Lenvatinib Suppresses Protein Kinase B Signaling and Induces Apoptosis in Osteosarcoma Cells.

BACKGROUND/AIM: Lenvatinib, an oral multikinase inhibitor, has demonstrated promising activity in patients with osteosarcoma (OS). Therefore, it is worth exploring the inhibitory efficacy and mechanism of action of lenvatinib in osteosarcoma. The primary goal of this study was to examine the inhibitory effectiveness and mechanism of lenvatinib on the growth and invasion of OS cells. MATERIALS AND METHODS: The effects of lenvatinib on cell viability, apoptosis, protein kinase B (AKT) activation, its downstream effector proteins involved in tumor progression, and invasion capability were assessed using MTT assay, flow cytometry, western blotting, and invasion/migration assay on U-2 OS and MG63 cells. RESULTS: Lenvatinib effectively induced cytotoxicity, apoptosis, as well as extrinsic and intrinsic apoptotic signaling in OS cells. Lenvatinib also significantly decreased the invasion/migration capability, AKT activation, and downstream effector proteins. CONCLUSION: The anti-OS effect of lenvatinib may be associated with the induction of apoptosis and the inactivation of AKT.

Yoga versus massage in the treatment of aromatase inhibitor-associated knee joint pain in breast cancer survivors: a randomized controlled trial.

Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with oestrogen receptor-positive, early-stage, and metastatic breast cancer. Although effective, the risk of falls due to AI-associated knee joint pain significantly increased. The aim of this study was to evaluate the therapeutic effects of yoga and massage on AI-associated knee joint pain. Breast cancer survivors were randomly assigned to a 6-week yoga intervention-2-week rest-6-week massage exposure (Yoga first, n = 30) or a 6-week massage intervention-2-week rest-6-week yoga exposure (Massage first, n = 30). Evaluations of the treatment efficacy were made at baseline, post-intervention, and post-exposure using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale, plasma cytokine levels, and changes in meridian energy. The results showed that yoga, superior to massage intervention, significantly reduced AI-associated knee joint pain, as demonstrated by the WOMAC pain score. The yoga intervention improvements were also associated with changes in plasma cytokine levels and meridian energy changes. In conclusion, this study provides scientific evidence that yoga was more effective than massage for reducing AI-associated knee joint pain. Meridian energy changes may provide another scientific, objective, non-invasive way to monitor the therapeutic effects of yoga and investigate another alternative, complementary medicine.

Correlations between 18F-FDG PET/CT parameters and pathological findings in patients with rectal cancer.

PURPOSE: This study examined the correlations between F-FDG PET/CT results and tumor specimen pathology in patients with rectal cancer. METHODS: Sixty-seven patients with rectal cancer who had received preoperative PET/CT were included in this study. Autosegmentation methods were used to determine the maximum PET/CT-based tumor length (TL), tumor width (TW), and metabolic tumor volume for each patient. The TL and TW values were compared with the maximum pathological length and width of the tumor specimen. To forecast the pathological T and N stages, a receiver operating characteristic curve was created for each parameter to evaluate its predictive ability. Logistic regression analysis was used to identify the predictors of pathology. RESULTS: The values of 30% of maximum uptake for TL and 40% of maximum uptake for TW provided the best match with the maximum pathological tumor length and width (Pearson r = 0.72, P < 0.001; r = 0.44, P < 0.001, respectively). Metabolic tumor volume with a fixed threshold of 2.5 emerged as an independent factor for predicting the pathological T3 or T4 stage (P = 0.001; odds ratio, 1.81; 95% confidence interval, 1.26-2.60). CONCLUSIONS: Preoperative PET/CT can be used as a supplemental tool in predicting pathological findings for patients with rectal cancer requiring operation.

Pretreatment maximal standardized uptake value of the primary tumor predicts outcome to radiotherapy in patients with pharyngeal cancer.

This study aimed to investigate whether the combination of clinical information, tumor volume and pretreatment SUVmax at the primary tumors might improve the prognostic stratification in pharyngeal cancer (PC) patients treated with radiotherapy (RT). Sixty-two patients with PC (35 oropharynx; 27 hypopharynx) treated with RT were enrolled in this retrospective analysis. All patients received pretreatment FDG- PET or PET/CT. The primary tumor relapse-free survival (PRFS) was calculated according to different variables. The median values of the SUVmax for the primary tumors (SUVp-max) and the gross tumor volume (GTVp) were used to divide patients into two groups. Independent prognosticators were identified by the Cox regression analysis. In this study, the median SUVp-max and GTVp was 11 and 15.5 ml. Patients having tumors with SUVp-max > 11 had a significantly inferior 2-year PRFS (41% vs. 75%, p = 0.003) compared with patients having lower uptake tumors. Multivariate analysis of the PRFS showed two prognostic factors: SUVp-max > 11 (p = 0.04, hazard ratio = 2.67) and GTVp > 15.5 ml (p = 0.03, hazard ratio = 2.88). For patients with a GTVp less than 15.5 ml, there was a more significant impact of SUVmax-p on their PRFS compared to that for those with large ones. We disclosed a higher pretreatment SUVp-max is a predictor for primary recurrence in PC patients treated with RT, particularly for those with smaller tumor volumes. Patients with a large tumor volume or a higher SUVp-max should be considered for requiring more aggressive treatment approaches.

Meta-analysis study of lymph node staging by 18 F-FDG PET/CT scan in non-small cell lung cancer: comparison of TB and non-TB endemic regions.

UNLABELLED: Lymph node staging in non-small cell lung cancer (NSCLC) is challenging and important for deciding treatment policy. The role of PET/CT scans in lymph node staging of NSCLC remains controversial when comparing TB and non-TB endemic regions. This study systematically reviews the literature regarding the diagnostic performance of PET/CT in lymph node staging of patients with NSCLC, and determines its pooled sensitivity and specificity. METHODS: The databases of PubMed, Medline, and Cochrane library were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. A meta-analysis of the reported sensitivity and specificity of each study was performed. RESULTS: Seven of 86 studies were included. These studies had moderate to good methodological quality. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for patient-based analyses (five studies) were 66%, 92.7%, 5.86%, and 0.41%, respectively, and those for lesion-based analyses (six studies) were 59.4%, 96.5%, 9.37%, and 0.31%, respectively. Subanalysis of endemic regions of tuberculosis (TB) showed that these regions had lower sensitivity and similar specificity to non-TB endemic regions. CONCLUSION: PET/CT showed high specificity in the lymph node staging of NSCLC and lower sensitivity in TB endemic regions.

Clinical implications of the tumor volume reduction rate in head-and-neck cancer during definitive intensity-modulated radiotherapy for organ preservation.

PURPOSE: To investigate the prognostic value of the volume reduction rate (VRR) in patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Seventy-six patients with oropharyngeal cancer (OPC) and another 76 with hypopharyngeal cancer (HPC) were enrolled in volumetric analysis. All patients received allocated radiotherapy courses. Adaptive computed tomography was done 4 to 5 weeks after the start of IMRT. Primary tumor volume measurement was derived using separate images for the pretreatment gross tumor volume (pGTV) and the interval gross tumor volume. RESULTS: In the OPC group, the pGTV ranged from 6.6 to 242.6 mL (mean, 49.9 mL), whereas the value of the VRR ranged from 0.014 to 0.74 (mean, 0.43). In HPC patients, the pGTV ranged from 4.1 to 152.4 mL (mean, 35.6 mL), whereas the VRR ranged from -1.15 to 0.79 (mean, 0.33). Multivariate analysis of the primary tumor relapse-free survival for OPC revealed three prognostic factors: T4 tumor (p = 0.0001, hazard ratio 7.38), pGTV ≥20 mL (p = 0.01, hazard ratio 10.61), and VRR <0.5 (p = 0.001, hazard ratio 6.49). Multivariate analysis of the primary tumor relapse-free survival for HPC showed two prognostic factors: pGTV ≥30 mL (p = 0.001, hazard ratio 2.87) and VRR <0.5 (p = 0.03, hazard ratio 2.25). CONCLUSION: The VRR is an outcome predictor for local control in OPC and HPC patients treated with IMRT. Those with large tumor volumes or a VRR <0.5 should be considered for a salvage operation or a dose-escalation scheme.