Physical Signs and Clinical Features of Cervical Myelopathy in Elderly Patients, Especially 80 Years or Older: Comparison of 100 Consecutive Operative Cases across Three Age Groups.

STUDY DESIGN: Retrospective cohort study. PURPOSE: The present study aimed to examine the characteristics of physical signs in elderly patients with cervical myelopathy (CM) and to compare the findings in three different age groups. OVERVIEW OF LITERATURE: As the global population ages, the incidence of CM in elderly patients is increasing. METHODS: We evaluated 100 consecutive surgical patients with CM and divided them into the following groups: 80s (34 patients; mean age, 83.9 years), 70s (33 patients; mean age, 73.9 years), and 69 or younger (33 patients; mean age, 60.9 years). The clinical symptoms and physical signs were evaluated and recorded. RESULTS: Although the recovery rate decreased with increasing age, all groups demonstrated a significant improvement in clinical symptoms relative to preoperative values. The Hoffman sign and hyperreflexia of the triceps tendon were, respectively, present in 82% and 88% of patients in the 80s group, 74% and 64% of those in the 70s group, and 69% and 82% of those in the 69 or younger group, with no significant difference among the groups. In contrast, the rates of hyperreflexia of the patellar and Achilles tendons were, respectively, 59% and 32% in the 80s group, 85% and 48% in the 70s group, and 91% and 70% in the 69 or younger group, with significant differences. CONCLUSIONS: The positivity rate of the lower extremity hyperreflexia decreased significantly with increasing age in patients with CM. The absence of hyperreflexia, particularly lower extremity, is not uncommon in elderly patients with suspected CM.

Vascularized Origami Medial Femoral Condyle Flap for Finger Joint Reconstruction.

SUMMARY: Total finger joint reconstruction is challenging. Vascularized toe joint transfer is currently used for reconstruction, but it is difficult to perform, fails to achieve maximal joint flexibility, and is associated with donor-site complications. As an alternative, the authors developed a vascularized medial femoral condyle flap technique, wherein the vascularized corticoperiosteum is shaped via origami, with the donor tissue folded to fit the recipient site. In this article, the authors describe the use of this method for reconstruction of interphalangeal and metacarpophalangeal joints with a reduced range of motion. The mean age of the patients (three men and four women) was 51 years (range, 36 to 68 years), and the mean follow-up period was 3 years 1 month (range, 4 months to 5 years). In the reconstructed joints, the mean range of motion; Disabilities of the Arm, Shoulder, and Hand score; and pinch strength of the unaffected side were 55 degrees (range, 24 to 90 degrees), 2.3 (range, 0 to 6), and 98% (range, 70% to 38%), respectively. No donor-site morbidities were observed. Radiography and computed tomography scans revealed joint-like grafted tissue remodeling. The study findings suggest that the origami medial femoral condyle flap is useful for functional finger joint reconstruction. The procedure requires fabrication before grafting, but tissue harvest is relatively easy.

A Comparison of the Outcomes of Fiber-Wire® versus Stainless Steel Wire in Transosseous Wiring for Intra-Articular Fractures of the Distal Interphalangeal Joint.

Background: Different surgical techniques have been described for the treatment of intra-articular fractures involving extensor tendon insertion of the distal interphalangeal joint (DIPJ), including acute and chronic bony mallet injuries. We have been using transosseous stainless-steel wire (SSW) in select patients. In 2015, we started using a non-absorbable polyester suture (2-0 Fiber-Wire®, Arthrex, Naples, FL, USA) instead of SSWs. The aim of this study is to compare the outcomes of SSW and Fiber-Wire® (FBW) in transosseous wiring for intra-articular fractures of the DIPJ. Methods: This is a retrospective review of patients who underwent fixation of intra-articular fractures, including extensor tendon insertion of the DIPJ using a transosseous wiring technique, in the period from 2013 to 2018. SSW was used in the period from 2013 to 2014, and FBW was used from 2015 to 2018. Outcomes with regard to age, gender, time to union, range of motion at the DIPJ and complications were recorded and compared between the SSW and FBW groups. Results: Nine patients (mean age: 38 years) underwent fixation with SSW and 10 patients (mean age: 31 years) with FBW. The operative time was significantly lower in the FBW group, and all the fractures united. There were no statistically significant differences between both groups with regard to time to union or range of motion at the DIPJ. Similar complication rates were observed in both groups. Conclusions: The use of FBW in transosseous wiring for intra-articular fractures of the DIPJ can reduce operative time and provide functional results similar to that of SSWs. It can be considered as an alternative fixation technique for difficult intra-articular comminuted fractures of the DIPJ, including acute and chronic bony mallet injuries with joint subluxation. Level of Evidence: Level III (Therapeutic).

Clinical outcomes of limb salvage surgery with postoperative intensity-modulated radiation therapy for soft-tissue sarcoma and metastasis.

OBJECTIVE: The primary aim of intensity-modulated radiation therapy (IMRT) for treating soft tissue sarcoma of an extremity is the reduction of morbidity and maintenance of local control. METHODS: We evaluated the outcomes and toxicity of adjuvant IMRT following function-preserving surgery to treat patients with soft tissue sarcoma and metastasis of the extremities. We retrospectively reviewed prospective databases at Kure Medical Center and Aichi Medical University between 2013 and 2016 and identified 10 patients with lower extremity soft tissue sarcoma who underwent both limb-sparing surgery and postoperative IMRT at one of our institutions. RESULTS: There were 7 men and 3 women (mean age, 67.2 years; range, 48-87 years) included in the study. Of these, four patients were continuously disease-free, two showed no evidence of disease, and four died due to disease. The average functional score was 82% (range, 53-100%). Among the 10 patients, 2 (22%) had grade 1-2 edema and 1 (11%) had grade 2 joint stiffness. Another patient developed grade 2 acute dermatitis. There were no severe complications such as infection, tissue necrosis, fracture, or nerve palsy. CONCLUSION: Although the number of patients in this study was small, our results show that adjuvant IMRT following function-preserving surgery for soft tissue sarcoma of the extremity can be valuable for treating unmanageable tumors.

Factors associated with the decision of operative procedure for proximal femoral bone metastasis: Questionnaire survey to institutions participating the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group.

BACKGROUND: Pathological fracture of the proximal femur is a main cause of cancer patients losing their ability to walk. Although both osteosynthetic devices (predominantly intramedullary nails) and prosthetic replacement have been widely performed for treatment, controversies exist regarding which procedure should be used for the various conditions. In order to decide the eligibility criteria of a planned randomized prospective study about the treatment of pathological fractures of the proximal femur, we assessed the factors affecting the selection of operative procedures using questionnaires sent to the members of the Bone and Soft Tissue Tumor Study Group (BSTTSG) of the Japan Clinical Oncology Group (JCOG). METHODS: Questionnaire surveys to evaluate (1) the priority levels of the factors, (2) the equipoise range of each factor in situations where either procedure could be applied, (3) risk and benefit of each procedure, and (4) the degree of bone destruction affecting the selection of operative procedures, were sent to 26 institutions. RESULTS: Over 80% of the institutions answered. Orthopaedic surgeons of BSTTSG decided on the procedure according to the following factors in descending order: life expectancy, performance status before fracture, the degree of bone destruction, walking ability before fracture, general complications, the number of bone metastases in other sites, and the visceral metastasis status. With regard to bone destruction, (1) the involvement of the head, neck, calcar, and intertrochanteric region, (2) transverse destruction >1/2, and (3) soft-tissue tumor extension, were the factors that led to the choice of prosthesis treatment. CONCLUSIONS: Using these identified factors, the inclusion criteria for the prospective randomized study of the surgical treatment of metastatic bone tumors of the proximal femur were optimized. The evaluation system about the bone destruction of metastases needs to be refined through the following prospective randomized study.

Novel sluggish speed signs on ultrasound is indicative of hemangiomas.

Background Hemangiomas are sometimes difficult to diagnose with current techniques. Sluggish speed signs (SSS) are a phenomenon that: (i) cannot be depicted as Doppler flow on Doppler ultrasound; (ii) can be observed as fluid movements on Doppler ultrasound; and (iii) cannot be depicted as waveforms on pulse Doppler mode. We hypothesized that SSS could be diagnostic indicators for hemangiomas. Purpose To evaluate whether ultrasound findings, in particular those relating to SSS, are a reliable tool for detecting hemangiomas compared to magnetic resonance imaging (MRI) and the gold standard for hemangioma diagnosis: pathological examination by biopsy or after surgical resection. Material and Methods Totally, 105 patients (mean age, 44.9 years) with soft-tissue tumors underwent MRI and ultrasound examination before biopsy or tumor resection. Ultrasound findings were compared with MRI as well as pathological findings, which were used as reference. Results Hemangiomas were identified in 16 (6.25%) of the 105 patients. On MRI, flow voids showed sensitivity and specificity values of 81.3% and 96.6%, respectively. On ultrasound examination, SSS was the only finding to show equally high sensitivity (93.8%) and specificity (96.6%) for diagnosing hemangiomas. There was no significant difference in the diagnostic capabilities between these two parameters ( P = 0.479). Conclusion SSS showed a high sensitivity and specificity for diagnosing hemangiomas and therefore are useful diagnostic tools to supplement MRI.

Prognostic value of SS18-SSX fusion type in synovial sarcoma; systematic review and meta-analysis.

SS18-SSX (formerly called SYT-SSX) fusion gene has been established clinically as a molecular diagnostic test for synovial sarcoma, but the prognostic value of the fusion gene variant for survival is controversial. The objective of this systematic review is to provide an up-to-date and unprecedented summary of the prognostic impact of SS18-SSX fusion type in synovial sarcoma. Studies evaluating SS18-SSX fusion type as a prognostic marker in synovial sarcoma were systematically searched for in MEDLINE, EMBASE, and Web of Science. Comparative analysis of the pooled hazard ratios (HR) between fusion types was carried out, in order to assess the likelihood of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and metastasis-free survival (MFS). A total of 10 studies comprising 902 patients with synovial sarcoma were considered for the meta-analysis. The pooled HR for eight eligible studies evaluating for OS or DSS was 1.28 (95% confidence interval: 0.81-2.00), suggesting no significant difference between SS18-SSX1 and SS18-SSX2 (P = 0.29). For seven studies which evaluated for PFS or MFS, the presence of SS18-SSX1 may indicate a lower survival probability than that of SS18-SSX2, although the effect did not reach a level of statistical significance (P = 0.09). There was no significant difference in OS or DSS between SS18-SSX1 and SS18-SSX2, but there were indications of SS18-SSX1 being an unfavorable prognostic factor of PFS or MFS. Further studies including cohorts with a longer follow-up period are needed.

Quantitative (201)thallium scintigraphy for prediction of histological response to neoadjuvant chemotherapy in osteosarcoma; systematic review and meta-analysis.

PURPOSE: The histological assessment of tumor necrosis of the excised lesion after neoadjuvant chemotherapy is the most important prognostic factor for patients with osteosarcoma, but more early prognostic factors are needed for the adjustment of adjuvant treatment regimen. The objective of this systematic review is to provide an up-to-date and unprecedented summary of the value of (201)thallium ((201)Tl) scintigraphy for the preoperative evaluation of the chemotherapy response of osteosarcoma. METHODS: Studies evaluating (201)Tl scintigraphy for the preoperative evaluation of the chemotherapy response of osteosarcoma were systematically searched for in MEDLINE, EMBASE, and Web of Science. Pooled sensitivity and specificity for each study were calculated into 2 × 2 contingency tables. The DerSimonian-Laird random-effects method was used for determining the pooled diagnostic odds ratio and the area under curve (AUC) of the summary receiver operating characteristic (SROC) curve. RESULTS: A total of six studies with 139 patients who fulfilled all of the inclusion criteria were considered for the meta-analysis. The pooled sensitivity and specificity were 0.93 (95% CI, 0.83-0.98) and 0.63 (95% CI, 0.52-0.74), respectively. A significant difference was found between the good and poor responders in the diagnostic odds ratio. The SROC curve showed that the AUC was 0.840, indicating excellent diagnostic accuracy. There was no statistically significant heterogeneity among the six studies. CONCLUSIONS: The alteration ratio derived from (201)Tl scintigraphy was useful for evaluating the histological response of patients to neoadjuvant chemotherapy in osteosarcoma.

Prognostic value of PAX3/7-FOXO1 fusion status in alveolar rhabdomyosarcoma: Systematic review and meta-analysis.

PURPOSE: The objective of this systematic review is to provide an unprecedented summary of the prognostic impact of PAX3/7-FOXO1 fusion status in alveolar rhabdomyosarcoma. METHODS: Studies evaluating PAX3/7-FOXO1 fusion gene or its variants as a prognostic marker were systematically searched and comparative meta-analysis of overall survival was carried out. RESULTS: A total of 7 studies comprising 993 patients with rhabdomyosarcoma were included. Three eligible studies showed no significant difference of survival between fusion positive and negative alveolar rhabdomyosarcoma. Four eligible studies showed that PAX3-FOXO1 fusion variant may indicate a lower survival probability than PAX7-FOXO1, although the effect did not reach a level of statistical significance (pooled hazard ratios, 1.66; 95% CI, 0.95-2.89; p=0.07). CONCLUSIONS: There was no significant difference in the overall survival between patients with the positive and negative fusion gene, but there were indications of PAX3-FOXO1 being an unfavorable prognostic factor.

Does expression of glucose transporter protein-1 relate to prognosis and angiogenesis in osteosarcoma?

BACKGROUND: The survival of patients who present with nonmetastatic extremity osteosarcoma has dramatically improved, but there are some patients who do not respond to chemotherapy. The ability to identify patients with a poorer prognosis might allow us to target different therapy for these patients. Glucose transporter protein-1 (Glut-1), one of the key factors in glucose metabolism, has been reported to be an independent prognostic factor in various tumors. However, little is known about the role of the Glut-1 pathway in osteosarcoma. QUESTIONS/PURPOSES: We asked (1) if Glut-1 expression is a prognostic marker for survival in patients with osteosarcoma, and (2) if there is a relationship between Glut-1 expression and tumor angiogenesis. PATIENTS AND METHODS: Thirty-seven patients with resectable high-grade osteosarcomas treated between 1982 and 2007 were reviewed retrospectively. Patients were excluded if representative biopsy material and followup data were not available. The expression of Glut-1 and the number of CD34-positive microvessels for angiogenic activity were measured immunohistochemically. The median followup was 6 years 6 months (range, 11-211 months). Survival analyses were evaluated using the Kaplan-Meier method and the Cox proportional hazards model. The association between Glut-1 expression and microvessel density was analyzed using Student's t-test and chi-square test. For 12 (32.4%) of 37 patients with osteosarcoma, the expression of Glut-1 was positive, with four patients (10.8%) showing strong expression of Glut-1 protein. RESULTS: The expression of Glut-1 correlated with a shorter disease-free survival period (relative risk, 20.13; 95% CI, 1.77-229.3; p=0.0016). The microvessel density mean value of positive Glut-1 expression (mean±SD, 26.5±19.4) was lower than that of negative expression (mean±SD, 46.4±35.3; Student's t-test, p=0.038). When more than 50 was defined as a high microvessel density, positive expression of Glut-1 was significantly associated with low microvessel density (chi-square test, p=0.049). CONCLUSIONS: These findings indicate that Glut-1 is a potential predictor of survival in patients with osteosarcoma and that glucose metabolism may be negatively associated with angiogenesis. If substantiated in larger numbers of patients, these findings might stimulate the development of novel treatments for patients with a poorer prognosis. LEVEL OF EVIDENCE: Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

A novel assessment method of serum alkaline phosphatase for the diagnosis of osteosarcoma in children and adolescents.

BACKGROUND: A high serum alkaline phosphatase (ALP) level is valuable for the diagnosis of osteosarcoma in adults, but its use in teenagers is problematic because ALP levels are affected by age, gender, and pubertal stage. Because serum acid phosphatase (ACP) shows the same tetraphasic pattern as serum ALP in children and adolescents, we presumed that serum levels of ALP and ACP would have a strong correlation and that the ratio of ALP to ACP (ALP/ACP) would show little variation and would be useful for the diagnosis of osteosarcoma in teenagers. The purpose of this study was to evaluate the correlation between the serum levels of ALP and ACP and to investigate the validity of ALP/ACP in the differential diagnosis of osteosarcoma in children and adolescents. METHODS: We retrospectively examined 538 patients aged 1-18 years, including 24 with osteosarcomas, 8 with other malignant bone tumors, 56 with benign bone tumors, and with 450 non-tumor lesions (controls). We evaluated the serum levels of ALP and ACP, both obtained by preoperative examination. RESULTS: There were significant correlations between the serum ALP and ACP levels in the controls (r = 0.805 in males and r = 0.860 in females). The ratios of ALP to ACP in the controls showed little variation with age. In ROC curve analysis, to discriminate between the osteosarcomas and the controls, the cutoff levels of serum ALP and ALP/ACP were 956 (U/l) and 50.9 in males and 748 (U/l) and 43.3 in females, respectively. The sensitivity and specificity of serum ALP and ALP/ACP in the differential diagnosis of osteosarcoma were 50.0 and 89.0%, and 60.0 and 94.1%, respectively in males, and 61.5 and 72.7%, and 69.2 and 84.2%, respectively, in females. CONCLUSIONS: The results suggest that ALP/ACP is more useful than the serum ALP level in diagnosing osteosarcoma because it is little affected by the age.

T2 Mapping Magnetic Resonance Imaging Encourages an Arthroscopic Approach for Osteoid Osteoma in the Acetabulum.

Intra-articular osteoid osteoma (OO) is uncommon, especially in the hip joint. Delayed treatment may cause early osteoarthritis; however, diagnosis and complete excision are often challenging. We describe the feasibility of the combination of T2 mapping magnetic resonance imaging evaluation and arthroscopic excision of OO in the acetabulum. A 12-year-old boy presented with a 6-month history of hip pain. An undifferentiated tumor of the medial wall of the acetabulum was suspected on radiographs and computed tomography. T2 mapping showed joint effusion, and the T2 value of the acetabular cartilage just above the tumor was significantly high. These findings suggested OO in the acetabulum. An arthroscopic excision was performed for biopsy and excision of the tumor to avoid damage to the normal cartilage and growth plate. Histologic examination confirmed the OO. At 16 months' follow-up, there was no evidence of recurrence. This is the first report to evaluate intra-articular OO by T2 mapping and to treat it arthroscopically. Arthroscopic treatment assisted by T2 mapping has excellent potential as a minimally invasive technique to enable us to approach the tumor from the area of discriminative abnormal cartilage with minimal damage to the normal cartilage and surrounding tissue.

Exosome-formed synthetic microRNA-143 is transferred to osteosarcoma cells and inhibits their migration.

MicroRNAs (miRNAs) have emerged as potential anticancer agents, but their clinical application is limited by the lack of an effective delivery system to tumors. Exosomes are small vesicles that play important roles in intercellular communication. Here, we show that synthetic miR-143 introduced into cells is released enveloped in exosomes and that the secreted exosome-formed miR-143 is transferred to osteosarcoma cells. The delivery of exosome-formed miR-143 significantly reduced the migration of osteosarcoma cells. The delivery efficiency of exosome-formed miR-143 was less than that achieved with lipofection, but the migratory potential of osteosarcoma cells was similarly inhibited after both strategies. Our results suggest that exosomes can deliver synthetic miR-143 and are a potentially efficient and functional delivery system.

Extraosseous extension caused by epidural hematoma in Gaucher disease mimicking malignant bone tumor.

Gaucher disease is an inherited autosomal-recessive disorder caused by the defective hydrolysis of glucocerebroside. The resultant hepatosplenomegaly, hematological changes, and orthopedic complications are the predominant symptoms. However, extraosseous manifestation of Gaucher disease, mimicking malignant bone tumor, is supposed to be rare. No reports of extraosseous manifestation of Gaucher disease caused by epidural hematoma were identified in the English literature. A 64-year-old man visited a nearby clinic for low back pain and was referred to our tumor clinic on suspicion of malignant bone tumor on sacral MRI. MRI revealed a demarcated solid lesion extending into the surrounding soft tissues on both sides of the sacral roots. During preoperative examination, he suffered from pathologic fracture in right mid-femur. We performed internal fixation with intramedullary nailing, simultaneously harvesting tissue specimens. Histopathological analysis showed aggregates of Gaucher cells in the right femur and hematoma in the sacrum. Epidural hematoma in Gaucher disease, usually attributed to thrombocytopenia, is a rare manifestation of skeletal complication, mimicking malignant processes.

Therapeutic effect and risk factors for complications of excision in 76 patients with schwannoma.

BACKGROUND: Benign schwannoma is the most common tumor of peripheral nerves. However, the clinical course of excision and risk factors associated with postoperative neurological deficits are not well known. We evaluated the incidence of preoperative symptoms, the incidence of postoperative neurological deficits, and the risk factors of neurological deficits. METHODS: We retrospectively reviewed data of 76 patients with schwannomas treated at our institution. We reviewed the clinical characteristics, and postoperative results, and determined the possible risk factors influencing the development of complications. RESULTS: Excision of schwannoma improved the Tinel-like signs in 47 of 51 patients and spontaneous pain in 14 of 15. Eleven of 17 patients with sensory deficits showed complete recovery, but six continued to show deficits with or without improvement. Motor deficits that were observed in four patients persisted in one. New neurological deficits developed in 21 patients and persisted until final follow-up in 8. Tinel-like signs was the risk factor of surgery-related neurological deficits (p = 0.009). CONCLUSIONS: New deficits developed predominantly in patients with preoperative Tinel-like signs. Attention should be given to patients with the factor.

Intra-articular osteoid osteoma of the lateral tibial plateau treated with arthroscopically assisted removal and retrograde osteochondral grafting.

The treatment of an intra-articular osteoid osteoma is sometimes challenging, because of its location. We report a patient with an intra-articular osteoid osteoma of the lateral tibial plateau which was excised under an arthroscopically assisted procedure. After total resection of the intra-articular osteoid osteoma, the osteochondral defect of the lateral tibial plateau was reconstructed with a retrograde autogenous osteochondral graft which was harvested from the non-weightbearing area of the distal femur.

Diversity of angiogenesis among malignant bone tumors.

Several studies have demonstrated that angiogenesis assessed by microvessel density (MVD) correlates with patient prognosis in various types of cancer, whereas data regarding the relevance of angiogenesis and prognosis in malignant bone tumors are scarce and controversial. The aim of this study was to examine MVD in representative malignant bone tumors, such as osteosarcoma, chondrosarcoma and Ewing's sarcoma, in order to clarify the role of angiogenesis in prognosis. A total of 69 patients with malignant bone tumors, including 44 osteosarcomas, 20 chondrosarcomas and 5 Ewing's sarcomas, were reviewed retrospectively and treated at our hospital between 1980 and 2007. Biopsy or pre-chemotherapy surgical specimens were immunohistochemically stained with anti-CD34 antibody. The MVD values of osteosarcomas and Ewing's sarcomas were significantly higher compared to chondrosarcoma. In osteosarcomas with high MVD, American Joint Committee on Cancer stage IIA, good histological response to chemotherapy was significantly correlated with better disease-free survival, while MVD was closely associated with age and chemotherapy response. In chondrosarcomas, the surgical margin (marginal and intralesional), MVD (high), tumor size (≥8) and histological grade (grades 2 and 3) significantly correlated with a shorter disease-free survival, while MVD was closely associated with age and histological grade. These findings showed that osteosarcomas and Ewing's sarcomas were hypervascular, compared to chondrosarcomas. In osteosarcomas, hypervascularity induced good chemotherapy response, leading to better prognosis, while in chondrosarcomas, high MVD was associated with histological grade and predicted poor prognosis.

Correlation between p38 mitogen-activated protein kinase and human telomerase reverse transcriptase in sarcomas.

BACKGROUND: One of the major components of telomerase is the human telomerase reverse transcriptase (hTERT) as the catalytic protein. hTERT mRNA expression are reported to be associated with prognosis and tumor progression in several sarcomas. However, there is no clear understanding of the mechanisms of hTERT in human sarcomas. Recent studies have suggested that signals transmitted through p38 mitogen-activated protein kinase (MAPK) can increase or decrease hTERT transcription in human cells. The purpose of this study was to analyse the correlation between p38 MAPK and hTERT in sarcoma samples. METHODS: We investigated 36 soft tissue malignant fibrous histiocytomas (MFH), 24 liposarcomas (LS) and 9 bone MFH samples for hTERT and p38 MAPK expression. Quantitative detection of hTERT and p38 MAPK was performed by RT-PCR. RESULTS: There was a significant positive correlation between the values of hTERT and p38 MAPK in all samples (r = 0.445, p = 0.0001), soft tissue MFH (r = 0.352, p = 0.0352), LS (r = 0.704, p = 0.0001) and bone MFH samples (r = 0.802, p = 0.0093). Patients who had a higher than average expression of p38 MAPK had a significantly worse prognosis than other patients (p = 0.0036). CONCLUSIONS: p38 MAPK may play a role in up-regulation of hTERT, and therefore, p38 MAPK may be a useful marker in the assessment of hTERT and patients' prognosis in sarcomas.

Antitumor effects of telomerase inhibitor TMPyP4 in osteosarcoma cell lines.

Telomere studies in carcinomas have been extensively reported for prognostic utility and effective methods for targeting telomerase therapy has been described, but efficacy of telomerase inhibitor remained unknown in sarcoma cells. In this study, we investigated the effects of telomerase inhibitor cationic porphyrin TMPyP4 on telomerase activity, telomere length, cell growth, and apoptosis in osteosarcoma cell lines. TMPyP4 significantly inhibited telomerase activity in telomerase positive HOS and Saos-2, but not in MG-63. TMPyP4 significantly induced telomere shortening, and inhibition of the cell growth in HOS and Saos-2 with over 17% apoptosis rates. In terms of MG-63, TMPyP4 did not induce inhibition of both telomerase activity and cell growth, although it induced significant telomere shortening. Telomere length after treatment was 5.60 kb in HOS, 4.00 kb in Saos-2, and 9.89 kb in MG-63. These results may suggest that both telomerase activity loss and sufficient telomere shortening are necessary to inhibit cell growth in telomerase positive osteosarcoma cells. TMPyP4 did not induced telomere shortening but significantly inhibited the growth with 22.6% apoptosis rate in telomerase negative with extremely longer telomere-U2OS, may indicating the antitumor effect of TMPyP4 may be related to DNA damage including telomere dysfunction through G-quadruplex stabilization, independent on telomere length.