5-HT7 Receptor Is Involved in Electroacupuncture Inhibition of Chronic Pain in the Spinal Cord.

Knee osteoarthritis (KOA) is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT1, 5-HT2, and 5-HT3 receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT7 receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT7 receptor is involved in EA analgesia. The 5-HT7 receptor is a stimulatory G-protein (Gs)-coupled receptor that activates adenylyl cyclase (AC) to stimulate cyclic adenosine monophosphate (cAMP) formation, which in turn activates protein kinase A (PKA). In the present study, we found that EA significantly increased the tactile threshold and the expression of the 5-HT7 receptor in the dorsal spinal cord. Intrathecal injection of 5-HT7 receptor agonist AS-19 mimicked the analgesic effect of EA, while a selective 5-HT7 receptor antagonist reversed this effect. Moreover, intrathecal injection of AC and PKA antagonists prior to EA intervention prevented its anti-allodynic effect. In addition, GABAA receptor antagonist bicuculline administered (intrathecal, i.t.) prior to EA intervention blocked the EA effect on pain hypersensitivity. Our data suggest that the spinal 5-HT7 receptor activates GABAergic neurons through the Gs-cAMP-PKA pathway and participates in EA-mediated inhibition of chronic pain in a mouse model of KOA.

ECRG2 enhances the anti-cancer effects of cisplatin in cisplatin-resistant esophageal cancer cells via upregulation of p53 and downregulation of PCNA.

AIM: To explore the anti-tumor effects of esophageal cancer-related gene 2 (ECRG2) in combination with cisplatin (DDP) in DDP-resistant esophageal cancer cells (EC9706/DDP). METHODS: A drug-resistant cell model was established, with EC9706/DDP cells being treated with ECRG2 and/or DDP. Cell viability was examined by MTT assay. The rate of cell apoptosis was determined by flow cytometry. The mRNA expression levels of proliferating cell nuclear antigen (PCNA), metallothionein (MT), and p53 were determined by RT-PCR and PCNA, while MT and p53 protein expression levels were determined by western blotting. RESULTS: The anti-proliferative effect of ECRG2 in combination with DDP was superior when compared to ECRG2 or DDP alone. The inhibition rate for the combination reached its peak (51.33%) at 96 h. The early apoptotic rates of the control, ECRG2 alone, DDP alone, and ECRG2 plus DDP groups were 5.71% ± 0.27%, 12.68% ± 0.61%, 14.15% ± 0.87%, and 27.96% ± 0.36%, respectively. Although all treatment groups were significantly different from the control group (P < 0.05), the combination treatment of ECRG2 plus DDP performed significantly better when compared to either ECRG2 or DDP alone (P < 0.05). The combination of ECRG2 and DDP significantly upregulated p53 mRNA and protein levels and downregulated PCNA mRNA and protein levels compared to ECRG2 or DDP alone (P < 0.05). However, no changes were seen in the expression of MT mRNA or protein. CONCLUSION: ECRG2 in combination with DDP can inhibit viability and induce apoptosis in esophageal cancer DDP-resistant cells, possibly via upregulation of p53 expression and downregulation of PCNA expression. These findings suggest that the combination of ECRG2 and DDP may be a promising strategy for the clinical treatment of esophageal cancers that are resistant to DDP.

MYC and MXI1 protein expression: potential prognostic significance in women with breast cancer in China.

OBJECTIVE: To investigate the expression levels and the clinical significance of MYC and MXI1 proteins in breast cancer. METHODS: The expression levels of MYC and MXI1 were detected by immunohistochemical assay in 166 cases of breast cancer; the relationships among MYC, MXI1 and the clinicopathological parameters were analyzed by χ2 test. Univariate analysis and Cox's proportional hazards model were used to evaluate the prognostic significance of the 2 proteins. RESULTS: 27.71% of the tumor specimens showed high staining intensity for MYC (high-expression group, HEG-MYC) and 22.89% showed high staining intensity for MXI1 (HEG-MXI1); the expression of 2 proteins was negatively correlated (r = -0.177 p = 0.022). The Kaplan-Meier method for survival analysis showed that patients of the MYC-HEG demonstrated a significantly worse disease-specific survival than those of the MYC-low-expression group (LEG) (χ2 = 11.102, p = 0.001). However, patients of the MXI1-HEG had a significantly better disease-specific survival than those of the MXI1-LEG (χ2 = 7.858, p = 0.005). Both univariate analysis and Cox's proportional hazards model indicated that MYC and MXI1 could be independent prognostic molecular markers. CONCLUSION: MYC-HEG and MXI1-LEG levels are associated with poor prognosis in patients with breast cancer, suggesting that they may be useful molecular markers in breast cancer prognosis prediction.

Cytokine-induced killer cell therapy for advanced pancreatic adenocarcinoma: A case report and review of the literature.

Patients with advanced pancreatic adenocarcinoma have a poor prognosis, and to date, no treatment method has had a significant impact on the disease. In general, the mean overall survival time of such patients receiving conventional chemotherapy and radiotherapy is <6 months. In the present case report, a patient with advanced pancreatic adenocarcinoma experienced a longer progression-free survival (PFS) of >19 months, following cytokine-induced killer (CIK) cell therapy. To the best of our knowledge, no study has previously described such a beneficial effect on patients only receiving CIK cell immunotherapy. Based on these findings, CIK cell therapy may be a potential treatment regimen that is capable of leading to an improved prognosis in certain patients with advanced pancreatic adenocarcinoma.

[A descriptive analysis of mortality of brain tumor in China during 2004 - 2005].

OBJECTIVE: To analyze the level of mortality of brain tumor and its changes at different periods in China. METHODS: Death records for tumor of brain and central nervous system, which the code of international classification of diseases-10 (ICD-10) were C70-C72, were extracted from the database of the Third National Retrospective Sampling Survey of Death Causes in China during 2004 to 2005. The corresponding population data was linked to the data of death records, that the total population was 142 660 482 person years (72 970 241 person years in male, 69 690 241 person years in female). Then crude death rate, age-specific death rate, the constitute proportion to all death caused by tumor and the age-standardized death rate were calculated by taking reference of Chinese standard population or the world standard population. The indexes of mortality were compared with that of previous retrospective surveys of death causes at 1973 - 1975 and 1990 - 1992. RESULTS: The result showed that during 2004 to 2005, the number died from brain tumor was 4463 and the crude death rate in China was 3.13/100 000, which accounted for 2.30% of the all number died from tumor (193 841 cases). The age-standardized death rate by Chinese standard population was 2.37/100 000 and the age-standardized death rate by the world standard population was 2.90/100 000. Of which, there were 2556 death cases for males with crude death rate of 3.50/100 000. While for females, the crude death rate was 2.74/100 000 (1907 death cases). Age-standardized death rates by Chinese standard population in male and female were 2.71/100 000 and 2.03/100 000 respectively. The age-standardized death rate by world standard population was 3.31/100 000 for male and for female that was 2.48/100 000. The age-specific death rate of brain tumor in China was increasing as age growing. The crude death rates were 3.78/100 000 (1809/47 899 806), 2.80/100 000 (2654/94 760 676), and the age-standardized death rates by Chinese standard population were 2.71/100 000 and 2.20/100 000 for urban and rural area respectively, and the crude death rates of brain tumor in east, middle and west region were 3.60/100 000 (1894/52 556 694), 3.14/100 000 (1565/49 781 225), 2.49/100 000 (1004/40 322 563). The age-standardized death rates by Chinese population were 2.57/100 000, 2.43/100 000 and 2.02/100 000. Compared to the data in the first survey during 1973 to 1975, in which the crude death rate was 1.13/100 000 and age-standardized death rate by Chinese standard population was 1.10/100 000, the crude death rate and age-standardized death rate by Chinese standard population were increased by 176.99% and 115.45% respectively. While compared with the second survey during 1990 to 1992, that crude death rate was 1.89/100 000 and age-standardized death rate by Chinese standard population was 1.74/100 000, the rising percent of the rates were 65.61% and 36.21% respectively. CONCLUSION: The level of mortality of brain tumor has been changing with an increasing trend from the period of 1973 - 1975 to the period of 2004 - 2005. The rate in male was higher than that of female with great diversity in different areas in China.

[Increased subthalamic neuronal activity after dorsal raphe nucleus lesion by 5,7-dihydroxytryptamine in the rat].

In vivo extracellular recordings were made in the subthalamic nucleus (STN) of intact control rats and rats with 5,7-dihydroxytryptamine (5,7-DHT) -produced lesion of dorsal raphe nucleus (DRN). The results showed that the firing rate of STN neurons in control rats and DRN-lesioned rats were (6.93+/-6.55) Hz and (11.27+/-9.31) Hz, respectively, and the firing rate of DRN-lesioned rats significantly increased when compared to the control rats (P<0.01). In control rats, 13% of STN neurons discharged regularly, 46% irregularly and 41% in bursts. In DRN-lesioned rats, 9% of STN neurons discharged regularly, 14% irregularly and 77% in bursts, the percentage of STN neurons firing in bursts was obviously higher than that of the control rats (P<0.01). In addition, the mean interspike interval coefficient of variation of STN neurons in control rats and DRN-lesioned rats were (0.05+/-0.04) and (0.11+/-0.09), respectively. The mean interspike interval coefficient of variation of DRN-lesioned rats was significantly higher than that of the control rats (P<0.001). These results show that the firing rate and the bursting pattern rate of neurons in STN of DRN-lesioned rats increase significantly, suggesting that DRN inhibits the neuronal activity of the subthalamic neurons in the intact rat.