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1.
Injury ; : 111264, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38105150

RESUMEN

BACKGROUND: In acetabular fracture surgery, an infra-acetabular screw (IAS) is inserted from the anterior to the posterior column through the infra-acetabular corridor to stabilize both columns. Although the IAS is useful for increasing fixation strength, proper placement requires proficiency and often results in extraosseous screw penetration. The complex anatomy of the infra-acetabular corridor and difficult intraoperative detection of the ideal insertion point and angle make proper placement of the IAS challenging. This study aimed to detect the ideal insertion point and angle of the IAS based on anatomical landmarks that can be directly identified intraoperatively. METHODS: We retrospectively reviewed the pelvic CT of 50 adults who underwent serial slice CT imaging. The pelvic inlet plane (PIP), which contains the anterior border of both the sacroiliac joint and posterior superior edge of the pubic symphysis, was used as the reference plane for the pelvic coordinate system to simulate the ideal insertion of IAS. The distance from the posterior superior edge of the pubic symphysis to the ideal insertion point of the IAS (IAS distance) and the angle and length of the IAS that could be inserted from the ideal insertion point were measured. RESULTS: The mean IAS distance was 61.0 ± 5.7 mm (57.6 ± 4.3 mm in men and 64.4 ± 4.9 mm in women). The mean angle between ideal IAS and yz-plane on the outlet view (α-angle) was 8.4 ± 6.6 ° (6.4 ± 5.6° in men and 10.5 ± 7.0° in women). The mean angle between ideal IAS and y-axis on the yz-plane (ß-angle) was 86.5 ± 10.6 ° (86.0 ± 10.3° in men and 87.0 ± 10.9° in women). The length of IAS was 97.1 ± 4.7 mm in men and 89.2 ± 3.6 mm in women. CONCLUSION: The IAS ideal insertion point detected as a distance from the pubic symphysis may aid in the proper insertion of the IAS during surgery. The insertion angle was parallel or tilted 10 ° laterally to the longitudinal axis in the pelvic outlet plane and almost perpendicular to the PIP in the sagittal plane when inserted from the ideal insertion point.

2.
Acta Med Okayama ; 77(5): 511-516, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37899262

RESUMEN

Sarcopenia and malnutrition are increasing in older adults and are reported risk factors for functional impairment after hip fracture surgery. This study aimed to investigate the associations between skeletal muscle mass loss, malnutrition, and postoperative walking ability in patients with hip fracture. We retrospectively reviewed patients who underwent intertrochanteric fracture surgery at our institute. The psoas muscle index, controlling nutritional status score, and functional ambulation category (FAC) were used to evaluate skeletal muscle mass, nutritional status, and walking ability, respectively. Six months after surgery, walking ability was assessed as either "gait disturbance" or "independent gait". Multivariate binomial logistic regression analysis, with skeletal muscle mass, nutritional status, and other factors, was used to predict the risk of being assigned to the gait disturbance group. This study included 95 patients (mean age, 85.2 years; 70 women). Sixty-six patients had low skeletal muscle mass, 35 suffered from malnutrition, and 28 had both. Malnutrition and low skeletal muscle mass were significantly associated with postoperative gait disturbance (FAC < 3). Preoperative low skeletal muscle mass and malnutrition were risk factors for postoperative poor walking ability. Further preventive interventions focusing on skeletal muscle mass and nutritional status are required.


Asunto(s)
Fracturas de Cadera , Desnutrición , Sarcopenia , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Desnutrición/complicaciones , Desnutrición/patología , Sarcopenia/complicaciones , Sarcopenia/patología , Músculos , Caminata , Fracturas de Cadera/cirugía , Evaluación Nutricional , Músculo Esquelético/patología
3.
Trauma Case Rep ; 44: 100803, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36874951

RESUMEN

Although there are some reports highlighting the applicability of double plates in distal femoral fractures, there is no standard approach or fixation method for supracondylar fractures combined with posterior coronal shear fractures. We report a case of distal femoral fracture treated with a lateral locking plate and posterior buttress plate using anterolateral and posterolateral approaches from one incision. A 70-year-old man was hit by a motorcycle and had an intra-articular distal femoral fracture involving a long medial proximal spike and a single lateral condyle fragment, with the lateral condyle fragment posteriorly displaced. A 12-cm lateral skin incision was made, and the joint was developed using a para-patellar approach from the anterior to iliotibial band. Posterior buttress plate fixation was successfully performed from behind the iliotibial band using a posterolateral approach, followed by cannulated cancellous screw and lateral locking plate fixation from the anterolateral window. Combined anterolateral and posterolateral approaches from one incision enable intra-articular exposure and fixation based on fixation principles for lateral condyle fragments combined with supracondylar fracture.

4.
Cureus ; 15(2): e35440, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36994269

RESUMEN

Seat belts with shoulder restraints have decreased the frequency of life-threatening severe chest trauma caused by car accidents. However, the introduction of seat belt legislation has led to an increase in a specific pattern of blunt trauma known as seat belt syndrome, which includes rib, clavicle, spine, and sternum fractures, as well as rupture of hollow pelvic and abdominal viscera, mesenteric tears, and major vessel injuries. The shoulder restraint part of the three-point seat belt commonly rests near or over the female and male breast. A 54-year-old female presented to our emergency department complaining of swelling and pain in her left breast immediately after a traffic accident. The patient had used a seat belt with a shoulder restraint. Bruising was noted along her chest where there had been seat belt contact. Her breast hematoma was most likely caused by breast tissue compression between her rib and the seat belt. Contrast-enhanced computed tomography demonstrated a sizable breast hematoma with active arterial contrast material extravasation, as well as multiple left rib fractures. The patient was conservatively treated with analgesic and anti-inflammatory drugs. Complete resolution was achieved, and her breast returned to its normal appearance. Although endovascular treatment and surgical hemostasis have been proposed for the treatment of breast injuries with active bleeding, conservative treatment such as compression hemostasis may be feasible.

5.
Foot Ankle Surg ; 29(1): 97-102, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36473825

RESUMEN

BACKGROUND: The optimal treatment of displaced intra-articular calcaneal fractures (DIACF) is controversial. This study compared the fixation stability of screws and locking plates in DIACF treated via the sinus tarsi approach (STA). METHODS: We retrospectively evaluated 118 DIACF cases treated via STA and extracted data that could affect treatment outcomes. Loss of Böhler's angle after surgery was measured to compare fixation stability. RESULTS: The loss of Böhler's angles was significantly smaller in the locking plate group than in the screw group (2.6 ± 2.7º vs. 5.6 ± 5.3º, P < 0.01). There was no difference in the clinical outcomes between the groups. On multivariate logistic regression analysis, screw fixation was significantly associated with loss of Böhler's angle by> 10º (odds ratio, 8.63; 95% confidence interval, 1.16-64.4; P < 0.05). CONCLUSIONS: Locking plate fixation is more reliable than screw fixation for preventing correction loss in DIACF treated via STA. LEVEL OF EVIDENCE: III.


Asunto(s)
Traumatismos del Tobillo , Calcáneo , Fracturas Óseas , Fracturas Intraarticulares , Humanos , Talón , Estudios Retrospectivos , Fijación Interna de Fracturas , Calcáneo/cirugía , Fracturas Intraarticulares/diagnóstico por imagen , Fracturas Intraarticulares/cirugía , Estudios de Seguimiento , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Resultado del Tratamiento , Placas Óseas , Tornillos Óseos
6.
J Hand Surg Asian Pac Vol ; 27(4): 691-697, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35965373

RESUMEN

Background: Identification of the risk factors for surgical site infection (SSI) can be a straightforward and cost-effective measure to reduce or prevent the occurrence of SSI. However, there are no studies that revealed risk factors for SSI for traumatic upper extremity amputation. The aim of this study is to investigate the risk factors that promote SSI after surgery for traumatic upper extremity amputation using a large nationwide database. Methods: We used data from the Japan Trauma Data Bank. Diagnoses were defined using the Abbreviated Injury Scale code. We applied multivariate logistic regression to evaluate the infection risk factor. We chose age, sex, vital signs, cause and type of trauma, concomitant injury, diabetes, amputation level, Glasgow coma scale, Injury Severity Score (ISS) and blood transfusion within 24 hours following hospital arrival as confounders. Receiver operating characteristic (ROC) curve analysis was adopted to identify thresholds for change in infection risk. We also applied propensity score (PS) matching to adjust for confounding factors that may affect the outcome. Results: A total of 1,150 patients (967 males, 183 females) had traumatic upper extremity amputation. The mean patient age was 46.5 years. A total of 21 patients (1.8%) suffered from SSI. ISS, blood transfusion, systolic blood pressure (BP) and the upper extremity amputation except for finger were identified as the independent significant risk factors for SSI occurrence by the multivariate analysis (p < 0.05, p < 0.005, p < 0.05 and p < 0.005, respectively). ROC modelling revealed that patients with ISS of over 9 or systolic BP of over 160 had a risk for SSI. After PS matching, the patients with blood transfusion or systolic BP of over 160 had a significantly higher risk of infection (OR 9.0; p = 0.01 and OR 7.0; p = 0.03, respectively). Conclusions: In treating patients with these risk factors, we must be especially careful in performing thorough debridement and wound care. Level of Evidence: Level II (Therapeutic).


Asunto(s)
Amputación Traumática , Amputación Quirúrgica/efectos adversos , Amputación Traumática/cirugía , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Factores de Riesgo , Extremidad Superior/cirugía
7.
BMC Emerg Med ; 21(1): 104, 2021 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-34530735

RESUMEN

BACKGROUND: Patients with traumatic cardiac arrest (TCA) are known to have poor prognoses. In 2003, the joint committee of the National Association of EMS Physicians and the American College of Surgeons Committee on Trauma proposed stopping unsuccessful cardiopulmonary resuscitation (CPR) sustained for > 15 min after TCA. However, in 2013, a specific time-limit for terminating resuscitation was dropped, due to the lack of conclusive studies or data. We aimed to define the association between emergency medical services transport time and survival to demonstrate the survival curve of TCA. METHODS: A retrospective review of the Japan Trauma Data Bank. Inclusion criteria were age ≥ 16, at least one trauma with Abbreviated Injury Scale score (AIS) ≥ 3, and CPR performed in a prehospital setting. Exclusion criteria were burn injury, AIS score of 6 in any region, and missing data. Estimated survival rate and risk ratio for survival were analyzed according to transport time for all patients. Analysis was also performed separately on patients with sustained TCA at arrival. RESULTS: Of 292,027 patients in the database, 5336 were included in the study with 4141 sustained TCA. Their median age was 53 years (interquartile range (IQR) 36-70), and 67.2% were male. Their median Injury Severity Score was 29 (IQR 22-41), and median transport time was 11 min (IQR 6-17). Overall survival after TCA was 4.5%; however, survival of patients with sustained TCA at arrival was only 1.2%. The estimated survival rate and risk ratio for sustained TCA rapidly decreased after 15 min of transport time, with estimated survival falling below 1%. CONCLUSION: The chances of survival for sustained TCA declined rapidly while the patient is transported with CPR support. Time should be one reasonable factor for considering termination of resuscitation in patients with sustained TCA, although clinical signs of life, and type and severity of trauma should be taken into account clinically.


Asunto(s)
Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco Extrahospitalario , Tasa de Supervivencia , Tiempo de Tratamiento , Adulto , Anciano , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
8.
Acta Med Okayama ; 75(2): 177-185, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33953423

RESUMEN

This retrospective study sought to elucidate the incidence rates of roof impaction (RI) and marginal impaction (MI) and radiological and clinical outcomes of open reduction and internal fixation (ORIF) for RI and MI in geriatric acetabular fractures. The cases of 68 patients aged ≥ 65 years (mean 71 years) treated with ORIF were analyzed. MI was present in 12 fractures (67%) and an RI of the weight-bearing surface was present in 24 (46%) of the potential fracture types. Regarding the reduction quality, 54% of the reductions were graded as anatomical, 37% as imperfect, and 9% as poor. In the clinical evaluations of the 45 patients who had > 1-year follow-up (follow-up rate: 66.2%), 18% were graded as excellent, 53% as good, 16% as fair, and 13% as poor. An anatomic reduction was strongly associated with good or excellent clinical and radiological outcomes. CT was superior to radiographs for detecting the residual displacement postoperatively. Postoperative deep infection occurred in four patients. Three patients (6.7%) underwent a total hip arthroplasty conversion due to secondary osteoarthritis of the hip. We recommend ORIF as the preferred surgical treatment option for displaced acetabular fractures in elderly patients.


Asunto(s)
Acetábulo/cirugía , Fijación Interna de Fracturas/métodos , Fracturas de Cadera/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Estudios Retrospectivos
9.
Arch Orthop Trauma Surg ; 141(7): 1139-1148, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32529385

RESUMEN

INTRODUCTION: Radiation-induced pathological fractures show high nonunion and infection rates. Successful treatment of postoperative infections of these fractures without limb amputation is extremely rare. METHODS: We report two cases of postoperative infection of pathological femoral fracture after radiation therapy for soft tissue tumors. Considering the poor condition of the irradiated site, a two-staged operation was selected to create the optimal situation for bone union. The treatment involved the Masquelet technique, latissimus dorsi (LD) flap, and a free vascularized fibula graft (FVFG). In the first stage, we drastically resected the necrotic bone and the surrounding infected tissue and placed antibiotic polymethylmethacrylate space on the bone gap according to the Masquelet technique. Next, we used an Ilizarov external fixator as a temporizing stabilizer and performed the LD flap. Six weeks later, in the second stage, we changed the external fixation to plate fixation; packed the artificial bone (ß-TCP) and autograft bone to the induced membrane; and performed FVFG on the other side of the plate. As postoperative therapy, toe touch was allowed immediately, and partial weight bearing was started 2 months after second surgery. RESULTS: Both patients achieved bone union and were able to walk without postoperative complications. At the 2-year follow-up, there was no recurrence of infection. CONCLUSION: Our treatment is effective for controlling postoperative infection of radiation-induced pathological fracture.


Asunto(s)
Fracturas del Fémur/cirugía , Fijación de Fractura/efectos adversos , Fracturas Espontáneas/cirugía , Infección de la Herida Quirúrgica , Humanos , Resultado del Tratamiento
10.
Trauma Case Rep ; 25: 100268, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31890833

RESUMEN

Septic arthritis in distal interphalangeal (DIP) joints sometimes occurs in association with mucous cysts or after the surgical treatment of mallet fingers. Recently, several studies have demonstrated the effectiveness of the Masquelet technique in the treatment of bone defects caused by trauma or infection. However, only few studies have reported the use of this technique for septic arthritis in small joints of the hand, and its effectiveness in treating septic arthritis in DIP joints remains unclear. We report the clinical and radiological outcomes of three patients who were treated with the Masquelet technique for septic arthritis in DIP joints. One patient had uncontrolled diabetes and another had rheumatoid arthritis treated with methotrexate and prednisolone. The first surgical stage involved thorough debridement of the infection site, including the middle and distal phalanx. We placed an external fixator from the middle to the distal phalanx and then packed the cavity of the DIP joint with antibiotic cement bead of polymethylmethacrylate (40 g) including 2 g of vancomycin and 200 mg of minocycline. At 4-6 weeks after the first surgical stage, the infection had cleared, and the second surgical stage was performed. The external fixator and cement bead were carefully removed while carefully preserving the surrounding osteo-induced membrane. The membrane was smooth and nonadherent to the cement block. In the second surgical stage, an autogenous bone graft was harvested from the iliac bone and inserted into the joint space, within the membrane. The bone graft, distal phalanx, and middle phalanx were fixed with Kirschner wires and/or a soft wire. Despite the high risk of infection, bone union was achieved in all patients without recurrence of infection. Although the Masquelet technique requires two surgeries, it can lead to favorable clinical and radiological outcomes for infected small joints of the hand.

11.
Rinsho Ketsueki ; 61(12): 1654-1659, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-33441516

RESUMEN

A 76-year-old male with lower-limb weakness was admitted to our hospital where thrombocytopenia and anemia were noticed. CT showed massive splenomegaly and multiple nodules inside the spleen. Bone marrow examination showed an increase of macrophages with large cytoplasm. Suspected of splenic lymphoma, the patient underwent splenectomy. Spleen specimens were histologically analyzed and suggested the probability of Gaucher's disease (GD). Leukocyte glucocerebrosidase (GBA) enzyme activity had decreased to 1.25 nmol/mg, and mutation analysis of GBA revealed two missense variants, p.D448H (D409H), p.L483P (L444P), which confirmed the diagnosis of type I GD. Fourteen months after splenectomy, he developed right buttock pain, and pelvic magnetic resonance imaging showed a fragile right pubic and pelvic fracture. We initiated injection of imiglucerase as enzyme replacement therapy (ERT) and administered bisphosphonate. His symptoms gradually improved without surgical treatment. In addition, thrombocytopenia and anemia also improved, and angiotensin-converting enzyme levels decreased. Type I GD should be considered a differential diagnosis of giant splenomegaly and thrombocytopenia, even in the elderly. ERT or substrate reduction therapy should be administrated to GD patients, while paying attention to the development of bone lesions.


Asunto(s)
Fracturas Óseas , Enfermedad de Gaucher , Glucosilceramidasa , Anciano , Terapia de Reemplazo Enzimático , Fracturas Óseas/complicaciones , Fracturas Óseas/tratamiento farmacológico , Enfermedad de Gaucher/complicaciones , Enfermedad de Gaucher/tratamiento farmacológico , Glucosilceramidasa/uso terapéutico , Humanos , Masculino , Esplenectomía
12.
Arch Orthop Trauma Surg ; 140(4): 481-485, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31642955

RESUMEN

BACKGROUND: Postoperative thrombosis of the external iliac artery (EIA) following open reduction and internal fixation for acetabular fracture is extremely rare. PURPOSE: To report a patient with EIA thrombosis following open reduction and internal fixation using the modified ilioinguinal approach for acetabular fractures. STUDY DESIGN: This is a case report of a 69-year-old male with a left acetabular fracture who was treated surgically. METHODS: A 69-year-old male presented with left hip pain after a 1.5-m fall. Radiographs revealed left acetabular anterior wall and posterior hemitransverse fractures with dome impaction. Computed tomography (CT) showed atherosclerotic changes in many arteries. Open reduction and internal fixation were performed using the modified ilioinguinal approach. Adhesion around the external iliac vessels was severe, and the external iliac vein (EIV) ruptured during exposure. After EIV repair, anatomical reduction was achieved and the fracture was fixed using a reconstruction plate. Nine hours after surgery, the left lower limb showed acute ischemic symptoms. Contrast-enhanced CT indicated complete occlusion of the left EIA. The patient was immediately taken for a thrombectomy via EIA cut-down using a Fogarty catheter. Postoperatively, he had palpable dorsalis pedis and posterior tibial pulses; however, post-reperfusion compartment syndrome developed. Fasciotomy of the left leg was performed. RESULTS: At the 2-year and 4-month follow-up, he was pain-free in his hip and leg. Although he was walking with a cane, activity was limited due to a mild foot drop. CONCLUSIONS: It is very important for surgeons to consider EIA thrombosis as a potential complication following open reduction and internal fixation. In this case, EIA thrombosis could be explained by preoperative atherosclerotic changes and intraoperative vascular handling procedures. Preoperative screening and management, and meticulous surgical procedures are necessary for patients with a high risk of thrombosis.


Asunto(s)
Arteria Ilíaca , Reducción Abierta/efectos adversos , Trombosis , Acetábulo/lesiones , Acetábulo/cirugía , Anciano , Fracturas de Cadera/cirugía , Humanos , Arteria Ilíaca/fisiopatología , Arteria Ilíaca/cirugía , Masculino , Trombosis/etiología , Trombosis/cirugía
13.
Int Immunol ; 31(4): 187-198, 2019 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-30508092

RESUMEN

CD11b+ myeloid subpopulations, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), play crucial roles in the suppression of T-cell-mediated anti-tumor immunity. Regulation of these cell types is a primary goal for achieving efficient cancer immunotherapy. We found that metformin (Met) induces CD11b+-cell-mediated growth inhibition of a K7M2neo osteosarcoma independent of T cells, as growth inhibition of K7M2neo was still observed in wild-type (WT) mice depleted of T cells by antibodies and in SCID; this contrasted with the effect of Met on Meth A fibrosarcoma, which was entirely T-cell-dependent. Moreover, the inhibitory effect seen in SCID was abrogated by anti-CD11b antibody injection. PMN-MDSCs were significantly reduced in both spleens and tumors following Met treatment. In TAMs, production of IL-12 and TNF-α, but not IL-10, became apparent, and elevation of MHC class II with reduction of CD206 was observed, indicating a shift from an M2- to M1-like phenotype via Met administration. Metabolically, Met treatment decreased basal respiration and the oxygen consumption rate (OCR)/extracellular acidification rate (ECAR) ratio of CD11b+ cells in tumors, but not in the spleen. In addition, decreased reactive oxygen species (ROS) production and proton leakage in MDSCs and TAMs were consistently observed in tumors. Uptake of both 2-deoxy-2-d-glucose (2-NBDG) and BODIPY® decreased in MDSCs, but only BODIPY® incorporation was decreased in TAMs. Overall, our results suggest that Met redirects the metabolism of CD11b+ cells to lower oxidative phosphorylation (OXPHOS) while elevating glycolysis, thereby pushing the microenvironment to a state that inhibits the growth of certain tumors.


Asunto(s)
Macrófagos/inmunología , Metformina/metabolismo , Células Mieloides/inmunología , Células Supresoras de Origen Mieloide/inmunología , Osteosarcoma/inmunología , Animales , Antígeno CD11b/metabolismo , Diferenciación Celular , Línea Celular Tumoral , Reprogramación Celular , Citocinas/metabolismo , Humanos , Inmunidad , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Fosforilación Oxidativa , Células TH1/inmunología , Células Th2/inmunología , Microambiente Tumoral
14.
Hum Cell ; 31(2): 167-174, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29450702

RESUMEN

Synovial sarcoma is an aggressive mesenchymal malignancy characterized by unique gene fusions. Tissue culture cells are essential tools for further understanding tumorigenesis and anti-cancer drug development; however, only a limited number of well-characterized synovial sarcoma cell lines exist. Thus, the objective of this study was to establish a patient-derived synovial sarcoma cell line. We established a synovial sarcoma cell line from tumor tissue isolated from a 72-year-old female patient. Prepared cells were analyzed for the presence of gene fusions by fluorescence in situ hybridization, RT-PCR, and karyotyping. In addition, the resulting cell line was characterized by viability, short tandem repeat, colony and spheroid formation, and invasion analyses. Differences in gene enrichment between the primary tumor and cell line were examined by mass spectrometric protein expression profiling and KEGG pathway analysis. Our analyses revealed that the primary tumor and NCC-SS1-C1 cell line harbored the SS18-SSX1 fusion gene typical of synovial sarcoma and similar proteomics profiles. In vitro analyses also confirmed that the established cell line harbored invasive, colony-forming, and spheroid-forming potentials. Moreover, drug screening with chemotherapeutic agents and tyrosine kinase inhibitors revealed that doxorubicin, a subset of tyrosine kinase inhibitors, and several molecular targeting drugs markedly decreased NCC-SS1-C1 cell viability. Results from the present study support that the NCC-SS1-C1 cell line will be an effective tool for sarcoma research.


Asunto(s)
Línea Celular Tumoral , Sarcoma Sinovial/genética , Sarcoma Sinovial/patología , Anciano , Antineoplásicos/farmacología , Medios de Cultivo , ADN Bacteriano , Resistencia a Antineoplásicos , Femenino , Humanos , Cariotipificación , Espectrometría de Masas , Mycoplasma/genética , Invasividad Neoplásica , Proteómica , Secuencias Repetidas en Tándem , Transcriptoma
15.
EBioMedicine ; 25: 154-164, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29066174

RESUMEN

CD4+CD25+ regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of naïve CD4+ T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1. Rapamycin and compound C, an inhibitor of AMP-activated protein kinase (AMPK) restored the iTreg generation, further indicating the involvement of mTORC1 and AMPK. The metabolic profile of iTreg, increased Glut1-expression, and reduced mitochondrial membrane-potential and ROS production of Ti-Treg aided in identifying enhanced glycolysis upon Met-treatment. The negative impact of Met on Ti-Treg may help generation of the sustained antitumor immunity.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Metformina/administración & dosificación , Neoplasias/tratamiento farmacológico , Microambiente Tumoral/efectos de los fármacos , Quinasas de la Proteína-Quinasa Activada por el AMP , Antígenos CD/genética , Antígeno CTLA-4/genética , Factores de Transcripción Forkhead/genética , Regulación de la Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 1/genética , Humanos , Cadenas alfa de Integrinas/genética , Interleucina-10/genética , Lectinas Tipo C/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Neoplasias/genética , Neoplasias/patología , Proteínas Quinasas/genética , Receptores Inmunológicos , Sirolimus/administración & dosificación , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Transactivadores/genética
16.
Oncotarget ; 8(20): 33375-33392, 2017 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-28380419

RESUMEN

BACKGROUND: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. METHODS: Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. RESULTS: Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. CONCLUSIONS: Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Óseas/genética , MicroARN Circulante , MicroARNs/genética , Osteosarcoma/genética , Adolescente , Adulto , Animales , Células Sanguíneas/metabolismo , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Estudios de Casos y Controles , Niño , Preescolar , Terapia Combinada , Modelos Animales de Enfermedad , Exosomas , Femenino , Perfilación de la Expresión Génica , Xenoinjertos , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Biopsia Líquida , Masculino , Ratones , Metástasis de la Neoplasia , Estadificación de Neoplasias , Osteosarcoma/diagnóstico , Osteosarcoma/mortalidad , Osteosarcoma/terapia , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Adulto Joven
17.
Biomed Res Int ; 2015: 820813, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26167500

RESUMEN

Although multimodal therapies including surgery, chemotherapy, and radiotherapy have improved clinical outcomes of patients with bone and soft tissue sarcomas, the prognosis of patients has plateaued over these 20 years. Immunotherapies have shown the effectiveness for several types of advanced tumors. Immunotherapies, such as cytokine therapies, vaccinations, and adoptive cell transfers, have also been investigated for bone and soft tissue sarcomas. Cytokine therapies with interleukin-2 or interferons have limited efficacy because of their cytotoxicities. Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), an activator of the innate immune system, has been approved as adjuvant therapeutics in combination with conventional chemotherapy in Europe, which has improved the 5-year overall survival of patients. Vaccinations and transfer of T cells transduced to express chimeric antigen receptors have shown some efficacy for sarcomas. Ipilimumab and nivolumab are monoclonal antibodies designed to inhibit immune checkpoint mechanisms. These antibodies have recently been shown to be effective for patients with melanoma and also investigated for patients with sarcomas. In this review, we provide an overview of various trials of immunotherapies for bone and soft tissue sarcomas, and discuss their potential as adjuvant therapies in combination with conventional therapies.


Asunto(s)
Neoplasias Óseas/terapia , Inmunoterapia , Neoplasias de los Tejidos Conjuntivo y Blando/terapia , Osteosarcoma/terapia , Sarcoma/terapia , Humanos
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