Metabolic profile and neoadjuvant chemotherapy sensitivity in high-grade bone sarcoma.

e22506 Background: Neoadjuvant chemotherapy with intercalated surgery is the standard of care for resectable high-grade bone sarcoma (BS) but identification of biomarkers for chemosensitivity prediction is still needed. Methods: We recruited 121 pts with new primary localized or metastatic BS, measured fasting blood glucose and insulin, body mass index (BMI). The HOMA-IR (Homeostasis Model Assessment) score ((Glucose (mmol/l) x Insulin) / 22.5), which has been proven to reliably detect insulin resistance was calculated, and patients with HOMA-IR > 2.6 were considered as insulin resistant (IR). We collected characteristics usually associated with insulin resistance (IR): age, obesity, diabetes, dyslipidemia and hypertension. Results: Out of 121 pts, 48 (40%) were IR: HOMA-IR > 2.6. Thirty IR patients (62%) had no cardiovascular risk factor. In univariate analysis, IR was associated with obesity (BMI > 30 kg/m2)(23% vs 3%, p = 0.0013), but not with age (median 38.4 vs 43.3 years, p = 0.15). IR was more prevalent in Ewing sarcoma (12/21; 57%) and chondrosarcoma (7/13; 54%) followed by osteosarcoma (25/61; 41%) and other rare bone sarcomas (4/26; 15.3%)(p = 0.037). After preoperative chemotherapy and surgery of Ewing tumor and osteosarcoma, pathologic tumor necrosis was higher in IR pts (85.8 vs 69.3%, p = 0.012). Using multivariate linear regression models, IR was independently associated with pathologic tumor necrosis (p = 0.042) but not with obesity (p = 0.55). Conclusions: Our results suggest that tumor-induced metabolic profile may help to discriminate best candidates for preoperative chemotherapy in high-grade bone sarcomas. Further studies are needed to confirm and explain these results.

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Metabolic Profiles in Obese Children and Adolescents with Insulin Resistance

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.097 ◽

2018 ◽

Vol 6 (3) ◽

pp. 511-518 ◽

Cited By ~ 2

Author(s):

Marko Kostovski ◽

Viktor Simeonovski ◽

Kristina Mironska ◽

Velibor Tasic ◽

Zoran Gucev

Keyword(s):

Insulin Resistance ◽

Children And Adolescents ◽

Plasma Glucose ◽

Metabolic Profile ◽

Total Serum ◽

Model Assessment ◽

Fasting Insulin ◽

Obese Children ◽

Insulin Resistant ◽

Study Results

BACKGROUND: In the past several decades, the increasing frequency of overweight and obese children and adolescents in the world has become a public health problem. It has contributed significantly to the already high tide of diabetes, cardiovascular and cerebrovascular diseases.AIM: To investigate the frequency of insulin resistance and to evaluate the metabolic profile of insulin resistant and non-insulin resistant obese children and adolescents.SUBJECTS AND METHODS: The study included 96 (45 boys, 51 girls) obese children and adolescents aged 4-17 years old (10.50 ± 2.87 years). Only participants with Body Mass Index ≥ 95 percentile were included. We analysed sera for fasting insulin levels (FI), fasting serum triglycerides (TG), total serum cholesterol (TC), fasting plasma glucose (FPG) and plasma glucose 2 hours after the performance of the oral glucose tolerance test (2-h G). Homeostatic model assessment for insulin resistance (HOMA-IR) index was calculated as fasting insulin concentration (microunits per millilitre) x fasting glucose concentration (millimolar)/22.5. The value of HOMA-IR above 3.16 was used as a cut-off value for both genders.RESULTS: Insulin resistance was determined in 58.33% of study participants. Insulin resistant participants had significantly higher level of 2-h G (p = 0.02), FI level (p = 0.000) as well as TG levels (p = 0.01), compared to non-insulin resistant group. Strikingly, 70.73% of the pubertal adolescents were insulin resistant in comparison to 49.09% of the preadolescents (p = 0.03). Significantly higher percentage of insulin-resistant participants were girls (p = 0.009). Moreover, a higher percentage of the girls (70.59%) than boys (44.44%) had HOMA-IR above 3.16 and had elevated FI levels (70.59% vs 48.89%). The difference in the frequency of insulin resistance among obese versus severely obese children and adolescents was not significant (p = 0.73, p > 0.05). Our study results also showed positive, but weak, correlation of HOMA-IR with age, FPG, TG and BMI of the participants (p < 0.05).CONCLUSION: Higher percentage of insulin-resistant participants was of female gender and was adolescents. In general, insulin resistant obese children and adolescents tend to have a worse metabolic profile in comparison to individuals without insulin resistance. It is of note that the highest insulin resistance was also linked with the highest concentrations of triglycerides.

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The Evaluation of Serum Tumor Necrosis Factor-Like Weak Inducer of Apoptosis, Interleukin-6, Fetuin-A, Homeostatic Model Assessment-Insulin Resistance, and Insulin Levels in Rheumatoid Arthritis Patients in Clinical Remission

Archives of Rheumatology ◽

10.5606/archrheumatol.2019.6722 ◽

2019 ◽

Vol 34 (1) ◽

pp. 71-78

Author(s):

Sinem Sağ

Keyword(s):

Rheumatoid Arthritis ◽

Insulin Resistance ◽

Tumor Necrosis Factor ◽

Interleukin 6 ◽

Tumor Necrosis ◽

Model Assessment ◽

Homeostatic Model Assessment ◽

Homeostatic Model ◽

Necrosis Factor ◽

Serum Tumor Necrosis

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Serum levels of the myokine irisin in relation to metabolic and renal function

Acta Endocrinologica ◽

10.1530/eje-13-1053 ◽

2014 ◽

Vol 170 (4) ◽

pp. 501-506 ◽

Cited By ~ 73

Author(s):

Thomas Ebert ◽

Denise Focke ◽

David Petroff ◽

Ulrike Wurst ◽

Judit Richter ◽

...

Keyword(s):

Insulin Resistance ◽

Renal Function ◽

Univariate Analysis ◽

Visceral Obesity ◽

Serum Levels ◽

Model Assessment ◽

Glucose And Lipid Metabolism ◽

The Metabolic Syndrome ◽

Physiological Relevance ◽

Ckd Stage

ObjectiveIrisin has recently been introduced as a novel myokine which reverses visceral obesity and improves glucose metabolism in mice. However, regulation of irisin in humans in relation to renal and metabolic disease has not been comprehensively studied.Design and methodsSerum irisin levels were quantified by ELISA and correlated with anthropometric and biochemical parameters of renal function, glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1–5 of chronic kidney disease (CKD).ResultsMedian serum irisin levels adjusted for age, gender, and BMI significantly decreased with increasing CKD stage and lowest concentrations were seen in patients with CKD stage 5. Furthermore, irisin concentrations were associated with facets of the metabolic syndrome including diastolic blood pressure, markers of impaired glucose tolerance, and dyslipidemia in univariate analysis. Moreover, markers of renal function, e.g. glomerular filtration rate, and insulin resistance, e.g. homeostasis model assessment of insulin resistance, remained independently associated with circulating irisin levels in robust multivariate analysis.ConclusionsWe show that irisin serum concentrations decrease with increasing CKD stage and are independently and positively predicted by renal function and insulin resistance. The physiological relevance of our findings, as well as the factors contributing to irisin regulation in humans, needs to be further defined in future experiments.

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Chemotherapy in the Management of Osteosarcoma and Ewing's Sarcoma

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2007.0039 ◽

2007 ◽

Vol 5 (4) ◽

pp. 449-455 ◽

Cited By ~ 11

Author(s):

Scott M. Schuetze

Keyword(s):

Ewing’S Sarcoma ◽

Ewing's Sarcoma ◽

Disease Patient ◽

Bone Sarcoma ◽

The United States ◽

High Grade ◽

Medical Oncologists ◽

Bone Sarcomas ◽

Localized Disease ◽

Relapsed Disease

Sarcomas of bone are rare malignancies diagnosed in fewer than 3000 individuals yearly in the United States. Ewing's sarcoma and most osteosarcoma are high-grade neoplasms and account for approximately one half of bone sarcoma cases. Fewer than 20% of patients presenting with localized Ewing's sarcoma or osteosarcoma are cured with surgery alone. Current management typically involves collaboration among orthopedic oncologists, medical oncologists, musculoskeletal radiologists, sarcoma pathologists, and radiation oncologists. Modern multidisciplinary management of Ewing's sarcoma and osteosarcoma has improved the cure rate of patients with localized disease to more than 50%. Primary chemotherapy for high-grade bone sarcomas often involves intensive, multiagent regimens, and few secondary chemotherapy options are available to treat refractory or relapsed disease. Patient participation in clinical trials of novel therapies for Ewing's sarcoma and osteosarcoma should be strongly encouraged.

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High-Circulating Leptin Levels Are Associated with Greater Risk of Hypertension in Men Independently of Body Mass and Insulin Resistance: Results of an Eight-Year Follow-Up Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-1280 ◽

2008 ◽

Vol 93 (10) ◽

pp. 3922-3926 ◽

Cited By ~ 63

Author(s):

F. Galletti ◽

L. D'Elia ◽

G. Barba ◽

A. Siani ◽

F. P. Cappuccio ◽

...

Keyword(s):

Insulin Resistance ◽

Body Mass ◽

Serum Insulin ◽

Univariate Analysis ◽

Assessment Model ◽

Model Assessment ◽

Male Population ◽

Baseline Serum ◽

Assessment Index

Background: We previously reported a significant association between plasma leptin (LPT) concentration and blood pressure (BP), which was partly independent of serum insulin levels and insulin resistance. The aims of this study were to detect whether serum LPT levels predict the development of hypertension (HPT) in the 8-yr follow-up investigation of a sample of an adult male population (the Olivetti Heart Study), and to evaluate the role of body mass index (BMI) and insulin resistance in this putative association. Patients and Methods: The study population was made up of 489 untreated normotensive subjects examined in 1994–1995 (age: 50.1 ± 6.7 yr; BMI: 26.3 ± 2.8 kg/m2; BP: 120 ± 10/78 ± 6 mm Hg; and homeostatic model assessment index: 2.1 ± 1.6). Results: The HPT incidence over 8 yr was 35%. The participants with incident HPT had similar age but higher BMI (P < 0.001), serum LPT (P < 0.001), and BP (P < 0.01) at baseline. One sd positive difference in baseline serum LPT log was associated at univariate analysis with a 49% higher rate of HPT [95% confidence interval (CI) 22–83; P < 0.001]). In three different models of multivariable logistical regression analysis, LPT was respectively associated with a 41% greater risk to develop HPT (95% CI 15–74; P < 0.001) upon adjustment for age and baseline BP, with a 48% (95% CI 20–81) greater risk when adding the homeostatic assessment model index to the model, and with 33% greater risk (95% CI 6–67; P < 0.02) upon adjustment for BMI. Conclusions: In this sample of originally normotensive men, circulating LPT level was a significant predictor of the risk to develop HPT over 8 yr, independently of BMI and insulin resistance.

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Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.9.1849 ◽

1994 ◽

Vol 12 (9) ◽

pp. 1849-1858 ◽

Cited By ~ 112

Author(s):

W G Ward ◽

K Mikaelian ◽

F Dorey ◽

J M Mirra ◽

A Sassoon ◽

...

Keyword(s):

Survival Rate ◽

Preoperative Chemotherapy ◽

Tumor Necrosis ◽

Resection Margin ◽

Pulmonary Metastases ◽

Pulmonary Nodules ◽

Postoperative Chemotherapy ◽

High Grade ◽

Primary Tumors ◽

Extremity Osteosarcoma

PURPOSE This study investigated prognostic factors in nonmetastatic high-grade extremity osteosarcoma and the prognosis following resection of subsequent pulmonary metastases, with emphasis on the effect of chemotherapy-induced tumor necrosis. PATIENTS AND METHODS We reviewed 111 consecutive patients with high-grade nonmetastatic extremity osteosarcoma treated with preoperative chemotherapy and surgical resection, with additional review of 36 patients who had subsequent pulmonary metastases resected. RESULTS The overall 5-year survival rate was 53%. In resected primary tumors, tumor-free resection margin (P < .001) and increasing chemotherapy-induced tumor necrosis (> 90% threshold, P < .003) correlated with increased metastasis-free survival. Relative risk factors for metastases were as follows: tumor-containing resection margin (most likely to metastasize); poor response to preoperative chemotherapy and/or lack of postoperative chemotherapy (next worse prognosis); and excellent response to preoperative chemotherapy (> or = 90% necrosis) combined with postoperative chemotherapy (best prognosis). The 5-year survival rate following pulmonary metastasis resection was 23%, whereas a 0% 4-year survival rate followed development of bony metastases (P < .001). The extent of tumor necrosis in resected pulmonary metastases did not affect prognosis. Survival was best in patients with three or fewer pulmonary nodules (P < .048), four or fewer recurrent pulmonary nodules (P < .047), unilateral pulmonary metastases (P < .037), or longer intervals between primary tumor resection and metastases (P < .082). CONCLUSION Intensive preoperative and postoperative chemotherapy combined with complete resection of both primary and metastatic pulmonary osteosarcomas is justified, with a goal of 100% tumor necrosis and excision. Although current treatment regimens allow effective salvage therapy for a few patients with pulmonary metastases, more effective systemic treatment is needed.

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Treatment of high-grade bone sarcomas with neoadjuvant chemotherapy: the utility of sequential color Doppler sonography in predicting histopathologic response.

American Journal of Roentgenology ◽

10.2214/ajr.165.1.7785571 ◽

1995 ◽

Vol 165 (1) ◽

pp. 125-133 ◽

Cited By ~ 45

Author(s):

H J van der Woude ◽

J L Bloem ◽

J A van Oostayen ◽

M A Nooy ◽

A H Taminiau ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Doppler Sonography ◽

Color Doppler ◽

Color Doppler Sonography ◽

High Grade ◽

Histopathologic Response ◽

Bone Sarcomas

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Prognostic Role of Histological Tumor Regression in Patients Receiving Neoadjuvant Chemotherapy for High-Grade Serous Tubo-ovarian Carcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000945 ◽

2017 ◽

Vol 27 (4) ◽

pp. 708-713 ◽

Cited By ~ 23

Author(s):

Edwina Coghlan ◽

Tarek M. Meniawy ◽

Aime Munro ◽

Max Bulsara ◽

Colin JR Stewart ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Ovarian Carcinoma ◽

Tumor Regression ◽

Univariate Analysis ◽

Prognostic Significance ◽

Rank Test ◽

Chemotherapy Response ◽

High Grade ◽

Prognostic Role

ObjectiveOur objective was to validate the prognostic role of the chemotherapy response score (CRS), which has been proposed for measuring tumor response to neoadjuvant chemotherapy in patients with high-grade serous tubo-ovarian carcinoma, in predicting progression-free survival (PFS) and overall survival (OS).MethodsA retrospective cohort study was conducted of patients with advanced high-grade serous tubo-ovarian carcinoma diagnosed between January 1, 2010, and December 31, 2014, and treated with neoadjuvant chemotherapy. Treatment-related tumor regression was determined according to the 3-tier CRS, and results were compared with standard clinicopathological variables. Survival analysis was performed using Cox proportional hazards models and the log-rank test.ResultsSeventy-one patients were eligible for analysis. Median OS was 25.5 months. Fifty-eight patients (82%) had disease recurrence and 32 (45%) had died at study census. Of the 71 patients, 19, 29, and 23 patients had a CRS of 1, 2, and 3, respectively. On univariate analysis, the CRS significantly predicted PFS (hazard ratio [HR], 3.77; 95% confidence interval [CI], 1.83–7.78; P = 0.000) and OS (HR, 2.81; 95% CI, 1.16–6.79; P = 0.022). In a multivariate model, the CRS was significantly associated with PFS (HR, 2.81; 95% CI, 1.16–6.79; P = 0.022) but not with OS (HR, 2.39; 95% CI, 0.47–3.08; P = 0.079). Patients with CRS of 1 and 2 combined were twice as likely to progress during the study period compared with patients with a CRS of 3 (HR, 2.0; 95% CI, 1.06–3.78; P = 0.032; median PFS, 16 vs 26 months). No significant association was observed for OS (CRS 1/2 vs 3; HR, 1.57; 95% CI, 0.68–3.65; P = 0.291).ConclusionsIn this study, the CRS showed independent prognostic significance for PFS but not for OS.

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