheng; Hansikova, Hana; Hajkova, Zuzana; Sladkova, Jana; Limpuangthip, Andrea; Backlund, Peter S.; Wesley, Robert; Martiniova, Lucia; Jochmanova, Ivana; Lendvai, Nikoletta K.; Breza, Jan; Yergey, Alfred L.; Paolocci, Nazareno; Tischler, Arthur S.; Zeman, Jiri; Porter, Forbes D.; Lehnert, Hendrik; Pacak, Karel

    2012-01-01

    A glycolytic profile unifies a group of pheochromocytomas and paragangliomas (PHEOs/PGLs) with distinct underlying gene defects, including von Hippel-Lindau (VHL) and succinate dehydrogenase B (SDHB) mutations. Nevertheless, their tumor aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently in SDHB-patients. To date, the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an excellent model to study aggressive PHEOs (mouse tumor tissue (MTT) cells) has been developed from mouse PHEO cells (MPC). We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness, which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2 in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell model and in support of decoupling of glycolysis, the Krebs cycle and oxidative phosphorylation (OXPHOS), SDHB tumors showed increased lactate dehydrogenase levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as expected, decreased at complex II. Moreover, protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors. Although there was no direct evidence for increased reactive oxygen species production, elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that despite dysfunction in complex II and evidence for a glycolytic phenotype, the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising therapeutic targets in other cancers. This study provides new insight into pathogenic mechanisms in aggressive human

  16. Overexpression of the growth-hormone-releasing hormone gene in acromegaly-associated pituitary tumors. An event associated with neoplastic progression and aggressive behavior.

    PubMed Central

    Thapar, K.; Kovacs, K.; Stefaneanu, L.; Scheithauer, B.; Killinger, D. W.; Lioyd, R. V.; Smyth, H. S.; Barr, A.; Thorner, M. O.; Gaylinn, B.; Laws, E. R.

    1997-01-01

    The clinical behavior of growth hormone (GH)-producing pituitary tumors is known to vary greatly; however, the events underlying this variability remain poorly understood. Herein we demonstrate that tumor overexpression of the GH-releasing hormone (GHRH) gene is one prognostically informative event associated with the clinical aggressiveness of somatotroph pituitary tumors. Accumulation of GHRH mRNA transcripts was demonstrated in 91 of a consecutive series of 100 somatotroph tumors by in situ hybridization; these findings were corroborated by Northern analysis and reverse transcriptase polymerase chain reaction, and protein translation was confirmed by Western blotting. By comparison, transcript accumulation was absent or negligibly low in 30 normal pituitary glands. GHRH transcripts were found to preferentially accumulate among clinically aggressive tumors. Specifically, GHRH mRNA signal intensity was 1) linearly correlated with Ki-67 tumor growth fractions (r = 0.71; P < 0.001), 2) linearly correlated with preoperative serum GH levels (r = 0.56; p = 0.01), 3) higher among invasive tumors (P < 0.001), and 4) highest in those tumors in which post-operative remission was not achieved (P < 0.001). Using multivariate logistic regression, a model of postoperative remission likelihood was derived wherein remission was defined by the single criterion of suppressibility of GH levels to less than 2 ng/ml during an oral glucose tolerance test. In this outcome model, GHRH mRNA signal intensity proved to be the most important explanatory variable overall, eclipsing any and all conventional clinicopathological predictors as the single most significant predictor of postoperative remission; increases in GHRH mRNA signal were associated with marked declines in remission likelihood. The generalizability of this outcome model was further validated by the model's significant performance in predicting postoperative remission in a random sample of 30 somatotroph tumors treated at

  17. Combination of anti-angiogenic therapies reduces osteolysis and tumor burden in experimental breast cancer bone metastasis.

    PubMed

    Bachelier, Richard; Confavreux, Cyrille B; Peyruchaud, Olivier; Croset, Martine; Goehrig, Delphine; van der Pluijm, Gabri; Clézardin, Philippe

    2014-09-15

    The clinical efficacy of anti-angiogenic monotherapies in metastatic breast cancer is less than originally anticipated, and it is not clear what the response of bone metastasis to anti-angiogenic therapies is. Here, we examined the impact of neutralizing tumor-derived vascular endothelial growth factor (VEGF) in animal models of subcutaneous tumor growth and bone metastasis formation. Silencing of VEGF expression (Sh-VEGF) in osteotropic human MDA-MB-231/B02 breast cancer cells led to a substantial growth inhibition of subcutaneous Sh-VEGF B02 tumor xenografts, as a result of reduced angiogenesis, when compared to that observed with animals bearing mock-transfected (Sc-VEGF) B02 tumors. However, there was scant evidence that either the silencing of tumor-derived VEGF or the use of a VEGF-neutralizing antibody (bevacizumab) affected B02 breast cancer bone metastasis progression in animals. We also examined the effect of vatalanib (a VEGF receptor tyrosine kinase inhibitor) in this mouse model of bone metastasis. However, vatalanib failed to inhibit bone metastasis caused by B02 breast cancer cells. In sharp contrast, vatalanib in combination with bevacizumab reduced not only bone destruction but also skeletal tumor growth in animals bearing breast cancer bone metastases, when compared with either agent alone. Thus, our study highlights the importance of targeting both the tumor compartment and the host tissue (i.e., skeleton) to efficiently block the development of bone metastasis. We believe this is a crucially important observation as the clinical benefit of anti-angiogenic monotherapies in metastatic breast cancer is relatively modest. PMID:24615579

  18. In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters.

    PubMed

    Luque, Raul M; Sampedro-Nuñez, Miguel; Gahete, Manuel D; Ramos-Levi, Ana; Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Serrano-Somavilla, Ana; Adrados, Magdalena; Culler, Michael D; Castaño, Justo P; Marazuela, Mónica

    2015-08-14

    Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value.

  19. In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters

    PubMed Central

    Gahete, Manuel D.; Ramos-Levi, Ana; Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Serrano-Somavilla, Ana; Adrados, Magdalena; Culler, Michael D.; Castaño, Justo P.; Marazuela, Mónica

    2015-01-01

    Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value. PMID:26124083

  20. Bone morphogenetic protein modulator BMPER is highly expressed in malignant tumors and controls invasive cell behavior.

    PubMed

    Heinke, J; Kerber, M; Rahner, S; Mnich, L; Lassmann, S; Helbing, T; Werner, M; Patterson, C; Bode, C; Moser, M

    2012-06-14

    Bone morphogenetic proteins (BMPs) are growth factors that exert important functions in cell proliferation, migration and differentiation. Till date, multiple human tumors have been reported to display a dysregulation of several members of the BMP pathway that is associated with enhanced malignant tumor growth and metastasis. BMPER (BMP endothelial cell precursor-derived regulator) is a direct BMP modulator that is necessary for BMPs to exert their full-range signaling activity. Moreover, BMPER is expressed by endothelial cells and their progenitors, and has pro-angiogenic features in these cells. Here, we describe the expression of BMPER in human specimens of lung, colon and cervix carcinomas and cell lines derived from such carcinomas. In contrast to healthy tissues, BMPER is highly expressed upon malignant deterioration. Functionally, loss of BMPER in the lung tumor cell line A549 impairs proliferation, migration, invasion as well as tumor cell-induced endothelial cell sprout formation. In contrast, stimulation of A549 cells with exogenous BMPER had no further effect. We found that the BMPER effect may be transduced by regulation of the BMP target transcription factor inhibitor of DNA binding 1 (Id1) and matrix metalloproteinases (MMPs) 9 and 2. These facilitators of cell migration are downregulated when BMPER is absent. To prove the relevance of our in vitro results in vivo, we generated Lewis lung carcinoma cells with impaired BMPER expression and implanted them into the lungs of C57BL/6 mice. In this model, the absence of BMPER resulted in severely reduced tumor growth and tumor angiogenesis. Taken together, these data unequivocally demonstrate that the BMP modulator BMPER is highly expressed in malignant tumors and tumor growth is dependent on the presence of BMPER.

  1. Bone morphogenetic protein modulator BMPER is highly expressed in malignant tumors and controls invasive cell behavior

    PubMed Central

    Heinke, J; Kerber, M; Rahner, S; Mnich, L; Lassmann, S; Helbing, T; Werner, M; Patterson, C; Bode, C; Moser, M

    2012-01-01

    Bone morphogenetic proteins (BMPs) are growth factors that exert important functions in cell proliferation, migration and differentiation. Till date, multiple human tumors have been reported to display a dysregulation of several members of the BMP pathway that is associated with enhanced malignant tumor growth and metastasis. BMPER (BMP endothelial cell precursor-derived regulator) is a direct BMP modulator that is necessary for BMPs to exert their full-range signaling activity. Moreover, BMPER is expressed by endothelial cells and their progenitors, and has pro-angiogenic features in these cells. Here, we describe the expression of BMPER in human specimens of lung, colon and cervix carcinomas and cell lines derived from such carcinomas. In contrast to healthy tissues, BMPER is highly expressed upon malignant deterioration. Functionally, loss of BMPER in the lung tumor cell line A549 impairs proliferation, migration, invasion as well as tumor cell-induced endothelial cell sprout formation. In contrast, stimulation of A549 cells with exogenous BMPER had no further effect. We found that the BMPER effect may be transduced by regulation of the BMP target transcription factor inhibitor of DNA binding 1 (Id1) and matrix metalloproteinases (MMPs) 9 and 2. These facilitators of cell migration are down-regulated when BMPER is absent. To prove the relevance of our in vitro results in vivo, we generated Lewis lung carcinoma cells with impaired BMPER expression and implanted them into the lungs of C57BL/6 mice. In this model, the absence of BMPER resulted in severely reduced tumor growth and tumor angiogenesis. Taken together, these data unequivocally demonstrate that the BMP modulator BMPER is highly expressed in malignant tumors and tumor growth is dependent on the presence of BMPER. PMID:22020334

  2. EXCISION OF GIANT CELL TUMOR OF TENDON SHEATH WITH BONE INVOLVEMENT BY MEANS OF DOUBLE ACCESS APPROACH: CASE REPORT

    PubMed Central

    Alves, Marcelo de Pinho Teixeira

    2015-01-01

    Giant cell tumors of the tendon sheath are common lesions and are the second most frequent tumors in the hand, after synovial cysts. They are diagnosed by means of clinical examination and complementary examinations (simple radiography and magnetic resonance). Erosion and invasion of the phalangeal bone affected may be seen on radiological examination. Magnetic resonance may show a “fluorescent or radiant effect” may be observed, caused by the high quantity of hemosiderin inside the tumor. Surgical treatment is the commonest practice, and complete excision is important for avoiding recurrence of the tumor, especially when bone invasion is observed on imaging examinations, which is generally related to greater tumor recurrence. In this paper, a case of a giant cell tumor of the tendon sheath in the middle phalanx of the third finger of a 45-year-old female patient is presented. This was successfully treated by means of surgery using a double access approach (dorsal and volar). PMID:27026996

  3. Comparative proteomics analysis of human osteosarcomas and benign tumor of bone.

    PubMed

    Li, Y; Liang, Q; Wen, Y-q; Chen, L-l; Wang, L-t; Liu, Y-l; Luo, C-q; Liang, H-z; Li, M-t; Li, Z

    2010-04-15

    We conducted comparative proteomic analysis of osteosarcoma, with hopes of identifying the specific protein markers of osteosarcoma and improve the understanding of tumorigenesis and progression of osteosarcoma. Proteins extracted from osteosarcoma tissue and benign bone tumors, including osteoblastoma, chondroblastoma, and giant cell tumor of bone, were examined using two-dimensional gel electrophoresis followed by mass spectrometry analysis and database searches. We also validated the expression levels of interesting proteins by Western blotting assay and immunohistochemical staining. Intensity alterations of 30 spots were detected in osteosarcoma, and 18 of these spots were finally identified, including 12 up-regulated proteins and 6 down-regulated ones. The up-regulated proteins include VIM, TUBA1C, ZNF133, EZR, ACTG1, TF, and so on. The six down-regulated proteins include ADCY1, ATP5B, TUBB, RCN3, ACTB, and YWHAZ. Subsequent immunohistochemical staining and Western blotting assay for TUBA1C and ZNF133 in osteosarcoma samples confirmed the observation obtained by proteomic analysis. Our results suggest that these identified proteins may be potential biomarkers for osteosarcoma tumorigenesis and therapeutics. Aberrant expression of cytoskeletal- and microtubule-associated proteins in osteosarcoma may provide an advantage for tumor invasion and metastasis by affecting the stability of microtubule, which consequently influences the prognosis of patients. PMID:20362224

  4. Reconstruction by bone transport after resection of benign tumors of tibia: A retrospective study of 38 patients

    PubMed Central

    Borzunov, Dmitry Y; Balaev, Pavel I; Subramanyam, Koushik N

    2015-01-01

    Background: The commonly used reconstructive options after post resection defects in bone tumors like megaprosthesis, autograft, allograft, bone graft substitutes and recycled bone have their own demerits on a long term. Bone transport that regenerates patient's own bone is a less explored option of reconstruction after resection of benign bone tumors and reports on this are limited. This technique is very much relevant in tibia where Ilizarov fixator is surgeon and patient friendly. We report our experience. Materials and Methods: This is a retrospective series of resection and bone transport in 38 patients with benign tumor of tibia. There were 14 males and 24 females with mean age of 23.40 years (range 9–40 years). Lesion was located in proximal third tibia in 27, middle third in two and distal third in nine patients. The diagnosis was giant cell tumor in 32, chondroblastoma in three, chondromyxoid fibroma, enchondroma and desmoplasic fibroma in one patient each. The resection was intercalary in 28 and transarticular in 10 patients. Osteosynthesis was monofocal in three, bifocal in 31 and polyfocal in four cases. Results: Mean followup was 7.22 years (range 1.5–15 years). Mean resection length was 10.21 cm (range 3–22 cm). The mean duration of external fixator was 308.03 days (range 89–677 days) and mean external fixator index was 36.14 days/cm (range 16.84–97.43 days/cm). Twelve patients had difficulties in the form of 11 problems and five obstacles that were successfully managed. None of the patients had local recurrence of tumor or any long term complication. Mean Musculo-skeletal Tumour Society score at final followup was 27.18 (90.60%). Conclusions: Bone transport is an excellent option after resection of benign tumors of tibia with good local control and functional outcome, despite minor difficulties that need timely management. PMID:26538757

  5. Activation of EGFR, HER2 and HER3 by neurotensin/neurotensin receptor 1 renders breast tumors aggressive yet highly responsive to lapatinib and metformin in mice

    PubMed Central

    Mourra, Najat; Liu, Jin; De Wever, Olivier; Llorca, Frédérique Penault; Cayre, Anne; Kouchkar, Amal; Gompel, Anne; Forgez, Patricia

    2014-01-01

    A present challenge in breast oncology research is to identify therapeutical targets which could impact tumor progression. Neurotensin (NTS) and its high affinity receptor (NTSR1) are up regulated in 20% of breast cancers, and NTSR1 overexpression was shown to predict a poor prognosis for 5 year overall survival in invasive breast carcinomas. Interactions between NTS and NTSR1 induce pro-oncogenic biological effects associated with neoplastic processes and tumor progression. Here, we depict the cellular mechanisms activated by NTS, and contributing to breast cancer cell aggressiveness. We show that neurotensin (NTS) and its high affinity receptor (NTSR1) contribute to the enhancement of experimental tumor growth and metastasis emergence in an experimental mice model. This effect ensued following EGFR, HER2, and HER3 over-expression and autocrine activation and was associated with an increase of metalloproteinase MMP9, HB-EGF and Neuregulin 2 in the culture media. EGFR over expression ensued in a more intense response to EGF on cellular migration and invasion. Accordingly, lapatinib, an EGFR/HER2 tyrosine kinase inhibitor, as well as metformin, reduced the tumor growth of cells overexpressing NTS and NTSR1. All cellular effects, such as adherence, migration, invasion, altered by NTS/NTSR1 were abolished by a specific NTSR1 antagonist. A strong statistical correlation between NTS-NTSR1-and HER3 (p< 0.0001) as well as NTS-NTSR1-and HER3- HER2 (p< 0.001) expression was found in human breast tumors. Expression of NTS/NTSR1 on breast tumoral cells creates a cellular context associated with cancer aggressiveness by enhancing epidermal growth factor receptor activity. We propose the use of labeled NTS/NTSR1 complexes to enlarge the population eligible for therapy targeting HERs tyrosine kinase inhibitor or HER2 overexpression. PMID:25249538

  6. Bone mesenchymal stem cells differentiate into myofibroblasts in the tumor microenvironment

    PubMed Central

    ZHANG, JING; SUN, DINGQI; FU, QIANG; CAO, QINGWEI; ZHANG, HUI; ZHANG, KEQIN

    2016-01-01

    The aim of the present study was to investigate the tropism of mesenchymal stem cells (MSCs) to the tumor microenvironment, and to evaluate the feasibility of bone marrow mesenchymal stem cells differentiating into myofibroblasts in vitro. A total of 1 ml bone marrow was extracted from the greater trochanter of one male New Zealand rabbit, and MSCs were obtained by density gradient centrifugation and cultured routinely. The surface markers were analyzed by flow cytometry. A VX2 tumor was aseptically excised from another male New Zealand rabbit and primary cultured. The tropism of MSCs for 30% and 50% VX2 conditioned medium was determined by using Transwell migration assays. MSCs were incubated in 30% VX2 conditioned medium for 7 or 14 days. The messenger (m)RNA levels and protein expression of α-smooth muscle actin (α-SMA) and vimentin were measured by reverse transcription-polymerase chain reaction and western blotting. MSCs were observed to have a spindle shape. The cultured MSCs were cluster of differentiation (CD)44+, CD105+, CD106+ and CD34−. VX2 cells demonstrated a spindle or polygon shape. In the Transwell assay, it was observed that the migrated cells appeared more frequently in the 30% VX2 conditioned medium group compared with the other groups when microscopically examined, which was additionally confirmed by the results of a colorimetric assay. The mRNA levels and protein expression of α-SMA and vimentin significantly increased in the test group compared with the control group at 7 days (P<0.01), and further increased in the test group at 14 days (P<0.01). The results of the present study demonstrated that MSCs have tropism for the tumor microenvironment and furthermore, may differentiate into myofibroblasts in the tumor microenvironment in vitro. The present study suggested that MSCs may migrate to the tumor and subsequently differentiate into myofibroblasts due to the tumor microenvironment, which may lead to promotion of the growth of the tumor

  7. [Intraoperative extracorporeal irradiation and replantation in local treatment of primary malignant bone tumors].

    PubMed

    Sabo, D; Bernd, L; Buchner, M; Treiber, M; Wannenmacher, M; Ewerbeck, V; Parsch, D

    2003-11-01

    In 13 patients with primary malignant bone tumors (10 Ewing's sarcoma, 1 parosteal osteosarcoma, 1 adamantinoma recurrence, and 1 MFH) local therapy was performed as intraoperative extracorporeal irradiation and replantation (IEIR) of the involved bone segment (5 tibia, 2 femur, and 6 pelvis). Of the 13 patients (69%), 9 are alive at the time of the follow-up (5 CDF, 4 AWM(treated)) and 4 patients died of disease (DOD). Up to now during the follow-up of 32 months (6-57), no local recurrence was observed in the replanted bone segments. The complication rate was very high (18 complications in 11 of the 13 patients, including 6 cases with complication V degrees according to Ruggieri with loss of the reconstruction). The typical complication is severe local infection necessitating removal of the replant. In cases of mechanical failure, the replanted segment could mostly be preserved by surgical revision and autologous bone grafting. If serious complications can be managed or avoided, functional results can be achieved. IEIR must be seen as an extraordinary reconstruction procedure in cases where established procedures such as endoprosthesis, biological reconstructions, or rotationplasties cannot be used or are refused by the patient. PMID:14615850

  8. A mouse model of luciferase-transfected stromal cells of giant cell tumor of bone.

    PubMed

    Lau, Carol P Y; Wong, Kwok Chuen; Huang, Lin; Li, Gang; Tsui, Stephen K W; Kumta, Shekhar Madhukar

    2015-11-01

    A major barrier towards the study of the effects of drugs on Giant Cell Tumor of Bone (GCT) has been the lack of an animal model. In this study, we created an animal model in which GCT stromal cells survived and functioned as proliferating neoplastic cells. A proliferative cell line of GCT stromal cells was used to create a stable and luciferase-transduced cell line, Luc-G33. The cell line was characterized and was found that there were no significant differences on cell proliferation rate and recruitment of monocytes when compared with the wild type GCT stromal cells. We delivered the Luc-G33 cells either subcutaneously on the back or to the tibiae of the nude mice. The presence of viable Luc-G33 cells was assessed using real-time live imaging by the IVIS 200 bioluminescent imaging (BLI) system. The tumor cells initially propagated and remained viable on site for 7 weeks in the subcutaneous tumor model. We also tested in vivo antitumor effects of Zoledronate (ZOL) and Geranylgeranyl transferase-I inhibitor (GGTI-298) alone or their combinations in Luc-G33-transplanted nude mice. ZOL alone at 400 µg/kg and the co-treatment of ZOL at 400 µg/kg and GGTI-298 at 1.16 mg/kg reduced tumor cell viability in the model. Furthermore, the anti-tumor effects by ZOL, GGTI-298 and the co-treatment in subcutaneous tumor model were also confirmed by immunohistochemical (IHC) staining. In conclusion, we established a nude mice model of GCT stromal cells which allows non-invasive, real-time assessments of tumor development and testing the in vivo effects of different adjuvants for treating GCT.

  9. Heparanase-mediated Loss of Nuclear Syndecan-1 Enhances Histone Acetyltransferase (HAT) Activity to Promote Expression of Genes That Drive an Aggressive Tumor Phenotype*

    PubMed Central

    Purushothaman, Anurag; Hurst, Douglas R.; Pisano, Claudio; Mizumoto, Shuji; Sugahara, Kazuyuki; Sanderson, Ralph D.

    2011-01-01

    Heparanase acts as a master regulator of the aggressive tumor phenotype in part by enhancing expression of proteins known to drive tumor progression (e.g. VEGF, MMP-9, hepatocyte growth factor (HGF), and RANKL). However, the mechanism whereby this enzyme regulates gene expression remains unknown. We previously reported that elevation of heparanase levels in myeloma cells causes a dramatic reduction in the amount of syndecan-1 in the nucleus. Because syndecan-1 has heparan sulfate chains and because exogenous heparan sulfate has been shown to inhibit the activity of histone acetyltransferase (HAT) enzymes in vitro, we hypothesized that the reduction in nuclear syndecan-1 in cells expressing high levels of heparanase would result in increased HAT activity leading to stimulation of protein transcription. We found that myeloma cells or tumors expressing high levels of heparanase and low levels of nuclear syndecan-1 had significantly higher levels of HAT activity when compared with cells or tumors expressing low levels of heparanase. High levels of HAT activity in heparanase-high cells were blocked by SST0001, an inhibitor of heparanase. Restoration of high syndecan-1 levels in heparanase-high cells diminished nuclear HAT activity, establishing syndecan-1 as a potent inhibitor of HAT. Exposure of heparanase-high cells to anacardic acid, an inhibitor of HAT activity, significantly suppressed their expression of VEGF and MMP-9, two genes known to be up-regulated following elevation of heparanase. These results reveal a novel mechanistic pathway driven by heparanase expression, which leads to decreased nuclear syndecan-1, increased HAT activity, and up-regulation of transcription of multiple genes that drive an aggressive tumor phenotype. PMID:21757697

  10. Bone cysts: unicameral and aneurysmal bone cyst.

    PubMed

    Mascard, E; Gomez-Brouchet, A; Lambot, K

    2015-02-01

    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy. PMID:25579825

  11. Malignant transformation of aggressive osteoblastoma to ostesarcoma.

    PubMed

    Görgün, Ömer; Salduz, Ahmet; Kebudi, Rejin; Özger, Harzem; Bilgiç, Bilge

    2016-08-01

    Osteoblastoma is a rare, bone-forming tumor, characterized by osteoid and woven bone production. A 13-year-old boy patient presented to our clinic with complaint of pain in his left proximal tibia. We performed curettage and bone grafting for the lesion diagnosed as osteoblastoma. Two years later, the patient admitted to the hospital with a mass in the same region which was diagnosed by biopsy to be osteosarcoma. Patient was performed reconstruction operation with local resection and mega prosthesis. Fourteen months after termination of chemotherapy, lung metastasis developed and the patient died consequently. In this article, we reported a patient with aggressive osteoblastoma of the left proximal tibia which recurred as an osteosarcoma and discussed the difficulties in the histopathological diagnosis and management of these patients. As some other cases in the literature, our case indicates that osteoblastomas may undergo malignant transformation. PMID:27499324

  12. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models

    PubMed Central

    Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M.; Zhao, Ming

    2015-01-01

    Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting. PMID:26431498

  13. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models.

    PubMed

    Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M; Zhao, Ming

    2015-10-13

    Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.

  14. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma.

    PubMed

    Yang, J; He, J; Wang, J; Cao, Y; Ling, J; Qian, J; Lu, Y; Li, H; Zheng, Y; Lan, Y; Hong, S; Matthews, J; Starbuck, M W; Navone, N M; Orlowski, R Z; Lin, P; Kwak, L W; Yi, Q

    2012-09-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into severe combined immunodeficient (SCID) or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism-activation of p38 signaling in myeloma cells-by which myeloma cells induce osteolytic bone lesions, and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  15. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    PubMed Central

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  16. Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer

    PubMed Central

    Gupta, Shilpi; Kumar, Prabhat; Kaur, Harsimrut; Sharma, Nishi; Saluja, Daman; Bharti, Alok C.; Das, Bhudev C.

    2015-01-01

    Tongue squamous cell carcinoma (TSCC) is most aggressive head and neck cancer often associated with HR-HPV infection. The role of AP-1 which is an essential regulator of HPV oncogene expression and tumorigenesis is not reported in tongue cancer. One hundred tongue tissue biopsies comprising precancer, cancer and adjacent controls including two tongue cancer cell lines were employed to study the role of HPV infection and AP-1 family proteins. An exclusive prevalence (28%) of HR-HPV type 16 was observed mainly in well differentiated tongue carcinomas (78.5%). A higher expression and DNA binding activity of AP-1 was observed in tongue tumors and cancer cell lines with c-Fos and Fra-2 as the major binding partners forming the functional AP-1 complex but c-Jun participated only in HPV negative and poorly differentiated carcinoma. Knocking down of Fra-2 responsible for aggressive tongue tumorigenesis led to significant reduction in c-Fos, c-Jun, MMP-9 and HPVE6/E7 expression but Fra-1 and p53 were upregulated. The binding and expression of c-Fos/Fra-2 increased as a function of severity of tongue lesions, yet selective participation of c-Jun appears to promote poor differentiation and aggressive tumorigenesis only in HPV negative cases while HPV infection leads to well differentiation and better prognosis preferably in nonsmokers. PMID:26581505

  17. Influence of preharvest tumor cell contamination in bone marrow or blood does not predict resultant tumor cell contamination of granulocyte colony-stimulating factor mobilized stem cells.

    PubMed

    Krüger, W; Kröger, N; Tögel, F; Badbaran, A; Renges, H; Gieseking, F; Gutensohn, K; Jänicke, F; Zander, A R

    2001-04-01

    Tumor cell contamination of stem cell collections harvested from breast cancer patients is a common phenomenon described by several investigators but with findings that vary among reports. Although so-called co-mobilization of these cells has been hypothesized, the origin of tumor cell contamination in stem cells is still unknown. A total of 47 G-CSF mobilized stem cell grafts from patients with nodal-positive (n = 30), chemosensitive metastatic (n = 11), and 5 women with inflammatory breast cancer were evaluated for cancer cells by immunocytochemistry. Additionally, 40 bone marrow aspirations and 23 peripheral blood samples collected prior to apheresis and after one to two cycles of conventional chemotherapy were available for examination. Tumor cell contamination of leukapheresis correlated best with preharvest blood state. This was valid when the nominal (positive/negative) presence of tumor cells in blood was compared to the nominal presence of tumor cells in apheresis samples and when the it was correlated to the tumor cell load of apheresis samples (TCL = tumor cells per 10(6) nucleated cells investigated). The correlation between blood and stem cells was better (nominal and quantitative) than that between marrow and stem cells, despite the larger sample size of marrow aspirations. The presence or absence of cancer cells in apheresis samples could not be safely predicted by the presence or absence of tumor cells in marrow or blood alone. Diagnostic specificity seems to improve from a combination of results from marrow and blood analysis. No correlation was found in quantitative analysis of tumor cell contamination between marrow and blood. In conclusion, the results suggest that blood and bone marrow represent different compartments for epithelial cancer cells and that contaminating tumor cells in stem cell harvests may be derived from the blood and/or marrow compartment. The tumor cell contamination of a stem cell harvest cannot be safely predicted by a

  18. T cells stimulate catabolic gene expression by the stromal cells from giant cell tumor of bone

    SciTech Connect

    Cowan, Robert W.; Ghert, Michelle; Singh, Gurmit

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Two T cell lines stimulate PTHrP, RANKL, MMP13 gene expression in GCT cell cultures. Black-Right-Pointing-Pointer CD40 expressed by stromal cells; CD40L detected in whole tumor but not cultures. Black-Right-Pointing-Pointer Effect of CD40L treatment on GCT cells increased PTHrP and MMP13 gene expression. Black-Right-Pointing-Pointer PTHrP treatment increased MMP13 expression, while inhibition decreased expression. Black-Right-Pointing-Pointer T cells may stimulate GCT stromal cells and promote the osteolysis of the tumor. -- Abstract: The factors that promote the localized bone resorption by giant cell tumor of bone (GCT) are not fully understood. We investigated whether T cells could contribute to bone resorption by stimulating expression of genes for parathyroid hormone-related protein (PTHrP), matrix metalloproteinase (MMP)-13, and the receptor activator of nuclear-factor {kappa}B ligand (RANKL). Two cell lines, Jurkat clone E6-1 and D1.1, were co-cultured with isolated GCT stromal cells. Real-time PCR analyses demonstrated a significant increase of all three genes following 48 h incubation, and PTHrP and MMP-13 gene expression was also increased at 24 h. Further, we examined the expression of CD40 ligand (CD40L), a protein expressed by activated T cells, and its receptor, CD40, in GCT. Immunohistochemistry results revealed expression of the CD40 receptor in both the stromal cells and giant cells of the tumor. RNA collected from whole GCT tissues showed expression of CD40LG, which was absent in cultured stromal cells, and suggests that CD40L is expressed within GCT. Stimulation of GCT stromal cells with CD40L significantly increased expression of the PTHrP and MMP-13 genes. Moreover, we show that inhibition of PTHrP with neutralizing antibodies significantly decreased MMP13 expression by the stromal cells compared to IgG-matched controls, whereas stimulation with PTHrP (1-34) increased MMP-13 gene expression. These

  19. Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone

    PubMed Central

    Zhang, Baohui; Huo, Lihong; Lai, Kevin; Li, Xinmin; Galet, Colette; Grogan, Tristan R.; Elashoff, David; Freedland, Stephen J.; Rettig, Matthew; Aronson, William J.; Knudsen, Beatrice S.; Lewis, Michael S.; Garraway, Isla P.

    2016-01-01

    Background Benign human prostate tubule-initiating cells (TIC) and aggressive prostate cancer display common traits, including tolerance of low androgen levels, resistance to apoptosis, and microenvironment interactions that drive epithelial budding and outgrowth. TIC can be distinguished from epithelial and stromal cells that comprise prostate tissue via cell sorting based upon Epcam, CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess a similar antigenic profile to adult TIC and are capable of inducing tubule formation. To identify the TIC niche in human prostate tissue, differential keratin (KRT) expression was evaluated. Results Gene expression data generated from Affymetrix Gene Chip human U133 Plus 2.0 array of sorted adult and fetal epithelial cells revealed KRT13 to be significantly enriched in FC and TIC compared to basal cells (BC) and luminal cells (LC) (p<0.001). Enriched KRT13 expression was confirmed by RT-PCR and cytospin immunostaining. Immunohistochemical analysis of KRT13 expression revealed rare KRT13+ epithelia throughout prostatic ducts/acini in adult tissue specimens and differentiated tubules in 24-week recombinant grafts, In contrast, abundant KRT13 expression was observed in developing ducts/acini in fetal prostate and cord-like structures composing 8-week recombinant grafts. Immunostaining of a prostate tissue microarray revealed KRT13+ tumor foci in approximately 9% of cases, and this subset displayed significantly shorter time to recurrence (p = 0.031), metastases (p = 0.032), and decreased overall survival (p = 0.004). Diagnostic prostate needle biopsies (PNBX) from untreated patients with concurrent bone metastases (clinical stage M1) displayed KRT13+ tumor foci, as did bone metastatic foci. Conclusions The expression profile of KRT13 in benign fetal and adult prostate tissue and in recombinant grafts, as well as the frequency of KRT13 expression in primary and metastatic prostate cancer indicates that it

  20. Dietary soy isoflavones increase metastasis to lungs in an experimental model of breast cancer with bone micro-tumors.

    PubMed

    Yang, Xujuan; Belosay, Aashvini; Hartman, James A; Song, Huaxin; Zhang, Yukun; Wang, Wendan; Doerge, Daniel R; Helferich, William G

    2015-04-01

    Bone is one of the most common sites for metastasis in breast cancer (BC). Micro-metastasis in bone marrow was detected in 30% of patients with stage I, II, or III BC at primary surgery and is a strong indicator of poor prognosis. The role dietary soy isoflavones play in BC with bone micro-metastasis is unclear. In this study, we examined the effects of genistein, daidzein, (-)-equol or a mixture of soy isoflavones on BC with bone micro-metastasis using an experimental model of murine mammary cancer 4T1 cells engineered with luciferase. A small number (1000) of 4T1 cells were injected into the tibia of female Balb/c mice to establish micro-tumors in bone. Soy isoflavones were supplemented in the AIN-93G diet at 750 mg/kg and were provided to mice from 3 weeks before to 3 weeks after cell injection. Bioluminescent imaging was conducted on day 2 (D2), D6, D8, D16 and D20 post cell injection and the results indicated dietary soy isoflavones enhanced the growth of bone micro-tumors on D8. Furthermore, dietary soy isoflavones stimulated metastatic tumor formation in lungs and increased Ki-67 protein expression in these metastasized tumors. In vitro, soy isoflavones (<10 µM) had limited effects on the growth, motility or invasion of 4T1 cells. Thus, the in vivo stimulatory effect could be likely due to systemic effects between the host, 4T1 tumors and soy isoflavones. In conclusion, soy isoflavones stimulate BC with bone micro-metastasis in mice and further investigations are needed regarding their consumption by BC survivors.

  1. The cystine/glutamate antiporter system xc− drives breast tumor cell glutamate release and cancer-induced bone pain

    PubMed Central

    Slosky, Lauren M.; BassiriRad, Neemah M.; Symons, Ashley M.; Thompson, Michelle; Doyle, Timothy; Forte, Brittany L.; Staatz, William D.; Bui, Lynn; Neumann, William L.; Mantyh, Patrick W.; Salvemini, Daniela; Largent-Milnes, Tally M.; Vanderah, Todd W.

    2016-01-01

    Abstract Bone is one of the leading sites of metastasis for frequently diagnosed malignancies, including those arising in the breast, prostate and lung. Although these cancers develop unnoticed and are painless in their primary sites, bone metastases result in debilitating pain. Deeper investigation of this pain may reveal etiology and lead to early cancer detection. Cancer-induced bone pain (CIBP) is inadequately managed with current standard-of-care analgesics and dramatically diminishes patient quality of life. While CIBP etiology is multifaceted, elevated levels of glutamate, an excitatory neurotransmitter, in the bone-tumor microenvironment may drive maladaptive nociceptive signaling. Here, we establish a relationship between the reactive nitrogen species peroxynitrite, tumor-derived glutamate, and CIBP. In vitro and in a syngeneic in vivo model of breast CIBP, murine mammary adenocarcinoma cells significantly elevated glutamate via the cystine/glutamate antiporter system xc−. The well-known system xc− inhibitor sulfasalazine significantly reduced levels of glutamate and attenuated CIBP-associated flinching and guarding behaviors. Peroxynitrite, a highly reactive species produced in tumors, significantly increased system xc− functional expression and tumor cell glutamate release. Scavenging peroxynitrite with the iron and mangano-based porphyrins, FeTMPyP and SRI10, significantly diminished tumor cell system xc− functional expression, reduced femur glutamate levels and mitigated CIBP. In sum, we demonstrate how breast cancer bone metastases upregulate a cystine/glutamate co-transporter to elevate extracellular glutamate. Pharmacological manipulation of peroxynitrite or system xc− attenuates CIBP, supporting a role for tumor-derived glutamate in CIBP and validating the targeting of system xc− as a novel therapeutic strategy for the management of metastatic bone pain. PMID:27482630

  2. What role for radiobiphosphonates bone scintigraphy in the monitoring of an unusual bone giant cell tumor: a case report and literature review

    PubMed Central

    Oueriagli, Salah Nabih; Ghfir, Imad; Guerrouj, Hassna El; Raïs, Nouzha Ben

    2016-01-01

    We report the case of 24 years old female patient, followed since ten years ago for bone giant cell tumor (GCT) of the right knee, which was complicated by pulmonary metastases. Surgical treatment and pulmonary metastasectomies have not allowed definitive cure of this disease with the appearance of metachronous bone lesions after eight years of evolution. The literature review confirms the originality of this observation: the age of the patient, the initial and metastasis locations and the occurrence of lung metastases with unfavorable prognosis. Through this clinical case, the authors highlight the role of radiobiphosphonates bone scintigraphy in detecting synchronous or metachronous bone lesions, and in monitoring of these locations under medical treatment. PMID:27186440

  3. What role for radiobiphosphonates bone scintigraphy in the monitoring of an unusual bone giant cell tumor: a case report and literature review.

    PubMed

    Oueriagli, Salah Nabih; Ghfir, Imad; Guerrouj, Hassna El; Raïs, Nouzha Ben

    2016-01-01

    We report the case of 24 years old female patient, followed since ten years ago for bone giant cell tumor (GCT) of the right knee, which was complicated by pulmonary metastases. Surgical treatment and pulmonary metastasectomies have not allowed definitive cure of this disease with the appearance of metachronous bone lesions after eight years of evolution. The literature review confirms the originality of this observation: the age of the patient, the initial and metastasis locations and the occurrence of lung metastases with unfavorable prognosis. Through this clinical case, the authors highlight the role of radiobiphosphonates bone scintigraphy in detecting synchronous or metachronous bone lesions, and in monitoring of these locations under medical treatment. PMID:27186440

  4. A promising approach for treatment of tumor-induced bone diseases: utilizing bisphosphonate derivatives of nucleoside antimetabolites.

    PubMed

    Reinholz, Monica M; Zinnen, Shawn P; Dueck, Amylou C; Dingli, David; Reinholz, Gregory G; Jonart, Leslie A; Kitzmann, Kathleen A; Bruzek, Amy K; Negron, Vivian; Abdalla, Abdalla K; Arendt, Bonnie K; Croatt, Anthony J; Sanchez-Perez, Luis; Sebesta, David P; Lönnberg, Harri; Yoneda, Toshiyuki; Nath, Karl A; Jelinek, Diane F; Russell, Stephen J; Ingle, James N; Spelsberg, Thomas C; Dixon, Henry B F Hal; Karpeisky, Alexander; Lingle, Wilma L

    2010-07-01

    Despite palliative treatments, tumor-induced bone disease (TIBD) remains highly debilitating for many cancer patients and progression typically results in death within two years. Therefore, more effective therapies with enhanced anti-resorptive and cytotoxic characteristics are needed. We developed bisphosphonate-chemotherapeutic conjugates designed to bind bone and hydrolyze, releasing both compounds, thereby targeting both osteoclasts and tumor cells. This study examined the effects of our lead compound, MBC-11 (the anhydride formed between arabinocytidine (AraC)-5'-phosphate and etidronate), on bone tumor burden, bone volume, femur bone mineral density (BMD), and overall survival using two distinct mouse models of TIBD, the 4T1/luc breast cancer and the KAS-6/1-MIP1alpha multiple myeloma models. In mice orthotopically inoculated with 4T1/luc mouse mammary cells, MBC-11 (0.04 microg/day; s.c.) reduced the incidence of bone metastases to 40% (4/10), compared to 90% (9/10; p=0.057) and 100% (5/5; p=0.04) of PBS- or similarly-dosed, zoledronate-treated mice, respectively. MBC-11 also significantly decreased bone tumor burden compared to PBS- or zoledronate-treated mice (p=0.021, p=0.017, respectively). MBC-11 and zoledronate (0.04 microg/day) significantly increased bone volume by two- and four-fold, respectively, compared to PBS-treated mice (p=0.005, p<0.001, respectively). In mice systemically injected with human multiple myeloma KAS-6/1-MIP1alpha cells, 0.04 and 4.0 microg/day MBC-11 improved femur BMD by 13% and 16%, respectively, compared to PBS (p=0.025, p=0.017, respectively) at 10 weeks post-tumor cell injection and increased mean survival to 95 days compared to 77 days in mice treated with PBS (p=0.047). Similar doses of zoledronate also improved femur BMD (p< or =0.01 vs PBS) and increased mean survival to 86 days, but this was not significantly different than in PBS-treated mice (p=0.53). These results demonstrate that MBC-11 decreases bone tumor burden

  5. A Promising Approach for Treatment of Tumor-Induced Bone Diseases: Utilizing Bisphosphonate Derivatives of Nucleoside Antimetabolites*

    PubMed Central

    Reinholz, Monica M.; Zinnen, Shawn P.; Dueck, Amylou C.; Dingli, David; Reinholz, Gregory G.; Jonart, Leslie A.; Kitzmann, Kathleen A.; Bruzek, Amy K.; Negron, Vivian; Abdalla, Abdalla K.; Arendt, Bonnie K.; Croatt, Anthony J.; Sanchez-Perez, Luis; Sebesta, David P.; Lönnberg, Harri; Yoneda, Toshiyuki; Nath, Karl A.; Jelinek, Diane F.; Russell, Stephen J.; Ingle, James N.; Spelsberg, Thomas C.; (Hal) Dixon, Henry B.F.; Karpeisky, Alexander; Lingle, Wilma L.

    2010-01-01

    Despite palliative treatments, tumor-induced bone disease (TIBD) remains highly debilitating for many cancer patients and progression typically results in death within two years. Therefore, more effective therapies with enhanced antiresorptive and cytotoxic characteristics are needed. We developed bisphosphonate-chemotherapeutic conjugates designed to bind bone and hydrolyze, releasing both compounds, thereby targeting both osteoclasts and tumor cells. This study examined the effects of our lead compound, MBC-11 (the anhydride formed between arabinocytidine (AraC)-5’-phosphate and etidronate), on bone tumor burden, bone volume, femur bone mineral density (BMD), and overall survival using two distinct mouse models of TIBD, the 4T1/luc breast cancer and the KAS-6/1-MIP1α multiple myeloma models. In mice orthotopically inoculated with 4T1/luc mouse mammary cells, MBC-11 (0.04 µg/day; s.c.) reduced the incidence of bone metastases to 40% (4/10), compared to 90% (9/10; p=0.057) and 100% (5/5; p=0.04) of PBS- or similarly-dosed, zoledronate-treated mice, respectively. MBC-11 also significantly decreased bone tumor burden compared to PBS- or zoledronate-treated mice (p=0.021, p=0.017, respectively). MBC-11 and zoledronate (0.04 µg/day) significantly increased bone volume by two- and four-fold, respectively, compared to PBS-treated mice (p=0.005, p<0.001, respectively). In mice systemically injected with human multiple myeloma KAS-6/1-MIP1α cells, 0.04 and 4.0 µg/day MBC-11 improved femur BMD by 13% and 16%, respectively, compared to PBS (p=0.025, p=0.017, respectively) at 10 weeks post-tumor cell injection and increased mean survival to 95 days compared to 77 days in mice treated with PBS (p=0.047). Similar doses of zoledronate also improved femur BMD (p≤0.01 vs PBS) and increased mean survival to 86 days, but this was not significantly different than in PBS-treated mice (p=0.53). These results demonstrate that MBC-11 decreases bone tumor burden, maintains bone

  6. Giant Cell Tumor of Bone: Documented Progression over 4 Years from Its Origin at the Metaphysis to the Articular Surface

    PubMed Central

    Link, Thomas; Cho, Soo-Jin; Motamedi, Daria

    2016-01-01

    The exact location of origin for giant cell tumors of bone (GCTB) remains controversial, as lesions are not routinely imaged early but rather late when the tumor is large and clinically symptomatic. At the time of diagnosis, GCTB are classically described as lucent, eccentric lesions with nonsclerotic margins, located within the epiphysis to a greater extent than the metaphysis. Here we present a case of a biopsy proven GCTB initially incidentally seen on MRI as a small strictly metaphyseal lesion, which over the course of several years expanded across a closed physis to involve the epiphysis and abut the articular surface/subchondral bone plate. PMID:27630783

  7. Giant Cell Tumor of Bone: Documented Progression over 4 Years from Its Origin at the Metaphysis to the Articular Surface.

    PubMed

    Burke, Colin; Link, Thomas; O'Donnell, Richard J; Cho, Soo-Jin; Motamedi, Daria

    2016-01-01

    The exact location of origin for giant cell tumors of bone (GCTB) remains controversial, as lesions are not routinely imaged early but rather late when the tumor is large and clinically symptomatic. At the time of diagnosis, GCTB are classically described as lucent, eccentric lesions with nonsclerotic margins, located within the epiphysis to a greater extent than the metaphysis. Here we present a case of a biopsy proven GCTB initially incidentally seen on MRI as a small strictly metaphyseal lesion, which over the course of several years expanded across a closed physis to involve the epiphysis and abut the articular surface/subchondral bone plate. PMID:27630783

  8. Giant Cell Tumor of Bone: Documented Progression over 4 Years from Its Origin at the Metaphysis to the Articular Surface

    PubMed Central

    Link, Thomas; Cho, Soo-Jin; Motamedi, Daria

    2016-01-01

    The exact location of origin for giant cell tumors of bone (GCTB) remains controversial, as lesions are not routinely imaged early but rather late when the tumor is large and clinically symptomatic. At the time of diagnosis, GCTB are classically described as lucent, eccentric lesions with nonsclerotic margins, located within the epiphysis to a greater extent than the metaphysis. Here we present a case of a biopsy proven GCTB initially incidentally seen on MRI as a small strictly metaphyseal lesion, which over the course of several years expanded across a closed physis to involve the epiphysis and abut the articular surface/subchondral bone plate.

  9. Bone Fractures Following External Beam Radiotherapy and Limb-Preservation Surgery for Lower Extremity Soft Tissue Sarcoma: Relationship to Irradiated Bone Length, Volume, Tumor Location and Dose

    SciTech Connect

    Dickie, Colleen I.; Parent, Amy L.; Griffin, Anthony M.; Fung, Sharon; Chung, Peter W.M.; Catton, Charles N.; Ferguson, Peter C.; Wunder, Jay S.; Bell, Robert S.; Sharpe, Michael B.; O'Sullivan, Brian

    2009-11-15

    Purpose: To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). Methods and Materials: Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. Results: For fracture patients, mean dose to bone was 45 +- 8 Gy (mean dose at fracture site 59 +- 7 Gy), mean FS was 37 +- 8 cm, maximum dose was 64 +- 7 Gy, and V40 was 76 +- 17%, compared with 37 +- 11 Gy, 32 +- 9 cm, 59 +- 8 Gy, and 64 +- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. Conclusions: The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.

  10. Interleukin-1 and tumor necrosis factor-alpha induce collagenolysis and bone resorption by regulation of matrix metalloproteinase-2 in mouse calvarial bone cells.

    PubMed

    Kang, Bong-Seok; Park, Young-Guk; Cho, Jin-Young; Kim, June-Ki; Lee, Tae-Kyun; Kim, Dong-Wook; Gu, Yeun-Hwa; Suzuki, Ikukatsu; Chang, Young-Chae; Kim, Cheorl-Ho

    2003-08-01

    Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) greatly induces osteoclast formation and stimulates bone resorption of mouse calvaria in culture. We examined the effects of the two cytokines on the collagenolysis and bone resorption by induction of matrix metalloproteinases (MMPs). The cells were analyzed using zymographic analysis. It was shown that the mouse calvarial osteoblasts constitutively synthesize progelatinase-A (MMP-2). Interleukin-1beta markedly enhanced the messenger RNAs (mRNAs) expression of MMP-2 (gelatinase A), but slightly MMP-9 (gelatinase B), which associated with increases in bone matrix degradation. Both pro- and active-forms of MMP-2 were detected in the conditioned medium collected from calvarial cultures, and IL-1beta markedly stimulated both pro- and active-forms of the MMP-2. The expression of MMP-2 mRNAs could be detected, and they were markedly enhanced by IL-1beta on days 1 and 2. These results demonstrate that the potency of induction of MMP-2 by IL-1beta and TNF-alpha is closely linked to the respective bone-resorbing activity, suggesting that MMP-2-dependent degradation of bone matrix plays a key role in bone resorption induced by these cytokines. On the other hand, when the mouse osteoblasts were stimulated with parathyroid hormone, 1,25(OH)2D3, mononuclear cell conditioned medium (MCM) and IL-1 as bone resorption agents, collagenolysis was increased by producing the active gelatinase. Interleukin-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. Interleukin-1 stimulated bone resorption and produced marked resorption when present simultaneously. Furthermore, treatment of indomethacin and dexamethasone clearly abolished the responses of IL-1alpha and IL-1beta.

  11. The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival.

    PubMed

    Fogli, Anne; Chautard, Emmanuel; Vaurs-Barrière, Catherine; Pereira, Bruno; Müller-Barthélémy, Mélanie; Court, Franck; Biau, Julian; Pinto, Afonso Almeida; Kémény, Jean-Louis; Khalil, Toufic; Karayan-Tapon, Lucie; Verrelle, Pierre; Costa, Bruno Marques; Arnaud, Philippe

    2016-02-01

    Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ.

  12. The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival.

    PubMed

    Fogli, Anne; Chautard, Emmanuel; Vaurs-Barrière, Catherine; Pereira, Bruno; Müller-Barthélémy, Mélanie; Court, Franck; Biau, Julian; Pinto, Afonso Almeida; Kémény, Jean-Louis; Khalil, Toufic; Karayan-Tapon, Lucie; Verrelle, Pierre; Costa, Bruno Marques; Arnaud, Philippe

    2016-02-01

    Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ. PMID:26717998

  13. Trifolium-like Platinum Nanoparticle-Mediated Photothermal Therapy Inhibits Tumor Growth and Osteolysis in a Bone Metastasis Model.

    PubMed

    Wang, Changping; Cai, Xiaopan; Zhang, Jishen; Wang, Xinyu; Wang, Yu; Ge, Huyifeng; Yan, Wangjun; Huang, Quan; Xiao, Jianru; Zhang, Qiang; Cheng, Yiyun

    2015-05-01

    Bone metastasis is a frequent and fatal complication of cancer that lacks effective clinical treatment. Photothermal therapy represents a new strategy for the destruction of multiple cancers. In this study, trifolium-like platinum nanoparticles (TPNs) with small size and excellent photothermal conversion property are prepared via a facile and green method. TPNs show minimal cytotoxicity on normal cell lines and kill cancer cells upon exposure to a near-infrared light. These nanoparticles effectively inhibit tumor growth and prevent osteolysis in a bone metastasis model. This study offers a promising strategy in the treatment of bone metastasis.

  14. Computed tomographic characteristics of multilobular tumor of bone involving the cranium in 7 dogs and zygomatic arch in 2 dogs.

    PubMed

    Hathcock, J T; Newton, J C

    2000-01-01

    Computed tomography (CT) images of nine dogs with a multilobular tumor of bone of the head were reviewed. The CT characteristics of the neoplasms involving the calvarium (n = 7) were rounded, well defined with a fine granular, nonhomogeneous bone opacity usually in the occipital region. Cranial vault invasion (5 of 7) was commonly found with a significant portion of the mass within the vault. The neoplasms involving the zygomatic arch (n = 2) were also generally rounded and well defined but with a more coarse granular appearance. The common CT findings were best seen when the images were viewed in a bone window.

  15. Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors

    PubMed Central

    Gahete, Manuel D.; Serrano-Somavilla, Ana; Villa-Osaba, Alicia; Adrados, Magdalena; Ibáñez-Costa, Alejandro; Martín-Pérez, Elena; Culler, Michael D.

    2016-01-01

    Purpose Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors, and their biological behavior is not well known. We studied the presence and potential functional roles of somatostatin receptors (sst1-5), focusing particularly on the truncated variants (sst5TMD4, sst5TMD5) and on their relationships with the angiogenic system (Ang/Tie-2 and VEGF) in human GEP-NETs. Experimental Design We evaluated 42 tumor tissue samples (26 primary/16 metastatic) from 26 patients with GEP-NETs, and 30 non-tumoral tissues (26 from adjacent non-tumor regions and 4 from normal controls) from a single center. Expression of sst1-5, sst5TMD4, sst5TMD5, Ang1-2, Tie-2 and VEGF was analyzed using real-time qPCR, immunofluorescence and immunohistochemistry. Expression levels were associated with tumor characteristics and clinical outcomes. Functional role of sst5TMD4 was analyzed in GEP-NET cell lines. Results sst1 exhibited the highest expression in GEP-NET, whilst sst2 was the most frequently observed sst-subtype (90.2%). Expression levels of sst1, sst2, sst3, sst5TMD4, and sst5TMD5 were significantly higher in tumor tissues compared to their adjacent non-tumoral tissue. Lymph-node metastases expressed higher levels of sst5TMD4 than in its corresponding primary tumor tissue. sst5TMD4 was also significantly higher in intestinal tumor tissues from patients with residual disease of intestinal origin compared to those with non-residual disease. Functional assays demonstrated that the presence of sst5TMD4 was associated to enhanced malignant features in GEP-NET cells. Angiogenic markers correlated positively with sst5TMD4, which was confirmed by immunohistochemical/fluorescence studies. Conclusions sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs. PMID:26673010

  16. Panostotic expansile bone disease with massive jaw tumor formation and a novel mutation in the signal peptide of RANK.

    PubMed

    Schafer, Anne L; Mumm, Steven; El-Sayed, Ivan; McAlister, William H; Horvai, Andrew E; Tom, Andrea M; Hsiao, Edward C; Schaefer, Frederick V; Collins, Michael T; Anderson, Mark S; Whyte, Michael P; Shoback, Dolores M

    2014-04-01

    Precise regulation of bone resorption is critical for skeletal homeostasis. We report a 32-year-old man with a panostotic expansile bone disease and a massive hemorrhagic mandibular tumor. Originally from Mexico, he was deaf at birth and became bow-legged during childhood. There was no family history of skeletal disease. Puberty occurred normally, but during adolescence he experienced difficulty straightening his limbs, sustained multiple fractures, and developed a bony tumor on his chin. By age 18 years, all limbs were misshapen. The mandibular mass grew and protruded from the oral cavity, extending to the level of the lower ribs. Other bony defects included a similar maxillary mass and serpentine limbs. Upon referral at age 27 years, biochemical studies showed serum alkaline phosphatase of 1760 U/L (Nl: 29-111) and other elevated bone turnover markers. Radiography of the limbs showed medullary expansion and cortical thinning with severe bowing. Although the jaw tumors were initially deemed inoperable, mandibular mass excision and staged partial maxillectomy were eventually performed. Tumor histopathology showed curvilinear trabeculae of woven bone on a background of hypocellular fibrous tissue. Fibrous dysplasia of bone was suspected, but there was no mutation in codon 201 of GNAS in samples from blood or tumor. His clinical and radiographic findings, elevated serum markers, and disorganized bone morphology suggested amplified receptor activator of NF-κB (RANK) signaling, even though his disorder differed from conditions with known constitutive activation of RANK signaling (eg, familial expansile osteolysis). We found a unique 12-base pair duplication in the signal peptide of TNFRSF11A, the gene that encodes RANK. No exon or splice site mutations were found in the genes encoding RANK ligand or osteoprotegerin. Alendronate followed by pamidronate therapies substantially decreased his serum alkaline phosphatase activity. This unique patient expands the

  17. Panostotic Expansile Bone Disease With Massive Jaw Tumor Formation and a Novel Mutation in the Signal Peptide of RANK

    PubMed Central

    Schafer, Anne L; Mumm, Steven; El-Sayed, Ivan; McAlister, William H; Horvai, Andrew E; Tom, Andrea M; Hsiao, Edward C; Schaefer, Frederick V; Collins, Michael T; Anderson, Mark S; Whyte, Michael P; Shoback, Dolores M

    2015-01-01

    Precise regulation of bone resorption is critical for skeletal homeostasis. We report a 32-year-old man with a panostotic expansile bone disease and a massive hemorrhagic mandibular tumor. Originally from Mexico, he was deaf at birth and became bow-legged during childhood. There was no family history of skeletal disease. Puberty occurred normally, but during adolescence he experienced difficulty straightening his limbs, sustained multiple fractures, and developed a bony tumor on his chin. By age 18 years, all limbs were misshapen. The mandibular mass grew and protruded from the oral cavity, extending to the level of the lower ribs. Other bony defects included a similar maxillary mass and serpentine limbs. Upon referral at age 27 years, biochemical studies showed serum alkaline phosphatase of 1760 U/L (Nl: 29-111) and other elevated bone turnover markers. Radiography of the limbs showed medullary expansion and cortical thinning with severe bowing. Although the jaw tumors were initially deemed inoperable, mandibular mass excision and staged partial maxillectomy were eventually performed. Tumor histopathology showed curvilinear trabeculae of woven bone on a background of hypocellular fibrous tissue. Fibrous dysplasia of bone was suspected, but there was no mutation in codon 201 of GNAS in samples from blood or tumor. His clinical and radiographic findings, elevated serum markers, and disorganized bone morphology suggested amplified receptor activator of NF-κB (RANK) signaling, even though his disorder differed from conditions with known constitutive activation of RANK signaling (eg, familial expansile osteolysis). We found a unique 12-base pair duplication in the signal peptide of TNFRSF11A, the gene that encodes RANK. No exon or splice site mutations were found in the genes encoding RANK ligand or osteoprotegerin. Alendronate followed by pamidronate therapies substantially decreased his serum alkaline phosphatase activity. This unique patient expands the phenotypes

  18. Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long term TβRI/II kinase inhibition with LY2109761

    PubMed Central

    Connolly, Erin C.; Saunier, Elise F.; Quigley, David; Luu, Minh Thu; Sapio, Angela De; Hann, Byron; Yingling, Jonathan M.; Akhurst, Rosemary J.

    2011-01-01

    Transforming Growth Factor β (TGF-β) is produced excessively by many solid tumors and can drive malignant progression through multiple effects on the tumor cell and microenvironment. TGF-β signaling pathway inhibitors have shown efficacy in pre-clinical models of metastatic cancer. Here we investigated the effect of systemic LY2109761, a type I /II receptor (TβRI/TβRII) kinase inhibitor, in both a tumor allograft model and in the mouse skin model of de novo chemically-induced carcinogenesis in vivo. Systemic LY2109761 administration disrupted tumor vascular architecture and reduced myofibroblast differentiation of E4 skin carcinoma cells in a tumor allograft. In the 7,12 dimethyl-benzanthracene plus phorbol-myristate-acetate -induced skin chemical carcinogenesis model, acute dosing of established naïve primary carcinomas with LY2109761 (100mg/Kg) every eight hours for ten days (100mg/kg) diminished P-Smad2 levels and marginally decreased the expression of inflammatory and invasive markers. Sustained exposure to LY2109761 (100mg/kg/day) throughout the tumor outgrowth phase had no effect on carcinoma latency or incidence. However, molecular analysis of resultant carcinomas by microarray gene expression, Western blot and immunohistochemistry suggests that long term LY2109761 exposure leads to the outgrowth of carcinomas with elevated P-Smad2 levels that do not respond to drug. This is the first description of acquired resistance to a small molecule inhibitor of the TGF-βRI/II kinase. Resultant carcinomas were more aggressive and inflammatory in nature, with delocalized E-Cadherin and elevated expression of Il23a, laminin V and MMPs. Therefore, TGF-β inhibitors might be clinically useful for applications requiring acute administration, but chronic patient exposure to such drugs should be undertaken with caution. PMID:21282335

  19. The combinatorial activation of the PI3K and Ras/MAPK pathways is sufficient for aggressive tumor formation, while individual pathway activation supports cell persistence

    PubMed Central

    Thompson, Keyata N.; Whipple, Rebecca A.; Yoon, Jennifer R.; Lipsky, Michael; Charpentier, Monica S.; Boggs, Amanda E.; Chakrabarti, Kristi R.; Bhandary, Lekhana; Hessler, Lindsay K.; Martin, Stuart S.; Vitolo, Michele I.

    2015-01-01

    A high proportion of human tumors maintain activation of both the PI3K and Ras/MAPK pathways. In basal-like breast cancer (BBC), PTEN expression is decreased/lost in over 50% of cases, leading to aberrant activation of the PI3K pathway. Additionally, BBC cell lines and tumor models have been shown to exhibit an oncogenic Ras-like gene transcriptional signature, indicating activation of the Ras/MAPK pathway. To directly test how the PI3K and Ras/MAPK pathways contribute to tumorigenesis, we deleted PTEN and activated KRas within non-tumorigenic MCF-10A breast cells. Neither individual mutation was sufficient to promote tumorigenesis, but the combination promoted robust tumor growth in mice. However, in vivo bioluminescence reveals that each mutation has the ability to promote a persistent phenotype. Inherent in the concept of tumor cell dormancy, a stage in which residual disease is present but remains asymptomatic, viable cells with each individual mutation can persist in vivo during a period of latency. The persistent cells were excised from the mice and showed increased levels of the cell cycle arrest proteins p21 and p27 compared to the aggressively growing PTEN−/−KRAS(G12V) cells. Additionally, when these persistent cells were placed into growth-promoting conditions, they were able to re-enter the cell cycle and proliferate. These results highlight the potential for either PTEN loss or KRAS activation to promote cell survival in vivo, and the unique ability of the combined mutations to yield rapid tumor growth. This could have important implications in determining recurrence risk and disease progression in tumor subtypes where these mutations are common. PMID:26497685

  20. The combinatorial activation of the PI3K and Ras/MAPK pathways is sufficient for aggressive tumor formation, while individual pathway activation supports cell persistence.

    PubMed

    Thompson, Keyata N; Whipple, Rebecca A; Yoon, Jennifer R; Lipsky, Michael; Charpentier, Monica S; Boggs, Amanda E; Chakrabarti, Kristi R; Bhandary, Lekhana; Hessler, Lindsay K; Martin, Stuart S; Vitolo, Michele I

    2015-11-01

    A high proportion of human tumors maintain activation of both the PI3K and Ras/MAPK pathways. In basal-like breast cancer (BBC), PTEN expression is decreased/lost in over 50% of cases, leading to aberrant activation of the PI3K pathway. Additionally, BBC cell lines and tumor models have been shown to exhibit an oncogenic Ras-like gene transcriptional signature, indicating activation of the Ras/MAPK pathway. To directly test how the PI3K and Ras/MAPK pathways contribute to tumorigenesis, we deleted PTEN and activated KRas within non-tumorigenic MCF-10A breast cells. Neither individual mutation was sufficient to promote tumorigenesis, but the combination promoted robust tumor growth in mice. However, in vivo bioluminescence reveals that each mutation has the ability to promote a persistent phenotype. Inherent in the concept of tumor cell dormancy, a stage in which residual disease is present but remains asymptomatic, viable cells with each individual mutation can persist in vivo during a period of latency. The persistent cells were excised from the mice and showed increased levels of the cell cycle arrest proteins p21 and p27 compared to the aggressively growing PTEN-/-KRAS(G12V) cells. Additionally, when these persistent cells were placed into growth-promoting conditions, they were able to re-enter the cell cycle and proliferate. These results highlight the potential for either PTEN loss or KRAS activation to promote cell survival in vivo, and the unique ability of the combined mutations to yield rapid tumor growth. This could have important implications in determining recurrence risk and disease progression in tumor subtypes where these mutations are common. PMID:26497685

  1. Testosterone Replacement and Bone Mineral Density in Male Pituitary Tumor Patients

    PubMed Central

    Lee, Min Jeong; Ryu, Hyoung Kyu; An, So-Yeon; Jeon, Ja Young; Lee, Ji In

    2014-01-01

    Background Hypopituitarism is associated with osteoporosis and osteopenia especially when hypogonadotropic hypogonadism is present. Despite hypopituitarism being an important cause of secondary osteoporosis, osteoporosis in patients receiving surgery for pituitary tumors in Korea has not been studied. In this study, we evaluated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) in postoperative hypogonadal patients with pituitary tumors. Methods To examine the effect of TRT on BMD, we performed a retrospective observational study in 21 postoperative male patients who underwent pituitary tumor surgery between 2003 and 2012 at the Ajou University Hospital. Testosterone was replaced in postoperative hypogonadal patients by regular intramuscular injection, daily oral medication, or application of transdermal gel. BMD (g/cm2) measurements of central skeletal sites (lumbar spine, femoral neck, and total femur) were obtained using dual-energy X-ray absorptiometry (GE Lunar). For lumbar spine BMD, L1 to L4 values were chosen for analysis. Femur neck and total femur were also analyzed. Results During the follow-up period (mean, 56 months; range, 12 to 99 months) serum testosterone levels increased with the administration of TRT (P=0.007). There was significant improvement (4.56%±9.81%) in the lumbar spine BMD compared to baseline BMD. There were no significant changes in the femur neck BMD or total femur BMD. We did not find any statistically significant relationships between changes in testosterone levels and BMD using Spearman correlation analysis. Conclusion Our results indicated that TRT used in the postoperative period for hypogonadal pituitary tumor surgery patients may have beneficial effects on the BMD of the spine. PMID:24741454

  2. The Science and Practice of Bone Health in Oncology: Managing Bone Loss and Metastasis in Patients With Solid Tumors

    PubMed Central

    Lipton, Allan; Uzzo, Robert; Amato, Robert J.; Ellis, Georgiana K.; Hakimian, Behrooz; Roodman, G. David; Smith, Matthew R.

    2011-01-01

    Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis. PMID:19878635

  3. The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors.

    PubMed

    Lipton, Allan; Uzzo, Robert; Amato, Robert J; Ellis, Georgiana K; Hakimian, Behrooz; Roodman, G David; Smith, Matthew R

    2009-10-01

    Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis. PMID:19878635

  4. Surface vacuolar ATPase in ameloblastoma contributes to tumor invasion of the jaw bone.

    PubMed

    Yoshimoto, Shohei; Morita, Hiromitsu; Matsubara, Ryota; Mitsuyasu, Takeshi; Imai, Yuko; Kajioka, Shunichi; Yoneda, Masahiro; Ito, Yushi; Hirofuji, Takao; Nakamura, Seiji; Hirata, Masato

    2016-03-01

    Ameloblastoma is the most common benign odontogenic tumor in Japan. It is believed that it expands in the jaw bone through peritumoral activation of osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL) released from the ameloblastoma, as in bone metastases of cancer cells. However, the clinical features of ameloblastoma, including its growth rate and patterns of invasion, are quite different from those of bone metastasis of cancer cells, suggesting that different underlying mechanisms are involved. Therefore, in the present study, we examined the possible mechanisms underlying the invasive expansion of ameloblastoma in the jaw bone. Expression levels of RANKL assessed by western blotting were markedly lower in ameloblastoma (AM-1) cells than in highly metastatic oral squamous cell carcinoma (HSC-3) cells. Experiments coculturing mouse macrophages (RAW264.7) with AM-1 demonstrated low osteoclastogenic activity, as assessed by tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cell formation, probably because of low release of RANKL, whereas cocultures of RAW264.7 with HSC-3 cells exhibited very high osteoclastogenic activity. Thus, RANKL release from AM-1 appeared to be too low to generate osteoclasts. However, AM-1 cultured directly on calcium phosphate-coated plates formed resorption pits, and this was inhibited by application of bafilomycin A1. Furthermore, vacuolar-type H+-ATPase (V-ATPase) and H+/Cl- exchange transporter 7 (CLC-7) were detected on the surface of AM-1 cells by plasma membrane biotinylation and immunofluorescence analysis. Immunohistochemical analysis of clinical samples of ameloblastoma also showed plasma membrane-localized V-ATPase and CLC-7 in the epithelium of plexiform, follicular and basal cell types. The demineralization activity of AM-1 was only 1.7% of osteoclasts demineralization activity, and the growth rate was 20% of human normal skin keratinocytes and HSC-3 cells. These results suggest that the

  5. Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma.

    PubMed

    Hiasa, M; Teramachi, J; Oda, A; Amachi, R; Harada, T; Nakamura, S; Miki, H; Fujii, S; Kagawa, K; Watanabe, K; Endo, I; Kuroda, Y; Yoneda, T; Tsuji, D; Nakao, M; Tanaka, E; Hamada, K; Sano, S; Itoh, K; Matsumoto, T; Abe, M

    2015-01-01

    Pim-2 kinase is overexpressed in multiple myeloma (MM) cells to enhance their growth and survival, and regarded as a novel therapeutic target in MM. However, the impact of Pim-2 inhibition on bone disease in MM remains unknown. We demonstrated here that Pim-2 expression was also upregulated in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells in the presence of cytokines known as the inhibitors of osteoblastogenesis in MM, including interleukin-3 (IL-3), IL-7, tumor necrosis factor-α, transforming growth factor-β (TGF-β) and activin A, as well as MM cell conditioned media. The enforced expression of Pim-2 abrogated in vitro osteoblastogenesis by BMP-2, which suggested Pim-2 as a negative regulator for osteoblastogenesis. Treatment with Pim-2 short-interference RNA as well as the Pim inhibitor SMI-16a successfully restored osteoblastogenesis suppressed by all the above inhibitory factors and MM cells. The SMI-16a treatment potentiated BMP-2-mediated anabolic signaling while suppressing TGF-β signaling. Furthermore, treatment with the newly synthesized thiazolidine-2,4-dione congener, 12a-OH, as well as its prototypic SMI-16a effectively prevented bone destruction while suppressing MM tumor growth in MM animal models. Thus, Pim-2 may have a pivotal role in tumor progression and bone loss in MM, and Pim-2 inhibition may become an important therapeutic strategy to target the MM cell-bone marrow interaction. PMID:24787487

  6. Metacarpal resection with a contoured iliac bone graft and silicone rubber implant for metacarpal giant cell tumor: a case report.

    PubMed

    Carlow, S B; Khuri, S M

    1985-03-01

    A definitive surgical procedure for a giant cell tumor that combines metacarpal resection with an iliac bone graft and arthroplasty with a silicone rubber implant is proposed for the elderly patient. The results were encouraging in one patient who had a cosmetically and functionally acceptable hand and no evidence of recurrence.

  7. Clinical Outcomes of Surgical Treatments for Primary Malignant Bone Tumors Arising in the Acetabulum

    PubMed Central

    Fujiwara, Tomohiro; Ogura, Koichi; Kobayashi, Eisuke; Tanzawa, Yoshikazu; Nakatani, Fumihiko; Chuman, Hirokazu; Kawai, Akira

    2015-01-01

    The functional and oncologic results of eighteen patients with primary malignant periacetabular tumors were reviewed to determine the impact of surgical treatment. The reconstruction procedures were endoprosthesis (11), hip transposition (4), iliofemoral arthrodesis (2), and frozen bone autograft (1). After a mean follow-up of 62 months, 13 patients were alive and 5 had died of their disease; the 5-year overall survival rate was 67.2%. The corresponding mean MSTS scores of patients with endoprosthesis (11) and other reconstructions (7) were 42% and 55% (49%, 68%, and 50%), respectively. Overall, postoperative complications including deep infection or dislocation markedly worsened the functional outcome. Iliofemoral arthrodesis provided better function than the other procedures, whereas endoprosthetic reconstruction demonstrated poor functional outcome except for patients who were reconstructed with the adequate soft tissue coverage. Avoiding postoperative complications is highly important for achieving better function, suggesting that surgical procedures with adequate soft tissue coverage or without the massive use of nonbiological materials are preferable. Appropriate selection of the reconstructive procedures for individual patients, considering the amount of remaining bone and soft tissues, would lead to better clinical outcomes. PMID:26451129

  8. Inhibition of Wilms tumor 1 transactivation by bone marrow zinc finger 2, a novel transcriptional repressor.

    PubMed

    Lee, Tae Ho; Lwu, Shelly; Kim, Jungho; Pelletier, Jerry

    2002-11-22

    The Wilms tumor suppressor gene, wt1, encodes a zinc finger transcription factor that has been implicated in the regulation of a number of genes. Protein-protein interactions are known to modulate the transcription regulatory functions of Wilms tumor (WT1) and have also implicated WT1 in splicing. In this report, we identify a novel WT1-interacting protein, bone marrow zinc finger 2 (BMZF2), by affinity chromatography utilizing immobilized WT1 protein. BMZF2 is a potential transcription factor with 18 zinc fingers. The BMZF2 mRNA is mainly expressed in fetal tissues, and the protein is predominantly nuclear. Co-immunoprecipitation experiments are consistent with an in vivo association between WT1 and BMZF2. Glutathione S-transferase pulldown assays and far Western blots revealed that zinc fingers VI-X (amino acids 231-370) are required for interaction with the zinc finger region of WT1. Functionally, BMZF2 inhibits transcriptional activation by WT1. Moreover, a chimeric protein generated by fusion of BMZF2 to the GAL4 DNA-binding domain significantly decreases promoter activity of a reporter containing GAL4 DNA-binding sites, suggesting the presence of an active repressor domain within BMZF2. Our results suggest that BMZF2 interferes with the transactivation potential of WT1. PMID:12239212

  9. Use of Aromatase Inhibitors in Large Cell Calcifying Sertoli Cell Tumors: Effects on Gynecomastia, Growth Velocity, and Bone Age

    PubMed Central

    Crocker, Melissa K.; Gourgari, Evgenia; Stratakis, Constantine A.

    2014-01-01

    Context: Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz-Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedione to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia. Objective: To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs. Design: Case series of a very rare tumor and chart review of cases treated at other institutions. Setting: Tertiary care and referral center. Patients: Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT. Interventions: Patients were treated for a total of 6–60 months on AIT. Main Outcome Measures: Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured. Results: Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy. Conclusions: Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomes and safety monitoring are needed but these preliminary data suggest that mammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy. PMID:25226294

  10. FBI-1 Is Overexpressed in Gestational Trophoblastic Disease and Promotes Tumor Growth and Cell Aggressiveness of Choriocarcinoma via PI3K/Akt Signaling.

    PubMed

    Mak, Victor C Y; Wong, Oscar G W; Siu, Michelle K Y; Wong, Esther S Y; Ng, Wai-Yan; Wong, Richard W C; Chan, Ka-Kui; Ngan, Hextan Y S; Cheung, Annie N Y

    2015-07-01

    Human placental trophoblasts can be considered pseudomalignant, with tightly controlled proliferation, apoptosis, and invasiveness. Gestational trophoblastic disease (GTD) represents a family of heterogeneous trophoblastic lesions with aberrant apoptotic and proliferative activities and dysregulation of cell signaling pathways. We characterize the oncogenic effects of factor that binds to the inducer of short transcripts of HIV-1 [FBI-1, alias POZ and Krüppel erythroid myeloid ontogenic factor (POKEMON)/ZBTB7A] in GTD and its role in promoting cell aggressiveness in vitro and tumor growth in vivo. IHC studies showed increased nuclear expression of FBI-1, including hydatidiform moles, choriocarcinoma (CCA), and placental site trophoblastic tumor, in GTD. In JAR and JEG-3 CCA cells, ectopic FBI-1 expression opposed apoptosis through repression of proapoptotic genes (eg, BAK1, FAS, and CASP8). FBI-1 overexpression also promoted Akt activation, as indicated by Akt-pS473 phosphorylation. FBI-1 overexpression promoted mobility and invasiveness of JEG-3 and JAR, but not in the presence of the phosphoinositide 3-kinase inhibitor LY294002. These findings suggest that FBI-1 could promote cell migration and invasion via phosphoinositide 3-kinase/Akt signaling. In vivo, nude mice injected with CCA cells with stable FBI-1 knockdown demonstrated reduced tumor growth compared with that in control groups. These findings suggest that FBI-1 is clinically associated with the progression of, and may be a therapeutic target in, GTD, owing to its diverse oncogenic effects on dysregulated trophoblasts. PMID:26093985

  11. FBI-1 Is Overexpressed in Gestational Trophoblastic Disease and Promotes Tumor Growth and Cell Aggressiveness of Choriocarcinoma via PI3K/Akt Signaling.

    PubMed

    Mak, Victor C Y; Wong, Oscar G W; Siu, Michelle K Y; Wong, Esther S Y; Ng, Wai-Yan; Wong, Richard W C; Chan, Ka-Kui; Ngan, Hextan Y S; Cheung, Annie N Y

    2015-07-01

    Human placental trophoblasts can be considered pseudomalignant, with tightly controlled proliferation, apoptosis, and invasiveness. Gestational trophoblastic disease (GTD) represents a family of heterogeneous trophoblastic lesions with aberrant apoptotic and proliferative activities and dysregulation of cell signaling pathways. We characterize the oncogenic effects of factor that binds to the inducer of short transcripts of HIV-1 [FBI-1, alias POZ and Krüppel erythroid myeloid ontogenic factor (POKEMON)/ZBTB7A] in GTD and its role in promoting cell aggressiveness in vitro and tumor growth in vivo. IHC studies showed increased nuclear expression of FBI-1, including hydatidiform moles, choriocarcinoma (CCA), and placental site trophoblastic tumor, in GTD. In JAR and JEG-3 CCA cells, ectopic FBI-1 expression opposed apoptosis through repression of proapoptotic genes (eg, BAK1, FAS, and CASP8). FBI-1 overexpression also promoted Akt activation, as indicated by Akt-pS473 phosphorylation. FBI-1 overexpression promoted mobility and invasiveness of JEG-3 and JAR, but not in the presence of the phosphoinositide 3-kinase inhibitor LY294002. These findings suggest that FBI-1 could promote cell migration and invasion via phosphoinositide 3-kinase/Akt signaling. In vivo, nude mice injected with CCA cells with stable FBI-1 knockdown demonstrated reduced tumor growth compared with that in control groups. These findings suggest that FBI-1 is clinically associated with the progression of, and may be a therapeutic target in, GTD, owing to its diverse oncogenic effects on dysregulated trophoblasts.

  12. Dislodgement and gastrointestinal tract penetration of bone cement used for spinal reconstruction after lumbosacral vertebral tumor excision

    PubMed Central

    Nagae, Masateru; Mikami, Yasuo; Mizuno, Kentaro; Harada, Tomohisa; Ikeda, Takumi; Tonomura, Hitoshi; Takatori, Ryota; Fujiwara, Hiroyoshi; Kubo, Toshikazu

    2016-01-01

    Abstract Introduction: Polymethylmethacrylate (PMMA) cement is useful for spinal reconstruction, but can cause complications including new vertebral fractures, neurological disorders and pulmonary embolism. We report a case in PMMA cement used for spinal reconstruction after tumor curettage dislodged and penetrated the gastrointestinal tract. Diagnoses: The patient was diagnosed with a retroperitoneal extragonadal germ cell tumor at age 27 years. After chemotherapy and tumor resection, the tumor remained. It gradually increased in size and infiltrated lumbosacral vertebrae, causing him to present at age 35 years with increased low back pain. Image findings showed bone destruction in the vertebral bodies accompanied by neoplastic lesions. The left and right common iliac arteries and inferior vena cava were enclosed in the tumor on the anterior side of the vertebral bodies. Lumbosacral bone tumor due to direct extragonadal germ cell tumor infiltration was diagnosed. A 2-step operation was planned; first, fixation of the posterior side of the vertebral bodies, followed by tumor resection using an anterior transperitoneal approach, and spinal reconstruction using PMMA cement. After surgery, the PMMA cement gradually dislodged towards the anterior side and, 2 years 9 months after surgery, it had penetrated the retroperitoneum. The patient subsequently developed nausea and abdominal pain and was readmitted to hospital. The diagnosis was intestinal blockage with dislodged PMMA cement, and an operation was performed to remove the cement present in the small intestine. There was strong intra-abdominal adhesion, the peritoneum between the vertebral bodies and intestine could not be identified, and no additional treatment for vertebral body defects could be performed. After surgery, gastrointestinal symptoms resolved. Conclusion: Although this was a rare case, when using bone cement for vertebral body reconstruction, the way of anchoring for the cement must be thoroughly

  13. Point mutations in an epigenetic factor lead to multiple types of bone tumors: role of H3.3 histone variant in bone development and disease

    PubMed Central

    Kato, Shigeaki; Ishii, Takeaki; Kouzmenko, Alexander

    2015-01-01

    Coordinated post-translational modifications (PTMs) of nucleosomal histones emerge as a key mechanism of gene regulation by defining chromatin configuration. Patterns of histone modifications vary in different cells and constitute core elements of cell-specific epigenomes. Recently, in addition to canonical histone proteins produced during the S phase of cell cycle, several non-canonical histone variants have been identified and shown to express in a DNA replication-independent manner. These histone variants generate diversity in nucleosomal structures and add further complexity to mechanisms of epigenetic regulation. Cell-specific functions of histone variants remain to be determined. Several recent studies reported an association between some point mutations in the non-canonical histone H3.3 and particular types of brain and bone tumors. This suggests a possibility of differential physiological effects of histone variants in different cells and tissues, including bone. In this review, we outline the roles of histone variants and their PTMs in the epigenetic regulation of chromatin structure and discuss possible mechanisms of biological effects of the non-canonical histone mutations found in bone tumors on tumorigenesis in differentiating bone stem cells. PMID:26157578

  14. ME-03BONE MARROW DERIVED MICROGLIA AND THEIR FUNCTION WITHIN TUMOR MICROENVIRONMENT

    PubMed Central

    Burrell, Kelly; Singh, Sanjay; Agnihotri, Sameer; Hill, Richard; Aldape, Kenneth; Zadeh, Gelareh

    2014-01-01

    We have previously demonstrated that BMDC are recruited to Glioblastoma Multiforme (GBM), in a highly tumor-growth and region-dependent pattern, demonstrating that the majority of BMDCs differentiate into inflammatory cells, MAC3 + , and CD11b+ IBA1+ microglia-like cells. The majority of microglia seen in GBM microenvironment are derived from the BMDC rather than being resident brain microglia. The role of microglial cells in GBMs remains unknown, with evidence supporting both an anti- and pro- tumorgenic function. In this study we aimed to understand the contribution of microglia to GBM growth and tumor vascularity. Chimeric mice with reconstituted green-fluorescent bone marrow were used to create intracranial GBM xenografts, by implanting red fluorescent glioma stem cells or U87 into the frontal lobe. Using a known inhibitor of microglial activation, minocycline, we show that treatment with this agent increased tumor cell growth and invasiveness and reduced animal survival compared to controls. We show that Minocycline decreases activation of microglia, inhibits the phagocytic activity of microglia in GBMs and decreases the perivascular localization of microglia. The mRNA expression profile of microglia isolated from the GBM microenvironment showed, through Ingenuity Pathway Analysis (IPA), a loss of engulfment and migration of cells and phaocytotic pathways in BM-derived microglia, additionally we see a reorganization of cytoskeletal pathways leading to an increase in the migration and invasiveness of GBM cells following treatment with Minocycline. We also have preliminary data to suggest that this property of Minocycline is dependent on VEGF levels, where in the context of low VEGF Minocycline does not provide a significant anti-angiogenic role. We demonstrate that microglia in GBM microenvironment, are primarily recruited and differentiated from the BM and not resident, and that these cells have an anti-tumorgenic functions, and inhibition of the activated

  15. False Suggestion of Malignant Transformation of Benign Bone Tumor by 18F-FDG PET/CT: A Potential Pitfall.

    PubMed

    Chen, Yu-Ren; Kuo, Yu-Cheng; Hsu, Cheng-Nan; Hsieh, Te-Chun; Kao, Chia-Hung

    2016-10-01

    A 68-year-old man underwent serial F-FDG PET/CT scan follow-up for lung cancer. Then 5.5 years after the initial F-FDG PET/CT scan, the presumed benign bone tumor in the left clavicle showed markedly increased FDG uptake during follow-up; in contrast, the Tc-MDP bone scan paradoxically exhibited no apparent interval change since last bone scan 5.5 years earlier. He underwent a CT-guided biopsy, and the pathological diagnosis was benign fibrous histiocytoma. The result was consistent with the lack of progression in Tc-MDP bone scan, whereas the F-FDG PET/CT scan gave a false-positive impression of malignant transformation. PMID:27556801

  16. Breast cancer metastasis in a human bone NOD/SCID mouse model.

    PubMed

    Yang, Wenyi; Lam, Pearl; Kitching, Richard; Kahn, Harriette J; Yee, Albert; Aubin, Jane E; Seth, Arun

    2007-08-01

    A major dilemma facing patients with breast cancer is how to decide between over treating indolent tumors and failing to adequately treat aggressive, potentially lethal cancers. Determination of the metastatic potential of a patient's breast cancer would clearly help guide those treatment decisions. Breast cancer commonly spreads to bone in 70% of women with advanced disease. However, the mechanism of bone metastasis is not well understood. One possibility is that the microenvironment within bone marrow, highly rich in growth factors and cytokines, is suitable for the proliferation of breast cancer cells. In this study, we developed a method for implanting human bone in NOD/SCID mice and show that the human bone implants are viable for more than 20 weeks. This human bone NOD/SCID mouse model provides an opportunity to functionally characterize human breast cancer cell behavior in an in vivo human microenvironment. Several breast tumor cell lines have been shown to grow in the human-bone-NOD/SCID model system, however each line has a different functional profile. Here we show that cotransplantation of GFP-MDA-MB-231 breast cancer cells with morcellized human bone allows for tissue specific metastasis to an initially tumor free bone implant. Furthermore, metastasis of breast tumor cells to implanted tumor-free human bone was seen when patient bone containing a metastatic breast tumor was implanted in the host mouse. With this model, we can distinguish between primary invasive breast tumors with and without bone metastatic potential. PMID:17704641

  17. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

    PubMed

    Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema

    2015-05-10

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity.

  18. DNMT3B7 Expression Promotes Tumor Progression to a More Aggressive Phenotype in Breast Cancer Cells

    PubMed Central

    Brambert, Patrick R.; Kelpsch, Daniel J.; Hameed, Rabia; Desai, Charmi V.; Calafiore, Gianfranco; Godley, Lucy A.; Raimondi, Stacey L.

    2015-01-01

    Epigenetic changes, such as DNA methylation, have been shown to promote breast cancer progression. However, the mechanism by which cancer cells acquire and maintain abnormal DNA methylation is not well understood. We have previously identified an aberrant splice form of a DNA methyltransferase, DNMT3B7, expressed in virtually all cancer cell lines but at very low levels in normal cells. Furthermore, aggressive MDA-MB-231 breast cancer cells have been shown to express increased levels of DNMT3B7 compared to poorly invasive MCF-7 cells, indicating that DNMT3B7 may have a role in promoting a more invasive phenotype. Using data gathered from The Cancer Genome Atlas, we show that DNMT3B7 expression is increased in breast cancer patient tissues compared to normal tissue. To determine the mechanism by which DNMT3B7 was functioning in breast cancer cells, two poorly invasive breast cancer cell lines, MCF-7 and T-47D, were stably transfected with a DNMT3B7 expression construct. Expression of DNMT3B7 led to hypermethylation and down-regulation of E-cadherin, altered localization of β-catenin, as well as increased adhesion turnover, cell proliferation, and anchorage-independent growth. The novel results presented in this study suggest a role for DNMT3B7 in the progression of breast cancer to a more aggressive state and the potential for future development of novel therapeutics. PMID:25607950

  19. Case History Report: Immediate Rehabilitation with a Prefabricated Fibula Flap Following Removal of a Locally Aggressive Maxillary Tumor.

    PubMed

    Nkenke, Emeka; Agaimy, Abbas; Vairaktaris, Elefterios; Lell, Michael; von Wilmowsky, Cornelius; Eitner, Stephan

    2016-01-01

    The present clinical case history report describes an interdisciplinary treatment protocol that combines maxillary tumor resection with immediate reconstruction to achieve functional rehabilitation. A fibula flap that received four dental implants and a split-thickness graft epithelial layer was prefabricated for a 31-year-old man. The flap was designed so that it could be adapted to fit in different extents of tumor resection. Resection and immediate reconstruction were successfully performed 6 weeks after flap prefabrication, with the final bar-retained dental prosthesis delivered 4 weeks later. PMID:26757329

  20. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors.

    PubMed

    Manuel, Edwin R; Chen, Jeremy; D'Apuzzo, Massimo; Lampa, Melanie G; Kaltcheva, Teodora I; Thompson, Curtis B; Ludwig, Thomas; Chung, Vincent; Diamond, Don J

    2015-09-01

    Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases. In addition, CD8(+) T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC.

  1. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors

    PubMed Central

    Manuel, Edwin R.; Chen, Jeremy; D'Apuzzo, Massimo; Lampa, Melanie G.; Kaltcheva, Teodora I.; Thompson, Curtis B.; Ludwig, Thomas; Chung, Vincent; Diamond, Don J.

    2015-01-01

    Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for over twenty-five years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not observed using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex-vivo through mechanisms involving FasL and serine proteases. In addition, CD8+ T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC. PMID:26134178

  2. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors.

    PubMed

    Manuel, Edwin R; Chen, Jeremy; D'Apuzzo, Massimo; Lampa, Melanie G; Kaltcheva, Teodora I; Thompson, Curtis B; Ludwig, Thomas; Chung, Vincent; Diamond, Don J

    2015-09-01

    Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases. In addition, CD8(+) T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC. PMID:26134178

  3. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  4. Low intensity vibration mitigates tumor progression and protects bone quantity and quality in a murine model of myeloma.

    PubMed

    Pagnotti, Gabriel M; Chan, M Ete; Adler, Benjamin J; Shroyer, Kenneth R; Rubin, Janet; Bain, Steven D; Rubin, Clinton T

    2016-09-01

    Myeloma facilitates destruction of bone and marrow. Since physical activity encourages musculoskeletal preservation we evaluated whether low-intensity vibration (LIV), a means to deliver mechanical signals, could protect bone and marrow during myeloma progression. Immunocompromised-mice (n=25) were injected with human-myeloma cells, while 8 (AC) were saline-injected. Myeloma-injected mice (LIV; n=13) were subjected to daily-mechanical loading (15min/d; 0.3g @ 90Hz) while 12 (MM) were sham-handled. At 8w, femurs had 86% less trabecular bone volume fraction (BV/TV) in MM than in AC, yet only a 21% decrease in LIV was observed in comparison to AC, reflecting a 76% increase versus MM. Cortical BV was 21% and 15% lower in MM and LIV, respectively, than in AC; LIV showing 30% improvement over MM. Similar outcomes were observed in the axial skeleton, showing a 35% loss in MM with a 27% improved retention of bone in the L5 of LIV-treated mice as compared to MM. Transcortical-perforations in the femur from myeloma-induced osteolysis were 9× higher in MM versus AC, reduced by 57% in LIV. Serum-TRACP5b, 61% greater in MM versus AC, rose by 33% in LIV compared to AC, a 45% reduction in activity when compared to MM. Histomorphometric analyses of femoral trabecular bone demonstrated a 70% elevation in eroded surfaces of MM versus AC, while measures in LIV were 58% below those in MM. 72% of marrow in the femur of MM mice contained tumor, contrasted by a 31% lower burden in LIV. MM mice (42%) presented advanced-stage necrosis of tibial marrow while present in just 8% of LIV. Myeloma infiltration inversely correlated to measures of bone quality, while LIV slowed the systemic, myeloma-associated decline in bone quality and inhibited tumor progression through the hindlimbs. PMID:27262776

  5. Rare Presentation of Giant Cell Tumor in the Internal Auditory Canal: Case Report and Review of the Literature

    PubMed Central

    Jada, Ajit S.; Shrivastava, Raj K.; Mannan, Abul; Kobets, Andrew; Manolidis, Spiros

    2015-01-01

    Giant cell tumor (GCT) is a benign but locally aggressive bone tumor that usually involves the end of long bones. It is a relatively common neoplasm in patients, constituting 5 to 10% of all benign bone tumors. Approximately 2% of GCTs occur in the craniofacial skeleton with a predilection for the ethmoid, sphenoid, and temporal bones. The skull base location is unique and not commonly described. Hearing loss, headache, tinnitus, and subcutaneous masses are the most commonly reported symptoms in GCTs of the skull base. In this case report we present the first description of a GCT within the internal auditory canal causing cranial neuropathy and review the recent pertinent literature. PMID:26251814

  6. "Primary" aggressive chondroblastoma of the humerus: a case report

    PubMed Central

    Harish, K; Janaki, MG; Alva, N Kishore

    2004-01-01

    Background Chondroblastomas are rare epiphyseal bone tumors. Very few cases with extra-cortical aggressive soft tissue invasion or metastasis are reported. Case presentation We report a 28 year-old adult male who presented with a large swelling over the left shoulder region. Pre-operative imaging revealed a large tumor arising from upper end of humerus with extensive soft tissue involvement necessitating a fore-quarter amputation. Patient received adjuvant radiation. Conclusions This patient is one of the largest chondroblastomas to be reported. Although chondroblastomas are typically benign, rarely they can be locally aggressive or metastatic. Early diagnosis and institution of proper primary therapy would prevent mutilating surgeries and recurrences. PMID:15113430

  7. Decreased expression of H3K27me3 in human ovarian carcinomas correlates with more aggressive tumor behavior and poor patient survival.

    PubMed

    He, W P; Li, Q; Zhou, J; H, Z S; Kung, H F; Guan, X Y; Xie, D; Yang, G F

    2015-01-01

    It has been confirmed that trimethylation of lysine 27 on histone H3 (H3K27me3) plays an important role in epigenetic process of tumorigenesis. However, the status of H3K27me3 in ovarian cancer and its impact on patients' clinicopathologic characteristics and prognosis are unclear. In the present study, the immunohistochemistry (IHC) was utilized to detect protein expression of H3K27me3 in 12 normal ovaries, 26 ovarian cystadenomas, 31 borderline ovarian tumors and 168 ovarian carcinomas by tissue microarray. The association between H3K27me3 expression with clinicopathologic features and patient prognosis were also evaluated using various statistical models. The expression of H3K27me3 was decreased in 2 of 12 (16.7%) cases of the normal ovaries, 8 of 26 (30.8%) cases of cystadenomas, 12 of 31 (38.7%) cases of borderline ovarian tumors, and 93 of 168 (55.4%) cases of primary ovarian carcinomas, respectively (P<0.05). Further correlation analysis suggested that decreased expression of H3K27me3 in ovarian carcinomas was significantly correlated with more advanced pM and FIGO stages (P<0.05). In addition, a significant association between decreased expression of H3K27me3 and shortened patient survival (mean 66 months versus 101 months, p=0.019) was demonstrated by univariate survival analysis of the ovarian carcinoma cohorts. Importantly, H3K27me3 expression provided a significant independent prognostic factor in multivariate analysis (p=0.028). These findings confirmed that decreased expression of H3K27me3 in primary ovarian cancer might be correlated with the acquisition of an invasive and/or aggressive phenotype of tumor, and might serve as an independent biomarker for poor prognosis in patients with ovarian carcinoma.

  8. Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor aggression in non-small cell lung carcinoma.

    PubMed

    Xiao, Guang-Qian; Li, Faqian; Findeis-Hosey, Jennifer; Hyrien, Ollivier; Unger, Pamela D; Xiao, Lu; Dunne, Richard; Kim, Eric S; Yang, Qi; McMahon, Loralee; Burstein, David E

    2015-11-01

    There are currently no effective prognostic biomarkers for lung cancer. Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a role in cell cycle progression and tumorigenicity in various cancers. The expression and value of PLZF in lung carcinoma, particularly in the subclass of non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous cell carcinoma and correlate the alteration of PLZF expression with tumor differentiation, lymph node metastasis, tumor stage, and overall survival. A total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and 91 squamous cell carcinomas) were investigated. Moderate to strong expression of PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium and most (89.9%) well-differentiated adenocarcinoma. The proportions of moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph node adenocarcinoma metastases that demonstrated negative or only weak PLZF reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in squamous cell carcinoma was mostly weak or absent and significantly lower than that in adenocarcinoma of the same grade (P < .0005). The loss of cytoplasmic PLZF strongly correlated with high tumor grade and lymph node metastasis in both squamous carcinoma and adenocarcinoma (P < .0001). Down-regulation of PLZF also correlated with higher tumor stage and shorter overall survival (P < .05). These results support a prognostic value for loss of cytoplasmic PLZF expression in the stratification of NSCLC and a possible role of cytoplasmic shift and down-regulation of PLZF in the pathogenesis of NSCLC.

  9. Metastatic tumors in the jaw bones: A retrospective clinicopathological study of 12 cases at Tertiary Cancer Center

    PubMed Central

    Nawale, Kundan Kisanrao; Vyas, Monika; Kane, Shubhada; Patil, Asawari

    2016-01-01

    Introduction: The metastatic disease of the jaw bones is very uncommon and accounts for approximately 1% of all malignancies of jaw. The most common location is molar region of mandible. Metastasis may go undetected on a routine skeletal survey for assessment of metastasis and rarely includes jaw bones. Aims and Objective: The aim of the study is to analyze primary malignancies in metastatic jaw tumors. Materials and Methods: We retrospectively studied clinicopathological features of 12 patients of metastasis to jaw bones diagnosed at tertiary cancer center between 2003 and 2011. All H and E and immunohistochemical slides were reviewed by two pathologists and relevant details were noted. Results: There were eight female and four male patients, with age range 12–71 years with metastases to jaws. All of them involved mandible with one case also showing the involvement of frontal sinuses. The types of metastatic tumors include adenocarcinoma (six cases), papillary thyroid carcinoma (four cases), carcinoma with neuroendocrine differentiation (one case) and neuroblastoma (one case). The diagnosis was made on biopsies in eight cases and on hemimandibulectomy in four cases. The primary site was known at the time of presentation only in four cases, all of them being thyroid carcinomas. Primary site was determined in seven cases after immunohistochemical workup on metastatic tumor and further investigations, whereas the primary site of carcinoma with neuroendocrine differentiation was unknown. Conclusion: Metastasis to jaw bones is rare and may be the first manifestation of unknown primary. A lesion predominantly involving bone with unusual morphology should raise a possibility of metastasis. PMID:27601818

  10. Hypothalamic tumor

    MedlinePlus

    ... occur at any age. They are often more aggressive in adults than in children. In adults, tumors ... The treatment depends on how aggressive the tumor is, and whether it is a glioma or another type of cancer. Treatment may involve combinations of surgery, radiation , ...

  11. Protease Activated Receptors 1 and 2 Correlate Differently with Breast Cancer Aggressiveness Depending on Tumor ER Status

    PubMed Central

    Lidfeldt, Jon; Bendahl, Pär-Ola; Forsare, Carina; Malmström, Per; Fernö, Mårten; Belting, Mattias

    2015-01-01

    Experimental models implicate protease activated receptors (PARs) as important sensors of the proteolytic tumor microenvironment during breast cancer development. However, the role of the major PARs, PAR-1 and PAR-2, in human breast tumors remains to be elucidated. Here, we have investigated how PAR-1 and PAR-2 protein expression correlate with established clinicopathological variables and patient outcome in a well-characterized cohort of 221 breast cancer patients. Univariable and multivariable hazard ratios (HR) were estimated by the Cox proportional hazards model, distant disease-free survival (DDFS) and overall survival by the Kaplan–Meier method, and survival in different strata was determined by the log-rank test. Associations between PARs and clinicopathological variables were analyzed using Pearson’s χ2-test. We find that PAR-2 associates with DDFS (HR = 3.1, P = 0.003), whereas no such association was found with PAR-1 (HR = 1.2, P = 0.6). Interestingly, the effect of PAR-2 was confined to the ER-positive sub-group (HR = 5.5, P = 0.003 vs. HR = 1.2 in ER-negative; P = 0.045 for differential effect), and PAR-2 was an independent prognostic factor specifically in ER-positive tumors (HR = 3.9, P = 0.045). On the contrary, PAR-1 correlated with worse prognosis specifically in the ER-negative group (HR = 2.6, P = 0.069 vs. HR = 0.5, P = 0.19 in ER-positive; P = 0.026 for differential effect). This study provides novel insight into the respective roles of PAR-1 and PAR-2 in human breast cancer and suggests a hitherto unknown association between PARs and ER signaling that warrants further investigation. PMID:26244666

  12. Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors.

    PubMed

    Agaram, Narasimhan P; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Chung, Catherine T; Antonescu, Cristina R; Fletcher, Christopher Dm

    2016-10-01

    The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. To define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, which were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft

  13. Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors.

    PubMed

    Agaram, Narasimhan P; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Chung, Catherine T; Antonescu, Cristina R; Fletcher, Christopher Dm

    2016-10-01

    The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. To define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, which were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft

  14. Possible involvement of tumor-producing VEGF-A in the recruitment of lymphatic endothelial progenitor cells from bone marrow.

    PubMed

    Tawada, Masahiro; Hayashi, Shin-Ichiro; Ikegame, Yuka; Nakashima, Shigeru; Yoshida, Kazuhiro

    2014-12-01

    Lymphatic metastasis of human malignant adenocarcinomas is a critical determinant of prognosis. Lymphangiogenesis, the growth of lymphatic vessels, is closely involved in lymphatic metastasis. However, the mechanisms of tumor lymphangiogenesis are not clearly understood. In a previous study, we showed that human gastric cancer MKN45 cells organize neighboring lymphatic vessels via recruitment of bone marrow-derived lymphatic endothelial progenitor cells in a nude mouse xenograft model. The present results also indicated that human colorectal cancer LS174T and breast cancer SK-BR-3 cells promoted lymphangiogenesis as well as the recruitment of lymphatic endothelial progenitor cells from bone marrow. Among growth factors, which are reported to be involved in lymphangiogenesis, only vascular endothelial growth factor (VEGF)-A was extensively secreted by these three types of adenocarcinoma cells in culture. The well-characterized lymphangiogenic factors VEGF-C and VEGF-D in the culture medium of these three types of adenocarcinoma cells were below the detectable levels in ELISA assay. Secretion of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) was not detected. In in vitro culture assay, VEGF-A directly induced the differentiation of bone marrow mononuclear cells into LYVE-1-positive lymphatic endothelial lineage cells. These data collectively suggest the possibility that VEGF-A-rich human adenocarcinomas induce tumor lymphangiogenesis via recruitment of lymphangiogenic endothelial progenitor cells from bone marrow. PMID:25242215

  15. Bone lesion biopsy

    MedlinePlus

    Benign (noncancerous) bone tumors include: Bone cyst Fibroma Osteoblastoma Osteoid osteoma Cancerous tumors include: Ewing sarcoma Multiple myeloma Osteosarcoma Other types of cancer that may have spread to the bone Abnormal ...

  16. Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption.

    PubMed

    Xu, Leqin; Luo, Jian; Jin, Rongrong; Yue, Zhiying; Sun, Peng; Yang, Zhengfeng; Yang, Xinghai; Wan, Wei; Zhang, Jishen; Li, Shichang; Liu, Mingyao; Xiao, Jianru

    2016-05-01

    Giant cell tumor of bone (GCTB) is a rare and highly osteolytic bone tumor that usually leads to an extensive bone lesion. The purpose of this study was to discover novel therapeutic targets and identify potential agents for treating GCTB. After screening the serum cytokine profiles in 52 GCTB patients and 10 normal individuals using the ELISA assay, we found that NF-κB signaling-related cytokines, including TNFα, MCP-1, IL1α, and IL17A, were significantly increased in GCTB patients. The results were confirmed by IHC that the expression and activity of p65 were significantly increased in GCTB patients. Moreover, all of the NF-κB inhibitors tested suppressed GCTB cell growth, and bortezomib (Velcade), a well-known proteasome inhibitor, was the most potent inhibitor in blocking GCTB cells growth. Our results showed that bortezomib not only induced GCTB neoplastic stromal cell (NSC) apoptosis, but also suppressed GCTB NSC-induced giant cell differentiation, formation, and resorption. Moreover, bortezomib specifically suppressed GCTB NSC-induced preosteoclast recruitment. Furthermore, bortezomib ameliorated GCTB cell-induced bone destruction in vivo As a result, bortezomib suppressed NF-κB-regulated gene expression in GCTB NSC apoptosis, monocyte migration, angiogenesis, and osteoclastogenesis. Particularly, the inhibitory effects of bortezomib were much better than zoledronic acid, a drug currently used in treating GCTB, in our in vitro experimental paradigms. Together, our results demonstrated that NF-κB signaling pathway is highly activated in GCTB, and bortezomib could suppress GCTB and osteolysis in vivo and in vitro, indicating that bortezomib is a potential agent in the treatment of GCTB. Mol Cancer Ther; 15(5); 854-65. ©2016 AACR.

  17. Chondroblastoma associated with aneurysmal cyst of the navicular bone: a case report.

    PubMed

    Fang, Zhenhua; Chen, Ming

    2013-02-28

    Chondroblastoma is a rare tumor. It is usually benign; however, it can have an aggressive course before or after operative treatment, even resulting in pulmonary metastases. The foot is a rare location for chondroblastoma, and to our knowledge, chondroblastoma occurring in the navicular bone has not been reported previously in the English literature. We describe a case of navicular chondroblastoma case associated with an aneurysmal bone cyst. Treatment consisted of aggressive curettage, phenolization, and bone allograft. The patient was able to resume normal activities after treatment, and there was no recurrence of the chondroblastoma during a follow-up of 3 years.

  18. Chondroblastoma associated with aneurysmal cyst of the navicular bone: a case report.

    PubMed

    Fang, Zhenhua; Chen, Ming

    2013-01-01

    Chondroblastoma is a rare tumor. It is usually benign; however, it can have an aggressive course before or after operative treatment, even resulting in pulmonary metastases. The foot is a rare location for chondroblastoma, and to our knowledge, chondroblastoma occurring in the navicular bone has not been reported previously in the English literature. We describe a case of navicular chondroblastoma case associated with an aneurysmal bone cyst. Treatment consisted of aggressive curettage, phenolization, and bone allograft. The patient was able to resume normal activities after treatment, and there was no recurrence of the chondroblastoma during a follow-up of 3 years. PMID:23448376

  19. The effect of walking speed on gait kinematics and kinetics after endoprosthetic knee replacement following bone tumor resection.

    PubMed

    Okita, Yusuke; Tatematsu, Noriatsu; Nagai, Koutatsu; Nakayama, Tomitaka; Nakamata, Takeharu; Okamoto, Takeshi; Toguchida, Junya; Ichihashi, Noriaki; Matsuda, Shuichi; Tsuboyama, Tadao

    2014-09-01

    Gait function is one of the most important components of functional outcome evaluation in patients with a tumor around the knee. In addition to walking at a preferred speed, the patients might be sometimes required to walk fast in daily life (e.g., schooling and working) because the major types of bone tumors often occur in adolescence and young adults. Therefore, recovering the ability to walk fast would increase the quality of life of these patients. To clarify which parts of the lower limb are exerted while walking fast, we investigated the kinematic and kinetic changes during fast walking in patients who underwent endoprosthetic knee replacement after bone tumor resection. Laboratory-based gait analysis was performed on eight patients who had undergone endoprosthetic knee replacement following resection of a tumor around the knee. Patients walked at a preferred and faster speed, and the gait parameters were compared between the two walking speeds for each leg. To increase walking speed, patients tended to rely on the bilateral hip, ankle, and contralateral knee to generate additional power. Kinetic analysis showed that involved-side vertical body support was not significantly increased during late stance to increase walking speed, which was associated with a small increase in ankle plantarflexion moment and concentric power. These results suggest to patients after knee reconstruction how to effectively increase their walking speed or redistribute the mechanical load on the muscles and joints to prevent excessive stress on the lower limbs.

  20. High levels of class III β-tubulin expression are associated with aggressive tumor features in breast cancer

    PubMed Central

    LEBOK, PATRICK; ÖZTÜRK, MELIKE; HEILENKÖTTER, UWE; JAENICKE, FRITZ; MÜLLER, VOLKMAR; PALUCHOWSKI, PETER; GEIST, STEFAN; WILKE, CHRISTIAN; BURANDT, EICKE; LEBEAU, ANNETTE; WILCZAK, WALDEMAR; KRECH, TILL; SIMON, RONALD; SAUTER, GUIDO; QUAAS, ALEXANDER

    2016-01-01

    Overexpression of class III β-tubulin (TUBB3), a factor that confers dynamic properties to microtubules, is a candidate biomarker for resistance to microtubule-targeting chemotherapeutics in breast and other types of solid cancer. Discrepant results from previous studies, with respect to the association of TUBB3 expression levels with breast cancer phenotype and patient prognosis, prompted the present study to investigate TUBB3 expression in a large cohort of breast cancer cases, with available clinical follow-up data. A preexisting breast cancer prognosis tissue microarray, containing a single 0.6 mm tissue core from each of 2,197 individual patients with breast cancer, was analyzed for TUBB3 expression by immunohistochemistry. The results of the present study revealed that TUBB3 expression was less frequent in lobular breast cancer cases (34%), compared with that of cancer cases of alternative histologies, including breast cancer of no special type (60%; P<0.0001). High TUBB3 positivity was associated with high tumor grade (P<0.0001), negativity for estrogen (P<0.0001) and progesterone receptors (P<0.004), as well as the presence of human epidermal growth factor 2 amplification (P<0.0001) and a triple-negative phenotype (P<0.0001). TUBB3 overexpression was additionally associated with reduced patient survival if all breast cancer cases of any histology were jointly analyzed (P=0.0088); however this link was not evident in the subset of breast cancer cases of no special type, or in a multivariate analysis including the established prognostic factors of tumor stage, grade and nodal stage. In conclusion, the present study demonstrated that TUBB3 overexpression was associated with adverse features of breast cancer, and that TUBB3 may possess a distinct role in lobular breast cancer cases, compared with alternative histological subtypes. The results of the present study do not support a clinically relevant role for TUBB3 as a prognostic marker in breast cancer. PMID

  1. [Multifocal epithelioid angiosarcoma of bone with lung metastases].

    PubMed

    Pacheco, C; Albalá, M D; Blanco, M; Hidalgo, F J

    2014-01-01

    Angiosarcoma is a rare mesenchymal neoplasm that may arise from vascular or lymphatic tissue. Bone primary angiosarcoma is extremely rare, representing less than 1% of all angiosarcomas. It́s a very aggressive neoplasm and patients have metastatic disease at initial diagnosis in a large percentage of cases. On radiographs, these lesions are usually aggressive osteolytic lesions, commonly with soft-tissue mass extension, and tumoral enhancement on CT or MR imaging. The appearance of the bone scan is variable, describing studies with tracer uptake or low uptake. These tumours are more often found in the long bones, but spinal involvement has been reported in 10% of patients. There are a few reports in the literature of bone angiosarcoma with lung metastases. We present a patient with multifocal epithelioid angiosarcoma (spine and ribs) and multiple lung metastasis, evidenced by CT and conventional bone scintigraphy, with a fast growth.

  2. A Consortium of Aggregatibacter actinomycetemcomitans, Streptococcus parasanguinis, and Filifactor alocis Is Present in Sites Prior to Bone Loss in a Longitudinal Study of Localized Aggressive Periodontitis

    PubMed Central

    Markowitz, Kenneth; Fairlie, Karen; Tischio-Bereski, Debbie; Ferrendiz, Javier; Furgang, David; Paster, Bruce J.; Dewhirst, Floyd E.

    2013-01-01

    Aggregatibacter actinomycetemcomitans-induced localized aggressive periodontitis (LAP) in African-American adolescents has been documented but is poorly understood. Two thousand fifty-eight adolescents aged 11 to 17 years were screened for their periodontal status and the presence of A. actinomycetemcomitans in their oral cavity. Seventy-one A. actinomycetemcomitans-negative and 63 A. actinomycetemcomitans-positive periodontally healthy subjects were enrolled, sampled, examined, and radiographed yearly for 3 years. Gingival and periodontal pocket depth and attachment levels were recorded. Disease presentation was characterized by bone loss (BL). Subgingival sites were sampled every 6 months to assess (i) the role of A. actinomycetemcomitans in BL and (ii) the association of A. actinomycetemcomitans and other microbes in their relationships to BL. Sixteen of 63 subjects with A. actinomycetemcomitans developed BL (the other 47 subjects with A. actinomycetemcomitans had no BL). No A. actinomycetemcomitans-negative subjects developed BL. Human oral microbe identification microarray (HOMIM) was used for subgingival microbial assessment. On a subject level, pooled data from A. actinomycetemcomitans-positive subjects who remained healthy had higher prevalences of Streptococcus and Actinomyces species, while A. actinomycetemcomitans-positive subjects with BL had higher prevalences of Parvimonas micra, Filifactor alocis, A. actinomycetemcomitans, and Peptostreptococcus sp. human oral taxon 113 (HOT-113). At vulnerable sites, A. actinomycetemcomitans, Streptococcus parasanguinis, and F. alocis levels were elevated prior to BL. In cases where the three-organism consortium (versus A. actinomycetemcomitans alone) was detected, the specificity for detecting sites of future BL increased from 62% to 99%, with a sensitivity of 89%. We conclude that detecting the presence of A. actinomycetemcomitans, S. parasanguinis, and F. alocis together indicates sites of future BL in LAP. A

  3. Computer-Assisted Planning and Patient-Specific Instruments for Bone Tumor Resection within the Pelvis: A Series of 11 Patients

    PubMed Central

    Gouin, François; Odri, Guillaume Anthony

    2014-01-01

    Pelvic bone tumor resection is challenging due to complex geometry, limited visibility, and restricted workspace. Accurate resection including a safe margin is required to decrease the risk of local recurrence. This clinical study reports 11 cases of pelvic bone tumor resected by using patient-specific instruments. Magnetic resonance imaging was used to delineate the tumor and computerized tomography to localize it in 3D. Resection planning consisted in desired cutting planes around the tumor including a safe margin. The instruments were designed to fit into unique position on the bony structure and to indicate the desired resection planes. Intraoperatively, instruments were positioned freehand by the surgeon and bone cutting was performed with an oscillating saw. Histopathological analysis of resected specimens showed tumor-free bone resection margins for all cases. Available postoperative computed tomography was registered to preoperative computed tomography to measure location accuracy (minimal distance between an achieved and desired cut planes) and errors on safe margin (minimal distance between the achieved cut planes and the tumor boundary). The location accuracy averaged 2.5 mm. Errors in safe margin averaged −0.8 mm. Instruments described in this study may improve bone tumor surgery within the pelvis by providing good cutting accuracy and clinically acceptable margins. PMID:25100921

  4. High level of CFTR expression is associated with tumor aggression and knockdown of CFTR suppresses proliferation of ovarian cancer in vitro and in vivo.

    PubMed

    Xu, Jiao; Yong, Min; Li, Jia; Dong, Xiaojing; Yu, Tinghe; Fu, Xiao; Hu, Lina

    2015-05-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the ATP-binding cassette (ABC) transporter family, members of which are involved in various types of cancer. The relationship between CFTR and ovarian cancer remains to be elucidated. The aim of the present study was to investigate the expression of CFTR in human ovarian cancer tissues and its clinical significance in the progression of ovarian cancer. The role of CFTR in the malignant invasion, migration and proliferation of ovarian cancer in vitro and in vivo was also investigated. Immunohistochemical staining analysis was performed to detect the expression of CFTR in 83 cases of human epithelial ovarian cancer specimens. Moreover, SKOV3 and A2780 stable cell lines containing shRNA gene specific for CFTR were established. Cell proliferation and motility were observed and compared with CFTR-RNAi cells. Tumorigenicity of CFTR-RNAi cells was investigated by tumor xenograft experiments conducted subcutaneously in nude mice. The expresssion of CFTR in ovarian cancer was significantly higher than that in benign ovarian tumor and normal ovaries (P<0.05). In ovarian cancer, CFTR expression was significantly associated with advanced FIGO stage, poor histopathological grade and serum Ca-125 (P<0.05). Furthermore, we observed that CFTR staining was stronger in the serous type as compared to the other types (P<0.05). Compared with the negative control, decreased cell invasion, migration, proliferation, adhesion and colony formation were observed in CFTR-RNAi cells in vitro. In vivo, tumorigenic abilities of CFTR-RNAi cells were significantly repressed compared with that of the control groups. CFTR overexpression may play an important role in the development and progression of ovarian cancer. Additionally, the downregulation of CFTR suppresses aggressive malignant biological behaviors of ovarian cancer cells in vitro and in vivo. PMID:25738998

  5. Approaches for modeling interstitial ultrasound ablation of tumors within or adjacent to bone: Theoretical and experimental evaluations

    PubMed Central

    Scott, Serena J.; Prakash, Punit; Salgaonkar, Vasant; Jones, Peter D.; Cam, Richard N.; Han, Misung; Rieke, Viola; Burdette, E. Clif; Diederich, Chris J.

    2014-01-01

    Purpose The objectives of this study were to develop numerical models of interstitial ultrasound ablation of tumors within or adjacent to bone, to evaluate model performance through theoretical analysis, and to validate the models and approximations used through comparison to experiments. Methods 3D transient biothermal and acoustic finite element models were developed, employing four approximations of 7 MHz ultrasound propagation at bone/soft tissue interfaces. The various approximations considered or excluded reflection, refraction, angle-dependence of transmission coefficients, shear mode conversion, and volumetric heat deposition. Simulations were performed for parametric and comparative studies. Experiments within ex vivo tissues and phantoms were performed to validate the models by comparison to simulations. Temperature measurements were conducted using needle thermocouples or MR temperature imaging (MRTI). Finite element models representing heterogeneous tissue geometries were created based on segmented MR images. Results High ultrasound absorption at bone/soft tissue interfaces increased the volumes of target tissue that could be ablated. Models using simplified approximations produced temperature profiles closely matching both more comprehensive models and experimental results, with good agreement between 3D calculations and MRTI. The correlation coefficients between simulated and measured temperature profiles in phantoms ranged from 0.852 to 0.967 (p-value < 0.01) for the four models. Conclusions Models using approximations of interstitial ultrasound energy deposition around bone/soft tissue interfaces produced temperature distributions in close agreement with comprehensive simulations and experimental measurements. These models may be applied to accurately predict temperatures produced by interstitial ultrasound ablation of tumors near and within bone, with applications toward treatment planning. PMID:24102393

  6. Pre-chemotherapy preservation of fertility in male patients with high-grade malignant bone and soft tissue tumors.

    PubMed

    Hoshi, Manabu; Oebisu, Naoto; Takada, Jun; Iwai, Tadashi; Tsuruta, Rie; Nakamura, Hiroaki

    2014-11-01

    Only a limited number of orthopedic oncologists make arrangements for pre-chemotherapy fertility preservation, such as sperm cryopreservation, for their patients. The purpose of this study was to offer fertility preservation to male patients with high-grade malignant bone and soft tissue tumors and assess the outcomes. The study included 14 male patients, aged <45 years, with high-grade bone and soft tissue tumors. The median age at diagnosis was 23.0±12.0 years (range, 8-42 years). Following pathological confirmation of high-grade malignant tumor, we informed all the patients and/or their guardians on the issue of chemotherapy-related male infertility. If the patients were interested in preserving fertility, they were referred to a team of reproductive specialists. We documented the patients' clinical characteristics and techniques used for fertility preservation. The majority of unmarried and childless patients were interested in fertility preservation. Four patients (28.5%) selected sperm cryopreservation and 1 patient (7.1%) selected hemi-testicular preservation, as he had developed erectile dysfunction following previous surgery for colon cancer. Married patients and those with children did not wish to preserve fertility. In conclusion, infertility following chemotherapy raises serious concerns for young male patients with high-grade bone and soft tissue tumors. Prior to initiating chemotherapy, the potential risks of chemotherapy should be explained, counseling should be provided and informed consent should be obtained from the patients, ideally without delaying commencement of cancer treatment. Prior to administering cancer chemotherapy, orthopedic oncologists are encouraged to offer sperm banking to young male patients at risk of infertility. PMID:25279207

  7. Matrix Rigidity Regulates the Transition of Tumor Cells to a Bone-Destructive Phenotype through Integrin β3 and TGF-β Receptor Type II

    PubMed Central

    Ruppender, Nazanin S.; Guo, Ruijing; Dadwal, Ushashi C.; Cannonier, Shellese; Basu, Sandip; Guelcher, Scott A.; Sterling, Julie A.

    2015-01-01

    Cancer patients frequently develop skeletal metastases that significantly impact quality of life. Since bone metastases remain incurable, a clearer understanding of molecular mechanisms regulating skeletal metastases is required to develop new therapeutics that block establishment of tumors in bone. While many studies have suggested that the microenvironment contributes to bone metastases, the factors mediating tumors to progress from a quiescent to a bone-destructive state remain unclear. In this study, we hypothesized that the “soil” of the bone microenvironment, specifically the rigid mineralized extracellular matrix, stimulates the transition of the tumor cells to a bone-destructive phenotype. To test this hypothesis, we synthesized 2D polyurethane (PUR) films with elastic moduli ranging from the basement membrane (70 MPa) to cortical bone (3800 MPa) and measured expression of genes associated with mechanotransduction and bone metastases. We found that expression of Integrin β3 (Iβ3), as well as tumor-produced factors associated with bone destruction (Gli2 and parathyroid hormone related protein (PTHrP)), significantly increased with matrix rigidity, and that blocking Iβ3 reduced Gli2 and PTHrP expression. To identify the mechanism by which Iβ3 regulates Gli2 and PTHrP (both are also known to be regulated by TGF-β), we performed Förster resonance energy transfer (FRET) and immunoprecipitation, which indicated that Iβ3 co-localized with TGF-β Receptor Type II (TGF-β RII) on rigid but not compliant films. Finally, transplantation of tumor cells expressing Iβ3 shRNA into the tibiae of athymic nude mice significantly reduced PTHrP and Gli2 expression, as well as bone destruction, suggesting a crucial role for tumor-produced Iβ3 in disease progression. This study demonstrates that the rigid mineralized bone matrix can alter gene expression and bone destruction in an Iβ3/TGF-β-dependent manner, and suggests that Iβ3 inhibitors are a potential

  8. Matrix rigidity regulates the transition of tumor cells to a bone-destructive phenotype through integrin β3 and TGF-β receptor type II.

    PubMed

    Page, Jonathan M; Merkel, Alyssa R; Ruppender, Nazanin S; Guo, Ruijing; Dadwal, Ushashi C; Cannonier, Shellese A; Basu, Sandip; Guelcher, Scott A; Sterling, Julie A

    2015-09-01

    Cancer patients frequently develop skeletal metastases that significantly impact quality of life. Since bone metastases remain incurable, a clearer understanding of molecular mechanisms regulating skeletal metastases is required to develop new therapeutics that block establishment of tumors in bone. While many studies have suggested that the microenvironment contributes to bone metastases, the factors mediating tumors to progress from a quiescent to a bone-destructive state remain unclear. In this study, we hypothesized that the "soil" of the bone microenvironment, specifically the rigid mineralized extracellular matrix, stimulates the transition of the tumor cells to a bone-destructive phenotype. To test this hypothesis, we synthesized 2D polyurethane (PUR) films with elastic moduli ranging from the basement membrane (70 MPa) to cortical bone (3800 MPa) and measured expression of genes associated with mechanotransduction and bone metastases. We found that expression of Integrin β3 (Iβ3), as well as tumor-produced factors associated with bone destruction (Gli2 and parathyroid hormone related protein (PTHrP)), significantly increased with matrix rigidity, and that blocking Iβ3 reduced Gli2 and PTHrP expression. To identify the mechanism by which Iβ3 regulates Gli2 and PTHrP (both are also known to be regulated by TGF-β), we performed Förster resonance energy transfer (FRET) and immunoprecipitation, which indicated that Iβ3 co-localized with TGF-β Receptor Type II (TGF-β RII) on rigid but not compliant films. Finally, transplantation of tumor cells expressing Iβ3 shRNA into the tibiae of athymic nude mice significantly reduced PTHrP and Gli2 expression, as well as bone destruction, suggesting a crucial role for tumor-produced Iβ3 in disease progression. This study demonstrates that the rigid mineralized bone matrix can alter gene expression and bone destruction in an Iβ3/TGF-β-dependent manner, and suggests that Iβ3 inhibitors are a potential

  9. CCR1 blockade reduces tumor burden and osteolysis in vivo in a mouse model of myeloma bone disease

    PubMed Central

    Oyajobi, Babatunde O.; Gupta, Anjana; McCluskey, Brandon; Miao, Shichang; Powers, Jay P.; Seitz, Lisa C.; Wang, Yu; Zeng, Yibin; Zhang, Penglie; Schall, Thomas J.; Jaen, Juan C.

    2012-01-01

    The chemokine CCL3/MIP-1α is a risk factor in the outcome of multiple myeloma (MM), particularly in the development of osteolytic bone disease. This chemokine, highly overexpressed by MM cells, can signal mainly through 2 receptors, CCR1 and CCR5, only 1 of which (CCR1) is responsive to CCL3 in human and mouse osteoclast precursors. CCR1 activation leads to the formation of osteolytic lesions and facilitates tumor growth. Here we show that formation of mature osteoclasts is blocked by the highly potent and selective CCR1 antagonist CCX721, an analog of the clinical compound CCX354. We also show that doses of CCX721 selected to completely inhibit CCR1 produce a profound decrease in tumor burden and osteolytic damage in the murine 5TGM1 model of MM bone disease. Similar effects were observed when the antagonist was used prophylactically or therapeutically, with comparable efficacy to that of zoledronic acid. 5TGM1 cells were shown to express minimal levels of CCR1 while secreting high levels of CCL3, suggesting that the therapeutic effects of CCX721 result from CCR1 inhibition on non-MM cells, most likely osteoclasts and osteoclast precursors. These results provide a strong rationale for further development of CCR1 antagonists for the treatment of MM and associated osteolytic bone disease. PMID:22618707

  10. Unusual multifocal intraosseous papillary intralymphatic angioendothelioma (Dabska tumor) of facial bones: a case report and review of literature

    PubMed Central

    2013-01-01

    Abstract Papillary intralymphatic angioendothelioma (PILA) or Dabska tumor is extremely rare, and often affects the skin and subcutaneous tissues of children. Since its first description by Dabska, only a few intraosseous cases have been described in the literature and none of them presents with multifocal osteolytic lesion of bones. We present a case of unusual multifocal intraosseous PILA in facial bones occurring in a 1 year 3 month old male child. Computed tomography (CT) scan revealed multifocal osteolytic lesions were located at the left zygoma, left orbital bone and right maxillary. Histologically, the lesions were ill-defined and composed of multiple delicate interconnecting vascular channels with papillae formation which projected into the lumen lined by atypical plumped endothelial cells. The vascular channels were also lined by plump cuboidal endothelial cells with focal hobnailed or “match-head” appearance. In some areas, endothelial cells formed solid-appearing aggregates with vessel lumens. By immunohistochemistry, the tumor cells were positive for CD31, CD34 and D2-40 at varying intensity. A final diagnosis of intraosseous PILA was made. To the best of our knowledge, this case is the first case of primary multifocal osseous PILA. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1919488629100787 PMID:24063649

  11. Aggressive fibromatosis: evaluation by computed tomography and angiography

    SciTech Connect

    Hudson, T.M.; Vandergriend, R.A.; Springfield, D.S.; Hawkins, I.F. Jr.; Spanier, S.S.; Enneking, W.F.; Hamlin, D.J.

    1984-02-01

    Fifteen CT scans of 13 patients who had aggressive fibromatosis were generally accurate in showing the extent of disease, although the CT definition of half or more of the margins of nine lesions was poor. Fibromatosis tumors were typically isodense or slightly hypodense with muscle when no contrast medium was used, and they enhanced to hyperdense with better delineation during infusion of contrast medium. Obliterated intermuscular planes did not always signify disease extension; the relationship to bone was often obscured by beam-hardening artifact; and small blood vessels were often invisible. Arteriograms of seven of eight patients showed some hypervascularity and helped to delineate lesions and vessels that were poorly seen on CT scans. In four instances CT findings were clearer, in two instances arteriographic findings were clearer, and twice the findings were equally clear. Three of six bone scintigrams added accurate information about involvement of adjacent bones.

  12. Bone tumors: General aspects and data on 8,547 cases. 4th Ed

    SciTech Connect

    Dahlin, D.C.; Unni, K.K.

    1986-01-01

    The classification of tumors is based on the matrix produced by the tumor and the cytologic findings. Each section contains information on the clinical, pathologic, and radiologic features, together with treatment and prognosis. There are new sections on subclassifications of tumors not mentioned in the earlier edition, such as high-grade surface osteosarcoma. In general, the new material consists of an updating of the statistics and additional references, much of which deal with the improving prognosis for many of the tumors.

  13. Signaling aggression.

    PubMed

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds.

  14. Artificial finger joint replacement due to a giant cell tumor of the tendon sheath with bone destruction: A case report

    PubMed Central

    LU, HUI; SHEN, HUI; CHEN, QIANG; SHEN, XIANG-QIAN; WU, SHOU-CHENG

    2015-01-01

    The current study presents the case of a 25-year-old male who developed tumor recurrence of the proximal phalange of the ring finger on the right hand 4 years after partial tumor resection surgery. An X-ray of the right hand showed that the distal bone of the proximal phalange on the ring finger was destroyed. An artificial finger joint replacement was performed using a silicone joint for this unusual tumor recurrence. The pathological findings were indicative of a giant cell tumor of the tendon sheath. As a result of surgery, the patient's proximal interphalangeal point motion recovered to the pre-operative level. The pre-operative and post-operative disabilities of the arm, at shoulder and hand and total activity measurement values were 1.67 and 3.33, and 255 and 243°, respectively. Complications such as tumor recurrence, joint dislocation and the requirement for prosthetic training were not observed during the 5-year follow-up period. PMID:26788157

  15. Low Infection Rate after Tumor Hip Arthroplasty for Metastatic Bone Disease in a Cohort Treated with Extended Antibiotic Prophylaxis

    PubMed Central

    Hettwer, Werner H.; Horstmann, Peter Frederik; Hovgaard, Thea Bechmann; Grum-Scwensen, Tomas Andreas; Petersen, Michael M.

    2015-01-01

    Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic prophylaxis for this patient population remains unknown. Material and Methods. To establish the infection rate associated with prolonged antibiotic prophylaxis in our department, we performed a retrospective review of all adult patients who underwent endoprosthetic reconstruction of the proximal femur after tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n = 105 patients). Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96% at 2 years, and the risk of amputation associated with infection was 25% (1/4 patients). Discussion. Preemptive eradication of bacterial contamination may be of value in certain clinical situations, where the risk level and consequences of implant-associated infection are unacceptable. Our findings suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur. PMID:25705521

  16. Low infection rate after tumor hip arthroplasty for metastatic bone disease in a cohort treated with extended antibiotic prophylaxis.

    PubMed

    Hettwer, Werner H; Horstmann, Peter Frederik; Hovgaard, Thea Bechmann; Grum-Scwensen, Tomas Andreas; Petersen, Michael M

    2015-01-01

    Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic prophylaxis for this patient population remains unknown. Material and Methods. To establish the infection rate associated with prolonged antibiotic prophylaxis in our department, we performed a retrospective review of all adult patients who underwent endoprosthetic reconstruction of the proximal femur after tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n = 105 patients). Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96% at 2 years, and the risk of amputation associated with infection was 25% (1/4 patients). Discussion. Preemptive eradication of bacterial contamination may be of value in certain clinical situations, where the risk level and consequences of implant-associated infection are unacceptable. Our findings suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur.

  17. Evaluation and management of the pregnant patient with suspected primary musculoskeletal tumor or metastatic carcinoma to bone.

    PubMed

    Puvanesarajah, Varun; Spiker, Andrea M; Shannon, Brett A; Grundy, Maureen; Levin, Adam S; Morris, Carol D

    2016-09-01

    Primary musculoskeletal cancer and metastatic disease to bone in pregnant patients presents major treatment challenges. Although uncommon, musculoskeletal malignancies in pregnant women have been reported. When diagnosing and treating these patients, the mother's health must be managed appropriately while ensuring that fetal development is not deleteriously affected. Extensive radiographic imaging and more advanced techniques are often necessary to fully characterize the extent of disease. When possible, magnetic resonance imaging should be used instead of computed tomography to limit exposure of the conceptus to radiation. If treatment is needed, therapeutic radiation, chemotherapy, and surgery should be considered. Surgical resection is the foundation of treatment of early-stage primary bone tumors and soft-tissue sarcomas during pregnancy. With surgery, anesthesia and thromboprophylaxis are important considerations. If chemotherapy is required, administration should be avoided in the first trimester to limit harm to the fetus. Therapeutic radiation should similarly be avoided during the first trimester and often can be postponed until after delivery. PMID:27566025

  18. Surgical treatment and outcomes of temporal bone chondroblastoma.

    PubMed

    Moon, In Seok; Kim, Jin; Lee, Ho-Ki; Lee, Won-Sang

    2008-12-01

    Chondroblastoma is an uncommon primary benign bone tumor that usually arises in the epiphyses of the long bones. Temporal bone chondroblastoma is a rare primary bone tumor that affects the floor of the middle cranial fossa and temporomandibular joint (TMJ). The biological nature of temporal bone chondroblastoma is occasionally aggressive because of local invasion and is known to have a high recurrence after curettage. Therefore, complete resection is recommended. However, the literature provides little information regarding long-term surgical outcomes and complications after surgical resection. The authors have retrospectively analyzed four cases of temporal bone chondroblastoma that had been completely excised by a single surgeon with an eventual long-term follow-up. A single surgeon operated on four patients, two males and two females, with a mean age of 34 years, at the Department of Otorhinolaryngology, Severance Hospital. In all cases, the tumor involved the middle cranial fossa dura and the mandibular fossa with variable degree of infiltration. All patients have had no tumor recurrence to date (mean follow-up period of 5 years). Complete surgical resection of the temporal bone chondroblastoma is the gold standard for treatment. Precise preoperative image evaluation of tumor extension and proper management of the dura mater and temporomandibular joint (TMJ) are the major important features in complete surgical removal that minimize complications in temporal bone chondroblastoma treatment.

  19. ¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay.

    PubMed

    Balter, Henia; Victoria, Trindade; Mariella, Terán; Javier, Gaudiano; Rodolfo, Ferrando; Andrea, Paolino; Graciela, Rodriguez; Juan, Hermida; Eugenia, De Marco; Patricia, Oliver

    2016-01-01

    Lutetium-177 is an emerging radionuclide due its convenient chemical and nuclear properties. In this paper we describe the development and evaluation in Uruguay of the targeted 177Lu labelled radiopharmaceuticals EDTMP (for bone pain palliation) and DOTA-TATE (neuroendocrine tumors). We optimized the preparation of these 177Lu radiopharmaceuticals including radiolabelling, quality control methods, in vitro and in vivo stability and their therapeutic application in patients. Radiation dosimetry aspects of 177Lu are also included. Nine male patients with prostate cancer and four female patients with breast carcinoma with multiple bone metastatic lesions were treated with 177Lu-EDTMP. Four patients with gastroentheropancreatic neuroendocrine tumors (GEP-NET) and one patient with bronchial NET were treated with 1- 3 cycles with a cumulative dose of 4.44-22.2 GBq of 177Lu-DOTA-TATE. Scintigraphic images of the patients treated with 177Lu-EDTMP evidenced high and rapid uptake in bone metastasis, remaining after 7 days post administration. Images allow skeletal visualization with high definition and demonstrate increased uptake in bone metastases. For 177Lu-DOTA-TATE, partial remissions were obtained in 4 patients and the remaining patient did not show significant progression 3 months after the second cycle. No serious adverse effects were registered, even in two patients with confirmed renal disease and high risk for renal disease Dosimetry assessments confirm the predictive value of the personalized therapy with radiolabelled peptides. We found it is possible to accumulate high therapeutic doses in tumours in sequential administrations of 177Lu-DOTA-TATE, increasing the probability of biological response without significant impairment of the renal function in patients with risk factors. These results demonstrate the attractive therapeutic properties of these two 177Lu labelled agents and the feasibility of this metabolic therapy in regions far away from 177Lu producing

  20. ¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay.

    PubMed

    Balter, Henia; Victoria, Trindade; Mariella, Terán; Javier, Gaudiano; Rodolfo, Ferrando; Andrea, Paolino; Graciela, Rodriguez; Juan, Hermida; Eugenia, De Marco; Patricia, Oliver

    2016-01-01

    Lutetium-177 is an emerging radionuclide due its convenient chemical and nuclear properties. In this paper we describe the development and evaluation in Uruguay of the targeted 177Lu labelled radiopharmaceuticals EDTMP (for bone pain palliation) and DOTA-TATE (neuroendocrine tumors). We optimized the preparation of these 177Lu radiopharmaceuticals including radiolabelling, quality control methods, in vitro and in vivo stability and their therapeutic application in patients. Radiation dosimetry aspects of 177Lu are also included. Nine male patients with prostate cancer and four female patients with breast carcinoma with multiple bone metastatic lesions were treated with 177Lu-EDTMP. Four patients with gastroentheropancreatic neuroendocrine tumors (GEP-NET) and one patient with bronchial NET were treated with 1- 3 cycles with a cumulative dose of 4.44-22.2 GBq of 177Lu-DOTA-TATE. Scintigraphic images of the patients treated with 177Lu-EDTMP evidenced high and rapid uptake in bone metastasis, remaining after 7 days post administration. Images allow skeletal visualization with high definition and demonstrate increased uptake in bone metastases. For 177Lu-DOTA-TATE, partial remissions were obtained in 4 patients and the remaining patient did not show significant progression 3 months after the second cycle. No serious adverse effects were registered, even in two patients with confirmed renal disease and high risk for renal disease Dosimetry assessments confirm the predictive value of the personalized therapy with radiolabelled peptides. We found it is possible to accumulate high therapeutic doses in tumours in sequential administrations of 177Lu-DOTA-TATE, increasing the probability of biological response without significant impairment of the renal function in patients with risk factors. These results demonstrate the attractive therapeutic properties of these two 177Lu labelled agents and the feasibility of this metabolic therapy in regions far away from 177Lu producing

  1. The Megavoltage Radiation Therapy in Treatment of Patients With Advanced or Difficult Giant Cell Tumors of Bone

    SciTech Connect

    Ruka, Wlodzimierz; Ptaszynski, Konrad; Bylina, Elzbieta

    2010-10-01

    Purpose: To assess the outcomes of radiotherapy, in terms of local control and treatment complications, of advanced or difficult giant cell tumors of bone (GCTB) that could not be treated by surgery. Methods and Materials: Among 122 consecutive patients with confirmed GCTB from 1985 to 2007, 77 patients were treated by megavoltage radiotherapy because they were inappropriate candidates for surgery. We have performed analysis of all data in terms of progression-free survival (PFS) and treatment morbidity. Median follow-up time was 58 months. Results: In the irradiated group, maximal tumor size ranged from 5 to 18 cm (median, 8.5). Anatomic distribution was as follows: femur, 27 cases; tibia, 19; radial/ulnar bone, 12; sacrum, 9; pelvic bones, 5; other, 5. Twenty-one patients (27%) were referred for local recurrence after {>=}1 other treatment procedures. The radiation doses ranged from 26 to 89 Gy (median, 56; administered 1.8-2.0 Gy/fraction with average total duration of treatment of 5-7 weeks); 8 patients (10%) received <50 Gy. All patients tolerated treatment well without acute or late complications. All patients except two are alive. Local control was achieved in 65 patients (84%; bone recalcification/restitution of joint functions), 12 patients showed signs of local progression, all within irradiated fields (9 were treated successfully with salvage surgery). Five- and 10-year local PFS were 83% and 73%, respectively. Three patients developed lungs metastases. Malignant transformation of GCTB occurred in two patients. Conclusions: GCTB can be safely and effectively treated with megavoltage radiotherapy with local control rate >80% at 5 years. Our study confirms that radiotherapy of GCTB offers an alternative to difficult or complex surgery and may be an option of choice in the treatment of inoperable patients.

  2. Safety of Percutaneous Cryoablation in Patients with Painful Bone and Soft Tissue Tumors: A Single Center Prospective Study (SCIRO-1502).

    PubMed

    Iguchi, Toshihiro; Sakurai, Jun; Hiraki, Takao; Gobara, Hideo; Fujiwara, Hiroyasu; Matsui, Yusuke; Masaoka, Yoshihisa; Kanazawa, Susumu

    2016-08-01

    This single center prospective study is being conducted to evaluate the safety of the cryoablation for patients with pathologically diagnosed painful bone and soft tissue tumors. Enrollment of 10 patients is planned over the 3-year recruitment period. Patients have related local pain after receiving medications or external radiation therapies will be included in this study. Cryoablation will be percutaneously performed under imaging guidance, and a temperature sensor will be used during treatment as necessary. The primary endpoint is prevalence of severe adverse events within 4 weeks after therapy. The secondary endpoint is effectiveness 4 weeks after the procedure. PMID:27549678

  3. Interleukin-6 expression and histomorphometry of bones from mice deficient in receptors for interleukin-1 or tumor necrosis factor.

    PubMed

    Vargas, S J; Naprta, A; Glaccum, M; Lee, S K; Kalinowski, J; Lorenzo, J A

    1996-11-01

    We examined the roles of interleukin-1 Type I receptor (IL-1R1) and tumor necrosis factor receptor 1 (TNFR1) in bone metabolism using mice rendered deficient in these receptors by gene targeting. Sections of decalcified paraffin-embedded calvariae and humeri from 11- to 12-week-old mice deficient in IL-1 Type I receptor (IL-1R1-/-) or TNF receptor 1 (TNFR1-/-) were examined by histomorphometry. Wild-type mice (C57BL/6J x 129/J, WILD) served as controls. Interleukin-6 (IL-6) production in primary osteoblastic and bone marrow stromal cell cultures in response to parathyroid hormone (PTH, 100 ng/ml), IL-1 alpha (10 ng/ml), and TNF-alpha (10 ng/ml) was also examined. IL-1R1-/- and TNFR1-/- mice were viable and appeared phenotypically normal. However, the body weights of the IL-1R1-/- mice were 30% less than WILD, while the TNFR1-/- mice weighed 30% more than WILD mice of equivalent age. Calvariae and humeri of IL-1R1-/- and TNFR1-/- mice were normal with respect to trabecular bone volume, osteoclast number, osteoclast surface, growth plate widths, and cortical thickness. Receptor deficiency was confirmed by determining the ability of PTH, IL-1 alpha, and TNF-alpha to stimulate IL-6 in the media of primary calvaria-derived osteoblastic cell cultures from CD-1 and cytokine receptor-deficient mice. After 24 h of treatment, IL-1 alpha and TNF-alpha did not stimulate IL-6 production in osteoblasts from IL-1R1-/- and TNFR1-/- mice, respectively. In contrast, PTH increased IL-6 levels in the cells from all mice. IL-6 protein levels in bone marrow supernatants and conditioned media from untreated bone marrow stromal cells were undetectable in WILD, IL-1R1-/-, and TNFR1-/- mice. PTH, IL-1 alpha and TNF-alpha increased IL-6 mRNA and protein production in the WILD bone marrow stromal cells. In contrast, PTH and TNF-alpha increased IL-6 mRNA and protein levels in IL-1R1-/- bone marrow stromal cells while IL-1 alpha had no effect. These findings demonstrate that normal bone

  4. A fractal analysis of the spatial distribution of tumoral mast cells in lymph nodes and bone marrow.

    PubMed

    Guidolin, Diego; Marinaccio, Christian; Tortorella, Cinzia; Ruggieri, Simona; Rizzi, Anna; Maiorano, Eugenio; Specchia, Giorgina; Ribatti, Domenico

    2015-11-15

    The spatial distribution of mast cells inside the tumor stroma has been little investigated. In this study, we have evaluated tumor mast cells distribution through the analysis of the morphological features of the spatial patterns generated by these cells, including size, shape, and architecture of the cell pattern. We have compared diffuse large B cells lymphoma (DLBCL) and systemic mastocytosis in two different anatomical localizations (lymph nodes for DLBCL and, respectively, bone marrow for mastocytosis). Results have indicated that, despite the high difference in size exhibited by the mast cells patterns in the two conditions, the spatial relationship between the mast cells forming the aggregates resulted similar, characterized by a significant tendency of the mast cells to self-organize in clusters.

  5. Bone scanning.

    PubMed

    Greenfield, L D; Bennett, L R

    1975-03-01

    Scanning is based on the uptake of a nuclide by the crystal lattice of bone and is related to bone blood flow. Cancer cells do not take up the tracer. Normally, the scan visualizes the highly vascular bones. Scans are useful and are indicated in metastatic bone disease, primary bone tumors, hematologic malignancies and some non-neoplastic diseases. The scan is more sensitive than x-ray in the detection of malignant diseases of the skeleton. PMID:1054210

  6. Tumor necrosis factor-α G-308A (rs1800629) polymorphism and aggressive periodontitis susceptibility: a meta-analysis of 16 case-control studies

    PubMed Central

    Wei, Xue-Mei; Chen, Yong-Ji; Wu, Lan; Cui, Li-Jun; Hu, Ding-Wei; Zeng, Xian-Tao

    2016-01-01

    Association between tumor necrosis factor-α (TNF-α) G-308A (rs1800629) polymorphism and susceptibility to aggressive periodontitis (AgP) were inconsistent, hence we performed this meta-analysis to clarify the association between them using Comprehensive Meta-Analysis v2.2 software. 16 case-control studies were searched from the PubMed, Embase and CNKI databases up to February 2, 2015. The meta-analysis showed a significantly increased risk in A vs. G (OR = 1.23, 95%CI = 1.04–1.44), AA vs. GG (OR = 2.07, 95%CI = 1.11–3.87), and AA vs. AG+GG genetic models (OR = 2.09, 95%CI = 1.13–3.86); however, the non-significantly increased risk was shown in AG vs. GG (OR = 1.06, 95%CI = 0.85–1.32) and AA+AG vs. GG genetic models (OR = 1.06, 95%CI = 0.85–1.31). Cumulative analysis showed that the association changed from non-significant to significant with new studies accumulated and the CIs became more and more narrow, sensitivity analysis indicated results were statistically robust. Stratified analyses of confirmed of HWE, Asians, Caucasians, and population-based controls obtained results similar to that of overall analysis. There was no evidence of publication bias. In summary, current evidence demonstrates that TNF-a G-308A polymorphism might be associated with AgP susceptibility, especially in Asians and Caucasians. PMID:26750615

  7. IRF1 and NF-kB restore MHC class I-restricted tumor antigen processing and presentation to cytotoxic T cells in aggressive neuroblastoma.

    PubMed

    Lorenzi, Silvia; Forloni, Matteo; Cifaldi, Loredana; Antonucci, Chiara; Citti, Arianna; Boldrini, Renata; Pezzullo, Marco; Castellano, Aurora; Russo, Vincenzo; van der Bruggen, Pierre; Giacomini, Patrizio; Locatelli, Franco; Fruci, Doriana

    2012-01-01

    Neuroblastoma (NB), the most common solid extracranial cancer of childhood, displays a remarkable low expression of Major Histocompatibility Complex class I (MHC-I) and Antigen Processing Machinery (APM) molecules, including Endoplasmic Reticulum (ER) Aminopeptidases, and poorly presents tumor antigens to Cytotoxic T Lymphocytes (CTL). We have previously shown that this is due to low expression of the transcription factor NF-kB p65. Herein, we show that not only NF-kB p65, but also the Interferon Regulatory Factor 1 (IRF1) and certain APM components are low in a subset of NB cell lines with aggressive features. Whereas single transfection with either IRF1, or NF-kB p65 is ineffective, co-transfection results in strong synergy and substantial reversion of the MHC-I/APM-low phenotype in all NB cell lines tested. Accordingly, linked immunohistochemistry expression patterns between nuclear IRF1 and p65 on the one hand, and MHC-I on the other hand, were observed in vivo. Absence and presence of the three molecules neatly segregated between high-grade and low-grade NB, respectively. Finally, APM reconstitution by double IRF1/p65 transfection rendered a NB cell line susceptible to killing by anti MAGE-A3 CTLs, lytic efficiency comparable to those seen upon IFN-γ treatment. This is the first demonstration that a complex immune escape phenotype can be rescued by reconstitution of a limited number of master regulatory genes. These findings provide molecular insight into defective MHC-I expression in NB cells and provide the rational for T cell-based immunotherapy in NB variants refractory to conventional therapy.

  8. Chondroblastoma of the temporal bone.

    PubMed

    Hatano, Miyako; De Donato, Giuseppe; Falcioni, Maurizio; Sanna, Mario

    2011-08-01

    Chondroblastomas are highly destructive tumors that are derived from immature cartilage cells. The occurrence of this tumor in the temporal bone or skull base is uncommon. Approximately 70 cases have previously been reported, several of which have involved the temporomandibular joint (TMJ). We report here the case of a 67-year-old woman who presented with right-sided mixed hearing loss, a right external auditory canal mass, ear fullness, otalgia, blood-stained otorrhea, and pain around the TMJ, associated with difficulty in opening the mouth. CT and MRI revealed a mass involving the TMJ, infratemporal fossa, and pterygopalatine fossa. The patient underwent tumor resection via an infratemporal fossa approach type B. Gross total tumor removal was achieved, with no facial nerve paralysis or other complications observed after surgery. No recurrence or residual tumors were observed on CT and MRI, even after 7.5 years of follow-up. We conclude that temporal bone chondroblastomas are extremely rare and aggressive, but the outcome after appropriate surgical treatment is favorable. From the review, it may be particularly important to deal with tumors that involve the TMJ, which could affect the long-term outcomes, as well as tumor recurrence.

  9. Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.

    PubMed

    Marsh, Timothy; Wong, Irene; Sceneay, Jaclyn; Barakat, Amey; Qin, Yuanbo; Sjödin, Andreas; Alspach, Elise; Nilsson, Björn; Stewart, Sheila A; McAllister, Sandra S

    2016-05-15

    Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow-derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells (BMC) upregulated CSF-1R and secreted the growth factor granulin to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the protumorigenic effects of activated BMCs. Cancer Res; 76(10); 2932-43. ©2016 AACR. PMID:27197230

  10. Spatiotemporal control of gene expression in bone-marrow derived cells of the tumor microenvironment induced by MRI guided focused ultrasound.

    PubMed

    Fortin, Pierre-Yves; Lepetit-Coiffé, Matthieu; Genevois, Coralie; Debeissat, Christelle; Quesson, Bruno; Moonen, Chrit T W; Konsman, Jan Pieter; Couillaud, Franck

    2015-09-15

    The tumor microenvironment is an interesting target for anticancer therapies but modifying this compartment is challenging. Here, we demonstrate the feasibility of a gene therapy strategy that combined targeting to bone marrow-derived tumor microenvironment using genetically modified bone-marrow derived cells and control of transgene expression by local hyperthermia through a thermo-inducible promoter. Chimera were obtained by engraftment of bone marrow from transgenic mice expressing reporter genes under transcriptional control of heat shock promoter and inoculated sub-cutaneously with tumors cells. Heat shocks were applied at the tumor site using a water bath or magnetic resonance guided high intensity focused ultrasound device. Reporter gene expression was followed by bioluminescence and fluorescence imaging and immunohistochemistry. Bone marrow-derived cells expressing reporter genes were identified to be mainly tumor-associated macrophages. We thus provide the proof of concept for a gene therapy strategy that allows for spatiotemporal control of transgenes expression by macrophages targeted to the tumor microenvironment. PMID:26299614

  11. Spatiotemporal control of gene expression in bone-marrow derived cells of the tumor microenvironment induced by MRI guided focused ultrasound.

    PubMed

    Fortin, Pierre-Yves; Lepetit-Coiffé, Matthieu; Genevois, Coralie; Debeissat, Christelle; Quesson, Bruno; Moonen, Chrit T W; Konsman, Jan Pieter; Couillaud, Franck

    2015-09-15

    The tumor microenvironment is an interesting target for anticancer therapies but modifying this compartment is challenging. Here, we demonstrate the feasibility of a gene therapy strategy that combined targeting to bone marrow-derived tumor microenvironment using genetically modified bone-marrow derived cells and control of transgene expression by local hyperthermia through a thermo-inducible promoter. Chimera were obtained by engraftment of bone marrow from transgenic mice expressing reporter genes under transcriptional control of heat shock promoter and inoculated sub-cutaneously with tumors cells. Heat shocks were applied at the tumor site using a water bath or magnetic resonance guided high intensity focused ultrasound device. Reporter gene expression was followed by bioluminescence and fluorescence imaging and immunohistochemistry. Bone marrow-derived cells expressing reporter genes were identified to be mainly tumor-associated macrophages. We thus provide the proof of concept for a gene therapy strategy that allows for spatiotemporal control of transgenes expression by macrophages targeted to the tumor microenvironment.

  12. Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer

    PubMed Central

    Sawant, Anandi; Deshane, Jessy; Jules, Joel; Lee, Carnella M.; Harris, Brittney A.; Feng, Xu; Ponnazhagan, Selvarangan

    2012-01-01

    Enhanced bone destruction is a hallmark of various carcinomas such as breast cancer, where osteolytic bone metastasis is associated with increased morbidity and mortality. Immune cells contribute to osteolysis in cancer growth but the factors contributing to aggressive bone destruction are not well understood. In this study, we demonstrate the importance of myeloid-derived suppressor cells (MDSC) in this process at bone metastatic sites. Since MDSC originate from the same myeloid lineage as macrophages, which are osteoclast precursors, we hypothesized that MDSC may undergo osteoclast differentiation and contribute to enhanced bone destruction and tumor growth. Using an immunocompetent mouse model of breast cancer bone metastasis, we confirmed that MDSC isolated from the tumor-bone microenvironment differentiated into functional osteoclasts both in vitro and in vivo. Mechanistic investigations revealed that nitric oxide signaling was critical for differentiation of MDSC into osteoclasts. Remarkably, osteoclast differentiation did not occur in MDSC isolated from control or tumor-bearing mice that lacked bone metastasis, signifying the essential cross-talk between tumor cells and myeloid progenitors in the bone microenvironment as a requirement for osteoclast differentiation of MDSC. Overall, our results identify a wholly new facet to the multifunctionality of MDSC in driving tumor progression, in this case as a novel osteoclast progenitor that specifically drives bone metastasis during cancer progression. PMID:23243021

  13. High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis

    PubMed Central

    Shimazu, Kazuhiro; Fukuda, Koji; Yoshida, Taichi; Inoue, Masahiro; Shibata, Hiroyuki

    2016-01-01

    AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis. METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 mL of peripheral venous blood drawn using a CellSearch kit and a CellTracks AutoPrep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells (CTC) count and therapeutic outcomes. RESULTS: Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 mL of peripheral blood (median of 1724). These values were much higher than common gastric cancers (2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d (median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance (Y = 234.6 - 0.03X, P = 0.085). CONCLUSION: High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome. PMID:27468200

  14. CD44 standard and variant isoform expression in human epidermal skin tumors is not correlated with tumor aggressiveness but down-regulated during proliferation and tumor de-differentiation.

    PubMed

    Seelentag, W K; Günthert, U; Saremaslani, P; Futo, E; Pfaltz, M; Heitz, P U; Roth, J

    1996-06-21

    CD44 isoforms have been reported to be involved in tumor invasion and metastasis formation. Normal human skin expresses high levels of CD44 isoforms, but little is known about their expression in epidermal skin tumors. Expression of CD44 standard (CD44s) and variant exon (CD44v3, -v4, -v5, -v6, -v9)-encoded gene products has been studied in 74 benign, semi-malignant and malignant human epithelial skin tumors using a panel of well-characterized, variant exon-specific monoclonal antibodies (MAbs). Sensitivity and resolution of the immunohistochemical staining in paraffin sections was substantially improved by using microwave-based antigen retrieval and an optimized streptavidin-biotin-peroxidase technique. Immunostaining was evaluated semi-quantitatively and correlated with tumor type and degree of histological differentiation by non-parametric statistical tests. Furthermore, the relationship between CD44 expression and cellular proliferation rate as defined by the Ki-67 antigen was analyzed in basal cell carcinomas. We found a significant correlation between tumor type and CD44 isoform expression. Basal cell carcinomas exhibited the weakest staining and keratoacanthomas the strongest. Squamous cell carcinomas ranged in between, with a tendency to down-regulate CD44 expression upon de-differentiation. In basal cell carcinomas, an inverse relationship between CD44 expression and proliferation rate was directly demonstrated at the cellular level using double immunolabelling. Our data indicate that qualitative and quantitative changes in CD44 splicevariant expression in human skin tumors do not correlate with invasive and metastatic potential but are rather related to the degree of tumor differentiation. PMID:8682591

  15. Wilms Tumor

    MedlinePlus

    ... diagnosis, and the condition, or histology , of the cancer cells when observed under a microscope. "Favorable" histology is associated with a good chance of a cure; tumors with "unfavorable" histology are more aggressive and ...

  16. Dendritic cells accumulate in the bone marrow of myeloma patients where they protect tumor plasma cells from CD8+ T-cell killing

    PubMed Central

    Leone, Patrizia; Berardi, Simona; Frassanito, Maria Antonia; Ria, Roberto; De Re, Valli; Cicco, Sebastiano; Battaglia, Stefano; Ditonno, Paolo; Dammacco, Franco; Vacca, Angelo

    2015-01-01

    Many researchers have speculated that the clinical progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) is driven by defects in dendritic cell (DC) function. However, evidence supporting this assumption is controversial, and no mechanism for the putative DC dysfunction has been demonstrated thus far. We studied DC subsets from the bone marrow of MM patients compared with those of MGUS patients and control subjects. We found that myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) accumulate in the bone marrow during the MGUS-to-MM progression. After engulfment of apoptotic tumor plasma cells via CD91, bone marrow mDCs and pDCs mature and are able to activate tumor-specific CD8+ T cells. However, by interacting directly with CD28 on live (nonapoptotic) tumor plasma cells, bone marrow mDCs downregulate the expression of proteasome subunits in these cells, thus enabling their evasion from human leukocyte antigen (HLA) class I–restricted CD8+ T-cell killing. These results suggest that DCs play a dual, but opposing, role in MM: for one, DCs activate CD8+ T cells against tumor plasma cells and, for the other, DCs protect tumor plasma cells from CD8+ T-cell killing. This information should be taken into account in designing immunotherapy approaches to enhance immune surveillance in MGUS and to break down immune tolerance in MM. PMID:26185130

  17. Inactivated autograft–prosthesis composite have a role for grade III giant cell tumor of bone around the knee

    PubMed Central

    2013-01-01

    Background Giant cell tumors (GCT) around the knee are common and pose a special problem of reconstruction after tumor excision, especially for grade III GCT. We questioned whether en bloc resection and reconstruction with alcohol inactivated autograft-prosthesis composite would provide (1) local control and long-term survival and (2) useful limb function in patients who had grade III GCT around the knee. Methods We retrospectively reviewed eight patients (5 males and 3 females) treated with this procedure with mean age of 31 years (range 20 to 43 years) from Jan 2007 to Oct 2008. 5 lesions were located in distal femur and 3 in proximal tibia. 4 patients were with primary tumor and the other 4 with recurrence. 2 patients showed pathological fracture. Results Mean Follow-up is 54 months ranging from 38 to 47 months. No recurrence, metastasis, prosthesis loosening were found. The mean healing time between autograft and host bone was 5.5 months. The mean MSTS score was 26.3 (88%) ranging from 25 to 29. The mean ISOLS composite graft score was 32.8 (88.5%) ranging from 28 to 35. Creeping substitution is possibly the main way in bony junction. The healing time in femoral lesion is faster than that in tibial lesion. Conclusions The technique of alcohol inactivated autograft-prosthesis composite could be able to achieve satisfactory oncological and functional outcomes in Grade III GCT. PMID:24209887

  18. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... fullstory_159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more ... News) -- When it comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may ...

  19. [Limb-preserving resection operations in the management of bone tumors of the shoulder region].

    PubMed

    Gáspár, L; Szepesi, K; Mandi, A; Mórocz, I

    1989-01-01

    Authors describe the frequency of bone tumours in the shoulder region and the anatomical characteristics of this region, that are important, regarding tumour surgery. Six cases are reported in whom resection was performed for malignant, semimalignant and benign bone tumours. In their material one primary and two secondary chondrosarcomas, one Ewing's sarcoma, one osteoclastoma and one benign chondroblastoma were found. Follow-up range was 3-7 years. In two patients partial and total scapulectomy was performed, in the later the proximal end of the humerus was resected only, in three of them endoprosthesis was given, and in one case the missing bone was replaced with a fibular graft. The function of the limbs was in every case, even in those in which the replacement of the bone segment was not carried out, adequate. Metastases developed in three patients, two of them were lost, one is alive. The rest of the patients was free of tumour at the follow-up. PMID:2571754

  20. Understanding Aggression.

    ERIC Educational Resources Information Center

    Scott, J. P.

    Research in many fields of the social and biological sciences indicates that there are ecological, cultural, social, psychological, physiological, and genetic causes of aggression. The agonistic behavior system, which adapts to situations of social conflict, includes several patterns of conduct ranging from overt fighting to complete passivity. In…

  1. Generation of tumor immunity by bone marrow-derived dendritic cells correlates with dendritic cell maturation stage.

    PubMed

    Labeur, M S; Roters, B; Pers, B; Mehling, A; Luger, T A; Schwarz, T; Grabbe, S

    1999-01-01

    Bone marrow-derived dendritic cells (BmDC) are potent APC and can promote antitumor immunity in mice when pulsed with tumor Ag. This study aimed to define the culture conditions and maturation stages of BmDC that enable them to optimally function as APC in vivo. BmDC cultured under various conditions (granulocyte-macrophage CSF (GM-CSF) or GM-CSF plus IL-4 alone or in combination with Flt3 ligand, TNF-alpha, LPS, or CD40 ligand (CD40L)) were analyzed morphologically, phenotypically, and functionally and were tested for their ability to promote prophylactic and/or therapeutic antitumor immunity. Each of the culture conditions generated typical BmDC. Whereas cells cultured in GM-CSF alone were functionally immature, cells incubated with CD40L or LPS were mature BmDC, as evident by morphology, capacity to internalize Ag, migration into regional lymph nodes, IL-12 secretion, and alloantigen or peptide Ag presentation in vitro. The remaining cultures exhibited intermediate dendritic cell maturation. The in vivo Ag-presenting capacity of BmDC was compared with respect to induction of both protective tumor immunity and immunotherapy of established tumors, using the poorly immunogenic squamous cell carcinoma, KLN205. In correspondence to their maturation stage, BmDC cultured in the presence of CD40L exhibited the most potent immunostimulatory effects. In general, although not entirely, the capacity of BmDC to induce an antitumor immune response in vivo correlated to their degree of maturation. The present data support the clinical use of mature, rather than immature, tumor Ag-pulsed dendritic cells as cancer vaccines and identifies CD40L as a potent stimulus to enhance their in vivo Ag-presenting capacity.

  2. Computer-aided resection and endoprosthesis design for the management of malignant bone tumors around the knee: outcomes of 12 cases

    PubMed Central

    2013-01-01

    Background To report the outcomes of computer-aided resection and endoprosthesis design for the management of malignant bone tumors around the knee. Methods Computed tomography (CT) and magnetic resonance imaging (MRI) data were input into computer software to produce three-dimensional (3D) models of the tumor extent. Imaging data was then used to create a template for surgical resection, and development of an individualized combined allogeneic bone/endoprosthesis. Surgical simulations were performed prior to the actual surgery. Results This study included 9 males and 3 females with a mean age of 25.3 years (range, 13 to 40 years). There were 9 tumors in the distal femur and 3 in the proximal tibia. There were no surgical complications. In all cases pathologically confirmed clear surgical margins were obtained. Postoperative radiographs showed the range of tumor resection was in accordance with the preoperative design, and the morphological reconstruction of the bone defect was satisfactory with complete bilateral symmetry. The mean follow-up time was 26.5 months. Two patients died of their disease and the remaining are alive and well without evidence of recurrence. All patients are able to ambulate freely without restrictions. At the last follow-up, the average International Society of Limb Salvage score was 25.8 (range, 18 to 27), and was excellent in 8 cases and good in 4 cases. Conclusions Computer-aided design and modeling for the surgical management of bone tumors and subsequent limb reconstruction provides accurate tumor removal with the salvage of a maximal amount of unaffected bone and precise endoprosthesis reconstruction. PMID:24267157

  3. Aneurysmal bone cyst involving the metacarpal bone in a child.

    PubMed

    Song, Kwang Soon; Lee, Si Wook; Bae, Ki Cheor; Sohn, Eun Seok

    2015-03-01

    Aneurysmal bone cysts associated with tubular bones of the hand occur rarely and require particular diagnostic and therapeutic management techniques. While optimal treatment has not been established, accepted treatments range from aggressive radical treatment, including en bloc resection and excision diaphysectomy with strut bone grafting, to relatively simple techniques, such as thorough curettage followed by bone graft. Aggressive treatment approaches may be optimal for the cases with articular surface involvement, full-bone invasion of the phalanx or metacarpal, or more than 1 recurrence. We report a monocentric case of aneurysmal bone cysts involving metacarpal bone in a child who achieved favorable outcome with curettage and morselized cancellous bone grafts. PMID:25750953

  4. Essential requirement of I-A region-identical host bone marrow or bone marrow-derived cells for tumor neutralization by primed L3T4+ T cells

    SciTech Connect

    Ozawa, H.; Iwaguchi, T.; Kataoka, T.

    1987-12-01

    The antitumor activity of Meth A-hyperimmunized BALB/c mouse spleen cells (Meth A-Im-SPL) was assayed by the Winn test in H-2 incompatible bone marrow chimeras in closed colony CD-1 (nu/nu), inbred DDD/1(nu/nu) (H-2s), or inbred BALB/c(nu/nu) (H-2d) mice as recipients. We found that Meth A-Im-SPL suppressed Meth A growth in the chimera nude mice which were reconstituted with bone marrow cells of the H-2d haplotype (i.e., BALB/c, DBA/2 and B10.D2), but not in the chimeras which were reconstituted with bone marrow cells of the H-2a, H-2b, or H-2k haplotype (i.e., B10.A, B10, and B10.BR). These results suggested that H-2 restriction occurred between Meth A-Im-SPL and bone marrow or bone marrow-derived cells in tumor neutralization. Furthermore, Meth A-Im-SPL did not suppress Meth 1 tumors (antigenically distinct from Meth A tumors) in the presence or absence of mitomycin C-treated Meth A in a Winn assay. These results suggested that there is tumor specificity in the effector phase as well as in the induction phase. The phenotype of the effectors in the Meth A-Im-SPL was Thy-1.2+ and L3T4+, because Meth A-Im-SPL lost their antitumor activity with pretreatment with anti-Thy-1.2 monoclonal antibody (mAb) and complement or anti-L3T4 mAb and complement, but not with anti-Lyt-2.2 mAb and complement or complement alone. Positively purified L3T4+ T cells from Meth A-Im-SPL (Meth A-Im-L3T4), obtained by the panning method, suppressed the tumor growth in the chimera nude mice which were reconstituted with bone marrow cells of B10.KEA2 mice (that were I-A region-identical with Meth A-Im-L3T4 cells but not others in H-2) as well as B10.D2 cells (that were fully identical with Meth A-Im-L3T4 cells in H-2). We conclude that Meth A-Im-SPL (L3T4+) neutralized the tumors in collaboration with I-A region-identical host bone marrow or bone marrow-derived cells, and the neutralization was not accompanied by the bystander effect.

  5. Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone.

    PubMed

    Gaston, Czar Louie; Grimer, Robert J; Parry, Michael; Stacchiotti, Silvia; Dei Tos, Angelo Paolo; Gelderblom, Hans; Ferrari, Stefano; Baldi, Giacomo G; Jones, Robin L; Chawla, Sant; Casali, Paolo; LeCesne, Axel; Blay, Jean-Yves; Dijkstra, Sander P D; Thomas, David M; Rutkowski, Piotr

    2016-01-01

    Denosumab is a monoclonal antibody to RANK ligand approved for use in giant cell tumour (GCT) of bone. Due to its efficacy, Denosumab is recommended as the first option in inoperable or metastatic GCT. Denosumab has also been used pre-operatively to downstage tumours with large soft tissue extension to allow for less morbid surgery. The role of Denosumab for conventional limb GCT of bone is yet to be defined. Further studies are required to determine whether local recurrence rates will be decreased with the adjuvant use of Denosumab along with surgery. The long term use and toxicity of this agent is unknown as is the proportion of patients with primary or secondary resistance. It is advised that complicated cases of GCT requiring Denosumab treatment should be referred and followed up at expert centres. Collaborative studies involving further clinical trials and rigorous data collection are strongly recommended to identify the optimum use of this drug. PMID:27651889

  6. CD10 and CD138 can be expressed in giant cell tumor of bone: An immunohistochemical study.

    PubMed

    Al-Abbadi, Mousa A; Al-Yousef, Mohammed J; Yousef, Mohammad M; Sheikh, Salwa S; Almasri, Nidal M; Amr, Samir S

    2016-01-01

    Giant cell tumor of bone (GCTB) is a primary bone neoplasm which is characterized by the presence of mononuclear cells (MCs) and osteoclast-like multinucleated giant cells (MNGCs). Up to our knowledge, CD10 immunoreactivity in GCTB has not yet been studied, and only one study touched on CD138 immunoreactivity in GCTB. The objective of this study is to investigate the immunoreactivity of CD10 and CD138 in GCTB. We offer a discussion of our findings in the context of the differential diagnosis, particularly in small biopsy material. We retrieved and reviewed 15 well-documented cases of GCTB from January 2008 to December 2014. Well-controlled standard immunohistochemical satins were performed on these cases for CD10 and CD138 and few other selected antibodies. Immunoreactivity for CD10 was membranous and was found in 14 (93%) cases. This immunoreactivity was found only in the MCs, whereas the MNGC were all negative. CD138 showed variable positivity in 11 (73%) while 4 (37%) were completely negative. Similar to CD10, staining for CD138 was only seen in the MC; however, the immunoreactivity was predominantly concentrated in the peri-vascular areas. Most of GCTB cases can show variable immunoreactivity for CD10 and CD138. The aforementioned immune-expression raise the possibility of a role in the pathogenesis of GCTB. Paying attention to this immunoreactivity is recommended when considering the clinical and radiological differential diagnosis, especially in small biopsy specimens. PMID:27390668

  7. CD10 and CD138 can be expressed in giant cell tumor of bone: An immunohistochemical study

    PubMed Central

    Al-Abbadi, Mousa A.; Al-Yousef, Mohammed J.; Yousef, Mohammad M.; Sheikh, Salwa S.; Almasri, Nidal M.; Amr, Samir S.

    2016-01-01

    Giant cell tumor of bone (GCTB) is a primary bone neoplasm which is characterized by the presence of mononuclear cells (MCs) and osteoclast-like multinucleated giant cells (MNGCs). Up to our knowledge, CD10 immunoreactivity in GCTB has not yet been studied, and only one study touched on CD138 immunoreactivity in GCTB. The objective of this study is to investigate the immunoreactivity of CD10 and CD138 in GCTB. We offer a discussion of our findings in the context of the differential diagnosis, particularly in small biopsy material. We retrieved and reviewed 15 well-documented cases of GCTB from January 2008 to December 2014. Well-controlled standard immunohistochemical satins were performed on these cases for CD10 and CD138 and few other selected antibodies. Immunoreactivity for CD10 was membranous and was found in 14 (93%) cases. This immunoreactivity was found only in the MCs, whereas the MNGC were all negative. CD138 showed variable positivity in 11 (73%) while 4 (37%) were completely negative. Similar to CD10, staining for CD138 was only seen in the MC; however, the immunoreactivity was predominantly concentrated in the peri-vascular areas. Most of GCTB cases can show variable immunoreactivity for CD10 and CD138. The aforementioned immune-expression raise the possibility of a role in the pathogenesis of GCTB. Paying attention to this immunoreactivity is recommended when considering the clinical and radiological differential diagnosis, especially in small biopsy specimens. PMID:27390668

  8. Tumor

    MedlinePlus

    ... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by viruses are: Cervical cancer (human papillomavirus) Hepatocellular carcinoma (hepatitis B and hepatitis C ...

  9. RITM and POCI: Pre and per-operative mini {gamma} cameras evaluation for bone tumor localization in theater blocks

    SciTech Connect

    Menard, L.; Mastrippolito, R.; Charon, Y.

    1996-12-31

    We have developed a multi-functional portable {gamma} radio-imager (RITM) based on a position sensitive photomultiplier tube (PSPMT) in order to evaluate the potential of such miniature {gamma} camera concept in radio-pharmacology and nuclear medicine. We report here an evaluation of our RITM device for cancer surgery. It concerns localization of the osteoid osteoma (bone benign tumor) performed in theater block before skin incision and during the surgical lesion extraction. Over 13 cases we studied, the diagnosis furnished by RITM was always confirmed by post-operation anatomo-pathological analysis. This shows how RITM can be used as an additional indicator to monitor the operation. Following this first experience, we are developing a new small field of view {gamma} per operative compact imager (POCI) performing a sub-millimeter spatial resolution. It consists of a high resolution collimator and a YAP:Ce crystal assembly coupled to an intensified position sensitive diode (IPSD). This hand held imaging probe is first dedicated to intra-operative monitoring for thyroid and neuroblastoma tumor removal. Characteristics of the POCI device and preliminary results are presented.

  10. EMMPRIN regulates tumor growth and metastasis by recruiting bone marrow-derived cells through paracrine signaling of SDF-1 and VEGF.

    PubMed

    Chen, Yanke; Gou, Xingchun; Kong, Derek Kai; Wang, Xiaofei; Wang, Jianhui; Chen, Zeming; Huang, Chen; Zhou, Jiangbing

    2015-10-20

    EMMPRIN, a cell adhesion molecule highly expressed in a variety of tumors, is associated with poor prognosis in cancer patients. Mechanistically, EMMPRIN has been characterized to contribute to tumor development and progression by controlling the expression of MMPs and VEGF. In the present study, by using fluorescently labeled bone marrow-derived cells (BMDCs), we found that the down-regulation of EMMPRIN expression in cancer cells reduces tumor growth and metastasis, and is associated with the reduced recruitment of BMDCs. Further protein profiling studies suggest that EMMPRIN controls BMDC recruitment through regulating the secretion of soluble factors, notably, VEGF and SDF-1. We demonstrate that the expression and secretion of SDF-1 in tumor cells are regulated by EMMPRIN. This study reveals a novel mechanism by which EMMPRIN promotes tumor growth and metastasis by recruitment of BMDCs through controlling secretion and paracrine signaling of SDF-1 and VEGF.

  11. Stages of Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  12. Enchondroma versus Chondrosarcoma in Long Bones of Appendicular Skeleton: Clinical and Radiological Criteria—A Follow-Up

    PubMed Central

    Ferrer-Santacreu, Eugenio M.; Ortiz-Cruz, Eduardo J.; Díaz-Almirón, Mariana; Pozo Kreilinger, Jose Juan

    2016-01-01

    As of today two types of cartilage tumors remain a challenge even for the orthopedic oncologist: enchondroma (E), a benign tumor, and chondrosarcoma (LGC), a malignant and low aggressiveness tumor. A prospective study of 133 patients with a cartilaginous tumor of low aggressiveness in the long bones of the appendicular skeleton was done to prove this difficult differential diagnosis. Parameters including medical history and radiological and nuclear imaging were collected and compared to the result of the biopsy. A scale of aggressiveness was applied to each patient according to the number of aggressiveness episodes present. A comparison of the results of the biopsy with the initial diagnosis made by the orthopedic oncologist based solely on clinical data and imaging tests was also made. Finally, a management algorithm for these cases was proposed. A statistical significance for LGC resulted from the parameter as follows: pain on palpation, involvement of cortical in either the CT or MRI, and Tc99 bone scan uptake equal or superior to anterosuperior iliac crest. In our series, a tumor scoring 5 points or higher in the scale of aggressiveness can have 50% more chance of being LGC. When compared with the gold standard (the biopsy), surgeon's initial judgement showed a sensitivity of 73.5% and a specificity of 94.1%. PMID:27034667

  13. Giant Cell Tumor of Bone in Skeletally Immature Patients - A Clinical Perspective

    PubMed Central

    Sharma, Vipin; Sharma, Seema; Mistry, Kewal A; Awasthi, Bhanu; Verma, Lucky; Singh, Uttam

    2015-01-01

    Introduction: Giant cell tumors of skeleton are very rare in pediatric and adolescent population. Here we report two cases-one a fifteen year old child with swelling distal humerus and another a case of a thirteen year old child with pain and swelling proximal tibia. Case Report: A fifteen year old child presented to department of orthopedics of our institute with complaint of difficulty in moving upper limb and swelling distal humerus. Another patient who was a 13 years old male had painful ambulation and swelling in upper tibia. MRI followed by core needle biopsy was done in both the patients confirming the mass to be giant cell tumor which is quite rare in this age group. First patient was managed by wide excision and total elbow replacement and second one by curettage, cementation and augmentation with plate-screw construct. Conclusion: Giant cell tumour of skeleton is highly uncommon in pediatric age group. It should be considered as one of the differential diagnosis of epiphyseo metaphyseal lesions in pediatric population in spite of its rarity. PMID:27299101

  14. The study of indicators of bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous injection of gold nanorods

    NASA Astrophysics Data System (ADS)

    Dikht, Nataliya I.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Terentyuk, Georgy S.; Matveeva, Olga V.; Navolokin, Nikita A.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.

    2015-03-01

    In study the evaluation of the influence of gold nanorods on morphological indicators of red bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous administration of gold nanorods was conducted. We used gold nanorods with length 41 ± 8 nm and diameter of 10.2±2 nm, synthesized in the laboratory of nanobiotechnology IBPPM RAS (Saratov). After intravenous administration of gold nanorods the decrease of leukocytes, platelets and lymphocytes was observed in animals of control group in blood. It was marked the decrease of the number of mature cellular elements of the leukocyte germ in bone marrow - stab neutrophils and segmented leukocytes, and the increase of immature elements- metamyelocytes, indicating the activation of leukocyte germ after nanoparticle administration. The decrease of leukocyte amount was noted in blood and the increase of cellular elements of the leukocyte germ was revealed in bone marrow, indicating the activation of leukocyte germ in rats with alloxan diabetes and transplanted tumors. The changes of morphological indicators of blood and bone marrow testify about stimulation of myelocytic sprouts of hemopoiesis in bone marrow as a result of reduction of mature cells in peripheral blood after gold nanoparticle administration.

  15. Primary intraosseous hybrid nerve sheath tumor of femur: a hitherto undescribed occurrence in bone with secondary aneurysmal bone cyst formation resulting in pathological fracture.

    PubMed

    Chow, Louis Tsun Cheung

    2015-05-01

    Soft tissue perineurioma besides its pure form may coexist with schwannoma as hybrid nerve sheath tumor (HNST) which occurs in the limbs, head and neck, trunk and occasionally colon but origination in other organ sites has not been reported. We report the first case of primary intraosseous HNST. An 18-year-old man suffered from pathological fracture of his right femur after an impact which was preceded by a similar episode two weeks previously. Plain radiograph revealed a displaced fracture in the superior diaphysis of the right femur where an expansile osteolytic lesion with relatively well defined borders was seen. Histologic examination of the curetted lesion showed a well circumscribed spindle cell neoplasm displaying predominantly storiform but focally whorled patterns. In areas, the cells possessed thin wavy spindle nuclei and delicate elongated bipolar cytoplasmic processes supported in a fibromyxoid stroma. They stained positively for EMA, claudin, CD34, collagen 4 and focally for S100 but negatively for MUC4 and BCL-2, indicative of perineurial differentiation. Situated in the periphery of some of these perineurial whorls are spindle cells bearing plump tapering wavy nuclei and palely eosinophilic cytoplasm with indistinct cell borders. They stained intensely for S100 but negatively for EMA, claudin, CD34, collagen 4, MUC4 and BCL-2, consistent with schwannian differentiation. Focally, these two varieties of cells intimately intermingled with each other. Features of aneurysmal bone cyst (ABC) formation were present but no mitotic figures, establishing the final diagnosis of primary intraosseous HNST with secondary ABC formation. The patient remained well 7 months after curettage and internal fixation of his fracture.

  16. Effects of letrozole on breast cancer micro-metastatic tumor growth in bone and lung in mice inoculated with murine 4T1 cells.

    PubMed

    Wang, Wendan; Belosay, Aashvini; Yang, Xujuan; Hartman, James A; Song, Huaxin; Iwaniec, Urszula T; Turner, Russell T; Churchwell, Mona I; Doerge, Daniel R; Helferich, William G

    2016-06-01

    Breast cancer (BC) is the leading cancer in women worldwide. Metastasis occurs in stage IV BC with bone and lung being common metastatic sites. Here we evaluate the effects of the aromatase inhibitor letrozole on BC micro-metastatic tumor growth in bone and lung metastasis in intact and ovariectomized (OVX) mice with murine estrogen receptor negative (ER-) BC cells inoculated in tibia. Forty-eight BALB/c mice were randomly assigned to one of four groups: OVX, OVX + Letrozole, Intact, and Intact + Letrozole, and injected with 4T1 cells intra-tibially. Letrozole was subcutaneously injected daily for 23 days at a dose of 1.75 µg/g body weight. Tumor progression was monitored by bioluminescence imaging (BLI). Following necropsy, inoculated tibiae were scanned via µCT and bone response to tumor was scored from 0 (no ectopic mineralization/osteolysis) to 5 (extensive ectopic mineralization/osteolysis). OVX mice had higher tibial pathology scores indicative of more extensive bone destruction than intact mice, irrespective of letrozole treatment. Letrozole decreased serum estradiol levels and reduced lung surface tumor numbers in intact animals. Furthermore, mice receiving letrozole had significantly fewer tumor colonies and fewer proliferative cells in the lung than OVX and intact controls based on H&E and Ki-67 staining, respectively. In conclusion, BC-inoculated OVX animals had higher tibia pathology scores than BC-inoculated intact animals and letrozole reduced BC metastases to lungs. These findings suggest that, by lowering systemic estrogen level and/or by interacting with the host organ, the aromatase inhibitor letrozole has the potential to reduce ER- BC metastasis to lung. PMID:27209469

  17. Targeting Bone Marrow to Potentiate the Anti-Tumor Effect of Tyrosine Kinase Inhibitor in Preclinical Rat Model of Human Glioblastoma

    PubMed Central

    Shaaban, S.; Alsulami, M.; Arbab, S.A.; Ara, R.; Shankar, A.; Iskander, A.; Angara, K.; Jain, M.; Bagher-Ebadian, H.; Achyut, B.R.; Arbab, A.S.

    2016-01-01

    Antiangiogenic agents caused paradoxical increase in pro-growth and pro-angiogenic factors and caused tumor growth in glioblastoma (GBM). It is hypothesized that paradoxical increase in pro-angiogenic factors would mobilize Bone Marrow Derived Cells (BMDCs) to the treated tumor and cause refractory tumor growth. The purposes of the studies were to determine whether whole body irradiation (WBIR) or a CXCR4 antagonist (AMD3100) will potentiate the effect of vatalanib (a VEGFR2 tyrosine kinase inhibitor) and prevent the refractory growth of GBM. Human GBM were grown orthotopically in three groups of rats (control, pretreated with WBIR and AMD3100) and randomly selected for vehicle or vatalanib treatments for 2 weeks. Then all animals underwent Magnetic Resonance Imaging (MRI) followed by euthanasia and histochemical analysis. Tumor volume and different vascular parameters (plasma volume (vp), forward transfer constant (Ktrans), back flow constant (kep), extravascular extracellular space volume (ve) were determined from MRI. In control group, vatalanib treatment increased the tumor growth significantly compared to that of vehicle treatment but by preventing the mobilization of BMDCs and interaction of CXCR4-SDF-1 using WBIR and ADM3100, respectively, paradoxical growth of tumor was controlled. Pretreatment with WBIR or AMD3100 also decreased tumor cell migration, despite the fact that ADM3100 increased the accumulation of M1 and M2 macrophages in the tumors. Vatalanib also increased Ktrans and ve in control animals but both of the vascular parameters were decreased when the animals were pretreated with WBIR and AMD3100. In conclusion, depleting bone marrow cells or CXCR4 interaction can potentiate the effect of vatalanib. PMID:27429653

  18. Expression of Wnt and TGF-β pathway components and key adrenal transcription factors in adrenocortical tumors: association to carcinoma aggressiveness.

    PubMed

    Parviainen, Helka; Schrade, Anja; Kiiveri, Sanne; Prunskaite-Hyyryläinen, Renata; Haglund, Caj; Vainio, Seppo; Wilson, David B; Arola, Johanna; Heikinheimo, Markku

    2013-08-01

    Factors controlling benign and malignant adrenocortical tumorigenesis are largely unknown, but several mouse models suggest an important role for inhibin-alpha (INHA). To show that findings in the mouse are relevant to human tumors and clinical outcome, we investigated the expression of signaling proteins and transcription factors involved in the regulation of INHA in human tumor samples⋅ Thirty-one adrenocortical tumor samples, including 13 adrenocortical carcinomas (ACCs), were categorized according to Weiss score, hormonal profile, and patient survival data and analyzed using immunohistochemistry and RT-PCR. Expression of the TGF-β signaling mediator SMAD3 varied inversely with Weiss score, so that SMAD3 expression was lowest in the most malignant tumors. By contrast, SMAD2 expression was upregulated in most malignant tumors. Wnt pathway co-receptors LRP5 and LRP6 were predominantly expressed in benign adrenocortical tumors. In ACCs, expression of transcription factors GATA-6 and SF-1 correlated with that of their target gene INHA. Moreover, the diminished expression of GATA-6 and SF-1 in ACCs correlated with poor outcome. We conclude that the factors driving INHA expression are reduced in ACCs with poor outcome, implicating a role for INHA as a tumor suppressor in humans.

  19. Expression of Wnt and TGF-β pathway components and key adrenal transcription factors in adrenocortical tumors – association to carcinoma aggressiveness

    PubMed Central

    Parviainen, Helka; Schrade, Anja; Kiiveri, Sanne; Prunskaite-Hyyryläinen, Renata; Haglund, Caj; Vainio, Seppo; Wilson, David B.; Arola, Johanna; Heikinheimo, Markku

    2013-01-01

    Factors controlling benign and malignant adrenocortical tumorigenesis are largely unknown, but several mouse models suggest an important role for inhibin-alpha (INHA). To show that findings in the mouse are relevant to human tumors and clinical outcome, we investigated the expression of signaling proteins and transcription factors involved in the regulation of INHA in human tumor samples. Thirty-one adrenocortical tumor samples, including 13 adrenocortical carcinomas (ACCs), were categorized according to Weiss score, hormonal profile, and patient survival data and analyzed using immunohistochemistry and RT-PCR. Expression of the TGF-β signaling mediator SMAD3 varied inversely with Weiss score, so that SMAD3 expression was lowest in the most malignant tumors. By contrast, SMAD2 expression was upregulated in most malignant tumors. Wnt pathway co-receptors LRP5 and LRP6 were predominantly expressed in benign adrenocortical tumors. In ACCs, expression of transcription factors GATA-6 and SF-1 correlated with that of their target gene INHA. Moreover, the diminished expression of GATA-6 and SF-1 in ACCs correlated with poor outcome. We conclude that the factors driving INHA expression are reduced in ACCs with poor outcome, implicating a role for INHAas a tumor suppressor in humans. PMID:23866946

  20. Tumor necrosis factor alpha and interleukin-1 stimulate bone resorption in vivo as measured by urinary ( sup 3 H)tetracycline excretion from prelabeled mice

    SciTech Connect

    Koenig, A.M.; Muehlbauer, R.C.F.; Fleisch, H. )

    1988-12-01

    Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to stimulate bone resorption in vitro. We have now investigated whether these cytokines also cause a similar action when administered in vivo. This was made possible by the adaptation of a newly developed technique that enables the continual assessment of bone resorption in vivo in mice by measuring urinary excretion of {sup 3}H from ({sup 3}H)tetracycline-prelabeled animals. Experiments using maneuvers known to influence bone resorption, such as a change in dietary calcium or administration of parathyroid hormone or dichloromethylenebisphosphonate, indicate that the technique is reliable and sensitive in mice. Daily intravenous administration of either recombinant human or recombinant murine TNF-alpha, as well as subcutaneous administration of recombinant human IL-1 alpha, were found to stimulate bone resorption in a dose-dependent manner. The effect was maximal within 2 days. Thus, exogenous TNF-alpha and IL-1 alpha can stimulate bone resorption in vivo, suggesting that these cytokines may also exert a systemic effect on bone.

  1. Genetics Home Reference: desmoid tumor

    MedlinePlus

    ... in my area? Other Names for This Condition aggressive fibromatosis deep fibromatosis desmoid fibromatosis familial infiltrative fibromatosis ... catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). Am J Pathol. 1997 Aug; ...

  2. Molecular and genetic aspects of odontogenic tumors: a review

    PubMed Central

    Garg, Kavita; Chandra, Shaleen; Raj, Vineet; Fareed, Wamiq; Zafar, Muhammad

    2015-01-01

    Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/conttrollers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors. PMID:26221475

  3. Tumors of the anterior skull base.

    PubMed

    Ivan, Michael E; Han, Seunggu J; Aghi, Manish K

    2014-04-01

    A variety of histologic tumor types are present in the anterior skull base. Primary tumors of this area may be derived from the bone, paranasal sinuses, nasopharynx, dura, cranial nerves, pituitary gland and brain. Symptoms are caused mostly through mass effect but, if the tumor becomes aggressive, also through invasion. Selection of surgical approaches to the anterior skull base is based upon balancing risk reduction with maximizing extent of resection. Here we review a spectrum of neoplastic entities found in the anterior skull base in adults and discuss clinical and radiographic presentation, treatment options, and outcomes. Surgical resection remains the mainstay in treatment of these tumors, particularly in the hands of experienced surgeons exercising proper patient and case selection. PMID:24564556

  4. Strong Expression of Hypoxia-Inducible Factor-1α (HIF-1α) Is Associated with Axl Expression and Features of Aggressive Tumors in African Breast Cancer

    PubMed Central

    Nalwoga, Hawa; Ahmed, Lavina; Arnes, Jarle B.; Wabinga, Henry; Akslen, Lars A.

    2016-01-01

    Purpose Inhibition of hypoxia-inducible factor (HIF) and Axl receptor tyrosine kinase is being evaluated for targeted therapy in solid tumors. Both HIF-1α and Axl influence tumor growth and metastatic potential, and they have been linked to treatment failure in many cancers. However, there is a lack of reports on HIF-1α expression in African breast cancer, which has a poor prognosis, and novel treatment targets must therefore be established. Here, we aimed to evaluate HIF-1α in relation to Axl expression, angiogenesis markers, and other tumor characteristics in a series of African breast cancer. Methods Using immunohistochemistry, we examined 261 invasive breast cancers on tissue microarrays for HIF-1α and Axl as well as several other markers, and a subset of 185 cases had information on VEGF (vascular endothelial growth factor) expression, microvessel density (MVD), proliferating microvessel density (pMVD) and vascular proliferation index (VPI) for important comparisons. Results Strong HIF-1α expression was associated with increased Axl (p = 0.007), VEGF (p<0.0005), and p53 (p = 0.032) expression, as well as high tumor cell proliferation by Ki-67 (p = 0.006), and high tumor grade (p = 0.003). Tumors with strong HIF-1α expression had significantly higher MVD (p = 0.019) and higher pMVD (p = 0.027) than tumors with weak expression. Conclusions High HIF-1α expression is significantly associated with Axl and VEGF expression, and with markers of poor prognosis in this series of breast cancer, suggesting HIF-1α and Axl as potential therapeutic targets in African breast cancer. PMID:26760782

  5. High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

    PubMed

    Long, Elodie; Ilie, Marius; Bence, Coraline; Butori, Catherine; Selva, Eric; Lalvée, Salomé; Bonnetaud, Christelle; Poissonnet, Gilles; Lacour, Jean-Philippe; Bahadoran, Philippe; Brest, Patrick; Gilson, Eric; Ballotti, Robert; Hofman, Véronique; Hofman, Paul

    2016-06-01

    Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs.

  6. High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

    PubMed

    Long, Elodie; Ilie, Marius; Bence, Coraline; Butori, Catherine; Selva, Eric; Lalvée, Salomé; Bonnetaud, Christelle; Poissonnet, Gilles; Lacour, Jean-Philippe; Bahadoran, Philippe; Brest, Patrick; Gilson, Eric; Ballotti, Robert; Hofman, Véronique; Hofman, Paul

    2016-06-01

    Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs. PMID:26945789

  7. CONCEPT ANALYSIS: AGGRESSION

    PubMed Central

    Liu, Jianghong

    2006-01-01

    The concept of aggression is important to nursing because further knowledge of aggression can help generate a better theoretical model to drive more effective intervention and prevention approaches. This paper outlines a conceptual analysis of aggression. First, the different forms of aggression are reviewed, including the clinical classification and the stimulus-based classification. Then the manifestations and measurement of aggression are described. Finally, the causes and consequences of aggression are outlined. It is argued that a better understanding of aggression and the causal factors underlying it are essential for learning how to prevent negative aggression in the future. PMID:15371137

  8. Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth

    PubMed Central

    Adamo, Hanibal; Thysell, Elin; Jernberg, Emma; Stattin, Pär; Widmark, Anders; Wikström, Pernilla; Bergh, Anders

    2016-01-01

    Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer. PMID:27280718

  9. A Comparative Study of Bone Scan Findings and Serum Levels of Tumor Marker CA15-3 in Patients with Breast Carcinoma.

    PubMed

    Ghadge, Meera S; Naik, Purva P; Tiwari, Bijaynath P; Hegde, Ruprekha M; Matale, Tanaji J

    2012-01-01

    Breast cancer is one of the most frequent malignancies in the world. Available staging procedures to detect breast cancer are bone scan, chest X-ray, liver ultrasonography, computerized tomography, estimation of tumor markers like carbohydrate antigen (CA15-3) and carcino embryonic antigen. These procedures are expensive and may not be required in all cases. Out of 70 patients studied, 55 had normal CA15-3 and 15 had elevated levels of Ca15-3. Eight (14.5%) of the 55 patients with normal CA15-3 had abnormal bone scan. Fifteen patients had CA15-3 levels above the normal range and among these 9 (60%) had abnormal bone scan. While prime facie it would appear that a high level of CA15-3 correlate with abnormal bone scan, it is also true that the numbers are small at present and conclusions about the validity of CA15-3 as marker of bone metastasis may be premature.

  10. Benign ear cyst or tumor

    MedlinePlus

    Osteomas; Exostoses; Tumor - ear; Cysts - ear; Ear cysts; Ear tumors; Bony tumor of the ear canal ... bony tumors of the ear canal (exostoses and osteomas) are caused by excess growth of bone. Repeated ...

  11. Aggression in humans: what is its biological foundation?

    PubMed

    Albert, D J; Walsh, M L; Jonik, R H

    1993-01-01

    Although human aggression is frequently inferred to parallel aggression based on testosterone in nonprimate mammals, there is little concrete support for this position. High- and low-aggression individuals do not consistently differ in serum testosterone. Aggression does not change at puberty when testosterone levels increase. Aggression does not increase in hypogonadal males (or females) when exogenous testosterone is administered to support sexual activity. Similarly, there are no reports that aggression increases in hirsute females even though testosterone levels may rise to 200% above normal. Conversely, castration or antiandrogen administration to human males is not associated with a consistent decrease in aggression. Finally, changes in human aggression associated with neuropathology are not consistent with current knowledge of the neural basis of testosterone-dependent aggression. In contrast, human aggression does have a substantial number of features in common with defensive aggression seen in nonprimate mammals. It is present at all age levels, is displayed by both males and females, is directed at both males and females, and is not dependent on seasonal changes in hormone levels or experiential events such as sexual activity. As would be expected from current knowledge of the neural system controlling defensive aggression, aggression in humans increases with tumors in the medial hypothalamus and septal region, and with seizure activity in the amygdala. It decreases with lesions in the amygdala. The inference that human aggression has its roots in the defensive aggression of nonprimate mammals is in general agreement with evidence on the consistency of human aggressiveness over age, with similarities in male and female aggressiveness in laboratory studies, and with observations that some neurological disturbances contribute to criminal violence. This evidence suggests that human aggression has its biological roots in the defensive aggression of nonprimate

  12. Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients

    PubMed Central

    Vincenzi, Bruno; Gaeta, Laura; Pantano, Francesco; Russo, Antonio; Ortega, Cinzia; Porta, Camillo; Galluzzo, Sara; Armento, Grazia; La Verde, Nicla; Caroti, Cinzia; Treilleux, Isabelle; Ruggiero, Alessandro; Perrone, Giuseppe; Addeo, Raffaele; Clezardin, Philippe; Muda, Andrea Onetti; Tonini, Giuseppe

    2011-01-01

    Background Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. Materials and Methods We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. Results Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that “RANK-negative” and “RANK-positive” patients had a SDFS of 105.7 months (95% CI: 73.9–124.4) and 58.9 months (95% CI: 34.7–68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029). Conclusions This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients. PMID:21559440

  13. Mutation Analysis of H3F3A and H3F3B as a Diagnostic Tool for Giant Cell Tumor of Bone and Chondroblastoma.

    PubMed

    Cleven, Arjen H G; Höcker, Saskia; Briaire-de Bruijn, Inge; Szuhai, Karoly; Cleton-Jansen, Anne-Marie; Bovée, Judith V M G

    2015-11-01

    Specific H3F3A driver mutations and IDH2 mutations were recently described in giant cell tumor of bone (GCTB) and H3F3B driver mutations in chondroblastoma; these may be helpful as a diagnostic tool for giant cell-containing tumors of the bone. Using Sanger sequencing, we determined the frequency of H3F3A, H3F3B, IDH1, and IDH2 mutations in GCTBs (n=60), chondroblastomas (n=12), and other giant cell-containing tumors (n=24), including aneurysmal bone cyst, chondromyxoid fibroma, and telangiectatic osteosarcoma. To find an easy applicable marker for H3F3A mutation status, H3K36 trimethylation and ATRX expression were correlated with H3F3A mutations. In total, 69% of all GCTBs harbored an H3F3A (G34W/V) mutation compared with 0% of all other giant cell-containing tumors (P<0.001), whereas 70% of chondroblastomas showed an H3F3B (K36M) mutation compared with 0% of other giant cell-containing tumors (P<0.001). Diffuse H3K36 trimethylation positivity was more often seen in mutated H3F3A GCTBs compared with other giant cell-containing tumors (P=0.005). ATRX protein expression was not correlated with H3F3A mutation status. Hotspot mutations in IDH1 or IDH2 were absent. Our results show that H3F3A and H3F3B mutation analysis appears to be a highly specific, although less sensitive, diagnostic tool for the distinction of GCTB and chondroblastoma from other giant cell-containing tumors. Although H3K36 trimethylation and ATRX immunohistochemistry cannot be used as surrogate markers for H3F3A mutation status, mutations in H3F3A are associated with increased H3K36 trimethylation, suggesting that methylation at this residue may play a role in the etiology of the disease.

  14. Mutation Analysis of H3F3A and H3F3B as a Diagnostic Tool for Giant Cell Tumor of Bone and Chondroblastoma.

    PubMed

    Cleven, Arjen H G; Höcker, Saskia; Briaire-de Bruijn, Inge; Szuhai, Karoly; Cleton-Jansen, Anne-Marie; Bovée, Judith V M G

    2015-11-01

    Specific H3F3A driver mutations and IDH2 mutations were recently described in giant cell tumor of bone (GCTB) and H3F3B driver mutations in chondroblastoma; these may be helpful as a diagnostic tool for giant cell-containing tumors of the bone. Using Sanger sequencing, we determined the frequency of H3F3A, H3F3B, IDH1, and IDH2 mutations in GCTBs (n=60), chondroblastomas (n=12), and other giant cell-containing tumors (n=24), including aneurysmal bone cyst, chondromyxoid fibroma, and telangiectatic osteosarcoma. To find an easy applicable marker for H3F3A mutation status, H3K36 trimethylation and ATRX expression were correlated with H3F3A mutations. In total, 69% of all GCTBs harbored an H3F3A (G34W/V) mutation compared with 0% of all other giant cell-containing tumors (P<0.001), whereas 70% of chondroblastomas showed an H3F3B (K36M) mutation compared with 0% of other giant cell-containing tumors (P<0.001). Diffuse H3K36 trimethylation positivity was more often seen in mutated H3F3A GCTBs compared with other giant cell-containing tumors (P=0.005). ATRX protein expression was not correlated with H3F3A mutation status. Hotspot mutations in IDH1 or IDH2 were absent. Our results show that H3F3A and H3F3B mutation analysis appears to be a highly specific, although less sensitive, diagnostic tool for the distinction of GCTB and chondroblastoma from other giant cell-containing tumors. Although H3K36 trimethylation and ATRX immunohistochemistry cannot be used as surrogate markers for H3F3A mutation status, mutations in H3F3A are associated with increased H3K36 trimethylation, suggesting that methylation at this residue may play a role in the etiology of the disease. PMID:26457357

  15. A not so solitary fibrous tumor of the liver.

    PubMed

    Brochard, C; Michalak, S; Aubé, C; Singeorzan, C; Fournier, H-D; Laccourreye, L; Calès, P; Boursier, J

    2010-12-01

    Solitary fibrous tumor (SFT) is a rare neoplasm. Liver parenchyma is a rare location of SFT and, in this case, it usually follows a benign course. We report here the case of a 54-year-old man who presented a large SFT tumor of the right hepatic lobe. The tumor was surgically resected. Local recurrence occurred 6 years later as a 15 cm diameter liver tumor. Histological examination of the resected lesion showed features of an aggressive form of SFT. Two years later, the patient presented with complaints of neck pain and ensuing examinations revealed a tumor of the cranial base. A new surgical resection was performed and histological examination confirmed a metastasis of the SFT. Few weeks later, the patient presented an irreducible psoitis due to an iliac bone metastasis. He died within 1 month.

  16. Aggressive behavior problems.

    PubMed

    Beaver, B V

    1986-12-01

    Accurate diagnosis of the cause of aggression in horses is essential to determining the appropriate course of action. The affective forms of aggression include fear-induced, pain-induced, intermale, dominance, protective, maternal, learned, and redirected aggressions. Non-affective aggression includes play and sex-related forms. Irritable aggression and hypertestosteronism in mares are medical problems, whereas genetic factors, brain dysfunction, and self-mutilation are also concerns. PMID:3492250

  17. Impact of Local Management on Long-Term Outcomes in Ewing Tumors of the Pelvis and Sacral Bones: University of Florida Experience

    SciTech Connect

    Indelicato, Daniel J. Keole, Sameer R.; Shahlaee, Amir H.; Gibbs, C. Parker; Scarborough, Mark T.; Marcus, Robert B.

    2008-09-01

    Purpose: This retrospective analysis describes our 35-year experience with respect to disease control and functional status. Patients and Methods: Thirty-five patients with localized Ewing tumors of the pelvis and sacral bones were treated from 1970 to 2005. Twenty-six patients were treated with definitive radiotherapy (RT), and 9 patients were treated with combined local therapy in the form of surgery + RT. The median RT dose was 55.2 Gy. The patients who received RT alone were more likely to be older men with larger tumors exhibiting soft-tissue extension. Patients in the definitive RT group were more likely to receive etoposide and ifosfamide or undergo bone marrow transplant. Median potential follow-up was 19.4 years. Results: The 15-year actuarial cause-specific survival, freedom from relapse rate, and local control rates were 26% vs. 76% (p = 0.016), 28% vs. 78% (p = 0.015), and 64% vs. 100% (p = 0.087), respectively, for patients treated with definitive RT and combined therapy. Overall, tumors <8 cm had significantly better cause-specific survival, but this was unrelated to local control. The median Toronto Extremity Salvage Score for the definitive RT and combined therapy groups were 99 and 94, respectively (p = 0.19). Seven definitive RT patients (27%) had serious complications. Conclusion: Combined modality local therapy should be considered if pelvic Ewing tumors are resectable. However, because of the extent of local disease, most patients have unresectable or partially resectable tumors and therefore require RT in some capacity. For this reason, innovative RT strategies are needed to improve long-term disease outcomes and minimize side effects while maintaining an acceptable functional result.

  18. Interleukin-1 and tumor necrosis factor antagonists attenuate ethanol-induced inhibition of bone formation in a rat model of distraction osteogenesis.

    PubMed

    Perrien, Daniel S; Brown, Elizabeth C; Fletcher, Terry W; Irby, David J; Aronson, James; Gao, Guan G; Skinner, Robert A; Hogue, William R; Feige, Ulrich; Suva, Larry J; Ronis, Martin J J; Badger, Thomas M; Lumpkin, Charles K

    2002-12-01

    Chronic ethanol exposure inhibits rapid bone formation during distraction osteogenesis (DO; fracture and limb lengthening) and decreases volumetric bone mineral density (BMD) in a model of intragastric dietary infusion [total enteral nutrition (TEN)] in the rat. The hypothesis tested herein was that overexpression of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha mediates these deleterious effects of ethanol on the rat skeleton. Two studies (study 1, female rats; study 2, male rats) were performed to test the potential protective effects of the IL-1 and TNF antagonists: IL-1 receptor antagonist (IL-1ra) and 30-kDa polyethylene glycol-conjugated soluble TNF receptor type 1 (sTNFR1). All rats were infused with a liquid diet +/- ethanol (EtOH) and underwent tibial fractures and DO. During distraction, the animals received a combination of IL-1ra (1.8-2.0 mg/kg/day) and sTNFR1 (2.0 mg/kg/2 days) or vehicle. A comparison of distracted tibial histological sections demonstrated 1) significant antagonist-related increases in bone column formation over the EtOH controls (studies 1 and 2), and 2) restoration of new bone equivalent to that of the TEN controls (study 2). In contrast, examination of intact proximal tibial metaphyses by peripheral quantitative computerized tomography revealed decreases in volumetric BMD of both EtOH control and EtOH antagonist groups (study 2). These results demonstrate that short-term systemic administration of IL-1 and TNF antagonists together protect rapid bone formation during DO from the deleterious effects of chronic ethanol but are ineffective in regard to intact bone homeostasis.

  19. NF1 frameshift mutation (c.6520_6523delGAGA) association with nervous system tumors and bone abnormalities in a Chinese patient with neurofibromatosis type 1.

    PubMed

    Su, S Y; Zhou, X; Pang, X M; Chen, C Y; Li, S H; Liu, J L

    2016-01-01

    Neurofibromatosis type 1, also known as NF1 or von Recklinghausen's disease, is a common neurocutaneous syndrome that presents with multiple café-au-lait patches, skinfold freckling, dermatofibromas, neurofibromas, and Lisch nodules. The mutations of the gene NF1, encoding the protein neurofibromin, have been identified as the cause of this disease. Here, we report a clinical and molecular study of a Chinese patient with multiple café-au-lait skin freckles, dermatofibroma, central and peripheral nervous system tumors, and bone abnormalities attributed to NF1. The patient showed >6 café-au-lait spots on the body and multiple dermatofibromas. A brain glioma and multiple nerve sheath tumors inside and outside the vertebral canal were identified by magnetic resonance imaging, which also showed multiple intercostal nerve schwannomas and hydrocephalies above the cerebellar tentorium. Talipes equinus was also apparent. A mutation analysis of the NF1 gene revealed a novel frameshift mutation in exon 43, consisting of a heterozygous deletion of four nucleotides (GAGA) between positions 6520 and 6523. No NF1 mutations were detected in the patient's parents or younger brother. These results extend the list of known mutations in this gene. The absence of the NF1 mutation in the healthy family members suggests that it is responsible for the NF1 phenotype. To our knowledge, this frameshift mutation represents a novel NF1 case, and may be associated with nervous system tumors and bone abnormalities. PMID:27173220

  20. Mandibular and para-mandibular tumors in children. Report of 16 cases.

    PubMed

    Kozlowski, K; Masel, J; Sprague, P; Tamaela, L; Kan, A; Middleton, R

    1981-01-01

    Sixteen cases of mandibular tumors or paramandibular soft tissue tumors with mandibular involvement are reported. These include such rare mandibular tumors or tumor-like conditions as melanotic progonoma, intraosseous haematoma secondary to von Willebrand's disease, post-irradiation osteosarcoma, monostotic eosinophilic granuloma, aneurysmal bone cyst and osseous hemangiopericytoma. Three cases of cherubism, one of fibrous dysplasia or aggressive fibromatosis and one of central giant cell reparative granuloma are also reported. The soft tissue tumors comprise round cell sarcoma, parotid adeno-carcinoma with generalised metastases, embryonal rhabdo-myo-sarcoma, neuro-fibro-sarcoma and congenital cystic hygroma. In all the cases the disease was well advanced when the patient presented for X-ray examination. The specific X-ray diagnosis of mandibular and paramandibular tumors in childhood is more difficult than that of similar tumors in other parts of the body. PMID:6275331

  1. General Information about Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  2. Treatment Option Overview (Pituitary Tumors)

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  3. Radiation-induced systemic and local bone tumors: Two types of late effects with possible different origins?

    SciTech Connect

    Mueller, W.A.; Luz, A.; Linzner, U.

    1994-06-01

    Bone sarcomas may be induced throughout the skeleton (systemic) in mice by relatively low internal {alpha}-particle doses that are distributed over the whole skeleton. The induction of local (periosteal) bone sarcomas after paratibial deposition of insoluble radiocolloids required much higher doses, and in addition high energies of emitted particles. Paratibial deposition of {alpha}-particle-emitting radiocolloids of {sup 227}Th and {sup 228}Th resulted in formation of both local and systemic bone sarcomas. The latter were most probably induced by the released radium daughters of the thorium isotopes and were distributed about the skeleton. Paratibial injections with {beta}-particle emitters {sup 144}Ce+{sup 144}Pr (29 kBq per mouse) showed an incidence of local bone sarcomas of more than 80%. An estimation of the local effective doses led to values of more than 1000 Gy for the {beta}-particle emitter {sup 144}Ce and around 150 Gy for the thorium isotopes. Thus induction of local bone sarcomas required doses considerably greater than those needed for systemic bone sarcomas. The local induction of bone sarcomas has been reported for high-energy {beta} particles using similar high doses of {sup 144}Ce+{sup 144}Pr in rats and for external {sup 90}Sr+{sup 90}Y irradiation in mice. We conclude that the processes involved in the induction of local and systemic bone sarcomas by radiation may be quite different. 35 refs., 1 fig., 3 tabs.

  4. Hybrid Single-Photon Emission Computed Tomography/Computed Tomography Imaging Features of Tumoral Calcinosis in Technetium-99m Methylene Diphosphonate Bone Scintigraphy

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusamy; Asokumar, Premkumar; Malaikkal, Anjali; Mohanan, Vyshakh; Shinto, Ajit Sugunan

    2015-01-01

    Tumoral calcinosis (TC) is an uncommon ectopic calcification syndrome. TC is a benign condition characterized by the presence of large calcific soft tissue deposits occurring predominantly in a periarticular location. It generally occurs as a complication of renal dialysis or trauma, and is rarely seen in familial and sporadic cases. Bone scintigraphy is a sensitive method for diagnosing TC. We report a case of year old female with. She underwent bone scintigraphy to see the sites of involvement, which showed intense foci of tracer activity in soft tissue in bilateral thigh and gluteal region. Hybrid single-photon emission computed tomography/computed tomography of the pelvis and thigh localized tracer uptake to the calcification in the gluteal and thigh region. PMID:26097427

  5. Hybrid Single-Photon Emission Computed Tomography/Computed Tomography Imaging Features of Tumoral Calcinosis in Technetium-99m Methylene Diphosphonate Bone Scintigraphy.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Asokumar, Premkumar; Malaikkal, Anjali; Mohanan, Vyshakh; Shinto, Ajit Sugunan

    2015-01-01

    Tumoral calcinosis (TC) is an uncommon ectopic calcification syndrome. TC is a benign condition characterized by the presence of large calcific soft tissue deposits occurring predominantly in a periarticular location. It generally occurs as a complication of renal dialysis or trauma, and is rarely seen in familial and sporadic cases. Bone scintigraphy is a sensitive method for diagnosing TC. We report a case of year old female with. She underwent bone scintigraphy to see the sites of involvement, which showed intense foci of tracer activity in soft tissue in bilateral thigh and gluteal region. Hybrid single-photon emission computed tomography/computed tomography of the pelvis and thigh localized tracer uptake to the calcification in the gluteal and thigh region.

  6. Dietary zinc deficiency induces oxidative stress and promotes tumor necrosis factor-α- and interleukin-1β-induced RANKL expression in rat bone

    PubMed Central

    Suzuki, Takako; Katsumata, Shin-ichi; Matsuzaki, Hiroshi; Suzuki, Kazuharu

    2016-01-01

    We investigated the effects of dietary zinc deficiency on oxidative stress and bone metabolism. Four-week-old male Wistar rats were randomly assigned to one of three groups for 4 weeks: a zinc-adequate group (30 ppm); a zinc-deficient group (1 ppm); and a pair-fed group (30 ppm) that was pair-fed to the zinc-deficient group. The iron content and the thiobarbituric acid reactive substance level in bone were higher in the zinc-deficient group than in the zinc-adequate and pair-fed groups. The mRNA expression level of osteoblastogenesis-related genes such as bone morphogenetic protein 2 and runt-related transcription factor 2 was lower in the zinc-deficient group than in the zinc-adequate and pair-fed groups. In contrast, the mRNA expression levels of tumor necrosis factor-α, interleukin-1β and osteoclastogenesis-related genes such as receptor activator of nuclear factor-κB ligand and nuclear factor of activated T cells cytoplasmic 1 were higher in the zinc-deficient group than in the zinc-adequate and pair-fed groups. These findings suggested that dietary zinc deficiency reduced osteoblastogenesis via a decrease in the expression of bone morphogenetic protein 2 and increased osteoclastogenesis via enhancement of the expression of receptor for activator of nuclear factor-κB ligand induced by oxidative stress-stimulated tumor necrosis factor-α and interleukin-1β. PMID:27013778

  7. Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

    ClinicalTrials.gov

    2015-12-01

    Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

  8. BRCA-associated protein 1 mutant cholangiocarcinoma: an aggressive disease subtype

    PubMed Central

    Al-Shamsi, Humaid O.; Anand, Deepa; Shroff, Rachna T.; Jain, Apurva; Zuo, Mingxin; Conrad, Claudius; Vauthey, Jean-Nicolas

    2016-01-01

    Background BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined. Methods The records of CCA patients who underwent next-generation sequencing (NGS) were reviewed, and data on clinical, histopathological, genetic, and radiological features; response to therapy; time to progression; and survival were analyzed. Results Twenty-two cases of BAP1-mutation associated CCA were diagnosed from January 1, 2009, to February 1, 2015, at our center. Twenty patients had intrahepatic CCA and two had extrahepatic CCA. Tumor sizes (largest dimension) ranged from 2 to 16 cm (mean, 8.5 cm). Twelve patients had tumors that were poorly differentiated. Majority of the patients had advanced disease at presentation and 13 had bone metastases. Thirteen patients (59%) experienced rapidly progressive disease following primary therapy (chemotherapy or surgical resection). The mean time to tumor progression was 3.8 months after the first line chemotherapy. Conclusions BAP1 mutation in CCA may be associated with aggressive disease and poor response to standard therapies. Therefore, BAP1-targeted therapies need to be investigated. PMID:27563445

  9. PET/CT Helps Downgrade an Aggressive-Appearing Rib Mass to a Probable Benign Lesion in a 9-Year-Old Girl.

    PubMed

    Ghaderi, Kimeya F; Yoo, Don C; Hart, Jesse

    2016-03-01

    We present a case of a 9-year-old girl with no significant medical history who developed acute onset of shortness of breath and upper chest pain during cheerleading practice. Laboratory results and physical examination were unremarkable. Chest radiograph and chest CT showed an expansile lytic aggressive-appearing mass within the left sixth rib. Subsequent F-FDG PET/CT showed a left sixth rib lesion that was not hypermetabolic and appeared benign. Biopsy yielded a diagnosis of enchondroma, a benign intramedullary tumor that accounts for 24% of all bone tumors in children as well as adolescents.

  10. IDO is highly expressed in breast cancer and breast cancer-derived circulating microvesicles and associated to aggressive types of tumors by in silico analysis.

    PubMed

    Isla Larrain, M T; Rabassa, M E; Lacunza, E; Barbera, A; Cretón, A; Segal-Eiras, A; Croce, M V

    2014-07-01

    Indoleamine-2,3-dioxygenase (IDO) has been established as a normal mechanism of peripheral tolerance and immunosuppression. Besides, malignant tumors release microvesicles (MV) related with tumor dissemination. The aims of this study were to determine the expression of IDO in breast cancer and circulating microvesicles from breast cancer patients and to perform an in silico analysis to find genes co-expressed to IDO. One hundred and twenty-two tissue and serum breast samples (91 malignant, 21 benign, and 10 normal), and MCF7, MDA-MB-231, and T47D breast cancer cell lines were included. Standard immunohistochemistry (IHC), immunocytochemistry (ICC), Western blot (WB), and RT-PCR were employed. Microvesicle isolation from plasma samples was obtained by serial centrifugation and ultracentrifugation. By IHC, 60 % breast cancer, 43 % benign, and 20 % normal samples were positive. Significant differences were found among normal, benign, and malignant samples. Breast cancer stages I, II, and III expressed IDO in 42, 66, and 71 % of samples, respectively, while breast cancer cell lines also reacted; by WB, 9/25 microvesicles fractions showed bands at 42 kD. In silico analysis of IDO 1 gene expression in breast cancer showed its association with several genes related to immune response and apoptosis. Moreover, IDO and co-expressed genes were found predominately in basal and erbB2 subtypes. The cumulative data indicate a high expression of IDO in breast cancer which increased with higher stages. Furthermore, IDO was found in association with circulating breast cancer MV, while experimental and in silico gene expression revealed that IDO was mainly expressed in a triple-negative subgroup.

  11. Properties of immature myeloid progenitors with nitric-oxide-dependent immunosuppressive activity isolated from bone marrow of tumor-free mice.

    PubMed

    Forghani, Parvin; Harris, Wayne; Giver, Cynthia R; Mirshafiey, Abbas; Galipeau, Jacques; Waller, Edmund K

    2013-01-01

    Myeloid derived suppressor cells (MDSCs) from tumor-bearing mice are important negative regulators of anti-cancer immune responses, but the role for immature myeloid cells (IMCs) in non-tumor-bearing mice in the regulation of immune responses are poorly described. We studied the immune-suppressive activity of IMCs from the bone marrow (BM) of C57Bl/6 mice and the mechanism(s) by which they inhibit T-cell activation and proliferation. IMCs, isolated from BM by high-speed FACS, inhibited mitogen-induced proliferation of CD4(+) and CD8(+) T-cells in vitro. Cell-to-cell contact of T-cells with viable IMCs was required for suppression. Neither neutralizing antibodies to TGFβ1, nor genetic disruption of indolamine 2,3-dioxygenase, abrogated IMC-mediated suppressive activity. In contrast, suppression of T-cell proliferation was absent in cultures containing IMCs from interferon-γ (IFN-γ) receptor KO mice or T-cells from IFN-γ KO mice (on the C57Bl/6 background). The addition of NO inhibitors to co-cultures of T-cells and IMC significantly reduced the suppressive activity of IMCs. IFN-γ signaling between T-cells and IMCs induced paracrine Nitric Oxide (NO) release in culture, and the degree of inhibition of T-cell proliferation was proportional to NO levels. The suppressive activity of IMCs from the bone marrow of tumor-free mice was comparable with MDSCs from BALB/c bearing mice 4T1 mammary tumors. These results indicate that IMCs have a role in regulating T-cell activation and proliferation in the BM microenvironment.

  12. Combination Short-Course Preoperative Irradiation, Surgical Resection, and Reduced-Field High-Dose Postoperative Irradiation in the Treatment of Tumors Involving the Bone

    SciTech Connect

    Wagner, Timothy D. Kobayashi, Wendy; Dean, Susan; Goldberg, Saveli I.; Kirsch, David G.; Suit, Herman D.; Hornicek, Francis J.; Pedlow, Francis X.; Raskin, Kevin A.; Springfield, Dempsey S.; Yoon, Sam S.; Gebhardt, Marc C.; Mankin, Henry J.; DeLaney, Thomas F.

    2009-01-01

    Purpose: To assess the feasibility and outcomes of combination short-course preoperative radiation, resection, and reduced-field (tumor bed without operative field coverage) high-dose postoperative radiation for patients with solid tumors mainly involving the spine and pelvis. Methods and Materials: Between 1982 and 2006, a total of 48 patients were treated using this treatment strategy for solid tumors involving bone. Radiation treatments used both photons and protons. Results: Of those treated, 52% had chordoma, 31% had chondrosarcoma, 8% had osteosarcoma, and 4% had Ewing's sarcoma, with 71% involving the pelvis/sacrum and 21% elsewhere in the spine. Median preoperative dose was 20 Gy, with a median of 50.4 Gy postoperatively. With 31.8-month median follow-up, the 5-year overall survival (OS) rate is 65%; 5-year disease-free survival (DFS) rate, 53.8%; and 5-year local control (LC) rate, 72%. There were no significant differences in OS, DFS, and LC according to histologic characteristics. Between primary and recurrent disease, there was no significant difference in OS rates (74.4% vs. 51.4%, respectively; p = 0.128), in contrast to DFS (71.5% vs. 18.3%; p = 0.0014) and LC rates (88.9% vs. 30.9%; p = 0.0011) favoring primary disease. After resection, 10 patients experienced delayed wound healing that did not significantly impact on OS, DFS, or LC. Conclusion: This approach is promising for patients with bone sarcomas in which resection will likely yield close/positive margins. It appears to inhibit tumor seeding with an acceptable rate of wound-healing complications. Dose escalation is accomplished without high-dose preoperative radiation (likely associated with higher rates of acute wound healing delays) or large-field postoperative radiation only (likely associated with late normal tissue toxicity). The LC and DFS rates are substantially better for patients with primary than recurrent sarcomas.

  13. Interaction of platelet-derived autotaxin with tumor integrin αVβ3 controls metastasis of breast cancer cells to bone.

    PubMed

    Leblanc, Raphael; Lee, Sue-Chin; David, Marion; Bordet, Jean-Claude; Norman, Derek D; Patil, Renukadevi; Miller, Duane; Sahay, Debashish; Ribeiro, Johnny; Clézardin, Philippe; Tigyi, Gabor J; Peyruchaud, Olivier

    2014-11-13

    Autotaxin (ATX), through its lysophospholipase D activity controls physiological levels of lysophosphatidic acid (LPA) in blood. ATX is overexpressed in multiple types of cancers, and together with LPA generated during platelet activation promotes skeletal metastasis of breast cancer. However, the pathophysiological sequelae of regulated interactions between circulating LPA, ATX, and platelets remain undefined in cancer. In this study, we show that ATX is stored in α-granules of resting human platelets and released upon tumor cell-induced platelet aggregation, leading to the production of LPA. Our in vitro and in vivo experiments using human breast cancer cells that do not express ATX (MDA-MB-231 and MDA-B02) demonstrate that nontumoral ATX controls the early stage of bone colonization by tumor cells. Moreover, expression of a dominant negative integrin αvβ3-Δ744 or treatment with the anti-human αvβ3 monoclonal antibody LM609, completely abolished binding of ATX to tumor cells, demonstrating the requirement of a fully active integrin αvβ3 in this process. The present results establish a new mechanism for platelet contribution to LPA-dependent metastasis of breast cancer cells, and demonstrate the therapeutic potential of disrupting the binding of nontumor-derived ATX with the tumor cells for the prevention of metastasis.

  14. Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone.

    PubMed

    Behjati, Sam; Tarpey, Patrick S; Presneau, Nadège; Scheipl, Susanne; Pillay, Nischalan; Van Loo, Peter; Wedge, David C; Cooke, Susanna L; Gundem, Gunes; Davies, Helen; Nik-Zainal, Serena; Martin, Sancha; McLaren, Stuart; Goody, Victoria; Goodie, Victoria; Robinson, Ben; Butler, Adam; Teague, Jon W; Halai, Dina; Khatri, Bhavisha; Myklebost, Ola; Baumhoer, Daniel; Jundt, Gernot; Hamoudi, Rifat; Tirabosco, Roberto; Amary, M Fernanda; Futreal, P Andrew; Stratton, Michael R; Campbell, Peter J; Flanagan, Adrienne M

    2013-12-01

    It is recognized that some mutated cancer genes contribute to the development of many cancer types, whereas others are cancer type specific. For genes that are mutated in multiple cancer classes, mutations are usually similar in the different affected cancer types. Here, however, we report exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases of chondroblastoma (95%), we found p.Lys36Met alterations predominantly encoded in H3F3B, which is one of two genes for histone H3.3. In contrast, in 92% (49/53) of giant cell tumors of bone, we found histone H3.3 alterations exclusively in H3F3A, leading to p.Gly34Trp or, in one case, p.Gly34Leu alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding p.Lys27Met and p.Gly34Arg or p.Gly34Val alterations in childhood brain tumors, a remarkable picture of tumor type specificity for histone H3.3 driver alterations emerges, indicating that histone H3.3 residues, mutations and genes have distinct functions.

  15. Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice.

    PubMed Central

    Kitazawa, R; Kimble, R B; Vannice, J L; Kung, V T; Pacifici, R

    1994-01-01

    To investigate the contribution of IL-1, IL-6, and TNF to the increased osteoclastogenesis induced by estrogen deficiency, ovariectomized (ovx) mice were treated with either IL-1 receptor antagonist (IL-1ra), a competitive inhibitor of IL-1, TNF binding protein (TNFbp), an inhibitor of TNF, or the anti-IL-6 antibody (Ab) 20F3 for the first 2 wk after surgery. ovx increased the bone marrow cells secretion of IL-1 and TNF, but not IL-6, and the formation of TRAP-positive osteoclast-like multinucleated cells (MNCs) in bone marrow cultures treated with 1,25(OH)2D3. The increase in MNC formation induced by ovx was prevented by in vivo treatment with either 17 beta estradiol, IL-1ra, TNFbp, or anti-IL-6 Ab. However, the percent change in MNC formation induced by the anti-IL-6 Ab was similar in ovx and sham-operated animals, whereas IL-1ra and TNFbp were effective only in ovx mice. MNC formation was also decreased by in vitro treatment of bone marrow cultures with IL-1ra and TNFbp, but not with anti-IL-6 Ab. Ovx also increased bone resorption in vivo and in vitro, as assessed by the urinary excretion of pyridinoline cross links and the formation of resorption pits, respectively. IL-1ra, TNFbp and estrogen decreased bone resorption in vivo and in vitro whereas the anti-IL-6 Ab inhibited bone resorption in vitro but not in vivo. In conclusion, these data indicate that IL-1 and TNF play a direct role in mediating the effects of ovx on osteoclastogenesis and bone resorption. The data also suggest that IL-6 is not essential for increasing bone resorption in the early postovariectomy period. Images PMID:7989596

  16. Juvenile ossifying fibroma of the maxilla: a rare aggressive case in a young patient.

    PubMed

    Cicciù, Marco; Herford, Alan Scott; Juodžbalys, Gintaras; Cicciù, Domenico

    2013-01-01

    Juvenile Ossifying Fibroma may be considered a fibro-osseous tumor which usually occurs in young children and arises in craniofacial bones, most commonly seen in the maxilla. This kind of lesion usually occurs in young patients and because of its aggrssive nature, clinicians should try to recognize it as soon as possible in order to avoid future functional and aesthetics problems. Moreover, untreated cases over a long period may result in large bone defects during the surgical removal of the lesion. Here reported is a case of a six-year-old girl who developed a rare aggressive fibroma localized in the right upper jaw. The clinical, radiographic and histopathologic findings, plus differential diagnoses of the case and treatement options are also presented. PMID:23771389

  17. The role of TMPRSS2:ERG in molecular stratification of PCa and its association with tumor aggressiveness: a study in Brazilian patients.

    PubMed

    Eguchi, Flávia C; Faria, Eliney F; Scapulatempo Neto, Cristovam; Longatto-Filho, Adhemar; Zanardo-Oliveira, Cleyton; Taboga, Sebastião R; Campos, Silvana G P

    2014-07-10

    Recurrent gene fusions between the genes TMPRSS2 and ERG have been described in prostate cancer (PCa) and are found in 27% to 79% of radical prostatectomy. This fusion transcription results in ERG overexpression, which can be detected by immunohistochemistry (IHC) and provide a potential diagnostic marker for PCa. Three tissue microarrays (TMAs) containing samples from 98 patients with PCa and one TMA of 27 samples from individuals without PCa were tested for ERG immunostaining, and the presence of TMPRSS2:ERG transcripts was confirmed by quantitative real time PCR (qRT-PCR). The results showed that 46.9% of tumors tested positive for ERG immunostaining, and this finding was consistent with the results of qRT-PCR testing (k = 0.694, p < 0.001). IHC had a specificity of 83.3% and a sensitivity of 81% in detecting TMPRSS2:ERG fusion. Patients with PSA < 4.0 ng/mL showed positive immunoreactivity for ERG (p = 0.031). Kaplan-Meier analysis suggested that ERG expression did not influence the time of biochemical recurrence. This study demonstrates that both IHC and qRT-PCR are useful tools in detecting TMPRSS2:ERG fusions. A correlation between ERG expression and clinical and pathological parameters was not found, but the frequency, specificity and recurrence of ERG in PCa suggests that it may be a potential adjunct diagnostic tool.

  18. Targeting Yes-associated Protein with Evolved Peptide Aptamers to Disrupt TGF-β Signaling Pathway: Therapeutic Implication for Bone Tumor.

    PubMed

    Ji, Wei-Ping; Dong, Yang

    2015-11-01

    The binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors is an important event in activating transforming growth factor-β (TGF-β) signaling pathway, which is involved in the tumorigenicity and metastasis of bone tumor. Design of peptide aptamers to disrupt YAPSmad interaction has been established as a promising approach for bone tumor therapy. Here, an evolution strategy was used to optimize Smad-derived peptides for high potency binding to YAP WW2 domain, resulting in an improved peptide population, from which those high-scoring candidates were characterized rigorously using molecular dynamics (MD) simulations and interaction free energy calculations. With the computational protocol we were able to generate a number of potential domain binders, which were then substantiated by using fluorescence spectroscopy assay. Subsequently, the complex structure of YAP WW2 domain with a high-affinity peptide was modeled and examined in detail, which was then used to guide structure-based peptide optimization to obtain several strong domain binders. Structural and energetic analysis revealed that electrostatic complementarity is primarily responsible for domainpeptide recognition, while other nonbonded interactions such as hydrogen bonding and salt bridges can contribute significantly to the recognition specificity. PMID:27491038

  19. Targeting Yes-associated Protein with Evolved Peptide Aptamers to Disrupt TGF-β Signaling Pathway: Therapeutic Implication for Bone Tumor.

    PubMed

    Ji, Wei-Ping; Dong, Yang

    2015-11-01

    The binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors is an important event in activating transforming growth factor-β (TGF-β) signaling pathway, which is involved in the tumorigenicity and metastasis of bone tumor. Design of peptide aptamers to disrupt YAPSmad interaction has been established as a promising approach for bone tumor therapy. Here, an evolution strategy was used to optimize Smad-derived peptides for high potency binding to YAP WW2 domain, resulting in an improved peptide population, from which those high-scoring candidates were characterized rigorously using molecular dynamics (MD) simulations and interaction free energy calculations. With the computational protocol we were able to generate a number of potential domain binders, which were then substantiated by using fluorescence spectroscopy assay. Subsequently, the complex structure of YAP WW2 domain with a high-affinity peptide was modeled and examined in detail, which was then used to guide structure-based peptide optimization to obtain several strong domain binders. Structural and energetic analysis revealed that electrostatic complementarity is primarily responsible for domainpeptide recognition, while other nonbonded interactions such as hydrogen bonding and salt bridges can contribute significantly to the recognition specificity.

  20. Tumor necrosis factor alpha represses bone morphogenetic protein (BMP) signaling by interfering with the DNA binding of Smads through the activation of NF-kappaB.

    PubMed

    Yamazaki, Masato; Fukushima, Hidefumi; Shin, Masashi; Katagiri, Takenobu; Doi, Takahiro; Takahashi, Tetsu; Jimi, Eijiro

    2009-12-18

    Bone morphogenetic proteins (BMPs) induce not only bone formation in vivo but also osteoblast differentiation of mesenchymal cells in vitro. Tumor necrosis factor alpha (TNFalpha) inhibits both osteoblast differentiation and bone formation induced by BMPs. However, the molecular mechanisms of these inhibitions remain unknown. In this study, we found that TNFalpha inhibited the alkaline phosphatase activity and markedly reduced BMP2- and Smad-induced reporter activity in MC3T3-E1 cells. TNFalpha had no effect on the phosphorylation of Smad1, Smad5, and Smad8 or on the nuclear translocation of the Smad1-Smad4 complex. In p65-deficient mouse embryonic fibroblasts, overexpression of p65, a subunit of NF-kappaB, inhibited BMP2- and Smad-induced reporter activity in a dose-dependent manner. Furthermore, this p65-mediated inhibition of BMP2- and Smad-responsive promoter activity was restored after inhibition of NF-kappaB by the overexpression of the dominant negative IkappaBalpha. Although TNFalpha failed to affect receptor-dependent formation of the Smad1-Smad4 complex, p65 associated with the complex. Chromatin immunoprecipitation and electrophoresis mobility shift assays revealed that TNFalpha suppressed the DNA binding of Smad proteins to the target gene. Importantly, the specific NF-kappaB inhibitor, BAY11-7082, abolished these phenomena. These results suggest that TNFalpha inhibits BMP signaling by interfering with the DNA binding of Smads through the activation of NF-kappaB.

  1. Leptin increases prostate cancer aggressiveness.

    PubMed

    López Fontana, Constanza M; Maselli, María E; Pérez Elizalde, Rafael F; Di Milta Mónaco, Nicolás A; Uvilla Recupero, Ana L; López Laur, José D

    2011-12-01

    Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.

  2. Assessment of Treatment Response by Total Tumor Volume and Global Apparent Diffusion Coefficient Using Diffusion-Weighted MRI in Patients with Metastatic Bone Disease: A Feasibility Study

    PubMed Central

    Blackledge, Matthew D.; Collins, David J.; Tunariu, Nina; Orton, Matthew R.; Padhani, Anwar R.; Leach, Martin O.; Koh, Dow-Mu

    2014-01-01

    We describe our semi-automatic segmentation of whole-body diffusion-weighted MRI (WBDWI) using a Markov random field (MRF) model to derive tumor total diffusion volume (tDV) and associated global apparent diffusion coefficient (gADC); and demonstrate the feasibility of using these indices for assessing tumor burden and response to treatment in patients with bone metastases. WBDWI was performed on eleven patients diagnosed with bone metastases from breast and prostate cancers before and after anti-cancer therapies. Semi-automatic segmentation incorporating a MRF model was performed in all patients below the C4 vertebra by an experienced radiologist with over eight years of clinical experience in body DWI. Changes in tDV and gADC distributions were compared with overall response determined by all imaging, tumor markers and clinical findings at serial follow up. The segmentation technique was possible in all patients although erroneous volumes of interest were generated in one patient because of poor fat suppression in the pelvis, requiring manual correction. Responding patients showed a larger increase in gADC (median change = +0.18, range = −0.07 to +0.78×10−3 mm2/s) after treatment compared to non-responding patients (median change = −0.02, range = −0.10 to +0.05×10−3 mm2/s, p = 0.05, Mann-Whitney test), whereas non-responding patients showed a significantly larger increase in tDV (median change = +26%, range = +3 to +284%) compared to responding patients (median change = −50%, range = −85 to +27%, p = 0.02, Mann-Whitney test). Semi-automatic segmentation of WBDWI is feasible for metastatic bone disease in this pilot cohort of 11 patients, and could be used to quantify tumor total diffusion volume and median global ADC for assessing response to treatment. PMID:24710083

  3. Primitive Neuroectodermal Tumor of the Stomach: A Case Report.

    PubMed

    Song, Min Jeong; An, Soyeon; Lee, Seung Soo; Kim, Beom Su; Kim, Jihun

    2016-09-01

    Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is a highly aggressive small round cell tumor that mainly occurs in the bone or soft tissue of children or young adults but is extremely rare in the stomach. A 55-year-old man presented with melena and anemia. On endoscopy, an ulcerofungating mass was observed in the high body and total gastrectomy was performed. Histologically, the mass consisted of small round cells with scanty cytoplasm and inconspicuous nucleoli. They often formed perivascular pseudorosettes and multinucleated giant cells were frequently observed. The tumor cells strongly expressed CD99, FLI1, and chromogranin and weakly expressed synaptophysin and CD56. EWS-FLI1 fusion transcript was confirmed by reverse transcription-polymerase chain reaction. ES/PNET is frequently misdiagnosed because of its similarity with small cell carcinoma. Although gastric ES/PNET is very rare, it should be included in differential diagnoses of small round cell tumor in the stomach. PMID:27006299

  4. Surgery for Bone Cancer

    MedlinePlus

    ... heat. The heat helps kill any remaining tumor cells. This allows PMMA to be used without cryosurgery for some types of bone tumors. Surgical treatment of metastasis To be able to cure a bone cancer, it and any existing metastases must be removed ...

  5. Relational aggression in marriage.

    PubMed

    Carroll, Jason S; Nelson, David A; Yorgason, Jeremy B; Harper, James M; Ashton, Ruth Hagmann; Jensen, Alexander C

    2010-01-01

    Drawing from developmental theories of relational aggression, this article reports on a study designed to identify if spouses use relationally aggressive tactics when dealing with conflict in their marriage and the association of these behaviors with marital outcomes. Using a sample of 336 married couples (672 spouses), results revealed that the majority of couples reported that relationally aggressive behaviors, such as social sabotage and love withdrawal, were a part of their marital dynamics, at least to some degree. Gender comparisons of partner reports of their spouse's behavior revealed that wives were significantly more likely to be relationally aggressive than husbands. Structural equation modeling demonstrated that relational aggression is associated with lower levels of marital quality and greater marital instability for both husbands and wives. Implications are drawn for the use of relational aggression theory in the future study of couple conflict and marital aggression.

  6. TGF-β in cancer and bone: implications for treatment of bone metastases.

    PubMed

    Juárez, Patricia; Guise, Theresa A

    2011-01-01

    Bone metastases are common in patients with advanced breast, prostate and lung cancer. Tumor cells co-opt bone cells to drive a feed-forward cycle which disrupts normal bone remodeling to result in abnormal bone destruction or formation and tumor growth in bone. Transforming growth factor-beta (TGF-β) is a major bone-derived factor, which contributes to this vicious cycle of bone metastasis. TGF-β released from bone matrix during osteoclastic resorption stimulates tumor cells to produce osteolytic factors further increasing bone resorption adjacent to the tumor cells. TGF-β also regulates 1) key components of the metastatic cascade such as epithelial-mesenchymal transition, tumor cell invasion, angiogenesis and immunosuppression as well as 2) normal bone remodeling and coupling of bone resorption and formation. Preclinical models demonstrate that blockade of TGF-β signaling is effective to treat and prevent bone metastases as well as to increase bone mass.

  7. [Enophthalmos in an orbital tumor].

    PubMed

    Szabo, Bianca; Szabo, I; Nicula, Cristina; Popescu, Livia Adriana

    2013-01-01

    Enophtalmus is an unusual sign of the orbital tumors often represented by proptosis. One patient with enophtalmus and intraorbital tumor and aplasy is presented. The treatment of choice of orbital tumor is complete surgical excision and careful follow-up. Considering the more aggressive course followed by recurrent tumor, correct diagnosis and management is essential.

  8. Primary bone tumors of the spine revisited: A 10-year single-center experience of the management and outcome in a neurosurgical department

    PubMed Central

    Munoz-Bendix, Christopher; Slotty, Phillip Jorg; Ahmadi, Sebastian Alexander; Bostelmann, Richard; Steiger, Hans-Jakob; Cornelius, Jan Frederick

    2015-01-01

    Objective: To report a large clinical series of primary bone tumors of the spine (PBTS) and review the current concepts of management. Materials and Methods: We retrospectively analyzed a clinical series of PBTS treated over the last decade (2004-2014) in the spine unit of a large European tertiary care center. Every PBTS was identified from an electronic medical-record system. Analysis comprised medical records and clinical imaging. Overall survival and outcome was measured using the Glasgow Outcome Scale (GOS) at six weeks, six months and one year postoperatively. Surgical management and adjuvant/neoadjuvant strategies were analyzed. A thorough review of the current literature was performed. Results: A total of 79 patients were included. Of these, 44 (55.7%) were male. The age ranged from 9 to 90 years (mean 55), and most patients were adults (93.6%). Local pain was the most common symptom and was present in 91.1% of the patients. The majority of the tumors occurred in the thoracic spine (52 patients, 65.8%). Overall 86% (68 patients) of PBTS were classified as malignant and at the time of diagnosis, 7 patients (8.9%) presented with non-spinal metastasis. The most common histologic types were hematopoietic tumors (72.2%), followed by chondrogenic ones (12.7%). Within hematopoietic tumors, plasmacytoma was the most frequent type (49 patients, 62%). In 12 patients (15.2%) recurrences were seen during the follow-up period. Overall mean survival of benign PBTS was 100%, malignant non-hematopoietic PBTS 50% and, malignant hematopoietic PBTS 84% at one year, respectively. At six weeks and one year after the initial surgery, 79% and 54% of the patients presented a GOS >3, respectively. Conclusion: PBTS were almost exclusively seen in adults. Malignant tumors were markedly more frequent than benign tumors, with hematopoietic tumors being the most common type. For PBTS, early surgery is important in order to restore spinal stability and decompress the spinal cord. This

  9. Evaluation and correlation of risk recurrence in early breast cancer assessed by Oncotype DX(®), clinicopathological markers and tumor cell dissemination in the blood and bone marrow.

    PubMed

    Aktas, Bahriye; Bankfalvi, Agnes; Heubner, Martin; Kimmig, Rainer; Kasimir-Bauer, Sabine

    2013-11-01

    The Oncotype DX(®) assay is a validated genomic test that predicts the likelihood of breast cancer recurrence, patient survival within ten years of diagnosis and the benefit of chemotherapy in early-stage, node-negative, estrogen receptor-positive breast cancer. Further markers of recurrence include disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in the blood, particularly stemness-like tumor cells (slCTCs). In this study, Oncotype DX, DTCs, CTCs and slCTCs were used to evaluate the risk of recurrence in 68 patients with human epidermal growth factor receptor 2-negative, early-stage breast cancer. Formalin-fixed, paraffin-embedded tissue sections were analyzed for the expression of 16 cancer genes and 5 reference genes by Oncotype DX, yielding a recurrence score (RS). G2 tumors were evaluated for urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitor type 1 (PAI1) and Ki-67. Two BM aspirates were analyzed by immunocytochemistry for DTCs using the pan-cytokeratin antibody A45-B/B3. CTCs and slCTCs in the blood were detected using the AdnaTest BreastCancer, AdnaTest EMT and the AdnaTest TumorStemCell. Oncotype DX was performed in 68 cases, yielding a low RS in 30/68 patients (44%), an intermediate RS in 29/68 patients (43%) and a high RS in 9/68 patients (13%). DTCs were detected in 19/68 patients (28%), CTCs in 13/68 patients (19%) and slCTCs in 26/68 (38%) patients. Moreover, 8/68 patients (12%) with G2 tumors were positive for uPA, 6/68 (9%) for PAI1 and 21/68 (31%) for Ki-67. Ki-67, progesterone receptor (PR) and G3 tumors were significantly correlated with RS (P<0.001; P=0.006; and P=0,002, respectively), whereas no correlation was identified between DTCs, CTCs, slCTCs and RS. Ki-67 may support therapeutic decisions in cases where Oncotype DX is not feasible. Larger patient cohorts are required to estimate the additional detection of DTCs and CTCs for the determination of risk recurrence.

  10. Bone metastasis: mechanisms and therapeutic opportunities

    PubMed Central

    Suva, Larry J.; Washam, Charity; Nicholas, Richard W.; Griffin, Robert J.

    2011-01-01

    The skeleton is one of the most common sites for metastatic cancer, and tumors arising from the breast or prostate possess an increased propensity to spread to this site. The growth of disseminated tumor cells in the skeleton requires tumor cells to inhabit the bone marrow, from which they stimulate local bone cell activity. Crosstalk between tumor cells and resident bone and bone marrow cells disrupts normal bone homeostasis, which leads to tumor growth in bone. The metastatic tumor cells have the ability to elicit responses that stimulate bone resorption, bone formation or both. The net result of these activities is profound skeletal destruction that can have dire consequences for patients. The molecular mechanisms that underlie these painful and often incurable consequences of tumor metastasis to bone are beginning to be recognized, and they represent promising new molecular targets for therapy. PMID:21200394

  11. Interferon-γ and Tumor Necrosis Factor-α Polarize Bone Marrow Stromal Cells Uniformly to a Th1 Phenotype

    PubMed Central

    Jin, Ping; Zhao, Yuanlong; Liu, Hui; Chen, Jinguo; Ren, Jiaqiang; Jin, Jianjian; Bedognetti, Davide; Liu, Shutong; Wang, Ena; Marincola, Francesco; Stroncek, David

    2016-01-01

    Activated T cells polarize mesenchymal stromal cells (MSCs) to a proinflammatory Th1 phenotype which likely has an important role in amplifying the immune response in the tumor microenvironment. We investigated the role of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), two factors produced by activated T cells, in MSC polarization. Gene expression and culture supernatant analysis showed that TNF-α and IFN-γ stimulated MSCs expressed distinct sets of proinflammatory factors. The combination of IFN-γ and TNF-α was synergistic and induced a transcriptome most similar to that found in MSCs stimulated with activated T cells and similar to that found in the inflamed tumor microenvironment; a Th1 phenotype with the expression of the immunosuppressive factors IL-4, IL-10, CD274/PD-L1 and indoleamine 2,3 dioxygenase (IDO). Single cell qRT-PCR analysis showed that the combination of IFN-γ and TNF-α polarized uniformly to this phenotype. The combination of IFN-γ and TNF-α results in the synergist uniform polarization of MSCs toward a primarily Th1 phenotype. The stimulation of MSCs by IFN-γ and TNF-α released from activated tumor infiltrating T cells is likely responsible for the production of many factors that characterize the tumor microenvironment. PMID:27211104

  12. Genomic instability at the 13q31 locus and somatic mtDNA mutation in the D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases

    PubMed Central

    dos Santos, Gilson Costa; de Souza Góes, Andréa Carla; de Vitto, Humberto; Moreira, Carla Cristina; Avvad, Elizabeth; Rumjanek, Franklin David; de Moura Gallo, Claudia Vitoria

    2012-01-01

    OBJECTIVE: Genomic instability is a hallmark of malignant tissues. In this work, we aimed to characterize nuclear and mitochondrial instabilities by determining short tandem repeats and somatic mitochondrial mutations, respectively, in a cohort of Brazilian sporadic breast cancer cases. Furthermore, we performed an association analysis of the molecular findings and the clinical pathological data. METHODS: We analyzed 64 matched pairs of breast cancer and adjacent non-cancerous breast samples by genotyping 13 nuclear short tandem repeat loci (namely, D2S123, TPOX, D3S1358, D3S1611, FGA, D7S820, TH01, D13S317, D13S790, D16S539, D17S796, intron 12 BRCA1 and intron 1 TP53) that were amplified with the fluorescent AmpFlSTR Identifiler Genotyping system (Applied Biosystems, USA) and by silver nitrate staining following 6% denaturing polyacrylamide gel electrophoresis. Somatic mtDNA mutations in the D-loop site were assessed with direct sequencing of the hypervariable HVI and HVII mitochondrial regions. RESULTS: Half of the cancer tissues presented some nuclear instability. Interestingly, the D13S790 locus was the most frequently affected (36%), while the D2S123 locus presented no alterations. Forty-two percent of the cases showed somatic mitochondrial mutations, the majority at region 303-315 poly-C. We identified associations between Elston grade III, instabilities at 13q31 region (p = 0.0264) and mtDNA mutations (p = 0.0041). Furthermore, instabilities at 13q31 region were also associated with TP53 mutations in the invasive ductal carcinoma cases (p = 0.0207). CONCLUSION: Instabilities at 13q31 region and the presence of somatic mtDNA mutations in a D-loop site correlated with tumor aggressiveness. PMID:23070345

  13. Bone and soft tissue tumors presenting as sciatic notch dumbbell masses: A critical differential diagnosis of sciatica

    PubMed Central

    Matsumoto, Yoshihiro; Matsunobu, Tomoya; Harimaya, Katsumi; Kawaguchi, Kenichi; Hayashida, Mitsumasa; Okada, Seiji; Doi, Toshio; Iwamoto, Yukihide

    2016-01-01

    AIM To study the clinical findings and characteristic features in sciatic notch dumbbell tumors (SNDTs). METHODS We retrospectively reviewed the clinical outcomes and characteristic features of consecutive cases of SNDTs (n = 8). RESULTS Buttock masses occurred in three patients with SNDT (37.5%). Severe buttock tenderness and pain at rest were observed in seven patients with SNDTs (87.5%). Remarkably, none of the patients with SNDTs experienced back pain. Mean tumor size was 8.4 ± 2.0 cm (range, 3.9 to 10.6 cm) and part of the tumor mass was detected in 2 patients in the sagittal view of lumbar magnetic resonance imaging (MRI). CONCLUSION The clinical information regarding to SNDTs is scarce. The authors consider that above mentioned characteristic findings may facilitate the suspicion of pelvic pathology and a search for SNDT by MRI or computed tomography should be considered in patients presenting with sciatica without evidence of spinal diseases. PMID:27777884

  14. Methylated APC and GSTP1 genes in serum DNA correlate with the presence of circulating blood tumor cells and are associated with a more aggressive and advanced breast cancer disease

    PubMed Central

    2010-01-01

    significantly correlated with positive Her2/neu status (p = 0.003). Elevated serum CA15.3 was strongly correlated with methylated APC and CTC detection (both p = 0.000). Methylated ESR1 failed to exhibit significant correlations with any of the above mentioned parameters. The presence of CTC in peripheral blood was significantly associated with methylated APC (p = 0.012) and methylated GSTP1 (p = 0.001). Conclusion The detection of methylated APC and GSTP1 DNA in serum correlated with the presence of CTC in the blood of breast cancer patients. Both methylated DNA and CTC correlated with a more aggressive tumor biology and advanced disease. PMID:20696638

  15. Reducing bone cancer cell functions using selenium nanocomposites.

    PubMed

    Stolzoff, Michelle; Webster, Thomas J

    2016-02-01

    Cancer recurrence at the site of tumor resection remains a major threat to patient survival despite modern cancer therapeutic advances. Osteosarcoma, in particular, is a very aggressive primary bone cancer that commonly recurs after surgical resection, radiation, and chemotherapeutic treatment. The objective of the present in vitro study was to develop a material that could decrease bone cancer cell recurrence while promoting healthy bone cell functions. Selenium is a natural part of our diet which has shown promise for reducing cancer cell functions, inhibiting bacteria, and promoting healthy cells functions, yet, it has not been widely explored for osteosarcoma applications. For this purpose, due to their increased surface area, selenium nanoparticles (SeNP) were precipitated on a very common orthopedic tissue engineering material, poly-l-lactic acid (or PLLA). Selenium-coated PLLA materials were shown to selectively decrease long-term osteosarcoma cell density while promoting healthy, noncancerous, osteoblast functions (for example, up to two times more alkaline phosphatase activity on selenium coated compared to osteoblasts grown on typical tissue culture plates), suggesting they should be further studied for replacing tumorous bone tissue with healthy bone tissue. Importantly, results of this study were achieved without the use of chemotherapeutics or pharmaceutical agents, which have negative side effects. PMID:26454004

  16. Reducing bone cancer cell functions using selenium nanocomposites.

    PubMed

    Stolzoff, Michelle; Webster, Thomas J

    2016-02-01

    Cancer recurrence at the site of tumor resection remains a major threat to patient survival despite modern cancer therapeutic advances. Osteosarcoma, in particular, is a very aggressive primary bone cancer that commonly recurs after surgical resection, radiation, and chemotherapeutic treatment. The objective of the present in vitro study was to develop a material that could decrease bone cancer cell recurrence while promoting healthy bone cell functions. Selenium is a natural part of our diet which has shown promise for reducing cancer cell functions, inhibiting bacteria, and promoting healthy cells functions, yet, it has not been widely explored for osteosarcoma applications. For this purpose, due to their increased surface area, selenium nanoparticles (SeNP) were precipitated on a very common orthopedic tissue engineering material, poly-l-lactic acid (or PLLA). Selenium-coated PLLA materials were shown to selectively decrease long-term osteosarcoma cell density while promoting healthy, noncancerous, osteoblast functions (for example, up to two times more alkaline phosphatase activity on selenium coated compared to osteoblasts grown on typical tissue culture plates), suggesting they should be further studied for replacing tumorous bone tissue with healthy bone tissue. Importantly, results of this study were achieved without the use of chemotherapeutics or pharmaceutical agents, which have negative side effects.

  17. Punishment of elicited aggression.

    PubMed

    Azrin, N H

    1970-07-01

    Aversive shocks are known to produce aggression when the shocks are not dependent on behavior and to suppress behavior when the shocks are arranged as a dependent punisher. These two processes were studied by presenting non-dependent shock to monkeys at regular intervals, thereby producing biting attacks on a pneumatic tube. Immediate shock punishment was stimultaneously delivered for each biting attack. The attacks were found to decrease as a function of increasing punishment intensity. These results show that aggression is eliminated by direct punishment of the aggression even when the stimulus that is used as a punisher otherwise causes the aggression. PMID:4988590

  18. Multimodality Treatment in Ewing's Sarcoma Family Tumors of the Maxilla and Maxillary Sinus: Review of the Literature

    PubMed Central

    Mamot, Christoph; Krasniqi, Fatime; Metternich, Frank

    2016-01-01

    The Ewing sarcoma family of tumors (ESFT) encompasses a group of highly aggressive, morphologically similar, malignant neoplasms sharing a common spontaneous genetic translocation that affect mostly children and young adults. These predominantly characteristic, small round-cell tumors include Ewing's sarcoma of the bone and soft tissue, as well as primitive neuroectodermal tumors (PNETs) involving the bone, soft tissue, and thoracopulmonary region (Askin's tumor). Extraosseous ESFTs are extremely rare, especially in the head and neck region, where literature to date consists of sporadic case reports and very small series. We hereby present a review of the literature published on ESFTs reported in the maxilla and maxillary sinus region from 1968 to 2016. PMID:27413360

  19. EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene.

    PubMed

    Antonescu, Cristina R; Zhang, Lei; Chang, Ning-En; Pawel, Bruce R; Travis, William; Katabi, Nora; Edelman, Morris; Rosenberg, Andrew E; Nielsen, G Petur; Dal Cin, Paola; Fletcher, Christopher D M

    2010-12-01

    The diagnosis of myoepithelial (ME) tumors outside salivary glands remains challenging, especially in unusual clinical presentations, such as bone or visceral locations. A few reports have indicated EWSR1 gene rearrangement in soft tissue ME tumors, and, in one case each, the fusion partner was identified as either PBX1 or ZNF444. However, larger studies to investigate whether these genetic abnormalities are recurrent or restricted to tumors in soft tissue locations are lacking. Sixty-six ME tumors mainly from soft tissue (71%), but also from skin, bone, and visceral locations, characterized by classic morphological features and supporting immunoprofile were studied. Gene rearrangements in EWSR1, FUS, PBX1, and ZNF444 were investigated by fluorescence in situ hybridization. EWSR1 gene rearrangement was detected in 45% of the cases. A EWSR1-POU5F1 fusion was identified in a pediatric soft tissue tumor by 3'Rapid Amplification of cDNA Euds (RACE) and subsequently confirmed in four additional soft tissue tumors in children and young adults. An EWSR1-PBX1 fusion was seen in five cases, whereas EWSR1-ZNF444 and FUS gene rearrangement was noted in one pulmonary tumor each. In conclusion, EWSR1 gene rearrangement is a common event in ME tumors arising outside salivary glands, irrespective of anatomical location. EWSR1-negative tumors were more often benign, superficially located, and showed ductal differentiation, suggesting the possibility of genetically distinct groups. A subset of soft tissue ME tumors with clear cell morphology harbor an EWSR1-POU5F1 fusion, which can be used as a molecular diagnostic test in difficult cases. These findings do not support a pathogenetic relationship between soft tissue ME tumors and their salivary gland counterparts.

  20. Squalene Selectively Protects Mouse Bone Marrow Progenitors Against Cisplatin and Carboplatin-Induced Cytotoxicity In Vivo Without Protecting Tumor Growth12

    PubMed Central

    Das, Bikul; Antoon, Roula; Tsuchida, Rika; Lotfi, Shamim; Morozova, Olena; Farhat, Walid; Malkin, David; Koren, Gideon; Yeger, Herman; Baruchel, Sylvain

    2008-01-01

    Squalene, an isoprenoid antioxidant is a potential cytoprotective agent against chemotherapy-induced toxicity. We have previously published that squalene protects light-density bone marrow cells against cis-diamminedichloroplatinum( II) (cisplatin)-induced toxicity without protecting tumor cells in vitro. Here, we developed an in vivo mouse model of cisplatin and cis-diammine (cyclobutane-1,1-dicarboxylato) platinum(II) (carboplatin)-induced toxicity to further investigate squalene-mediated LD-BM cytoprotection including the molecular mechanism behind selective cytoprotection. We found that squalene significantly reduced the body weight loss of cisplatin and carboplatin-treated mice. Light-density bone marrow cells from squalene-treated mice exhibited improved formation of hematopoietic colonies (colony-forming unit-granulocyte macrophage). Furthermore, squalene also protected mesenchymal stem cell colonies (colony-forming unit-fibroblast) from cisplatin and carboplatin-induced toxicity. Squalene-induced protection was associated with decreased reactive oxygen species and increased levels of glutathione and glutathione peroxidase/glutathione-S-transferase. Importantly, squalene did not protect neuroblastoma, small cell carcinoma, or medulloblastoma xenografts against cisplatin-induced toxicity. These results suggest that squalene is a potential candidate for future development as a cytoprotective agent against chemotherapeutic toxicity. PMID:18813359

  1. Tryptophan content for monitoring breast cancer cell aggressiveness by native fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Lin; Pu, Yang; Xue, Jianpeng; Pratavieira, Sebastião.; Xu, Baogang; Achilefu, Samuel; Alfano, R. R.

    2014-03-01

    This study shows tryptophan as the key native marker in cells to determine the level of aggressive cancer in breast cell lines using native fluorescence spectroscopy. An algorithm based on the ratio of tryptophan fluorescence intensity at 340 nm to intensity at 460 nm is associated with aggressiveness of the cancer cells. The higher the ratio is, the more aggressive the tumor towards metastasis.

  2. Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis.

    PubMed

    Ma, C H; Lv, Q; Yu, Y X; Zhang, Y; Kong, D; Niu, K R; Yi, C Q

    2015-10-01

    We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

  3. The genetic tumor background is an important determinant for heterogeneous MYCN‐amplified neuroblastoma

    PubMed Central

    Bogen, Dominik; Brunner, Clemens; Walder, Diana; Ziegler, Andrea; Abbasi, Reza; Ladenstein, Ruth L.; Noguera, Rosa; Martinsson, Tommy; Amann, Gabriele; Schilling, Freimut H.; Ussowicz, Marek; Benesch, Martin

    2016-01-01

    Amplification of MYCN is the signature genetic aberration of 20–25% of neuroblastoma and a stratifying marker associated with aggressive tumor behavior. The detection of heterogeneous MYCN amplification (hetMNA) poses a diagnostic dilemma due to the uncertainty of its relevance to tumor behavior. Here, we aimed to shed light on the genomic background which permits hetMNA in neuroblastoma and tied the occurrence to other stratifying markers and disease outcome. We performed SNP analysis using Affymetrix Cytoscan HD arrays on 63 samples including constitutional DNA, tumor, bone marrow and relapse samples of 26 patients with confirmed hetMNA by MYCN‐FISH. Tumors of patients ≤18m were mostly aneuploid with numeric chromosomal aberrations (NCAs), presented a prominent MNA subclone and carried none or a few segmental chromosomal aberrations (SCAs). In older patients, tumors were mostly di‐ or tetraploid, contained a lower number of MNA cells and displayed a multitude of SCAs including concomitant 11q deletions. These patients often suffered disease progression, tumor dissemination and relapse. Restricted to aneuploid tumors, we detected chromosomes with uniparental di‐ or trisomy (UPD/UPT) in almost every sample. UPD11 was exclusive to tumors of younger patients whereas older patients featured UPD14. In this study, the MNA subclone appears to be constraint by the tumor environment and thus less relevant for tumor behavior in aggressive tumors with a high genomic instability and many segmental aberrations. A more benign tumor background and lower tumor stage may favor an outgrowth of the MNA clone but tumors generally responded better to treatment. PMID:26910568

  4. Circulating tumor cells in blood of primary breast cancer patients assessed by a novel RT-PCR test kit and comparison with status of bone marrow-disseminated tumor cells.

    PubMed

    Schmitt, Manfred; Foekens, John A

    2009-01-01

    In breast cancer, circulating tumor cells (CTCs)/disseminated tumor cells (DTCs) may serve as independent adverse prognostic variables, to monitor the course of the disease and to predict response or failure to cancer therapy. Most of the techniques to enumerate DTCs in the bone marrow or CTCs in the bloodstream of breast cancer patients rely on a combination of an enrichment step and a detection step. A novel RT-PCR method, the AdnaTest BreastCancer kit, was developed for the enrichment of CTCs from peripheral blood of breast cancer patients followed by identification of CTC-associated marker transcripts by reverse transcription and PCR. Although this test has been demonstrated to identify breast cancer patients at risk, standardization of this technique and direct comparison with other established breast cancer CTC enrichment and detection techniques is still lacking, but highly needed. This is done best within prospective clinical trials, such as in the ongoing DETECT, SUCCESS, and BR-01-2004 trials.

  5. The triterpenoid CDDO-Me delays murine acute graft-versus-host disease with the preservation of graft-versus-tumor effects after allogeneic bone marrow transplantation

    PubMed Central

    Li, Minghui; Sun, Kai; Redelman, Doug; Welniak, Lisbeth A.; Murphy, William J.

    2010-01-01

    The occurrence of acute graft-versus-host disease (GVHD) and tumor relapse represent the two major obstacles impeding the efficacy of allogeneic bone marrow transplantation (BMT) in cancer. We have previously shown that the synthetic triterpenoid CDDO can inhibit murine early acute GVHD but anti-tumor effects were not assessed. In the current study, we found that a new derivative of CDDO, CDDO-Me, had an increased ability to inhibit allogeneic T cell responses and induce cell death of alloreactive T cells in vitro. Administration of CDDO-Me to mice following allogeneic BMT resulted in significant and increased protection from acute lethal GVHD compared to CDDO. This correlated with reduced TNF-α production, reduced donor T cell proliferation and decreased adhesion molecule (α4β7 integrin) expression on the donor T cells. CDDO-Me was also superior to CDDO in inhibiting leukemia growth in vitro. When CDDO-Me was administered following an allogeneic BMT to leukemia-bearing mice, significant increases in survival were observed. These findings suggest that CDDO-Me is superior to CDDO in delaying acute GVHD while preserving or possibly even augmenting GVT effects. PMID:20338256

  6. A Strategic Approach to Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    2001-01-01

    Discusses two issues raised by Underwood et al.: the distinction between indirect and relational forms of aggression, and implications of indirect aggression for definitions of aggression; and the normative view of aggression that indicates that aggressive individuals may be socially skilled. Suggests that both issues lead to the conclusion that…

  7. High-Dose Chemotherapy, Total-Body Irradiation, and Autologous Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Hematologic Cancer or Solid Tumors

    ClinicalTrials.gov

    2013-05-07

    Breast Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  8. The vasculature: a vessel for bone metastasis

    PubMed Central

    Raymaekers, Koen; Stegen, Steve; van Gastel, Nick; Carmeliet, Geert

    2015-01-01

    Emerging evidence indicates that the interactions between tumor cells and the bone microenvironment have a crucial role in the pathogenesis of bone metastasis and that they can influence tumor cell dissemination, quiescence and tumor growth in the bone. The vasculature is known to be critical for primary tumor growth, and anti-angiogenesis drugs are approved for the treatment of certain tumor types. The role of the vasculature in bone metastasis is less well known, but recent evidence shows that blood vessels in the bone are a key component of the local microenvironment for the tumor cells and contribute to the different consecutive phases of bone metastasis. A better insight in the importance of the vasculature for bone metastasis may help develop novel treatment modalities that either slow down tumor growth or, preferably, prevent or cure bone metastasis. PMID:27217954

  9. Girls' Aggressive Behavior

    ERIC Educational Resources Information Center

    Owens, Larry; Shute, Rosalyn; Slee, Phillip

    2004-01-01

    In contrast to boys' bullying behavior which is often overt and easily visible, girls' aggression is usually indirect and covert. Less research has been conducted on the types of bullying that girls usually engage in. Using focus groups composed of teenaged girls, Dr. Owens and colleagues examine the nature of teenage girls' indirect aggression.

  10. Third Person Instigated Aggression.

    ERIC Educational Resources Information Center

    Gaebelein, Jacquelyn

    Since many acts of aggression in society are more than simply an aggressor-victim encounter, the role played by third person instigated aggression also needs examination. The purpose of this study was to develop a laboratory procedure to systematically investigate instigation. In a competitive reaction time task, high and low Machiavellian Males…

  11. Social Aggression among Girls.

    ERIC Educational Resources Information Center

    Underwood, Marion K.

    Noting recent interest in girls' social or "relational" aggression, this volume offers a balanced, scholarly analysis of scientific knowledge in this area. The book integrates current research on emotion regulation, gender, and peer relations, to examine how girls are socialized to experience and express anger and aggression from infancy through…

  12. High total metabolic tumor volume in PET/CT predicts worse prognosis in diffuse large B cell lymphoma patients with bone marrow involvement in rituximab era.

    PubMed

    Song, Moo-Kon; Yang, Deok-Hwan; Lee, Gyeong-Won; Lim, Sung-Nam; Shin, Seunghyeon; Pak, Kyoung June; Kwon, Seong Young; Shim, Hye Kyung; Choi, Bong-Hoi; Kim, In-Suk; Shin, Dong-Hoon; Kim, Seong-Geun; Oh, So-Yeon

    2016-03-01

    Bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL) was naively regarded as an adverse clinical factor. However, it has been unknown which factor would separate clinical outcomes in DLBCL patients with BMI. Recently, metabolic tumor volume (MTV) on positron emission tomography/computed tomography (PET/CT) was suggested to predict prognosis in several lymphoma types. Therefore, we investigated whether MTV would separate the outcomes in DLBCL patients with BMI. MTV on PET/CT was defined as an initial tumor burden as target lesion ≥ standard uptake value, 2.5 in 107 patients with BMI. Intramedullary (IM) MTV was defined as extent of BMI and total MTV was as whole tumor burden. 260.5 cm(3) and 601.2 cm(3) were ideal cut-off values for dividing high and low MTV status in the IM and total lymphoma lesions in Receiver Operating Curve analysis. High risk NCCN-IPI (p<0.001, p<0.001), bulky disease (p=0.011, p=0.005), concordant subtype (p=0.025, p=0.029), high IM MTV status (p<0.001, p<0.001), high total MTV status (p<0.001, p<0.001), and ≥ 2CAs in BM (p=0.037, p=0.033) were significantly associated with progression-free survival (PFS) and overall survival (OS) than other groups. In multivariate analysis, high risk NCCN-IPI (PFS, p=0.006; OS, p=0.013), concordant subtype (PFS, p=0.005; OS, p=0.007), and high total MTV status (PFS, p<0.001; OS, p<0.001) had independent clinical impacts. MTV had prognostic significances for survivals in DLBCL with BMI. PMID:26851438

  13. The utility of SATB2 immunohistochemical expression in distinguishing between osteosarcomas and their malignant bone tumor mimickers, such as Ewing sarcomas and chondrosarcomas.

    PubMed

    Machado, Isidro; Navarro, Samuel; Picci, Piero; Llombart-Bosch, Antonio

    2016-09-01

    SATB2 is commonly expressed in osteosarcomas. Although apparently being a valuable diagnostic marker for differentiating between small cell osteosarcoma (SCO) and other small round cell tumors of bone, for instance Ewing sarcoma family of tumors (ESFT), it has not been tested in a large series of ESFT and chondrosarcomas so far. We studied the immunohistochemical expression of SATB2 in 42 osteosarcomas, 31 chondrosarcomas, and 371 genetically confirmed ESFT. SATB2 positivity was detected in 90.4% of osteosarcomas, 87.5% of SCO, 91.3% of osteoblastic osteosarcomas, and in all chondroblastic and parosteal osteosarcomas. The osteoblastic and SCO subtypes expressed SATB2 more intensely than other histological types. SATB2 was expressed in 46.6% of chondrosarcomas, and in 1.3% of ESFT. Sensitivity and specificity of SATB2 immunoexpression were 90.4% and 95.3%, respectively. The positive and negative predictive values in osteosarcoma diagnosis were 66.6% and 98.9%, respectively. In chondrosarcoma, SATB2 immunoexpression was more frequent and intense in high-grade chondrosarcoma (Grade III) and uncommon in chondrosarcoma grade I. SATB2 positivity was detected in 55.6% of chondrosarcomas grade II. SATB2 apparently cannot distinguish between chondroblastic osteosarcoma and high-grade chondrosarcoma. Nevertheless, SATB2 is frequently expressed in osteogenic tumors, but is rarely positive in ESFT, and with the support of CD99 expression and specific molecular studies, it is very useful for distinguishing between these two lesions. Although SATB2 immunoexpression helps to distinguish osteosarcoma from their mimickers, the identification of malignant osteoid matrix formation and the integration of clinical and radiological data remain the corner stone of osteosarcoma diagnosis and as yet no antibody has equalled the diagnostic value of this important morphologic hallmark. PMID:27465835

  14. Pleomorphic adenoma of the nasopharyngeal mucosal space with locally aggressive appearance (2010: 11b).

    PubMed

    Downer, Jonathan; Fryer, Eve; Capper, John; Woo, Eric K

    2011-02-01

    Pleomorphic adenoma arising from submucosal minor salivary gland tissue in the head and neck is well described in the published literature. Where associated bone changes are present, benign-appearing bone remodelling is the rule, reflecting the slow growth of this benign tumour. Aggressive-appearing bone destruction was observed in this case. This atypical appearance has not been widely described.

  15. Bone marrow macrophages support prostate cancer growth in bone

    PubMed Central

    Soki, Fabiana N.; Cho, Sun Wook; Kim, Yeo Won; Jones, Jacqueline D.; Park, Serk In; Koh, Amy J.; Entezami, Payam; Daignault-Newton, Stephanie; Pienta, Kenneth J.; Roca, Hernan; McCauley, Laurie K.

    2015-01-01

    Resident macrophages in bone play important roles in bone remodeling, repair, and hematopoietic stem cell maintenance, yet their role in skeletal metastasis remains under investigated. The purpose of this study was to determine the role of macrophages in prostate cancer skeletal metastasis, using two in vivo mouse models of conditional macrophage depletion. RM-1 syngeneic tumor growth was analyzed in an inducible macrophage (CSF-1 receptor positive cells) ablation model (MAFIA mice). There was a significant reduction in tumor growth in the tibiae of macrophage-ablated mice, compared with control non-ablated mice. Similar results were observed when macrophage ablation was performed using liposome-encapsulated clodronate and human PC-3 prostate cancer cells where tumor-bearing long bones had increased numbers of tumor associated-macrophages. Although tumors were consistently smaller in macrophage-depleted mice, paradoxical results of macrophage depletion on bone were observed. Histomorphometric and micro-CT analyses demonstrated that clodronate-treated mice had increased bone volume, while MAFIA mice had reduced bone volume. These results suggest that the effect of macrophage depletion on tumor growth was independent of its effect on bone responses and that macrophages in bone may be more important to tumor growth than the bone itself. In conclusion, resident macrophages play a pivotal role in prostate cancer growth in bone. PMID:26459393

  16. Intraoperative Navigation for Minimally Invasive Resection of Periarticular and Pelvic Tumors

    PubMed Central

    Wu, Kevin; Webber, Nicholas P.; Ward, Russell A.; Jones, Kevin B.; Randall, R. Lor

    2013-01-01

    The surgical approach to benign, metastatic, and some low-grade malignant tumors is often difficult due to their typically precarious locations. This article presents a series of cases where intraoperative stealth navigation was used to treat periarticular tumors. The use of paired point imaging with image fusion has made approaching tumors through an accurate and minimally invasive technique a viable option for the treatment of a subset of musculoskeletal tumors. Conventional resection of periarticular and pelvic tumors of bone usually requires an extensive surgical approach to adequately visualize the tumor and protect the nearby neurovascular structures. When tumors in periarticular locations are encountered, dislocation of the affected joint may be necessary, putting periarticular and subchondral bone at risk for osseous necrosis and articular surfaces at risk of mechanical insult at the time of dislocation. While arthroscopic techniques may enable a minimally invasive mode of surgical approach in certain anatomic locations, this is not always feasible and can add additional operative time and morbidity to the patient. This article describes 5 cases where locally aggressive tumors in challenging periarticular anatomic locations were treated in a minimally invasive manner with the assistance of image fusion and paired-point registration. PMID:21553742

  17. Nonodontogenic Tumors of the Jaws.

    PubMed

    Dyalram, Donita; Aslam-Pervez, Nawaf; Lubek, Joshua E

    2016-02-01

    Nonodontogenic tumors of the jaws are common in the pediatric population, accounting for approximately 70% of pediatric jaw tumors. This article focuses on the clinical characteristics and management of the benign nonodontogenic tumors (nonaggressive and aggressive) of the jaws most commonly encountered in children.

  18. Aggression in Pretend Play and Aggressive Behavior in the Classroom

    ERIC Educational Resources Information Center

    Fehr, Karla K.; Russ, Sandra W.

    2013-01-01

    Research Findings: Pretend play is an essential part of child development and adjustment. However, parents, teachers, and researchers debate the function of aggression in pretend play. Different models of aggression predict that the expression of aggression in play could either increase or decrease actual aggressive behavior. The current study…

  19. IFN-γ Receptor Deficient Donor T cells Mediate Protection from Graft-versus-Host Disease and Preserve Graft-versus-Tumor Responses After Allogeneic Bone Marrow Transplantation

    PubMed Central

    Sun, Kai; Hsiao, Hui-Hua; Li, Minghui; Ames, Erik; Bouchlaka, Myriam; Welniak, Lisbeth A.; Hagino, Takeshi; Jagdeo, Jared; Pai, Chien-Chun; Chen, Mingyi; Blazar, Bruce R.; Abedi, Mehrdad; Murphy, William J.

    2012-01-01

    Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT). It has been previously reported that lung GVHD severity directly correlates with the expansion of donor Th17 cells in the absence of IFN-γ. However, the consequence of Th17-associated lung GVHD in the presence of IFN-γ has not been well-characterized. In the current study, T cells from IFN-γ receptor knockout (IFN-γR-/-) mice, capable of producing IFN-γ but unable to signal in response to IFN-γ, have been used to further elucidate the role of IFN-γ in GVHD. We found the transfer of donor T cells from either IFN-γR-/- or IFN-γ knockout (IFN-γ-/-) mice resulted in significant increases in donor Th17 cells in the lung. Marked increases in IL4-producing Th2 cells infiltrating the lungs were also observed in the mice of donor IFN-γR-/- T cells. Interestingly, despite the presence of these cells, these mice did not show the severe immune mediated histopathological lung injury observed in mice receiving donor IFN-γ-/- T cells. Increases in lung GVHD did occur in mice with donor IFN-γR-/- T cells when treated in vivo with anti-IFN-γ demonstrating that the cytokine has a protective role on host tissues in GVHD. A survival benefit from acute GVHD was also observed using donor cells from IFN-γR-/-T cells compared with control donors. Importantly, tumor-bearing mice receiving IFN-γR-/- T cells, versus wild-type donor T cells, displayed similar graft-versus tumor (GVT) effects. These results demonstrate the critical role of the IFN-γ on host tissues and cell effector functions in GVHD/GVT. PMID:22778394

  20. Bone sialoprotein mediates the tumor cell-targeted prometastatic activity of TGF-β in a mouse model of breast cancer.

    PubMed Central

    Nam, Jeong-Seok; Suchar, Adam M.; Kang, Mi-Jin; Stuelten, Christina H.; Tang, Binwu; Michalowska, Aleksandra M.; Fisher, Larry W.; Fedarko, Neal S.; Jain, Alka; Pinkas, Jan; Lonning, Scott; Wakefield, Lalage M.

    2006-01-01

    Transforming growth factor-βs (TGF-βs) play a dual role in carcinogenesis, functioning as tumor suppressors early in the process, and then switching to act as pro-metastatic factors in late-stage disease. We have previously shown that high molecular weight TGF-β antagonists can suppress metastasis without the predicted toxicities (Yang et al., J. Clin. Invest. (2002) 109:1607-1615). To address the underlying mechanisms, we have used the 4T1 syngeneic mouse model of metastatic breast cancer. Treatment of mice with a monoclonal anti-TGF-β antibody (1D11) significantly suppressed metastasis of 4T1 cells to the lungs. When metastatic 4T1 cells were recovered from lungs of 1D11-treated and control mice, the most differentially expressed gene was found to be bone sialoprotein (Bsp). Immunostaining confirmed the loss of Bsp protein in 1D11-treated lung metastases, and TGF-β was shown to regulate and correlate with Bsp expression in vitro. Functionally, knockdown of Bsp in 4T1 cells reduced the ability of TGF-β to induce local collagen degradation and invasion in vitro, and treatment with recombinant BSP protected 4T1 cells from complement-mediated lysis. Finally, suppression of Bsp in 4T1 cells reduced metastasis in vivo. We conclude that Bsp is a plausible mediator of at least some of the tumor cell-targeted prometastatic activity of TGF-β in this model, and that Bsp expression in metastases can be successfully suppressed by systemic treatment with anti-TGF-β antibodies. PMID:16778210

  1. Bone-immune cell crosstalk: bone diseases.

    PubMed

    Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

    2015-01-01

    Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma. PMID:26000310

  2. Bone-immune cell crosstalk: bone diseases.

    PubMed

    Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

    2015-01-01

    Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma.

  3. Tumor Treated by Endoscopy

    PubMed Central

    Choi, Young; Kwak, Jae Man; Chung, So Hak; Jung, Gu Hee

    2014-01-01

    Background This study was conducted to examine the clinical usefulness and efficacy of endoscopic curettage on benign bone tumor. Methods Thirty-two patients (20 men and 12 women) with benign bone tumor were included in the study. The patients were aged between five and 76 years; the mean follow-up period was 27.05 months (range, 9.6 to 39.9 months). The primary sites include simple bone cyst (9 cases), fibrous dysplasia (6 cases), enchondroma (5 cases), non-ossifying fibroma (4 cases), bone infarct (3 cases), aneurysmal bone cyst (1 case), chondroblastoma (1 case), osteoblastoma (1 case), intraosseous lipoma (1 case), and Brodie abscess (1 case). A plain radiography was performed to assess the radiological recovery. Radiological outcomes, including local recurrence and bone union, were evaluated as excellent, good, poor, and recurred. Results In our series, there were 27 cases (84.4%) of good or better outcomes, six cases (18.8%) of complications (4 local recurrence, 1 wound infection, and 1 pathologic fracture). Conclusions Our results showed that endoscopic curettage and bone graft had a lower rate of recurrence and a higher cure rate in cases of benign bone tumor. It can, therefore, be concluded that endoscopic curettage and bone graft might be good treatment modalities for benign bone tumors. PMID:24605192

  4. Targeting VEGFR1- and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy

    PubMed Central

    Xu, Wen Wen; Li, Bin; Lam, Alfred KY; Tsao, Sai Wah; Law, Simon YK; Chan, Kwok Wah; Yuan, Qiu Ju; Cheung, Annie LM

    2015-01-01

    Increasing appreciation of tumor heterogeneity and the tumor-host interaction has stimulated interest in developing novel therapies that target both tumor cells and tumor microenvironment. Bone marrow derived cells (BMDCs) constitute important components of the tumor microenvironment. In this study, we aim to investigate the significance of VEGFR1- and VEGFR2-expressing non-tumor cells, including BMDCs, in esophageal