Biomedical subjects
Publications and source records attributed to L Mao.
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BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) seem to prevent several types of cancer, but could increase the risk of cardiovascular complications. We investigated whether use of NSAIDs was associated with a change in the incidence of oral cancer or overall or cardiovascular mortality. METHODS: We undertook a nested case-control study to analyse data from a population-based database (Cohort of Norway; CONOR), which consisted of prospectively obtained health data from all regions of Norway. People with oral cancer were identified from the 9241 individuals in CONOR who were at increased risk of oral cancer because of heavy smoking (15 pack-years), and matched controls were selected from the remaining heavy smokers (who did not have cancer). FINDINGS: We identified and analysed 454 (5%) people with oral cancer (279 men, 175 women, mean [SD] age at diagnosis 63.3 [13.2] years) and 454 matched controls (n=908); 263 (29%) had used NSAIDs, 83 (9%) had used paracetamol (for a minimum of 6 months), and 562 (62%) had used neither drug. NSAID use (but not paracetamol use) was associated with a reduced risk of oral cancer (including in active smokers; hazard ratio 0.47, 95% CI 0.37-0.60, p<0.0001). Smoking cessation also lowered the risk of oral cancer (0.41, 0.32-0.52, p<0.0001). Additionally, long-term use of NSAIDs (but not paracetamol) was associated with an increased risk of cardiovascular-disease-related death (2.06, 1.34-3.18, p=0.001). NSAID use did not significantly reduce overall mortality (p=0.17). INTERPRETATION: Long-term use of NSAIDs is associated with a reduced incidence of oral cancer (including in active smokers), but also with an increased risk of death due to cardiovascular disease. These findings highlight the need for a careful risk-benefit analysis when the long-term use of NSAIDs is considered.
The analgesic effects induced by two different kinds of peripheral conditioning stimulations, electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS), were compared in the rat using the latency of radiant heat-evoked tail flick reflex as nociceptive index. The parallel elevations of withdrawal latency of tail flick were produced by EA and TENS administrations at the acupoints of S36 and Sp6 with low intensity (1-2-3 mA) and one of three different frequencies (2, 15 and 100 Hz). Analgesic effects of EA or TENS were characterized by slow-on and slow-off nature, and a significant linear correlation was found between both at any one of three frequencies. Systemic naloxone hydrochloride (2 mg/kg) almost completely and partially antagonized 2 and 15 Hz EA- or TENS-induced analgesia, respectively, but failed to affect those induced by 100 Hz EA or TENS. Tolerance to EA stimulation with one of three frequencies reduced the corresponding frequency TENS-induced analgesia and vice versa. These data indicate that: (a) there is no significant difference in producing antinociception for two different peripheral conditioning stimulations when applied at the same sites and (b) the common neural mechanisms most likely process the analgesic effects of EA and TENS. The involvement of (an) endogenous opiate mechanism in the management of different frequency EA and TENS analgesia is discussed in detail.
BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors play an important role in regulating apoptosis. Recently, it was shown that the expression of TRAIL-R2, also known as KILLER, Trick or DR5, can be induced by either DNA damage or overexpression of a wild-type p53 transgene, suggesting a role for p53 in the death-signaling pathway. Furthermore, mutations in the death domain of TRAIL-R2 were reported in 10.6% of non-small cell lung cancer (NSCLC) patients in a Korean population, suggesting a role for TRAIL-R2 in lung tumorigenesis. MATERIALS AND METHODS: To determine the association between expression of TRAIL-R2 and p53 mutation status in lung cancers, we compared the two events in 20 small-cell lung cancer (SCLC) cell lines, 20 NSCLC cell lines, and 30 primary NSCLC tumors. We also sequenced the death domain of TRAIL-R2 in a total of 100 primary NSCLC. RESULTS: Lack of TRAIL-R2 expression was found in eight of 20 (40%) SCLC cell lines and in eleven of 20 (55%) NSCLC cell lines. Interestingly, in primary NSCLC, TRAIL-R2 was overexpressed in seven (23%) of the 30 tumors tested, and all primary tumors expressed TRAIL-R2. No association was found between the expression status of TRAIL-R2 and p53 mutation status in primary NSCLC tumors, SCLC cell lines or NSCLC cell lines. Further analysis of the death domain of TRAIL-R2 failed to identify any mutation in 100 primary NSCLC tumors. CONCLUSIONS: Our data indicate that the expression profile of TRAIL-R2 is significantly different in lung cancer cell lines and primary tumors, that the expression of TRAIL-R2 is independent from p53 mutation status and that mutations in the death domain of TRAIL-R2 play a minimal role in NSCLCs in white Americans.