Nitric oxide, synthesized from the semiessential amino acid L-arginine by nitric oxide synthase, is a remarkable regulatory molecule and plays an important role in physiological functions. However, the physiological role of nitric oxide in cardiovascular regulation by the central nervous system is not well understood. In this study we investigated the cardiovascular effects of nitric oxide in the lateral ventricle, nucleus tractus solitarii, area postrema, and rostral ventrolateral medulla in urethane-anesthetized male Sprague-Dawley rats. Microinjection of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, into the cerebral ventricle of rats elicited a dose-dependent increase in blood pressure and heart rate. This suggests that nitric oxide may be involved in central cardiovascular regulation. Unilateral microinjection (60 nL) of L-arginine (1 to 100 nmol) into the nucleus tractus solitarii and rostral ventrolateral medulla produced prominent dose-related depressor and bradycardic effects and reduced renal sympathetic nerve activity. However, L-arginine had no significant cardiovascular effects in the area postrema. In addition, 4 to 6 hours after intravenous injection of bacterial endotoxin-lipopolysaccharide (10 mg/kg), there was a time-related potentiation of the L-arginine-induced depressor and bradycardic effects in the nucleus tractus solitarii. These results indicate that nitric oxide is involved in central cardiovascular regulation. The depressor effect of nitric oxide in the nucleus tractus solitarii and rostral ventrolateral medulla may be through inhibition of renal sympathetic nerve activity.

BACKGROUND Inactivation of the tumor suppressor gene PTEN/MMAC1/TEP1, located on chromosome 10q23, is a common event in advanced stages of diverse human malignancies. However, the prognostic role of PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized. METHODS One hundred five resected specimens were collected from patients with HCC. Expression levels of PTEN and p53 in clinical samples were analyzed by immunohistochemistry. RESULTS Immunohistochemical analysis of 105 HCC tissue specimens revealed that decreased or absence of PTEN immunostaining was found in 43 specimens (40.9%). Reduced PTEN expression levels were correlated with increased tumor grade (P = 0.017), advanced disease stage (P = 0.016), and elevated serum α‐fetoprotein (αFP) levels (P = 0.001). Kaplan–Meier analysis indicated that patients with reduced PTEN levels had shorter overall survival (P = 0.001) and higher recurrence rates (P = 0.0007) compared with patients who had intact PTEN expression. Examining p53 expression unveiled an inverse correlation between p53 overexpression and reduced PTEN expression in patients with HCC (P = 0.004). In addition, patients with p53 overexpression had shorter overall survival compared with patients who were without p53 overexpression (P = 0.0014). Univariate and multivariate analyses revealed that reduced PTEN expression was an independent prognostic factor for survival in patients with HCC. CONCLUSIONS The current study demonstrated that reduced PTEN expression levels are involved in the pathogenesis of HCC. Moreover, decreased PTEN expression was correlated with tumor progression, high αFP levels, p53 overexpression, and poor prognosis in patients with HCC. Cancer 2003;97:1929–40. © 2003 American Cancer Society. DOI 10.1002/cncr.11266

OCT4 and SOX2 are biomarkers of tumorigenesis and early stage OSCC. SOX2 is an independent prognostic factor for OSCC.

The purposes of this study were to examine the attitudes of physicians regarding the optimal use of analgesics for cancer pain management (CPM), to evaluate their knowledge and attitudes toward opioid prescribing, and to comprehend their perceptions of the barriers to optimal CPM. A survey was conducted on 356 physicians with cancer patient care responsibilities practicing in two medical centers in Taiwan. A total of 204 (57%) physicians responded, including internists (28%), surgeons (27%), oncologists (11%), anesthesiologists (10%), and other specialties (24%). The majority of physicians displayed significantly inadequate knowledge and negative attitudes toward the optimal use of analgesics and opioid prescribing. Multivariate analyses showed that the following six categories of physicians would be inclined to have inadequate knowledge of opioid prescribing: 1) those with perception of good medical school training in CPM, 2) those with perception of poor residency or fellowship training in CPM, 3) those with a medical specialty in surgery, medicine, or oncology (vs. anesthesiology), 4) those with limited clinical experience in cancer patient care (number of patients less than 30), 5) those with a limited aim of pain relief, and 6) those with an underestimation of analgesic effect. Additionally, physicians with inadequate knowledge of opioid prescribing and with hesitation to intervene earlier with maximal dose of analgesia would be inclined to have reluctant attitudes toward opioid prescribing. The most important barriers to optimal CPM identified by physicians themselves were physician-related problems, such as inadequate guidance from a pain specialist, inadequate knowledge of CPM, and inadequate pain assessment. The results of this study suggest that active analgesic education programs are urgently needed in Taiwan.