Anti-inflammatory effect of methanol extracts of hemp leaf in IL-1β-induced synovitis

Purpose: To examine the effectiveness of some hemp (Canabis sativa) leaf extracts as an antiinflammatory agent on synovitis in vitro.Methods: Synovial fibroblast cell line SW982 was induced with 5 ng/mL of interleukin 1-beta (IL-1β) to trigger cellular inflammation. The cells were then treated with prepared extracts of hemp (Canabis sativa) leaf originating from three different cultivation sites with varying proportions of terpenoids and cannabinoids, especially cannabidiol (CBD) and tetrahydrocannabinol (THC). Nitric oxide (NO) and prostaglandin E2 (PGE2) production as well as expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and IL-1β genes were determined.Results: All hemp extracts reduced the production of NO and PGE2 in a dose-dependent manner. The expressions of iNOS, COX-2 and IL-1β genes were significantly decreased by the hemp extracts. This effect was likely related to the amount of sesquiterpenoids and THC. The extract from Huai Hoi (HH) cultivar showed the most promising results for further studies.Conclusion: The extracts of hemp leaf substantially reduces the level of biomarkers for inflammation in vitro. Therefore, the extracts have a potential application as an inflammatory counteractant in synovitis.Keywords: Canabis sativa, Hemp, Synovitis, Cannabinoids, Nitric oxide, Interleukin-1 bet

Sesamin Attenuates VEGFA-Induced Angiogenesis via Inhibition of Src and FAK Signaling in Chick Chorioallantoic Membrane Model and Human Endothelial EA.hy926 Cells

Sesamin, a major phytochemical in sesame seeds and oil, has been reported to have effects on physiological and pathological angiogenesis in several studies. Nevertheless, the underlying mechanisms of sesamin’s effect on angiogenesis are not understood well enough. This study aimed to investigate its effect on both physiological and pathological angiogenesis using the in vivo chick chorioallantoic membrane (CAM) model and the in vitro human endothelial cell line, EA.hy926, model. Sesamin inhibited the VEGFA-induced pathological angiogenesis significantly, although no effect was seen on angiogenesis without induction. It reduced the formation of vascular branches in the VEGFA-treated CAMs and also the proliferation and migration of EA.hy926 endothelial cells induced by VEGFA. Sesamin impeded the VEGF-mediated activation of Src and FAK signaling proteins, which may be responsible for sesamin-mediated reduction of pathological angiogenesis. Moreover, the effect of sesamin on the expressions of angiogenesis-related genes was then investigated and it was found that both mRNA and protein expressions of Notch1, the key pathway in vascular development, induced by VEGFA, were significantly reduced by sesamin. Our results altogether suggested that sesamin, by inhibiting pathological angiogenesis, has the potential to be employed in the prevention or treatment of diseases with over-angiogenesis, such as cancers

Surgical outcomes of extracorporeal irradiation and re-implantation in extremities for high grade osteosarcoma: A retrospective cohort study and a systematic review of the literature

Purpose: To assess the failure rate and mode failure of high-grade osteosarcoma patients who received extracorporeal irradiation and re-implantation (ECIR) in extremities. Patients and Methods: For the cohort study, patients who had received ECIR at a single institution between January 1996 and December 2014 were retrospectively evaluated. Characteristics of failure and time to failure were recorded and analyzed. In addition, a systematically search of published literatures regarding the use of ECIR for osteosarcoma was conducted. Failure rates and modes of failure were determined from the pooled data. Results: In the cohort study, the overall reconstruction failure was 46% (23 of 50 cases) of which 6% were due to mechanical failure, and 40% were due to non-mechanical failure. In the systematic review, 164 cases reached the criteria for analysis (50 diaphysis, 97 osteochondral of lower extremity, 6 knee resection, and 11 proximal humerus resection). Among those cases, overall failure rate was 29.9% (49 of 164 cases) of which 7.9% were due to mechanical failure, and 22.0% to non-mechanical failure. Diaphyseal resection with intercalary re-implantation had a significantly lower failure rate than osteochondral reconstruction of lower extremity (OR: 2.7, p < 0.02), and knee extra-articular resection osteochondral re-implantation (OR: 10.5, p < 0.01). Conclusions: Diaphyseal resection and extracorporeal irradiation of intercalary re-implantation offer the most promising outcome among other type of reconstructions. Availability of graft, fewer structural complications, and biological permanence are advantages of this reconstruction method. Keywords: Autogenous graft, Implantation, Irradiation, Osteosarcoma, Reconstructio

Prognostic score for life expectancy evaluation of lung cancer patients after bone metastasis

Background: This study identifies the overall survival status of lung cancer patients with bone metastasis and metastasis patterns. Poor prognostic factors were identified to develop a scoring system for estimating survival period after bone metastasis. Methods: A retrospective cohort analysis was performed at Chiang Mai University for the period January 1, 2006 and December 31, 2013. Time-to-event analysis was performed to estimate survival rate. The primary end point was death related to lung cancer. Univariate and multivariate analysis of the prognostic variables was done using the Cox's regression model. The score was derived from the corresponding estimated regression coefficients of significantly poor prognostic factors. Results: A total of 505 lung cancer with bone metastasis patients were analyzed. Four hundred two cases (79.6%) were concurrent diagnosis and 103 (20.4%) were subsequent diagnosis. The median survival time of lung cancer after bone metastasis 148 days. Male gender and ECOG 3–4 were significant poor prognostic factors for lung cancer after bone metastasis, with hazard ratios of 1.42 (95% CI 1.17–1.73), and 1.30 (95% CI 1.06–1.60), respectively. Prognosis score was determined using the binary term present/not-present for those factors. The curve from prognostic score summations of 2, 1 and 0 presented a good discrimination of survival expectancy, showing an expected median survival time of approximately 109, 146, and 225 days, respectively. Conclusions: Prognostic score is a clinically simple and easy method for estimating life expectancy and for guiding interventions in bone metastasis of lung cancer

Osteosarcoma-Specific Genes as a Diagnostic Tool and Clinical Predictor of Tumor Progression

A liquid biopsy is currently an interesting tool for measuring tumor material with the advantage of being non-invasive. The overexpression of vimentin and ezrin genes was associated with epithelial-mesenchymal transition (EMT), a key process in metastasis and progression in osteosarcoma (OS). In this study, we identified other OS-specific genes by calculating differential gene expression using the Gene Expression Omnibus (GEO) database, confirmed by using quantitative reverse transcription-PCR (qRT-PCR) to detect OS-specific genes, including VIM and ezrin in the buffy coat, which were obtained from the whole blood of OS patients and healthy donors. Furthermore, the diagnostic model for OS detection was generated by utilizing binary logistic regression with a multivariable fractional polynomial (MFP) algorithm. The model incorporating VIM, ezrin, and COL5A2 genes exhibited outstanding discriminative ability, as determined by the receiver operating characteristic curve (AUC = 0.9805, 95% CI 0.9603, 1.000). At the probability cut-off value of 0.3366, the sensitivity and the specificity of the model for detecting OS were 98.63% (95% CI 90.5, 99.7) and 94.94% (95% CI 87.5, 98.6), respectively. Bioinformatic analysis and qRT-PCR, in our study, identified three candidate genes that are potential diagnostic and prognostic genes for OS

Additional file 1: of Effects of sesamin on primary human synovial fibroblasts and SW982 cell line induced by tumor necrosis factor-alpha as a synovitis-like model

LDH released from hSF and SW982 cells. Cell viability testing was performed by LDH measurement in culture medium. a. LDH released from hSF cells under TNF-α alone, sesamin alone or combination of TNF-α and sesamin. b. LDH released from SW982 cells under TNF-α alone, sesamin alone or combination of TNF-α and sesamin. Values are presented as mean ± SEM (n = 3). (PNG 135 kb

Additional file 1: Table S1. of Safety and efficacy of intralesional steroid injection for aggressive fibromatosis

Subjective interviews with patients regarding unfavorable side effects from steroid use. Swelling of extremities was the only positive presentation during or after the ILSI procedure. Table S2. Blood pressure change before and after procedure. Table S3. Fasting blood sugar before and after procedures. Table S4. Morning cortisol level and ACTH stimulation test. Figure S1. Serum triamcinolone level 24 h after intralesional steroid injection. (DOC 124 kb

Establishment, characterization, and genetic profiling of patient-derived osteosarcoma cells from a patient with retinoblastoma

Abstract Osteosarcoma is the most common malignant bone cancer in pediatric patients. Patients who respond poorly to chemotherapy experience worse clinical outcomes with a high mortality rate. The major challenge is the lack of effective drugs for these patients. To introduce new drugs for clinical approval, preclinical studies based on in vitro models must demonstrate the potency of the tested drugs, enabling the drugs to enter phase 1 clinical trials. Patient-derived cell culture is a promising testing platform for in vitro studies, as they more accurately recapitulate cancer states and genetic profiles compared to cell lines. In the present study, we established patient-derived osteosarcoma cells (PDC) from a patient who had previously been diagnosed with retinoblastoma. We identified a new variant of a germline mutation in the RB1 gene in the tissue of the patient. The biological effects of this PDC were studied to observe whether the cryopreserved PDC retained a feature of fresh PDC. The cryopreserved PDC preserved the key biological effects, including cell growth, invasive capability, migration, and mineralization, that define the conserved phenotypes compared to fresh PDC. From whole genome sequencing analysis of osteosarcoma tissue and patient-derived cells, we found that cryopreserved PDC was a minor population in the origin tissue and was selectively grown under the culture conditions. The cryopreserved PDC has a high resistance to conventional chemotherapy. This study demonstrated that the established cryopreserved PDC has the aggressive characteristics of osteosarcoma, in particular the chemoresistance phenotype that might be used for further investigation in the chemoresistant mechanism of osteosarcoma. In conclusion, the approach we applied for primary cell culture might be a promising method to generate in vitro models for functional testing of osteosarcoma