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1.
Medicine (Baltimore) ; 99(12): e19538, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32195958

RESUMEN

To evaluate the improvement of radiologist performance in detecting bone metastases at follow up low-dose computed tomography (CT) by using a temporal subtraction (TS) technique based on an advanced nonrigid image registration algorithm.Twelve patients with bone metastases (males, 5; females, 7; mean age, 64.8 ±â€Š7.6 years; range 51-81 years) and 12 control patients without bone metastases (males, 5; females, 7; mean age, 64.8 ±â€Š7.6 years; 51-81 years) were included, who underwent initial and follow-up CT examinations between December 2005 and July 2016. Initial CT images were registered to follow-up CT images by the algorithm, and TS images were created. Three radiologists independently assessed the bone metastases with and without the TS images. The reader averaged jackknife alternative free-response receiver operating characteristics figure of merit was used to compare the diagnostic accuracy.The reader-averaged values of the jackknife alternative free-response receiver operating characteristics figures of merit (θ) significantly improved from 0.687 for the readout without TS and 0.803 for the readout with TS (P value = .031. F statistic = 5.24). The changes in the absolute value of CT attenuations in true-positive lesions were significantly larger than those in false-negative lesions (P < .001). Using TS, segment-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the readout with TS were 66.7%, 98.9%, 94.4%, 90.9%, and 94.8%, respectively.The TS images can significantly improve the radiologist's performance in the detection of bone metastases on low-dose and relatively thick-slice CT.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Metástasis de la Neoplasia/diagnóstico por imagen , Técnica de Sustracción/instrumentación , Tomografía Computarizada por Rayos X/métodos , Anciano , Algoritmos , Neoplasias Óseas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Valor Predictivo de las Pruebas , Radiólogos/estadística & datos numéricos , Estudios Retrospectivos , Sensibilidad y Especificidad , Análisis y Desempeño de Tareas
2.
Medicine (Baltimore) ; 99(7): e18993, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049793

RESUMEN

Long non-coding small nucleolar RNA host gene 7 (lncRNA SNHG7) is located on chromosome 9q34.3 in length of 984 bp. SNHG7 has been found to play the role of oncogene in varieties of cancers, and its dysregulation has been found to be associated with carcinogenesis and progression. In the present study, we examined the expression of SNHG7 in prostate cancer tissues and in paired adjacent normal prostate tissues, and we further explored the clinical significance and prognostic value of SNHG7 in prostate cancer patients.A total of 127 prostate cancer tissues were collected from prostate cancer patients who underwent radical prostatectomy between April 2011 and March 2019 at the department of urology, Pudong New Area People's Hospital. Real-time quantitative polymerase chain reaction experiment was performed to detect the relative expressions of SNHG7 in the prostate cancer tissues and normal prostate tissues. The Kaplan-Meier method was used to create survival curves and the log-rank test was used to determine statistical significance. A Cox proportional hazard analysis was used to evaluate the prognostic factors in univariate and multivariate analyses.Compared with paired adjacent normal prostatic tissues, SNHG7 expression was increased in prostate cancer tissues (P < .001). Increased SNHG7 expression correlated with Gleason score (P = .021), bone metastasis (P = .013), pelvic lymph node metastasis (P = .008), and TNM stage (P = .007). Multivariate Cox regression analyses revealed increased SNHG7 expression was independently associated with a poor prognosis of prostate cancer patients (hazard ratio [HR] = 2.839, 95% confidence interval [CI] = 1.921-8.382, P = .038).This study showed that lncRNA-SNHG7 was overexpressed in prostate cancer tissues, and it might contributes to the development and progression of prostate cancer. Furthermore, the SNHG7 expression was associated with the prognosis of prostate cancer, suggesting a potential target for the treatment and prognosis of prostate cancer. Nevertheless, the underlying modulatory mechanism by which SNHG7 aggravates prostate cancer progression need to be further studied.


Asunto(s)
Neoplasias Óseas/cirugía , Neoplasias de la Próstata/cirugía , ARN Largo no Codificante/genética , Regulación hacia Arriba , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Estadificación de Neoplasias , Pronóstico , Prostatectomía , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Análisis de Supervivencia , Resultado del Tratamiento
3.
Adv Exp Med Biol ; 1226: 57-72, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32030676

RESUMEN

It has been appreciated that the cross talk between bone metastatic cancer cells and bone marrow microenvironment influence one another to worsen bone metastatic disease progression. Bone marrow contains various cell types, including (1) cells of mesenchymal origin (e.g., osteoblasts, osteocytes, and adipocytes), (2) cells of hematopoietic origin (e.g., osteoclast and immune cells), and (3) others (e.g., endothelial cells and nerves). The recent studies have enabled us to discover many important cancer-derived factors responsible for the development of bone metastasis. However, many critical questions regarding the roles of bone microenvironment in bone metastatic progression remain elusive. To answer these questions, a deeper understanding of the cross talk between bone metastatic cancer and bone marrow microenvironment is clearly warranted.


Asunto(s)
Células de la Médula Ósea/patología , Médula Ósea/patología , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Microambiente Tumoral , Humanos
4.
Pathologe ; 41(2): 116-122, 2020 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-32060684

RESUMEN

Ewing sarcomas are highly malignant tumors that are mainly found in children and adolescents. In addition to early clinical diagnosis, correct histopathological and molecular genetic classification is the most important step. Although EWSR1-FLI1 fusion is by far the most common detectable change, there are also other representatives of the Ewing sarcoma family that cannot be distinguished histopathologically and immunohistochemically from classical Ewing sarcomas and that have different molecular genetic profiles. Although a precise molecular genetic differentiation of the various representatives of small round blue cell tumors does not yet lead to any change in the standard chemotherapy and surgical treatment applied, it does allow an estimation of the prognosis and will probably contribute in the future to an even more individualized treatment of Ewing sarcomas within the framework of personalized medicine.


Asunto(s)
Neoplasias Óseas/patología , Sarcoma de Ewing/patología , Neoplasias Óseas/terapia , Humanos , Pronóstico , Sarcoma de Ewing/terapia
5.
Pathologe ; 41(2): 143-152, 2020 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-32060685

RESUMEN

Cartilage tumors are a heterogeneous group of mesenchymal tumors whose common characteristic is the formation of a chondroblastic differentiated groundsubstance by the tumor cells. The basic features of their histological classification were already developed in the 1940s and supplemented by further entities in the following decades. Only in the past 10-15 years have fundamental new insights been gained through molecular genetic analysis. So, osteochondromas are characterized by alterations in the EXT1 and EXT2 genes. The description of mutations of isocitrate dehydrogenase 1 and 2 (IDH 1 and 2) in chondromas and chondrosarcomas is particularly important. The mesenchymal chondrosarcoma is characterized by a fusion of the HEY1-NCOA2 genes. The molecular genetic alterations characteristic for the individual tumor entities are first of all an essential supplement for the differential diagnosis of radiologically and histologically difficult cases. They also provide the basis for the establishment of molecular target therapies for malignant chondrogenic tumors. This applies in particular to conventional chondrosarcoma, for which all approaches to chemo- and radiotherapy have proven to be ineffective. However, the use of target therapies is still in its beginnings.


Asunto(s)
Neoplasias Óseas , Cartílago/patología , Terapia Molecular Dirigida , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Humanos
6.
Pathologe ; 41(2): 123-133, 2020 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-32078700

RESUMEN

Osteoid osteoma and osteoblastoma are the most important benign osteoid-forming tumors. They grow slowly and are well differentiated. Histologically, the tumor cells show no atypia and no increased mitoses. In typical cases, they can be clearly diagnosed. However, the rare cases on the dividing line between osteoblastoma and osteosarcoma are extremely problematic. In these cases, molecular genetic investigations should contribute to finding the correct diagnosis in the future.Juvenile highly malignant osteosarcoma is the most important malignant osteoid-forming tumor. About 40 years ago, neoadjuvant chemotherapy was introduced for the mostly young patients. This therapy highly significantly improved prognosis. However, a plateau phase was quickly reached and the last several decades have seen no further progress in conventional therapeutic approaches. There is no doubt that further progress can only be achieved on the basis of new molecular genetic and cell biological findings. The target-therapeutic strategies derived from these findings will be discussed in this review.The rare parosteal osteosarcoma and the even rarer periosteal osteosarcoma are mostly not highly malignant tumors that are located on the surface of bone. The parosteal osteosarcoma is usually G1 and the periosteal osteosarcoma G2. Occasionally, the differential diagnosis between a parosteal osteosarcoma and a fibrous dysplasia is difficult. In such rare cases, the detection of GNAS mutations in fibrous dysplasia can prove useful. In contrast to chondromas and chondrosarcomas, periosteal osteosarcomas do not contain IDH1 and IDH2 mutations.


Asunto(s)
Neoplasias Óseas/patología , Osteoblastoma/patología , Osteoma Osteoide/patología , Osteosarcoma/patología , Diagnóstico Diferencial , Humanos
7.
Pathologe ; 41(2): 134-142, 2020 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-32086536

RESUMEN

The histological picture of giant cell tumor of bone is characterized by numerous osteoclast-like giant cells. However, these are not the actual tumor cells, but constitute a reactive infiltrate. Rather, the tumor cells are mononuclear mesenchymal cells, which even reveal an osteoblastic line of differentiation. The CD68-positive macrophages form the second group of mononuclear cells. The receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL) system, which belongs to the tumor necrosis factor (TNF) cytokine family, is decisively involved in the activation of the giant cells. It is generally accepted that a RANKL expression of mononuclear stromal cells is responsible for the development and differentiation of osteoclast-like giant cells. Therefore, the RANKL inhibitor denosumab constituted an essential element for giant cell tumor therapy over the last several years, as it blocks the maturation of osteoclasts and thus the osteolytic activity and the spread of tumor. However, with time it became evident that the not risk-free therapy with denosumab may lead to extensive recurrences upon withdrawal, so this therapy is applied with caution today.At the molecular genetic level, the giant cell tumors of bone are characterized by point mutations in the H3F3A gene. The detection of this mutation is used for the diagnostic differentiation from other bone lesions containing giant cells. Giant cell osteosarcomas rarely contain H3F3A mutations. Chondroblastoma is characterized by mutations in the H3F3B gene.


Asunto(s)
Neoplasias Óseas/patología , Tumor Óseo de Células Gigantes/patología , Diagnóstico Diferencial , Humanos
8.
Pathologe ; 41(2): 153-162, 2020 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-32100085

RESUMEN

Chordomas are malignant bone tumours with a reported annual incidence of 0.08 per 100,000 cases. They show a notochordal differentiation and are characterised by their nuclear expression of brachyury (TBXT). Chordomas are localised in the axial skeleton, where they occur from the clivus to the sacrococcygeal region. They are slow growing, locally destructive tumours, and are often not diagnosed until they have reached an advanced stage. Putative precursor-lesions are benign notochordal cell lesions, which are microscopically small and intraosseous. Different histological chordoma subtypes exist, which differ in their prognosis. To date, there are no known recurrent genetic drivers for this disease. Brachyury seems to play a key role in the pathogenesis of chordoma, though the detailed mechanism still needs to be elucidated. Surgical en bloc resection with negative margins is the only curative treatment for this disease. High-dose irradiation, particularly with protons and carbon ions, is a therapeutic alternative in cases of inoperable tumours. Currently, there is no approved medical treatment for chordoma. Clinical trials exploring additional therapeutic modalities are ongoing.


Asunto(s)
Neoplasias Óseas/patología , Cordoma/patología , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/terapia , Cordoma/diagnóstico , Cordoma/terapia , Humanos
9.
Adv Exp Med Biol ; 1225: 1-18, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32030644

RESUMEN

Many cancers commonly metastasize to bone. After entering the bone, cancer cells can interact with surrounding stromal cells, which ultimately influences metastasis progression. Extracellular vesicles, direct cell contact and gap junctions, and cytokines are all mechanisms of intercellular communication that have been observed to occur in the bone microenvironment. These methods of cellular crosstalk can occur between cancer cells and a variety of stromal cells, with each interaction having a different impact on cancer progression. Communication between cancer cells and bone-resident cells has previously been implicated in processes such as cancer cell trafficking and arrest in bone, cancer cell dormancy, cancer cell reactivation, and proliferation. In this chapter we review innovative techniques and model systems that can be used to study bidirectional crosstalk between cancer cells and stromal cells in the bone, with an emphasis specifically on bone-metastatic breast cancer. Investigating how metastatic cancer cells interact with, and are influenced by, the bone microenvironment is crucial to better understanding of the progression of bone metastasis.


Asunto(s)
Neoplasias Óseas/secundario , Microambiente Tumoral , Neoplasias Óseas/patología , Huesos/patología , Comunicación Celular , Humanos
10.
J Surg Oncol ; 121(4): 612-619, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31919856

RESUMEN

BACKGROUND AND OBJECTIVES: We aimed to identify the overall survival (OS), surgical complications, survival of reconstruction, and functional outcome of patients who underwent extra-articular resection of the shoulder joint for primary bone sarcomas. The OS and local recurrence rates in patients who underwent an amputation were also evaluated for comparison. METHODS: Thirty-two patients treated between 1988 and 2017 were studied. The tumours were located in the humerus in 22 (69%) and scapula in 10 patients (31%). The resection types were Malawer type IV in 6 (19%), type V in 21 (66%), and type VI in 5 patients (15%). Reconstruction was performed with endoprosthesis in 23 patients (72%) while excision arthroplasty with the suspension of the humerus to the clavicle was performed in 9 patients (28%). Surgical margins were wide in 16, marginal in 8, intralesional in 3, and not available in 5 patients. During the study period, 40 patients underwent a forequarter amputation and 11 patients underwent a shoulder disarticulation. RESULTS: The 5-year OS for patients who underwent extra-articular resection of the shoulder joint was 42% which was not statistically different compared with that of patients who underwent amputation (5-year OS = 30%; P = .091). The 5-year survival of the reconstruction was 94%, similar for endoprosthesis and excision arthroplasty. Local recurrence and complications developed in 6 (19%) and 10 patients (31%), respectively. Failures of the reconstruction requiring revision surgery occurred in two patients (6%). Limb salvage was achieved in 30 patients (94%). The median Musculoskeletal Tumour Society functional score was 61% (interquartile range, 57%-70%) and was similar in the endoprosthesis and excision arthroplasty group. CONCLUSIONS: Extra-articular resection of the shoulder joint for bone sarcomas is an effective limb-salvage method. However, local recurrence remains a principal concern.


Asunto(s)
Neoplasias Óseas/cirugía , Recuperación del Miembro/métodos , Osteosarcoma/cirugía , Articulación del Hombro/cirugía , Adolescente , Adulto , Amputación/efectos adversos , Amputación/métodos , Amputación/mortalidad , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Desarticulación/efectos adversos , Desarticulación/métodos , Desarticulación/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Recuperación del Miembro/efectos adversos , Recuperación del Miembro/mortalidad , Masculino , Persona de Mediana Edad , Osteosarcoma/mortalidad , Osteosarcoma/patología , Prótesis e Implantes , Procedimientos Quirúrgicos Reconstructivos/efectos adversos , Procedimientos Quirúrgicos Reconstructivos/métodos , Procedimientos Quirúrgicos Reconstructivos/mortalidad , Estudios Retrospectivos , Articulación del Hombro/patología , Adulto Joven
11.
J Surg Oncol ; 121(4): 630-637, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31957034

RESUMEN

BACKGROUND AND OBJECTIVES: Limb salvage surgery remains the standard treatment in bone and soft tissue tumors. Toronto Extremity Salvage Score (TESS) is the most used quality of life measure. Our objective was to perform cross-cultural adaptation and validation in Italian, testing test-retest reliability, construct validity, and responsiveness. METHODS: We interviewed patients already treated for content validity. A total of 124 patients completed TESS and other questionnaires presurgery, at 3 months, 3 months + 2 weeks, and 6 months follow-up. We calculated intraclass correlation coefficients (ICCs) for reliability, associations with Pearson's r, and change over time with paired T tests. RESULTS: A new item regarding touch-screen devices was added to the upper extremity (UE) questionnaire. ICC resulted of 0.99 for lower extremity (LE) and 0.98 for UE patients, Pearson's r between TESS and Musculoskeletal Tumor Society was .66 and .64, EuroQol-5D-5L r was .62 and .61, and r between TESS and short form-36 physical function subscale was .76 and .71 for LE and UE groups, respectively. Paired T test results were statistically significant to detect change over time (0.03, 0.04, and 0.04 for LE groups and 0.03, 0.01, and 0.04 for UE groups). CONCLUSION: The Italian version of TESS can be used for the bone and soft tissue sarcoma population in clinical trials in Italy and with Italian speaking patients abroad to ensure patients' perspectives for efficacy and efficiency of treatments.


Asunto(s)
Neoplasias Óseas/psicología , Neoplasias Óseas/cirugía , Recuperación del Miembro/psicología , Osteosarcoma/psicología , Osteosarcoma/cirugía , Sarcoma/psicología , Sarcoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/patología , Comparación Transcultural , Extremidades/patología , Extremidades/cirugía , Femenino , Humanos , Italia , Lenguaje , Recuperación del Miembro/métodos , Masculino , Persona de Mediana Edad , Osteosarcoma/patología , Calidad de Vida , Reproducibilidad de los Resultados , Sarcoma/patología , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Traducción , Adulto Joven
12.
J Surg Oncol ; 121(4): 638-644, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31989655

RESUMEN

BACKGROUND: Conventional primary pelvic chondrosarcoma often presents as a low- or intermediate-grade tumor in older patients. Although this is the most common variant of pelvic chondrosarcoma, studies examining treatment outcomes are lacking. The purpose of this study was to evaluate patients with these tumors to determine their outcomes of treatment. METHODS: Seventy-three patients (grade I [n = 19, 26%] and grade II [n = 54, 74%]) were reviewed including 55 (75%) males and 18 (25%) females, with a mean age of 51 (range, 17-81) years and follow-up of 9 ± 5 years. RESULTS: The 10-year disease-specific survival was 71%. Grade II disease (hazard ratio [HR], 6.74; P = .04) and age ≥50 years (HR, 3.97; P = .02) was associated with death due to disease. The 10-year local recurrence- and metastatic-free survival were 79% and 72%. Of the patients with a local recurrence (n = 11), 7 (64%) recurred at a higher histological grade. Patient age ≥50 years was associated with local recurrence (HR, 10.03; P = .02) and metastatic disease (HR, 4.20; P = .02). CONCLUSION: Advancing patient age was an independent risk factor for worse survival and disease recurrence. Tumors often recurred locally at a higher grade and as such wide local excision remains the treatment of choice for these tumors.


Asunto(s)
Neoplasias Óseas/mortalidad , Neoplasias Óseas/cirugía , Condrosarcoma/mortalidad , Condrosarcoma/cirugía , Huesos Pélvicos/cirugía , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/patología , Condrosarcoma/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Huesos Pélvicos/patología , Modelos de Riesgos Proporcionales , Procedimientos Quirúrgicos Reconstructivos , Resultado del Tratamiento , Adulto Joven
13.
J Surg Oncol ; 121(3): 570-577, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31902136

RESUMEN

BACKGROUND: Joint-preserving intercalary tumor resection can result in better proprioception and a more normal joint function after reconstruction. However, most reported reconstruction techniques are usually associated with frequent complications. Therefore, the approach of reconstruction following joint-preserving tumor resection warrants further study. METHODS: Between September 2016 and October 2018, 12 patients with metaphyseal malignant bone tumors around the knee joint were treated by joint-preserving intercalary resections with the aid of three-dimensional (3D)-printed osteotomy guide plates and reconstructions using 3D-printed intercalary prostheses. We assessed the accuracy of the resection by comparing the cross sections at the resection plane with 3D-printed matching surface of the prostheses. The functional outcomes, complications and oncological status were also evaluated. RESULTS: All patients were observed for 7 to 32 months with an average follow-up of 22.5 months. The achieved resection was accurate, with accurate matching between the residual bone and prosthesis. The mean MSTS score was 28 (range, 26-30). Superficial infection occurred in two patients. Local recurrence was observed in one patient, while pulmonary metastasis was identified in one patient. CONCLUSIONS: The personalized osteotomy guide plate and prosthesis based on 3D printing technique facilitate joint-preserving tumor resection and functional reconstruction. However, longer follow-up and larger sample size are required to clarify its long-term outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Asunto(s)
Enfermedades Óseas/cirugía , Neoplasias Óseas/cirugía , Articulación de la Rodilla/cirugía , Tratamientos Conservadores del Órgano/métodos , Impresión Tridimensional/instrumentación , Implantación de Prótesis , Procedimientos Quirúrgicos Reconstructivos/métodos , Adolescente , Adulto , Neoplasias Óseas/patología , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteotomía , Pronóstico , Diseño de Prótesis , Estudios Retrospectivos
14.
Crit Rev Oncol Hematol ; 146: 102864, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31986318

RESUMEN

Chemotherapeutic agents (docetaxel, cabazitaxel), hormonal therapies (abiraterone, enzalutamide) and radium-223 improve survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC). Combinations of radium-223 with these agents or novel drugs have been investigated in order to improve survival and decrease bone-related morbidity. In mCRPC, clinical and preclinical data indicate that radium-223, abiraterone and enzalutamide have a direct effect on prostate cancer cells and bone microenvironment when administered as single agents. Initial results from studies of radium-223 and abiraterone, enzalutamide or docetaxel demonstrated efficacy without any safety concern in pre-treated mCRPC; however, this safety profile changed when radium-based combination therapies were administered in un-pretreated mCRPC. This review underline the biological rationale for combining radium strategies, investigating their effects on bone in terms of control of skeletal-related events and bone disease progression. The aim is to understand the possible reasons why different radium-based combination treatments can led to different clinical outcomes.


Asunto(s)
Antineoplásicos/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Radiofármacos/administración & dosificación , Radiofármacos/uso terapéutico , Radio (Elemento)/uso terapéutico , Androstenos/uso terapéutico , Neoplasias Óseas/secundario , Docetaxel/uso terapéutico , Humanos , Masculino , Orquiectomía , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/uso terapéutico , Radioisótopos/uso terapéutico , Resultado del Tratamiento , Microambiente Tumoral
15.
Pathologe ; 41(2): 106-115, 2020 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-31993697

RESUMEN

The integrative evaluation of histology and corresponding imaging is essential for the classification of bone tumors. Until a few years ago, there were hardly any molecular markers that could be used for diagnostic purposes. However, exome- and genome-wide sequencing analyses have since uncovered a number of tumor-specific aberrations that can be very helpful in ambiguous cases. In addition to characteristic gene mutations (e.g. H3F3A and H3F3B in giant-cell tumors and chondroblastomas), the detection of fusion transcripts (e.g. structural rearrangements in the AP­1 transcription factors FOS and FOSB in osteoid osteomas and osteoblastomas) plays an increasing role. The article gives an overview of the current state of knowledge of the most important alterations in bone tumors.


Asunto(s)
Neoplasias Óseas/patología , Neoplasias Óseas/diagnóstico , Humanos
16.
Virchows Arch ; 476(1): 147-157, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31741049

RESUMEN

Bone tumours are difficult to diagnose and treat, as they are rare and over 60 different subtypes are recognised. The emergence of next-generation sequencing has partly elucidated the molecular mechanisms behind these tumours, including the group of bone forming tumours (osteoma, osteoid osteoma, osteoblastoma and osteosarcoma). Increased knowledge on the molecular mechanism could help to identify novel diagnostic markers and/or treatment options. Osteoid osteoma and osteoblastoma are bone forming tumours without malignant potential that have overlapping morphology. They were recently shown to carry FOS and-to a lesser extent-FOSB rearrangements suggesting that these tumours are closely related. The presence of these rearrangements could help discriminate these entities from other lesions with woven bone deposition. Osteosarcoma is a malignant bone forming tumour for which different histological subtypes are recognised. High-grade osteosarcoma is the prototype of a complex karyotype tumour, and extensive research exploring its molecular background has identified phenomena like chromothripsis and kataegis and some recurrent alterations. Due to lack of specificity, this has not led to a valuable novel diagnostic marker so far. Nevertheless, these studies have also pointed towards potential targetable drivers of which the therapeutic merit remains to be further explored.


Asunto(s)
Neoplasias Óseas/patología , Osteoblastoma/patología , Osteoma Osteoide/patología , Osteosarcoma/patología , Neoplasias Óseas/genética , Reordenamiento Génico , Genes p53 , Predisposición Genética a la Enfermedad , Humanos , Osteoblastoma/genética , Osteoma/genética , Osteoma/patología , Osteoma Osteoide/genética , Proteína de Retinoblastoma/genética
17.
Virchows Arch ; 476(1): 109-119, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31802230

RESUMEN

Ewing sarcoma (ES) and Ewing-like sarcomas are highly aggressive round cell mesenchymal neoplasms, most often occurring in children and young adults. The identification of novel molecular alterations has greatly contributed to a profound reappraisal of classification, to the extent that the category of undifferentiated round cell sarcoma has significantly shrunk. In fact, in addition to Ewing sarcoma, we currently recognize three main categories: round cell sarcomas with EWSR1 gene fusion with non-ETS family members, CIC-rearranged sarcomas, and BCOR-rearranged sarcomas. Interestingly, despite significant morphologic overlap, most of these entities tend to exhibit morphologic features predictive of the underlying molecular alteration. Ewing sarcoma is the prototype of round cell sarcoma whereas in CIC sarcomas, focal pleomorphism and epithelioid morphology can predominate. BCOR sarcomas often exhibit a spindled neoplastic cell population. NFATC2 sarcoma may exhibit remarkable epithelioid features, and PATZ1 sarcomas often feature a sclerotic background. The differential diagnosis for these tumors is rather broad, and among round cell sarcomas includes alveolar rhabdomyosarcoma, desmoplastic small round cell tumor, poorly differentiated round cell synovial sarcoma, small cell osteosarcoma, and mesenchymal chondrosarcoma. A combination of morphologic, immunohistochemical, and molecular findings allows accurate classification in most cases. A granular diagnostic approach to Ewing sarcoma and Ewing-like sarcomas is justified by significant differences in terms of both response to chemotherapy and overall survival. As all these entities are in part defined by specific fusion genes, a molecular diagnostic approach based on NGS technology should be considered. In consideration of the extreme rarity of many of these tumor entities, referral to expert rare cancer centers or to rare cancer networks represents the best strategy in order to minimize diagnostic inaccuracy, and allow proper patient management.


Asunto(s)
Neoplasias Óseas/patología , Sarcoma de Ewing/patología , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/genética , Diagnóstico Diferencial , Proteínas de Homeodominio/genética , Humanos , Inmunohistoquímica , Proteínas Proto-Oncogénicas/genética , Proteína EWS de Unión a ARN/genética , Proteína FUS de Unión a ARN/genética , Proteínas Represoras/genética , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/genética
18.
DNA Cell Biol ; 39(1): 78-91, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31765229

RESUMEN

microRNA plays an important role in the development of tumors, including osteosarcoma. However, the role of miR-1225-5p in osteosarcoma is currently unclear. First, we found that miR-1225-5p was downregulated in osteosarcoma cells relative to its levels in normal bone tissue by analyzing GSE28423 data in the GEO database. Using GSE39040, we found that low miR-1225-5p expression is associated with poor prognosis in patients with osteosarcoma, and we also found low miR-1225-5p expression in patients with recurrent osteosarcoma. We later demonstrated that osteosarcoma cell lines transfected with miR-1225-5p mimic had decreased ability to proliferate, migrate, and invade relative to control cells. To elucidate the mechanism by which miR-1225-5p inhibits the development of osteosarcoma, we identified Sox9 as a target gene of miR-1225-5p using the TargetScan website. We confirmed that Sox9 is the target gene of miR-1225-5p using the luciferase reporter assay. We then found that Sox9 is highly expressed in osteosarcoma by analyzing the GSE16088 and GSE42352 datasets and that high expression of Sox9 is associated with poor prognosis in patients with osteosarcoma using the R2 database. Further analysis using the TARGET database uncovered that high Sox9 expression is associated with a high recurrence rate in patients with osteosarcoma. Transfection of Sox9 siRNA inhibited the proliferation, migration, and invasiveness of osteosarcoma cells. We transfected miR-1225-5p together with Sox9 siRNA into osteosarcoma cells, observing strong inhibition of proliferation, migration, and invasiveness. Finally, exogenous expression of Sox9 partially reversed the anticancer effects of miR-1225-5p in osteosarcoma cells. Taken together, our findings suggest that miR-1225-5p functions as a tumor suppressor in osteosarcoma by targeting Sox9, thereby revealing new therapeutic targets for osteosarcoma.


Asunto(s)
Neoplasias Óseas/genética , Genes Supresores de Tumor , MicroARNs/genética , Osteosarcoma/genética , Factor de Transcripción SOX9/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Niño , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Recurrencia Local de Neoplasia/genética , Osteosarcoma/patología , Pronóstico , Interferencia de ARN
19.
Gene ; 726: 144145, 2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-31743769

RESUMEN

Long non-coding RNA SNHG12 (lncSNHG12) plays important roles in the onset and progression of various cancers. However, the role of lncSNHG12 in osteosarcoma (OS) remains unclear. Therefore, the aim of the present study was to determine the function of lncSNHG12 in OS. A bioinformatics website was used to predict the downstream targets of lncSNHG12. In addition, qRT-PCR was employed to assess lncSNHG12 expression in OS cells. Cell migration and proliferation in vitro were verified using the transwell migration, clone formation, and CCK8 assays. Tumor metastasis and xenograft formation were monitored in nude mice with or without downregulation of lncSNHG12. The results show that lncSNHG12 was upregulated in OS cell lines. Downregulation lncSNHG12 suppressed the metastasis and proliferation both in vitro and in vivo. Also, lncSNHG12 downregulation suppressed the expression of insulin growth factor 1 receptor (IGF1R) expression through sponging miR-195-5p, which was verified with the luciferase reporter assay and rescue experiments. These findings suggest that downregulation of lncSNHG12 may suppress aggressive OS phenotypes. Moreover, lncSNHG12 silencing inhibited OS metastasis and growth by targeting the miR-195-5p/IGF1R axis, which represents a candidate marker and target for OS treatment and management.


Asunto(s)
Proliferación Celular/genética , Regulación hacia Abajo/genética , MicroARNs/genética , Metástasis de la Neoplasia/genética , Osteosarcoma/genética , ARN Largo no Codificante/genética , Receptor IGF Tipo 1/genética , Animales , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Línea Celular , Línea Celular Tumoral , Movimiento Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Osteoblastos/patología , Osteosarcoma/patología , Pronóstico , Regulación hacia Arriba/genética
20.
Cancer Sci ; 111(1): 36-46, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31705593

RESUMEN

Osteosarcoma (OS) is a highly malignant bone tumor and the prognosis for non-responders to chemotherapy remains poor. Previous studies have shown that human sarcomas contain sarcoma-initiating cells (SIC), which have the characteristics of high tumorigenesis and resistance to chemotherapy. In the present study, we characterized SIC of a novel OS cell line, screened for SIC-related genes, and tried to regulate the proliferation of OS by metabolic interference. Initially, we established a new human OS cell line (OS13) and isolated clones showing higher tumorigenesis as SIC (OSHIGH ) and counterpart clones. OSHIGH cells showed chemoresistance and their metabolism highly depended on aerobic glycolysis and suppressed oxidative phosphorylation. Using RNA-sequencing, we identified LIN28B as a SIC-related gene highly expressed in OSHIGH cells. mRNA of LIN28B was expressed in sarcoma cell lines including OS13, but its expression was not detectable in normal organs other than the testis and placenta. LIN28B protein was also detected in various sarcoma tissues. Knockdown of LIN28B in OS13 cells reduced tumorigenesis, decreased chemoresistance, and reversed oxidative phosphorylation function. Combination therapy consisting of a glycolysis inhibitor and low-dose chemotherapy had antitumor effects. In conclusion, manipulation of glycolysis combined with chemotherapy might be a good adjuvant treatment for OS. Development of immunotherapy targeting LIN28B, a so-called cancer/testis antigen, might be a good approach.


Asunto(s)
Neoplasias Óseas/genética , Glucólisis/genética , Osteosarcoma/genética , Proteínas de Unión al ARN/genética , Animales , Neoplasias Óseas/patología , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Osteosarcoma/patología , Fosforilación Oxidativa , Placenta/patología , Embarazo , Pronóstico , ARN Mensajero/genética , Testículo/patología
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