52 research outputs found

    Zoledronic acid inhibits macrophage SOCS3 expression and enhances cytokine production

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    Suppressor of cytokine signaling‐3 (SOCS3) has multiple functions including inhibition of Janus kinase (Jak) activity, regulation of protein degradation, and suppression of cytokine signaling. SOCS3 modulates macrophage response to cytokines such as IL‐6 and leptin that are systemically induced in obesity. Obesity is a suspected risk factor for SOCS3‐related pathology such as rheumatoid arthritis and Crohn's disease as well as zoledronic acid (ZA)‐induced osteonecrosis of the jaw (ONJ). Thus, understanding the ability of bisphosphonates to modulate SOCS3 is necessary to qualify their contribution to these disorders. ONJ occurs in up to 10% of patients using intravenous bisphosphonates and has an unknown pathogenesis that may be linked to decreased bone turnover, altered vascularity, bacterial invasion, and compromised wound healing. Given the increased risk of ONJ with obesity and importance of macrophages in wound healing, we hypothesized that amino‐bisphosphonates could contribute to the pathogenesis of ONJ by regulating macrophage responses to cytokines such as leptin and IL‐6. We report that ZA is a novel inhibitor of SOCS3 in primary macrophages and human ONJ biopsy specimens. Inhibition of SOCS3 by ZA resulted in significant increases in IL‐6 production. SOCS3 transcription is regulated by nuclear accumulation of phosphorylated‐Stat3 (P‐Stat3). We found that ZA decreased phosphorylation of Stat3 in a mevalonate‐pathway dependent manner. However, restoration of P‐Stat3 was not sufficient to correct SOCS3 inhibition. We propose that disruption of macrophage SOCS3 expression by amino‐bisphosphonates such as ZA may be a novel contributor to inflammatory phenotypes in obesity and the pathogenesis of ONJ. J. Cell. Biochem. 112: 3364–3372, 2011. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87102/1/23267_ftp.pd

    Oral cancer treatment costs in Greece and the effect of advanced disease

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    BACKGROUND: The main purpose of the study was to quantify the direct costs of oral cancer treatment to the healthcare system of Greece. Another aim was to identify factors that affect costs and potential cost reduction items. More specifically, we examined the relationship between stage of disease, modality of treatment and total direct costs. METHODS: The medical records and clinic files of the Oral and Maxillofacial Clinic of the Athens General Hospital "Genimatas" were abstracted to investigate clinical treatment characteristics, including length of hospitalization, modes of treatment, stage of disease etc. Records of 95 patients with oral squamous cell carcinoma (OSSC), with at least six months of follow-up, were examined. The clinical data was then used to calculate actual direct costs, based on 2001 market values. RESULTS: The mean total direct costs for OSSC treatment estimated at euro 8,450 or approximately US$ 7,450. Costs depended on the stage of the disease, with significant increases in stages III and IV, as compared with stages I and II (p < 0.05). Multi-modality treatment applied mainly to patients in stages III and IV was the factor that affected the cost. Disease stage was also associated with the total duration of hospitalization (p < 0.05). CONCLUSIONS: The clinical management of advanced oral cancer is strongly associated with higher costs. Although the ideal would be to prevent cancer, the combination of high-risk screening, early diagnosis and early treatment seems the most efficient way to reduce costs, and most importantly, prolong life

    Delayed woundhealing after tooth extraction and self–reportedkyphosis in Japanese men and women

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    It is unclear whether osteoporosis itself is a main risk factor for delayed wound healing after tooth extraction in humans. In this study, we evaluated the association between experience of delayed wound healing after last tooth extraction and self-reported kyphosis, with the possibility of having vertebral fractures, in Japanese patients. Among the 1,504 patients who responded to the structured questionnaire survey, 518 patients (134 men and 384 women) aged 55-97 years finally participated in this study. Patients who self-reported mild-moderate kyphosis were more likely to have problematic delayed wound healing after last tooth extraction than those who reported severe kyphosis (odds ratio [OR] 4.98; 95% confidence interval [CI], 1.86-13.38 and OR 2.30; 95% CI, 0.52-10.22, respectively) (p for trend = 0.005). Japanese patients with vertebral fractures may have a higher risk of having problematic delayed wound healing after tooth extraction

    Closing in on the Puzzle of ONJ

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    Oral cancer treatment costs in Greece and the effect of advanced disease

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    <p>Abstract</p> <p>Background</p> <p>The main purpose of the study was to quantify the direct costs of oral cancer treatment to the healthcare system of Greece. Another aim was to identify factors that affect costs and potential cost reduction items. More specifically, we examined the relationship between stage of disease, modality of treatment and total direct costs.</p> <p>Methods</p> <p>The medical records and clinic files of the Oral and Maxillofacial Clinic of the Athens General Hospital "Genimatas" were abstracted to investigate clinical treatment characteristics, including length of hospitalization, modes of treatment, stage of disease etc. Records of 95 patients with oral squamous cell carcinoma (OSSC), with at least six months of follow-up, were examined. The clinical data was then used to calculate actual direct costs, based on 2001 market values.</p> <p>Results</p> <p>The mean total direct costs for OSSC treatment estimated at euro 8,450 or approximately US$ 7,450. Costs depended on the stage of the disease, with significant increases in stages III and IV, as compared with stages I and II (p < 0.05). Multi-modality treatment applied mainly to patients in stages III and IV was the factor that affected the cost. Disease stage was also associated with the total duration of hospitalization (p < 0.05).</p> <p>Conclusions</p> <p>The clinical management of advanced oral cancer is strongly associated with higher costs. Although the ideal would be to prevent cancer, the combination of high-risk screening, early diagnosis and early treatment seems the most efficient way to reduce costs, and most importantly, prolong life.</p

    Factors associated with delay in the diagnosis of oral cancer

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    Early detection and treatment improve the prognosis for oral cancer. Delays from the onset of symptoms to clinical diagnosis are common. Our aim is to identify factors associated with this delay. Between 1995 and 1998, we interviewed 105 consecutive patients with histologically confirmed oral cancer in Greece. If 21 or more days elapsed from the time the patient noticed major symptoms to a definitive diagnosis, we called it a delay (52% of cases). We used logistic and linear regression to estimate odds ratios of delayed diagnosis and to identify correlates of length of delay, respectively. Former smokers had a 4.3 times greater risk of delayed diagnosis compared with current smokers (95% confidence interval: 1.1-17.1). The length of delay was greater among single patients, nonsmokers, or those with stage IV tumors. Clinicians should be advised that delay in the diagnosis of oral cancer occurs frequently, even in individuals who do not smoke heavily
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