Origins of surface potentials evoked by electrical stimulation of oculomotor nerves: are they related to electrooculographic or electromyographic events?

OBJECT: Evoked potentials elicited by electrical stimulation of the oculomotor nerve and recorded from surface electrodes placed on the skin around the eyeball reportedly originate in the eye and are represented on electrooculograms. Because evoked potentials recorded from surface electrodes are extremely similar to those of extraocular muscles, which are represented on electromyograms, the authors investigated the true origin of these potentials. METHODS: Evoked potentials elicited by electrical stimulation of the canine oculomotor nerve were recorded from surface electrodes placed on the skin around the eyeball. A thread sutured to the center of the cornea was pulled and the potentials that were evoked during the resultant eye movement were recorded. These potentials were confirmed to originate in the eye and to be represented on electrooculograms because their waveforms were unaffected by the administration of muscle relaxant. To eliminate the influence of this source, the retina, a main origin of standing potentials of the eyeball, was removed. This resulted in the disappearance of electrooculography (EOG) waves elicited by eye movement. Surface potentials elicited by oculomotor nerve stimulation were the same before and after removal of the retina. Again the oculomotor nerve was electrically stimulated and electromyography (EMG) response of the extraocular muscles was recorded at the same time that potentials were recorded from the surface electrodes. In their peak latencies, amplitudes, and waveforms, the evoked potentials obtained from surface electrodes were almost identical to EMG responses of extraocular muscles. CONCLUSIONS: Evoked potentials elicited by electrical stimulation of the oculomotor nerves and obtained from surface electrodes originated from EMG responses of extraocular muscles. These evoked potentials do not derive from the eye.     

砷对人淋巴细胞 DNA 氧化损伤的作用

目的：探讨砷（As)引起植物血凝集素（PHA）刺激和无刺激人外周血淋巴细胞DNA氧化性损伤。方法：用10μmol/L砷处理细胞2h,经单细胞凝胶电泳（SCGE,或彗星试验）－FPG（甲酰胺基嘧啶－DNA糖基化酶）消化法检测砷引起的DNA碱基损伤。结果：砷引起的DNA链断裂的修复过程与过氧化氢（H2O2）引起的修复过程类似,FPG消化产生的单链断裂,或砷引起的碱基损伤在PHA刺激淋巴细胞较未刺激细胞显著,在PHA刺激的淋巴细胞,砷和H2O2引起的DNA链断裂2h分别修复63％和68％,但在未刺激细胞分别修复大约34％和43％,在PHA刺激的淋巴细胞,砷和H2O2引起的碱基损伤2h分别修复40％和49％,但在未刺激细胞分别修复大约19％和21％。结果：微量砷可引起人类细胞DNA氧化性损伤,损伤的碱基主要是嘌呤或甲酰胺基嘧啶,未分裂（刺激）淋巴细胞修复砷与H2O2引起的DNA损伤较慢。     

Dose-dependent effect of dietary conjugated linoleic acid on the growth of rat hepatoma dRLh-84 cells in vivo

In this study, the effect of varying doses of conjugated linoleic acid (CLA) on the growth of transplanted hepatoma dRLh-84 cells and the relationship between tumor growth and prostaglandin (PG) E2 production or cyclooxygenase (COX)-2 expression were examined. Donryu rats were fed an experimental diet containing 0, 0.1, 0.5, or 2 wt.% CLA for 3 wk, and then dRLh-84 cells were transplanted into the liver. Results show that dietary CLA (0.5 and 2 wt.%) significantly enhanced the growth of the transplanted hepatoma cells compared to the non-CLA diet group at 20 d after cell transplantation. Tumor weight at 10 d after transplantation was also significantly higher in the 2 wt.% CLA group than in non-CLA fed rats. Ten days after transplantation, the PGE2 level in the tumor tissue was shown to be depressed in a CLA dose-dependent manner. Cyclooxygenase-2 (COX-2) mRNA expression in the tumor also tended to be lower in the CLA group than in the non-CLA diet group 10 d after transplantation. Dietary CLA did not affect the tumor phospholipid arachidonic acid level, which is a substrate for PG synthesis. These results indicate that dietary CLA of at least 0.5 wt.% enhances the growth of transplanted dRLh-84 cells in vivo. It is believed that growth promotion of dRLh-84 cells in vivo by CLA cannot be clarified by the PG synthesis dependent mechanism.     

Cytoplasmic expression of laminin gamma2 chain correlates with postoperative hepatic metastasis and poor prognosis in patients with pancreatic ductal adenocarcinoma

BACKGROUND: The laminin gamma2 chain is involved in tumor invasion and metastasis, but the significance of laminin gamma2 chain expression remains unclear in patients with pancreatic carcinoma. METHODS: Laminin gamma2 chain expression was examined immunohistochemically in 48 patients with pancreatic ductal adenocarcinoma who were followed closely to elucidate the correlations between clinicopathologic factors, postoperative recurrence, and overall survival. Prognostic factors for postoperative survival were examined comparing clinicopathologic factors and laminin gamma2 chain expression. RESULTS: Two different staining patterns of laminin gamma2 chain expression, cytoplasmic expression and basement membrane expression, were detected in tumors from all 48 patients. Tumors were then classified into two types according to the dominant pattern of laminin gamma2 chain expression: the cytoplasmic expression dominant type (CYT; n = 26 patients) and the basement membrane expression dominant type (BM; n = 22 patients). Tumor differentiation was associated statistically with the BM type of laminin gamma2 chain expression (P = 0.0002). The CYT type of laminin gamma2 chain expression was associated significantly with the occurrence of postoperative hepatic metastasis (P = 0.0011) and also was the strongest predictive factor for poorer overall survival in patients with pancreatic ductal adenocarcinomas (P = 0.0161). CONCLUSIONS: The cytoplasmic expression of the laminin gamma2 chain represents the high invasive potential of the tumor and is correlated with distant metastasis, especially hepatic metastasis, and with a poorer prognosis in patients with pancreatic ductal adenocarcinoma.     

Hyaluronan-CD44s signaling regulates matrix metalloproteinase-2 secretion in a human lung carcinoma cell line QG90

We investigated the production of matrix metalloproteinase (MMP) by hyaluronan(HA) stimulation in a human cancer cell line, QG90, that expresses a large amount of CD44s, a HA receptor. Treatment of QG90 with HA strongly activated MMP-2 secretion in a time- and dose-dependent manner. We found that expression of antisense CD44s in QG90 cells substantially inhibited the HA-dependent secretion of MMP-2, whereas overexpression of full-length CD44s augmented the HA-dependent secretion of MMP-2. In addition, pretreatment of cells with the neutralizing anti-CD44 antibody significantly inhibited both the HA-dependent MMP-2 secretion and the HA-dependent activation of mitogen-activated protein kinase in a dose-dependent manner. Similarly, treatment of cells with a Ras farnesyltransferase inhibitor, manumycin A, strongly inhibited the HA-dependent MMP-2 secretion. Moreover, in vitro invasiveness of QG90 and its activation by HA were clearly suppressed by the expression of antisense CD44s. In addition, treatment of cells with anti-CD44, a mitogen-activated protein/extracellular signal-regulated kinase kinase 1 inhibitor, PD98059, or phosphatidylinositol 3'-kinase inhibitors, wortmannin and LY294002, effectively blocked the HA-dependent activation of the invasiveness. In contrast, overexpression of full-length CD44 substantially activated the invasiveness of QG90. Taken together, HA-CD44s signaling plays a key role in the HA-dependent secretion of MMP-2 and, hence, in the invasiveness of QG90 cells.     

Glut-1 glucose transporter expression in esophageal squamous cell carcinoma is associated with tumor aggressiveness

BACKGROUND: Glucose transporter (Glut) proteins, which are membrane proteins responsible for the transport of glucose across cellular membranes, have six forms. To further elucidate the role of Glut-1 expression in esophageal squamous cell carcinoma, we examined the expression of Glut-1 protein immunohistochemically. MATERIALS AND METHODS: Immunohistochemical expression of Glut-1 was examined in surgically resected tissues from 95 patients with esophageal squamous cell carcinoma. RESULTS: Of the 95 esophageal carcinomas, 91 (95.8%) had some Glut-1 immunostaining in the membranes of the cancer cells. Positive staining (> 30% of cancer cells showing Glut-1 expression) was observed in 49 (51.6%) of the cases. Comparison of Glut-1 expression and clinicopathological characteristics in the 95 patients with esophageal cancer revealed significant associations between Glut-1 expression and tumor status (p < 0.001), lymph node status (p < 0.05), metastatic status (p < 0.01), and pathological stage (p < 0.001). The survival rates of patients with Glut-1-positive tumors were significantly lower than those of patients with Glut-1-negative tumors (log-rank p < 0.05). CONCLUSION: In conclusion, the level of Glut-1 expression may be a useful marker that can provide information on tumor aggressiveness and prognosis in patients with esophageal squamous cell carcinoma.     

Clinical characteristics of hepatocellular carcinoma with an extensive lymph node metastasis at diagnosis

Lymph node metastasis is reported to occur only rarely in patients with hepatocellular carcinoma (HCC). However, we have encountered patients with HCC with extensive lymph node metastases. Here we report the clinical characteristics of HCC associated with extensive lymph node metastasis at diagnosis. Ten patients with HCC in whom extensive lymph node metastases were observed at the initial medical examination were studied. The degree of disease progression was documented with ultrasonography and dynamic computed tomography. Primary liver lesions were classified in the following three types according to imaging characteristics: type A, massive type with portal vein tumor thrombus; type B, multinodular, nonencapsulated type; and type C: multinodular, encapsulated type. In patients with types A and B HCC, a large number of lymph node metastases was observed, whereas a small number of isolated metastases was observed in patients with type C. All patients with types A and B HCC died within 7 months (median survival, 4 months), whereas those with type C survived for 4 years or more after treatment with transcatheter arterial chemoembolization and surgery. A relationship exists between the type of primary HCC lesions and the pattern of lymph node metastasis. Long-term survival may be expected for patients with isolated lymph node metastases.     

Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors

Human tumor xenografts established in athymic rat brains were used to determine the feasibility of intravascular delivery of tumor suppressor genes to brain tumors. Both tumor size and number were compared to characterize the effect of tumor burden on tumor transduction efficacy by a control LacZ-containing adenoviral vector. Experiments with tumors grown in vivo for either 3, 5, or 7 days demonstrated that 5-day-old tumors provided the best target for vector infection and transgene expression by this mode of administration. Intra-arterial mannitol facilitated transduction efficiency. Tumor burden did not seem to affect transduction, while tumor location appeared to be an important factor. Based on these results, intra-arterial infusion of a p53-containing adenoviral vector was carried out and resulted in significant retardation of brain tumor growth 3 days after administration. Effects at longer time points were not as significant. These findings indicate that intra-arterial administration of adenoviral vectors containing p53 is efficient and can result in changes in tumor size, but that long-term control of tumor growth may require multiple adenoviral treatments.     

Metastatic urinary bladder tumor from extragonadal germ cell tumor: a case report

A 37-year old male patient complained of lower back pain. Investigations revealed a retroperitoneal tumor and left-sided cervical lymphadenopathy without abnormal findings in both testicles. The diagnosis of extragonadal germ cell tumor was made based on a lymph node biopsy. Following chemotherapy and retroperitoneal lymphoadenectomy, at outpatient follow-up, beta-HCG elevated again. He complained of gross hematuria, cystoscopy showed a bladder tumor, and abdominal MRI scan showed a right ureteral tumor. Total cystectomy and right nephroureterectomy were performed, which revealed that the bladder and ureteral tumors were metastatic germ cell tumors. Six months later, the patient developed hepatic and mesenteric lymph node metastases that failed to respond to treatment, and died. Germ cell tumors metastasizing to the urinary tract are extremely uncommon, and this is the first report of bladder metastases, other than through direct invasion, from an extratesticular germ cell tumor.     

Novel chondroitin sulfate-binding cationic liposomes loaded with cisplatin efficiently suppress the local growth and liver metastasis of tumor cells in vivo

An increased level of chondroitin sulfate (CS) expression on the cell surface is often associated with malignant transformation and the progression of tumor cells. In this study, CSs expressed on highly metastatic tumor cells were used as a target for the selective delivery of anticancer drugs by polyethylene glycol (PEG)-coated liposomes that contained a new cationic lipid 3,5-dipentadecycloxybenzamidine hydrochloride (TRX-20). We found that PEG-coated TRX-20 liposomes (TRX-20 liposomes) bound preferentially to certain CSs, such as CS B, CS D, and CS E, whereas PEG-coated liposomes lacking TRX-20 showed no significant binding to any of the glycosaminoglycans tested. In vitro, TRX-20 liposomes, but not plain PEG liposomes, avidly bound to and were readily internalized by highly metastatic tumor cells such as LM8G5 and ACHN cells, which express large amounts of CS on the cell surface. When TRX-20 liposomes were loaded with cisplatin, they effectively killed the CS-expressing tumor cells in vitro, whereas cisplatin-PEG liposomes lacking TRX-20 were totally ineffective. When injected systemically, TRX-20 liposomes preferentially accumulated in the liver and in solid s.c. LM8G5 tumors. Therapeutic experiments in mice bearing a s.c. LM8G5 tumor revealed that cisplatin-loaded TRX-20 liposomes were significantly more effective in reducing the local tumor growth than cisplatin-loaded plain PEG liposomes or free cisplatin. Furthermore, the cisplatin-loaded TRX-20 liposomes markedly suppressed metastatic spreading of LM8G5 tumor cells to the liver, significantly increasing the survival time of the tumor-bearing mice. These results demonstrate that the CS-targeted delivery of anticancer drugs by novel cationic liposomes represents a potentially useful strategy to prevent the local growth and metastasis, particularly to the liver, of tumor cells that have enhanced expression of CS.