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Objective: To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula (4HF) and doxorubicin in triple-negative breast cancer (TNBC). Methods: Murine-derived triple-negative mammary carcinoma cell line, 4T1 cells, was cultured and inoculated into mouse mammary glands. Sixty-six mice were randomly assigned into 6 groups (n=11 in ench): naïve, control, LD 4HF (low dose 4HF), HD 4HF (high dose 4HF), LD 4HF + D (low dose and doxorubicin), and D (doxorubicin). Apart from the naïve group, each mouse received subcutaneous inoculation with 5 × 105 4T1 cells resuspended in 100 µL of normal saline in the mammary fat pads. Starting from the day of tumor cell inoculation, tumors were grown for 6 days. The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF, respectively. The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin (5 mg/kg). The D group received weekly intraperitoneal injections of doxorubicin (5 mg/kg). The treatment naïve mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week. The control group received daily oral gavage of 0.2 mL double-distilled water. The treatment period was 30 days. At the end of treatment, mice organs were harvested to analyze immunological activities via immunophenotyping, gene and multiplex analysis, histological staining, and gut microbiota analysis. Results: Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens (P<0.05), altered the hypoxia and overall immune lymphocyte landscape, and manipulated gut microbiota to favor the anti-tumor immunological activities. Moreover, immunosuppressive genes, cytokines, and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated (P<0.05). 4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response (P<0.05). Conclusion: The above results provide evidence for evaluating the immune regulating mechanisms of 4HF in breast cancer and support its clinical significance in its potential as an adjunctive therapeutic agent or immune supplement. [ABSTRACT FROM AUTHOR]

Adverse outcome pathways (AOPs) are organized sequences of key events (KEs) that are triggered by a xenobiotic-induced molecular initiating event (MIE) and summit in an adverse outcome (AO) relevant to human or ecological health. The AOP framework causally connects toxicological mechanistic information with apical endpoints for application in regulatory sciences. AOPs are very useful to link endophenotypic, cellular endpoints in vitro to adverse health effects in vivo. In the field of in vitro developmental neurotoxicity (DNT), such cellular endpoints can be assessed using the human "Neurosphere Assay," which depicts different endophenotypes for a broad variety of neurodevelopmental KEs. Combining this model with large-scale transcriptomics, we evaluated DNT hazards of two selected Chinese herbal medicines (CHMs) Lei Gong Teng (LGT) and Tian Ma (TM), and provided further insight into their modes-of-action (MoA). LGT disrupted hNPC migration eliciting an exceptional migration endophenotype. Time-lapse microscopy and intervention studies indicated that LGT disturbs laminin-dependent cell adhesion. TM impaired oligodendrocyte differentiation in human but not rat NPCs and activated a gene expression network related to oxidative stress. The LGT results supported a previously published AOP on radial glia cell adhesion due to interference with integrin-laminin binding, while the results of TM exposure were incorporated into a novel putative, stressor-based AOP. This study demonstrates that the combination of phenotypic and transcriptomic analyses is a powerful tool to elucidate compounds' MoA and incorporate the results into novel or existing AOPs for a better perception of the DNT hazard in a regulatory context. Highlights: A 3D in vitro model based on human neural progenitor cells was applied for assessing DNT potential of two selected CHMs. Both CHMs caused DNT endophenotypes in vitro, e.g. disturbed radial glia migration or impaired oligodendrocyte differentiation. Combining phenotypic with transcriptomic analyses enlight compounds' modes-of-action. Application and development of AOPs for a better comprehension of DNT hazards. [ABSTRACT FROM AUTHOR]

Objectives: We employed the co-culture of CD34+ stem cell-derived human mast cells (HMC) and human monocyte-derived osteoclast precursors to evaluate if mast cells contribute to the pathogenesis of osteoporosis through regulation of osteoclast proliferation and activation. Methods: Mature HMC and osteoclast precursors were cultured from monocytes isolated from human buffy coat. The osteoclast precursors were incubated with HMC or receptor activator of nuclear factor kappa-B ligand (RANKL) for a week prior to determination of osteoclast maturation through characterization by their morphology and tartrate resistant acid phosphatase (TRAP) expression. The bone absorption activity was determined by pit formation on osteo-assay plate. Results: Mature osteoclasts were identified following co-culture of osteoclast precursors with HMC for one week in the absence of RANKL and they were capable of bone resorption. These actions of HMC on osteoclasts were not affected by mast cell activators such anti-IgE or substance P but could be reversed by osteoprotegerin (OPG) in the co-culture system suggesting the involvement of RANKL. The expression of RANKL on the cell surface of HMC was confirmed by flow cytometry and the density was not affected by activation of HMC. Conclusion: Our study provided direct evidence confirming the initiation of osteoclast proliferation and activation by mast cells through cell surface RANKL suggesting that mast cells may contribute to bone destruction in pathological conditions such as osteoporosis. [ABSTRACT FROM AUTHOR]

Clinical risk factors to predict fracture are useful in guiding management of patients with osteoporosis or falls. Clinical predictors may however be population specific because of differences in lifestyle, environment and ethnicity. Four thousand community-dwelling Chinese males and females with average ages of 72.4 and 72.6 years were followed up for incident fractures, with an average of 6.5 and 8.8 years, respectively. Clinical information was collected, and bone mineral density (BMD) measurements were carried out at baseline. Stepwise Cox regression models were used to identify risk factors of nonvertebral fractures, with BMD as covariate. Areas under the receiver-operating characteristic (ROC) curve (AUC) were compared among different risk models. The incidence rates of nonvertebral fractures were 10.3 and 20.5 per 1000 person years in males and females, respectively. In males, age ≥80, history of a fall in the past year, fracture history, chronic obstructive pulmonary disease, impaired visual depth perception and low physical health-related quality of life were significant fracture risk factors, independent of BMD. In females, the significant factors were fracture history, low visual acuity and slow narrow walking speed. The clinical risk factors had a significant influence on fracture risk irrespective of osteoporosis status, even having a better risk discrimination than BMD alone, especially in males. The best risk prediction model consisted both BMD and clinical risk factors. Clinical risk factors have additive value to hip BMD in predicting nonvertebral fractures in older Chinese people and may predict them better than BMD alone in older Chinese males. [ABSTRACT FROM AUTHOR]

Objective: To further investigate the {ptin vitro} effects of an osteoprotective herbal formula "ELP" ( Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae) using seropharmacological approach. Methods: Rats were fed with ELP or its individual component herbs for 2 days. The serum containing the postabsorbed ingredients of the herbal items were collected for cell culture using UMR106 cell, RAW264.7 cell and mesenchymal stem cell (MSC) isolated from the bone marrow of the rats. The effects of the herbal-containing serum on cell toxicity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay; bromodeoxyuridine assay was conducted to measure the cell proliferation of UMR106 cell and MSC; cell activity was measured using colorimetric method, and mRNA expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteopontin (OPN) of UMR106 and MSC as well as matrix metalloproteinase 9 (MMP-9), tartrate-resistant acid phosphatase (TRAP) and cathepsin K of RAW264.7 were analyzed using real-time reverse-transcription polymerase chain reaction. Results: ELP and its component serum exhibited no cytotoxic effects on the cells. The ELP-containing serum increased the proliferation of UMR106 cell and MSC by 25.7% and 14.4 %, respectively and the alkaline phosphatase activity of MSC was increased by 42.6%. On the contrary, it inhibited the RAW264.7 cell differentiation by 29.2 %. ELP serum upregulated the Runx2 expression of UMR and MSC by 1.18 fold and 1.27 fold, respectively. It also upregulated ALP and OPN expression in MSC by 1.69- and 2.12-fold, respectively. On the other hand, ELP serum down-regulated MMP-9 and cathepsin K expression of RAW264.7 cell by 0.46- and 0.36-fold, respectively. Conclusions: The serum of the animals fed with ELP contains active ingredients which are effective in promoting osteogenesis and inhibiting osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Objective: To assess the biological effects of the six-herb mixture Anti-Insomia Formula (AIF) extract using caffeine-induced insomnia Drosophila model and short-sleep mutants. Methods: Caffeineinduced insomnia wild-type Drosophila and short-sleep mutant flies minisleep (mns) and Hyperkinetic (Hk) were used to assess the hypnotic effects of the AIF in vivo. The night time activity, the amount of night time sleep and the number of sleep bouts were determined using Drosophila activity monitoring system. Sleep was defined as any period of uninterrupted behavioral immobility (0 count per minute) lasting > 5 min. Night time sleep was calculated by summing up the sleep time in the dark period. Number of sleep bouts was calculated by counting the number of sleep episodes in the dark period. Results: AIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness ( P<0.01) in wild-type Canton-S flies as indicated by the reduction of the sleep bouts, night time activities and increase of the amount of night time sleep. AIF also significantly reduced sleeping time of short-sleep Hk mutant flies ( P<0.01). However, AIF did not produce similar effect in mns mutants. Conclusion: AIF might be able to rescue the abnormal condition caused by mutated modulatory subunit of the tetrameric potassium channel, but not rescuing the abnormal nerve firing caused by Shaker gene mutation. This study provides the scientific evidence to support the use of AIF in Chinese medicine for promoting sleep quality in insomnia. [ABSTRACT FROM AUTHOR]

In this study, a traditional Chinese herbal medicine-PentaHerbs formula (PHF), usually used for the treatment of atopic dermatitis, was successfully coated onto cotton fabrics by means of dyeing methods, i.e., mordant dyeing and direct dyeing process. Alum, copper sulphate and calcium chloride were used as mordant agents, and the mordanting processes adopted were pre-mordanting and post-mordanting process. The coated cotton fabrics with herbal medicine were mainly analyzed in terms of colour strength ( K/ S value) and drug loading using spectrophotometric analysis. Besides, the change of weight of the coated fabrics was also measured via gravimetric method. It was found that the mordanting process could significantly improve the drug loading, especially for the pre-mordanting process, compared with the direct dyeing method. Among the three mordants, alum treated fabrics had the highest drug loading. The results indicate that mordant dyeing process might be a promising way to develop herbal medicine garments. [ABSTRACT FROM AUTHOR]

Objective: To investigate the protective effects of a Chinese herbal formula, Taikong Yangxin Prescription (太空养心方, TKYXP) against bone deterioration in a hindlimb unloaded (tail-suspension) rat model. Methods: Thirty-two male Sprague-Dawley rats were divided into 4 groups: tail-suspension group fed with 2.5 g•kg•day of TKYXP extract (high dose), tail-suspension group fed with 1.25 g•kg•day (low dose), tail-suspended group treated with water placebo (placebo control group) and non tail-suspended group. The effects of TKYXP on bone were assessed using peripheral quantitative computed tomography (pQCT), microcomputerized tomography (micro-CT) and three-point bending biomechanical test on the femur in vivo. Results: TKYXP had a significant protective effect against bone loss induced by tail-suspension on day 28, as shown in the reduction in bone mineral density (BMD) loss, preservation of bone micro-architecture and biomechanical strength. The administration ofhigh dose TKYXP could significantly reduce the total BMD loss by 4.8% and 8.0% at the femur and tibia regions, respectively, compared with the placebo control group ( P<0.01) on day 28. Its bone protective effect on the femur was further substantiated by the increases of the trabecular BMD (by 6.6%), bone volume fraction (by 20.9%), trabecular number (by 9.5%) and thickness (by 11.9%) as compared with the placebo control group. Conclusion: TKYXP may protect the bone under weightless inflfl uence from gradual structural deterioration in the tail-suspension model. [ABSTRACT FROM AUTHOR]

Purpose: In previous studies, we demonstrated that green tea ( Camellia sinensis, CS) water extract had potent anti-tumor and anti-metastasis effects in the 4T1 mouse breast cancer xenograft model, and the metronomic regimen (0.0125 mg/kg twice a week for 4 weeks) of zoledronic acid (ZOL) was also effective in decreasing tumor burden and metastasis when compared with the conventional regimen. This study aimed to investigate the combined use of CS water extract and metronomic ZOL against tumor metastasis and bone destruction in MDA-MB-231-TXSA human breast cancer. Methods: Female nude mice were injected with MDA-MB-231-TXSA cells into the marrow space of tibia and were treated with CS water extract and/or metronomic ZOL for 4 weeks. Tumor growth and metastasis to lungs and livers were assessed by in vivo bioluminescence imaging. Abilities of migration and invasion of MDA-MB-231-TXSA cells were also evaluated in vitro. Results: Our results demonstrated that combination of CS and ZOL had the most potent effects on tumor burden and metastasis to bone, lung and liver, while treatment with CS or ZOL alone significantly protected the bone from cancer-induced osteolysis. In vitro, the combined use of CS + ZOL significantly inhibited MDA-MB-231-TXSA cell migration and invasion. Mechanistic zymography studies showed that the enzyme activities of MMP-9 and MMP-2 were significantly suppressed by CS and CS + ZOL. Conclusions: The combination of CS plus metronomic ZOL demonstrated potent anti-tumor, anti-metastasis and anti-osteolysis effects against breast cancer, suggesting the potential clinical application against breast cancer patients. [ABSTRACT FROM AUTHOR]

Qualitative and quantitative characterization of natural saccharides, especially polysaccharides, in herb materials remains a challenge due to their complicated structures and high macromolecular masses. Currently available methods involve time-consuming and complicated operations, and present poor specificity. Here, a novel and rapid high-performance gel permeation chromatography (HPGPC)-based approach is described for quality assessment of saccharide-dominant herbal materials by simultaneous qualitative and quantitative analysis of saccharide components. Dendrobium officinale, one of the rarest tonic herbs worldwide, was employed as the model herb in this study. First, a HPGPC fingerprint based on the molecular weight distribution of its carbohydrate components was established for qualitative identification of D. officinale. Then, HPGPC-guided dominant holistic polysaccharide marker was separated using ultra-filtration followed by HPGPC determination for quantitative evaluation of D. officinale. The experimental results suggest that this method is more efficient, stable, and convenient compared with the currently available methods for authentication and quality evaluation of D. officinale, and we expect the method will have similar advantages when used for quality control of other saccharide-dominant herbal materials and products. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Purpose: To understand bladder contractility changes induced by chronic ketamine treatment, noting the prevalence of its abuse worldwide. Methods: A mouse model of chronic ketamine treatment was used and detrusor strip contractility was measured. Rising and falling phases of contractile responses as well as maximal, average sustained and phasic contractions were measured. Results: While maximal contractility of ketamine-treated strips was identical to the saline controls, the former displayed slower contraction rates under K-Krebs, carbachol and electrical stimulation. The decay phase of electrically stimulated responses was also slower at most stimulation frequencies in the ketamine-treated strips. Greater sensitivity to varying the strengths of stimuli was observed in the ketamine-treated strips. Conclusions: Altered contractility characteristics of the bladder after chronic ketamine treatment were revealed, which could potentially be useful in the development of improved treatment regimens. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy of a herbal formula in the prevention of influenza or influenza-like syndrome among elderies residing in old-people's home in Hong Kong. The secondary objectives are to investigate the quality of life (QOL) and symptomology changes among the herbal users and to evaluate the safety of this formula. Methods: In ten old people's home or community centres in New Territories, Hong Kong, 740 eligible subjects agreed to join the study and were randomized to receive a herbal formula or a placebo on alternate days over 8 weeks. Among those 740 participants, 113 had provided blood samples for immunological assessments before and after the study drug. Assessments were done at 0, 4, 8 and 12 weeks. Participants were instructed to keep a daily record of body temperature and any symptoms as sore throat, myalgia, running nose or cough, and to report to assessor accordingly. Those reporting body temperature of 37.8 °C and above would be visited and a proper nasopharyngeal swab be taken for viral study. Results: Seventy-two participants developed influenza-like-symptoms but none of them was proven influenza in their nasopharyngeal swabs, 40 of these patients belonged to the herbal group and 32 to the placebo group, without significant differences between groups. The difference on the changes in QOL between the two groups was not statistically significant. However, in the immunological study, the natural killer cell absolute count was significantly increased in the herbal group compared with the placebo group (463±253 vs 413±198, P<0.05). Conclusions: The herbal preparation was not effective compared with placebo in the prevention of influenza-like syndrome. It was however safe and possibly supporting immunological responses. [ABSTRACT FROM AUTHOR]

It has been established in the recent several decades that adult stem cells play a crucial role in tissue renewal and regeneration. Adult stem cells locate in certain organs can differentiate into functional entities such as macrophages and bone cells. Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are two of the most important populations of adult stem cells. The application of these stem cells offers a new insight in treating various pathological conditions, through replenishing cells of specific functions by turning on or off the differentiating program within quiescent stem cell niches. Apart from that, they are also capable to travel through the circulation, migrate to injury sites and differentiate to enhance regeneration process. Recently, Chinese medicine (CM) has shown to be potential candidates to activate adult stem cells for tissue regeneration. This review summarizes our own, as well as others' findings concerning the use of Chinese herbal medicine in the regulation processes of adult stem cells differentiation and their movement in tissue repair and rejuvenation. A number of Chinese herbs are used as therapeutic agents and presumably preventive agents on metabolic disorders. In our opinion, the activation of adult stem cells self-regeneration not only provides a novel way to repair tissue damage, but also reduces the use of targeted drug that adversely altering the normal metabolism of human subjects. [ABSTRACT FROM AUTHOR]

We assessed the relationship of bone density and microarchitecture between hand, peripheral, and axial skeletal sites using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy X-ray absorptiometry (DXA) in patients with rheumatoid arthritis (RA) and which factors influence these parameters. This was a cross-sectional study of 100 female patients (53.4 ± 9.3 years) with RA. HR-pQCT scans at distal radius and the second metacarpal head were performed to assess cortical and trabecular volumetric bone mineral density (vBMD) and microarchitecture. DXA scans at the hip, lumbar spine, and ultradistal radius were performed to assess areal BMD. There was significant correlation in vBMD and microarchitectural parameters between the second metacarpal head and distal radius ( r = 0.201−0.628). Areal BMD at the axial skeleton was moderately associated with vBMD at the peripheral sites ( r = 0.354-0.558). Factors related to disease severity/chronicity significantly correlated with vBMD and microarchitecture at the distal radius and the second metacarpal head. Factors related to disease activity were more likely to correlate with vBMD and microarchitecture at the second metacarpal head but not those at the distal radius. HR-pQCT is a promising technique that is capable of providing detailed quantitative assessment of disease-associated periarticular bone loss at both cortical and trabecular bone compartments in patients with RA. Future longitudinal studies will be needed to investigate whether assessment by HR-pQCT can be used as a marker of disease activity and a predictor of disease progression in RA. [ABSTRACT FROM AUTHOR]

In this study we analyzed the independent effect of angiotensin-converting enzyme (ACE) inhibitor use on bone loss in elderly Chinese. The subjects were from two cohort studies which investigated the risk factors of osteoporotic fractures in Hong Kong-dwelling elderly Chinese. A total of 2161 subjects (1280 male, 881 female) were selected for this analysis. The results showed that unadjusted annualized percentage bone loss of male ACE inhibitor users was not different from non-users; however, female ACE inhibitor users had significantly greater bone loss both in total hip and femoral neck than non-users. After adjusting for significant confounders, female continuous ACE inhibitor users had significantly greater bone loss at total hip and femoral neck. In conclusion, continuous use of ACE inhibitors over 4 years was associated with increased bone loss in total hip and femoral neck in older Chinese women. [ABSTRACT FROM AUTHOR]

Objective: To prevent the deterioration of osteopenia, a triple herb product Bo-gu Ling (补骨 灵, ELP) was created for a clinical trial on post-menopausal women suffering from osteopenia. Methods: The design of the clinical trial was of randomized, double-blind, placebo-controlled nature. A total of 150 women aged 40-60 years, who were after menopause for at least 1 year and their lumbar spine bone mineral density (BMD) must be lower than 0.891 g/cm, were recruited and randomly divided into the ELP group treated with ELP and the placebo group, with 75 in each group. The primary endpoint was the BMD of the lumbar spine that was assessed at baseline, 6 and 12 months after treatment. Secondary endpoints included peripheral quantitative computed tomography (pQCT) measurements of distal tibia and the changes in the quality of life (QOL). Results: The spine BMD of the ELP group was increased by 0.69% in the subjects who were more than 10 years after menopause. In contrast, the placebo group of the same stratum decreased by 0.61% ( P=0.067). In the subjects with more than 10 years duration of menopause, the hip BMD increased by 0.21% in the ELP group, compared with a decrease of 0.52% in the placebo group ( P=0.159). The tibia strengthstrain index was increased by 1.94% in the ELP group compared with 0.33% in the placebo group ( P=0.047). Physical function of SF-36 QOL questionnaire was remarkably improved compared with the baseline, but did not show dominance over the placebo group. Conclusion: ELP showed potential benefifit in improving BMD on the women who experienced over 10 years of menopause. [ABSTRACT FROM AUTHOR]

The surgeon aims at a direct, complete removal of the pathology. In spite of the modern advancements of imaging facilities and precision instrumentations, unsatisfactory results and recurrences are not uncommon. This paper provides a general review of the four specific areas in surgery that would benefit from Chinese medicine. Extensive searches were made on four surgical areas based on available English language journals, viz. low-back pain, chronic ulcers, renal calculus, and enuresis in children, in the past 10 years. The quoted communications are mainly related to clinical evidences, while a smaller number of crucial laboratory reports are also included. Low-back pain, a most frequent orthopaedic problem, would benefit from acupuncture treatment. Chronic leg ulcers could achieve better results of healing using herbal supplements. Problems of renal stones, besides the conventional methods of removal, could be further supplemented with herbal drinks that aim at prevention of recurrences. Enuresis in children, an untreatable common condition, may respond well to acupuncture. Surgeons should keep an open mind. In case of difficulties, they could seriously consider options of traditional treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the efficacy and safety of a once-yearly zoledronic acid treatment for Chinese women with postmenopausal osteoporosis in Taiwan and Hong Kong. This post hoc subpopulation analysis, from the Health Outcome and Reduced Incidence with Zoledronic Acid One Yearly Pivotal Fracture Trial, enrolled 323 Chinese women with osteoporosis who were randomly given either annual infusions of zoledronic acid or placebo for 3 consecutive years. The incidence of fractures and changes in bone mineral density (BMD) were measured; adverse events (AEs) and tolerability were recorded and assessed. The results of this study at 36 months demonstrate that there was a significantly reduced risk of morphometric vertebral fracture and clinical vertebral fracture in subjects treated with zoledronic acid (P < 0.05). In addition, there were significant increases of BMD by 4.9%, 4.3%, and 7.0% in the total hip, femoral neck, and trochanter, respectively, in the zoledronic acid group compared with the placebo group (P < 0.001 for all comparisons). The incidences of AEs were comparable between the two groups. Thus, once-yearly zoledronic acid treatment showed bone protection effects by reducing the risk of vertebral fracture and increasing BMD in Chinese women with postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

We present the clinical, radiographic and pathological features of a juxtacortical chondrosarcoma which underwent dedifferentiation to an osteosarcoma in a 47-year-old woman. The tumour, abutting the femoral diaphysis, had initially presented 20 years earlier. Local excision was performed at presentation and again 10 years later, but the tumour recurred on each occasion. Serial radiographs showed cortical saucerisation evolving to cortical buttressing and mounding. After 20 years a dramatic radiographic change heralded tumour dedifferentiation. [ABSTRACT FROM AUTHOR]

Intracortical osteosarcomas originate in the bone cortex and represent the rarest type of osteosarcoma. We describe the clinical, radiological and histological features of an intracortical osteosarcoma occurring in the femur of a young man and discuss the pertinent features of this tumour compared to those previously reported. [ABSTRACT FROM AUTHOR]

Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM) and migrate to adjacent tissues. This ultimately results metastasis. Hence, the present study investigated the in vitro effects of cyclopeptide glycoside, RA-XII on cell adhesion, invasion, proliferation and matrix degradation, and its underlying mechanism in murine breast tumour cells, 4T1. The effect of RA-XII on tumour growth and metastasis in 4T1-bearing mice was also investigated. Our results showed that RA-XII inhibited tumour cell adhesion to collagen, fibronectin and laminin, RA-XII also reduced the expressions of vascular cell adhesion molecule, intracellular adhesion molecule and integrins, and integrin binding. In addition, RA-XII significantly inhibited breast tumour cell migration via interfering cofilin signaling and chemokine receptors. The activities of matrix metalloproteinase-9 and urokinase-type of plasminogen activator, and the expressions of ECM-associated proteinases were attenuated significantly by RA-XII. Furthermore, RA-XII induced G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. RA-XII inhibited the expressions of molecules in PI3K/AKT, NF-kappaB, FAK/pSRC, MAPK and EGFR signaling. RA-XII was also shown to have anti-tumour, anti-angiogenic and anti-metastatic activities in metastatic breast tumour-bearing mice. These findings strongly suggested that RA-XII is a potential anti-metastatic agent for breast cancer. [ABSTRACT FROM AUTHOR]

The pneumo- and hepato-toxicity of 4-vinylphenol (4VP), a styrene metabolite, has been previously reported. Nevertheless, the present study reported the novel anti-angiogenic activities of 4VP which was firstly isolated from the aqueous extract of a Chinese medicinal herb Hedyotis diffusa. Our results showed that 4VP at non-toxic dose effectively suppressed migration, tube formation, adhesion to extracellular matrix proteins, as well as protein and mRNA expressions of metalloproteinase-2 of human endothelial cells (HUVEC and HMEC-1). Investigation of the signal transduction revealed that 4VP down-regulated PI3K/AKT and p38 MAPK. Besides, 4VP interfered with the phosphorylation of ERK1/2, the translocation and expression of NFkappaB. In zebrafish embryo model, the new blood vessel growth was significantly blocked by 4VP (6.25-12.5 μg/mL medium). The VEGF-induced blood vessel formation in Matrigel plugs in C57BL/6 mice was suppressed by 4VP (20-100 μg/mL matrigel). In addition, the blood vessel number and tumor size were reduced by intraperitoneal 4VP (0.2-2 mg/kg) in 4T1 breast tumor-bearing BALB/c mice, with doxorubicin as positive control. Together, the in vitro and in vivo anti-angiogenic activities of 4VP were demonstrated for the first time. These findings suggest that 4VP has great potential to be further developed as an anti-angiogenic agent. [ABSTRACT FROM AUTHOR]