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Biomedical subjects

Yoshitaka Fujii

Publications and source records attributed to Yoshitaka Fujii.

At least 55 records · Page 3Linked to original sources
PubMed2005

Flurbiprofen axetil preceded by venous occlusion in the prevention of pain on propofol injection in the hand: a prospective, randomized, double-blind, vehicle-controlled, dose-finding study in Japanese adult surgical patients.

BACKGROUND: Pain on injection is still a major problem with propofol used for general anesthesia. A number of techniques for reducing propofol-induced pain on injection have been tried, with variable results. Flurbiprofen axetil, a prodrug of the nonsteroidal anti-inflammatory drug flurbiprofen, has been used for postoperative pain management but has not been studied for managing pain on injection of propofol when preceded with venous occlusion. OBJECTIVE: The present study was undertaken to examine the efficacy of flurbiprofen axetil for reducing pain on propofol injection in Japanese adult surgical patients. METHODS: This prospective, randomized, double-blind, vehicle-controlled, dose-finding study was conducted at the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba, Japan. Japanese patients aged 18 to 65 years scheduled to undergo elective surgery were eligible. Patients were randomized to receive flurbiprofen axetil IV at 1 of 3 doses (25, 50, or 75 mg), or vehicle (control group), preceded by manual venous occlusion with a rubber tourniquet for 2 minutes and followed by administration of 25% of the total calculated dose of propofol (2 mg/kg), injected into the largest vein of the hand through a 20-gauge IV cannula. During propofol injection, a researcher who was blinded to treatment assignment asked each patient about his or her pain at the injection site. Responses were scored on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe). Median pain intensity scores in each group were determined. Adverse effects (AEs) at the injection site (pain, edema, wheal, or inflammation) were monitored for up to 24 hours after surgery. RESULTS: A total of 120 patients (62 men, 58 women; mean [SD] age, 41 [12] years, mean [SD] height, 162 [8] cm; mean [SD] body weight, 58 [10] kg) were enrolled. Each treatment group comprised 30 patients. No significant between-group differences in demographic characteristics were found. A significantly higher proportion of patients in the control group (77%) experienced pain compared with the flurbiprofen axetil 50- and 75-mg groups (47% and 43%, respectively; both, P < 0.01). The median pain intensity scores were significantly lower in the flurbiprofen axetil 50- and 75-mg groups (both, 0 [no pain]) compared with controls (2 [moderate]; both, P < 0.01). The incidence and intensity of propofol-induced pain were statistically similar between the flurbiprofen axetil 25-mg and control groups. The incidence and intensity of pain associated with the injection of propofol were significantly lower in the flurbiprofen axetil 50- and 75-mg groups compared with the 25-mg group (incidence, 70% [both, P < 0.05]; median pain intensity score, 1 [mild] [both, P < 0.01]). No AEs were observed. CONCLUSION: In this study of Japanese adult surgical patients, flurbiprofen axetil at doses of 50 and 75 mg, preceded by venous occlusion for 2 minutes, was found to be effective in reducing propofol-induced pain on injection.

Adult↗
PubMed2005

Effects of dexamethasone in preventing postoperative emetic symptoms after total knee replacement surgery: a prospective, randomized, double-blind, vehicle-controlled trial in adult Japanese patients.

BACKGROUND: Postoperative emetic symptoms (nausea, retching, and vomiting) are common following total joint replacement, with an incidence as high as 83% when no prophylactic antiemetic is provided. However, most antiemetics currently used in Japan, such as antihistamines (eg, hydroxyzine), butyrophenones (eg, droperidol), and dopamine receptor antagonists (eg, metoclopramide), have been associated with adverse effects (AEs), such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, and extrapyramidal symptoms. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of 3 doses of intravenous dexamethasone monotherapy versus vehicle in preventing emetic symptoms after total knee replacement performed under combined general and epidural anesthesia. METHODS: This prospective, randomized, double-blind, vehicle-controlled trial was conducted at the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba, Japan. Adult Japanese patients scheduled to undergo total knee replacement were eligible. Patients were randomly assigned to 1 of 4 treatment groups: dexamethasone 4, 8, or 16 mg, or vehicle (control). Patients received combination anesthesia with sevoflurane and nitrous oxide in pure oxygen (general) and lidocaine (epidural). Study drugs were administered intravenously after the completion of surgery. An investigator blinded to treatment assignment monitored patients for emetic symptoms for 24 hours after the patient awoke. Patients rated their satisfaction with the study drug using a linear, 11-point scale (0 = complete satisfaction to 10 = complete dissatisfaction). Tolerability was assessed by the study investigator using spontaneous reporting and patient interview. RESULTS: A total of 80 patients were enrolled (58 women, 22 men; mean [SD] age, 59 [10] years; mean [SD] height, 154 [7] cm; mean [SD] body weight, 55 [7] kg; 20 patients per treatment group). The demographic, clinical, and surgical data were comparable between the 4 treatment groups. The rates of emesis-free patients were 35% (7 patients), 70% (14), and 75% (15) with dexamethasone 4, 8, and 16 mg, respectively, compared with 30% (6) with vehicle (P = NS, 0.013, and 0.005, respectively). Median (range) patient satisfaction scores were significantly higher in the groups receiving dexamethasone 8 and 16 mg (both, 0.0 [0-9]) compared with controls (6.0 [0-10]) (P = 0.013 and 0.008, respectively). This effect was not found with the 4-mg dose. No clinically serious AEs attributed to the study drug were observed in any of the 4 treatment groups. CONCLUSIONS: In this study of a small, select group of adult Japanese patients undergoing total knee replacement, the rates of emesis-free patients were higher with dexamethasone 8 and 16 mg compared with vehicle 24 hours after anesthesia induction. This effect was not found with the 4-mg dose. All treatments were well tolerated.

Adult↗
PubMed2005

Reduction of postoperative emetic episodes and analgesic requirements with dexamethasone in patients scheduled for dental surgery.

STUDY OBJECTIVE: To evaluate the antiemetic and analgesic effects of dexamethasone for the first 24 hours postoperatively in patients scheduled for dental surgery. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: University hospital. PATIENTS: One hundred twenty ASA physical status I and II patients (45 men, 75 women; aged 17-48 years) undergoing general anesthesia for dental surgery. INTERVENTIONS: Patients received intravenously placebo or dexamethasone at 3 different doses (4, 8, or 16 mg) at the end of the surgical procedure. A standard general anesthetic technique, including sevoflurane and nitrous oxide in oxygen, was used. MEASUREMENT AND MAIN RESULTS: Emetic episodes and analgesic requirements were evaluated. The rate of patients who were emesis free (no nausea, retching, or vomiting) during 0 to 24 hours after anesthesia was 63% with dexamethasone 4 mg (P = NS), 83% with dexamethasone 8 mg (P < .05), and 90% with dexamethasone 16 mg (P < .05), compared to placebo (60%). The need for diclofenac sodium for intolerable pain was less in patients who had received dexamethasone 8 mg or dexamethasone 16 mg than in those who had received placebo or dexamethasone 4 mg (P < .05). No clinically important adverse events were observed in any group. CONCLUSIONS: Prophylactic dexamethasone 8 mg is effective for the prevention of nausea and vomiting after dental surgery and in the management of postoperative pain. Increasing the dose to 16 mg provides no further benefit.

Adult↗
PubMed2005

Endoscopic thoracic sympathectomy for palmar hyperhidrosis: efficacy of T2 and T3 ganglion resection.

BACKGROUND: Endoscopic thoracic sympathectomy has been considered an effective treatment for palmar hyperhidrosis. However, the extent of resection has not been determined in terms of efficacy and complications. We compared the efficacy and complications of 2-ganglion and single-ganglion resection in patients with palmar hyperhidrosis. METHODS: From 1995 to 2000, 75 patients underwent resection of thoracic ganglion T2 and T3. From 2000 to 2003, 67 patients underwent resection of only the T2 ganglion. Eighty of the 142 patients (56%) answered a detailed questionnaire, the results of which were analyzed. RESULTS: Gender, age, family history, and distribution of sweating were similar in both groups. Recurrence rates 1 and 2 years after endoscopic thoracic ganglionectomy were between 0% and 3% in T2 and T3 resection, and between 15% and 19% in T2 resection only. In the combined T2 and T3 resection group, 100% of patients noticed compensatory sweating; in T2 resection, 90% of patients noticed compensatory sweating. As for rates of satisfaction, T2 and T3 resection was superior to T2 resection. CONCLUSIONS: High recurrence rates of palmar hyperhidrosis after single-ganglion resection are reported in the present study. Two-ganglion resection is a superior surgical method to prevent recurrence of palmar hyperhidrosis.

Adolescent↗
PubMed2005

The utility of antiemetics in the prevention and treatment of postoperative nausea and vomiting in patients scheduled for laparoscopic cholecystectomy.

Postoperative nausea and vomiting (PONV) are distressing and frequent adverse events of anesthesia and surgery, with a relatively high incidence after laparoscopic cholecystectomy. Numerous antiemetics have been studied for the prevention and treatment of PONV in patients scheduled for laparoscopic cholecystectomy. Traditional antiemetics, including anticholinergics (e.g., scopolamine), antihistamines (e.g., dimenhydrinate), phenothiazines (e.g., promethazine), butyrophenones (e.g., droperidol), and benzamide (e.g., metoclopramide), are used for the control of PONV. The available nontraditional antiemetics for the prophylaxis against PONV are dexamethasone and propofol. Serotonin receptor antagonists (ondansetron, granisetron, tropisetron, dolasetron, and ramosetron), compared with traditional antiemetics, are highly efficacious for PONV. The prophylactic ondansetron, granisetron, tropisetron, and dolasetron in antiemetic efficacy are comparable. Ramosetron is effective for the long-term prevention of PONV. None of the available antiemetics is entirely effective, perhaps because most of them act through the blockade on one type of receptor. There is a possibility that combined antiemetics with different sites of activity would be more effective than one drug alone for the prophylaxis against PONV. Combination antiemetic therapy is often effective for the prevention of PONV following laparoscopic cholecystectomy. The efficacy of a combination of serotonin receptor antagonists (ondansetron and granisetron) and droperidol is superior to monotherapy with a serotonin receptor antagonist or droperidol. Similarly, adding dexamethasone to ondansetron or granisetron improves antiemetic efficacy in PONV. Knowledge regarding antiemetics is necessary to completely prevent and treatment of PONV in patients scheduled for laparoscopic cholecystectomy.

Antiemetics↗
PubMed2004

EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.

Receptor tyrosine kinase genes were sequenced in non-small cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinib-insensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib.

Adenocarcinoma↗
PubMed2004

Elevated serum epidermal growth factor receptor level in stage IV thymoma.

Using the enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as a predictor of the development and extension of thymoma. Serum samples were collected from 31 patients with thymoma and 16 patients with nonmalignant thoracic disease before clinical treatment. There was no difference between the serum EGFR levels of the patients with thymoma and the nonmalignant controls, being 49.1 +/- 136.3 and 22.6 +/- 7.3 fm/ml, respectively ( P = 0.11). However, patients with stage IV thymoma had significantly higher EGFR levels than those with stage I or stage II thymoma, the respective values being 127.8 +/- 243.9, 10.9 +/- 9.2 ( P = 0.02), and 19.7 +/- 10.6 ( P = 0.0433) fm/ml. The serum EGFR levels were similar in the pathological subtypes. These findings suggest that serum EGFR levels may serve as a marker that could be used as a diagnostic indicator of the invasion of thymoma.

Biomarkers, Tumor↗
PubMed2004

Lung injury after intestinal ischemia-reperfusion may be avoided by the reduced absorption of locally produced cytokines.

PURPOSE: It has been suggested that inflammatory mediators such as cytokines released during intestinal ischemia and reperfusion increase permeability in the lungs. Cytokines exist at concentrations several hundred times higher at the site of inflammation than in the blood. When absorbed, the locally produced cytokines may affect multiple remote organs. We thus investigated whether the isolation of the intestine in a bag during ischemia and reperfusion can reduce subsequent lung injury. METHODS: Rats were divided into three groups: group 1, simple laparotomy (sham); group 2, intestinal ischemia and reperfusion (I/R); and group 3, intestinal ischemia and reperfusion with an intestinal bag (IB). Lung permeability was assessed using the Evans Blue leakage method. Cytokines (interleukin-1beta, tumor necrosis factor alpha, interleukin-8) in the plasma and ascites were measured by enzyme-linked immunosorbent assay. RESULTS: The increase in lung permeability of I/R significantly decreased in IB (1.73 +/- 0.48 vs 1.05 +/- 0.22, P < 0.01). The plasma cytokine concentrations were also lower in IB than in I/R. In addition, the cytokine levels in the intestinal bag fluid were extremely high. CONCLUSION: The isolation of the intestine during ischemia and reperfusion was found to reduce the degree of subsequent lung injury, possibly due to the reduced absorption of locally produced cytokines via the parietal peritoneum.

Analysis of Variance↗
PubMed2004

Arg and DAP3 expression was correlated with human thymoma stage.

Thymoma is one of the most common solid tumors in the mediastinum. As there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular genetic analysis of patients' tissues. The recent reports showed that the gain of chromosome 1q regions was frequent in thymoma. We investigated the use of oligonucleotide arrays to monitor in vivo gene expression levels at chromosome 1q regions in the early- (stage I or II) and late-stage (stage IVa) thymoma tissues from patients. These in vivo gene expression profiles were verified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) using LightCycler for 36 thymoma patients. Using both the methods, candidate genes were come up. These are Arg tyrosine kinase and death-associated protein 3 (DAP3), which are known as ionizing radiation resistance conferring proteins. The Arg/GAPDH mRNA level in stage IV thymoma (90.716 +/- 177.851) was significantly higher than in stage I thymoma (10.335 +/- 25.744, P = 0.0465). The DAP3/GAPDH mRNA level in stage IV thymoma (17.424 +/- 20.649) was significantly higher than in stage I thymoma (5.184 +/- 3.878, P = 0.0305). DAP3 expression was also correlated with the WHO classification. The combined use of oligonucleotide microarray and real-time RT-PCR analyses provided a candidate molecular marker surrounding the development and progression of thymoma correlated with chromosome 1q.

Apoptosis Regulatory Proteins↗
PubMed2004

Histone deacetylase 1 mRNA expression in lung cancer.

Histone deacetylases (HDACs) play a crucial role in tumorigenesis, however, the expression status of HDACs in lung cancer tissues has not been reported. We have investigated that HIDAC 1 mRNA levels and other clinico-pathological data, including MTA 1 mRNA expression in lung cancer. The study included 102 lung cancer cases. The HDAC1 mRNA levels were quantified by real time reverse transcription-polymerase chain reaction (RT-PCR) using LightCycler (Roche Molecular Biochemicals, Mannheim, Germany). The HDAC1/GAPDH mRNA levels were not significantly different in tumor tissues from lung cancer (30.654 +/- 33.047) and adjacent non-malignant lung tissues (18.953 +/- 56.176 , P = 0.1827). No significant difference in HDAC1/GAPDH mRNA levels was found among age, gender, and lymph node metastasis. The HDAC1/GAPDH mRNA levels were significantly higher in stage III or IV lung cancer (50.929 +/- 120.433) than in stage I lung cancer (11.430 +/- 25.611, P = 0.0472). HDAC1/GAPDH mRNA levels were significantly higher in T3 or T4 lung carcinoma (54.326 +/- 127.018) than in T1 or T2 lung cancers (14.790 +/- 48.670, P = 0.1601). HDAC1/GAPDH mRNA levels were correlated with MTA1/GAPDH mRNA levels (y = 0.0106x + 2.5827 , P = 0.0352 ). HDAC1/GAPDH mRNA levels were also correlated with HDAC1 protein (P = 0.0484) expression by immunohistochemistry. Using the LightCycler RT-PCR assay, the HDAC1 gene expression might correlate with progression of lung cancers. However, further studies are needed to confirm the impact of HDAC1 for the molecular target of the lung cancer.

Adult↗
PubMed2004

Inhaled milrinone for the improvement of contractility of fatigued diaphragm in dogs: a dose-ranging study.

The present study was undertaken to evaluate the efficacy of inhaled milrinone on contractility of fatigued diaphragm in dogs. Animals were divided into four groups of seven each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Immediately after the end of a fatigue-producing period, Group I received inhaled vehicle; Group II received inhaled milrinone 0.1 mg/ml (1 mg); Group III received inhaled milrinone 0.2 mg/ml (2 mg); Group IV received 0.5 mg/ml (5 mg). Study drug was administered for 30 min. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). After the fatigue-producing period, in each group, Pdi at low-frequency (20 Hz) decreased from baseline values (P<0.05), and Pdi at high-frequency (100 Hz) stimulation did not change. In Groups III and IV, during milrinone inhalation, Pdi at both stimuli increased from fatigued values (P<0.05). The increase in Pdi was more in Group IV than in Group III (P<0.05). Compared with Group I, Pdi to each stimulus did not change in Group II. In conclusion, inhaled milrinone, in doses more than 0.2 mg/ml, is effective for improving contractility of fatigued diaphragm in dogs.

Animals↗
PubMed2004

Comparative effects of dopamine and dobutamine on hypercapnic depression of diaphragmatic contractility in dogs.

The present study was undertaken to evaluate the effects of dopamine and dobutamine on diaphragmatic contractility in dogs with induced hypercapnia. Animals were divided into three groups of ten each. In each group, hypercapnia (80-90 mmHg) was produced by adding 10% CO2 to the inspired gas. When hypercapnia was established, Group I received no study drug; Group II was infused with dopamine 10 microg/kg/min; Group III was infused with dobutamine 10 microg/kg/min. Study drugs were administered intravenously for 60 min. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). In the presence of hypercapnia, in each group, Pdi at low-frequency (20-Hz) and high-frequency (100-Hz) stimulation decreased from baseline (P<0.05). In Groups II and III, during the study drug administration, Pdi at both stimuli increased from hypercapnia-induced values (P<0.05). The increase in Pdi was more than in Group III than in Group II (P<0.05). In Group I, Pdi to each stimulus did not change from hypercapnia-induced values. In conclusion, compared with dopamine, dobutamine is effective in improving hypercapnic depression of diaphragmatic contractility in dogs.

Animals↗
PubMed2004

Randomized, double-blind comparison of subhypnotic-dose propofol alone and combined with dexamethasone for emesis in parturients undergoing cesarean delivery.

BACKGROUND: Nausea, retching, and vomiting are common in parturients undergoing cesarean delivery performed under regional anesthesia. Subhypnotic-dose propofol 1.0 mg/kg per hour has been used to reduce the incidence of these emetic symptoms. Dexamethasone has been shown to reduce chemotherapy-induced emesis when added to an antiemetic regimen. OBJECTIVE: The aim of this study was to examine the difference in efficacy and tolerability between subhypnoticdose propofol 1.0 mg/kg per hour alone and combined with dexamethasone 8 mg for reducing postdelivery emetic episodes in parturients undergoing cesarean delivery. METHODS: In a randomized, double-blind trial, parturients received IV placebo (saline) or dexamethasone 8 mg followed by a continuous infusion of propofol at subhypnotic dose (1.0 mg/kg per hour) immediately after clamping of the umbilical cord. Intraoperative, postdelivery emetic episodes and safety assessments were performed by an investigator. RESULTS: One hundred twenty parturients (mean [SD] age, 29 [5] years; age range, 21-38 years; mean [SD] height, 158 [7] cm; height range, 145-172 cm; mean [SD] body weight, 72 [8] kg; weight range, 54-90 kg) were enrolled in the study, 60 in each treatment group. The treatment groups were comparable with respect to maternal demographics and operative management. The rate of emetic symptoms (nausea, retching, and vomiting) in an intraoperative, postdelivery period was lower in patients who received the combination regimen than in those who received subhypnotic-dose propofol 1.0 mg/kg per hour alone (5% [3/60] vs 20% [12/60], respectively; P = 0.012). No clinically important adverse events attributable to the study drug were observed in either group. CONCLUSION: In the parturients undergoing cesarean delivery performed under spinal anesthesia in this study, the combination of subhypnotic-dose propofol 1.0 mg/kg per hour and dexamethasone 8 mg was more effective than propofol alone for reducing the incidence of postdelivery emetic symptoms.

Adult↗
PubMed2004

Effects of granisetron in the treatment of nausea and vomiting after laparoscopic cholecystectomy: a dose-ranging study.

BACKGROUND: Patients undergoing general anesthesia for laparoscopic cholecystectomy are at high risk for postoperative emetic symptoms (nausea, vomiting, and retching). Antihistamines, butyrophenones, dopamine receptor antagonists, and selective serotonin receptor antagonists (SSRAs) have been investigated for the prevention and treatment of emetic symptoms. However, these drugs are associated with undesirable adverse effects (AEs), such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, and extrapyramidal signs. Granisetron hydrochloride is a newer SSRA developed for the prevention and treatment of cytotoxic drug-induced emetic symptoms, but its effects in postoperative laparoscopic cholecystectomy have not been studied. OBJECTIVE: The aims of this study were to assess the efficacy and tolerability of 4 doses of granisetron, and to determine the minimum effective dose, for the control of established emetic symptoms in patients undergoing general anesthesia for laparoscopic cholecystectomy. METHODS: This prospective, randomized, double-blind, placebo-controlled, dose-ranging study was conducted in the Departments of Anesthesiology and Surgery, Toride Kyodo General Hospital (Toride, Japan). Male and female patients aged 23 to 68 years with American Society of Anesthesiologists physical status I (no organic, physiologic, biochemical, or psychiatric disturbance) who were experiencing nausea lasting >10 minutes or retching or vomiting within 3 hours after recovery from general anesthesia for laparoscopic cholecystectomy were enrolled. Patients were randomized to receive a single IV dose of placebo or granisetron at 1 of 4 doses (10, 20, 40, or 80 microg/kg). Patients were monitored for 24 hours after study drug administration. RESULTS: One hundred patients (60 women, 40 men; mean [SD] age, 48 [10] years [range, 23-68 years]; mean [SD] height, 158 [7] cm [range, 145-177 cm]; mean [SD] body weight, 56 [8] kg [range, 43-75 kg]) were enrolled. No significant differences in baseline demographic or clinical characteristics were found between the study groups. The proportions of patients who were free of emetic symptoms were significantly higher with granisetron 20, 40, and 80 microg/kg than with placebo (P = 0.02, 0.007, and 0.007, respectively). The difference between the granisetron 10-microg/kg group and the placebo group was not significant. No clinically significant AEs were reported in any group. CONCLUSIONS: Granisetron 20 microg/kg was the minimum effective dose for the treatment of established postoperative emetic symptoms in patients undergoing laparoscopic cholecystectomy. Increasing the dose to 80 microg/kg provided no further benefit.

Adult↗
PubMed2004

Endostatin gene transfection using a cationic lipid: advantages of transfection before tumor cell inoculation and repeated transfection.

Intravenous endostatin gene transfection results in tumor suppression in a murine pulmonary metastasis model. We transfected the endostatin gene at different times, in order to achieve an optimal protective effect. pST2-Endo encoding murine endostatin was injected in a complex with cationic lipid. Pulmonary metastases were caused by intravenous injection of murine fibrosarcoma cells. Mice were observed for 14 days following fibrosarcoma cell inoculation (FSI). In the study groups, the animals were transfected with pST2-Endo at three different times: 2 days before and 3 and 7 days after FSI. In the group transfected with pST2-Endo 2 days before FSI, the weights of the lungs and tumor-occupied area ratio were significantly less than in the other groups. Significant inhibition of tumor neovascularization was documented by means of CD31 immunohistochemistry. The effect of repeated endostatin transfection on survival after FSI was determined. Animals repeatedly transfected with the endostatin gene survived significantly longer than the groups treated with a single endostatin gene transfection. A stable endostatin-expressing fibrosarcoma transfectant was created and tested for migration and invasion. Compared with controls, endostatin expression reduced migration and invasion by 15%. It is concluded that endostation gene transfection before FSI and repeated transfection thereafter results in significant tumor suppression.

Animals↗
PubMed2004

Decreased Hrad6B expression in lung cancer.

Human homologues of yeast Rad 6 (Hrad6B) encode ubiquitin-conjugating enzymes and complement the DNA repair and UV mutagenesis defects of Saccharomyces cerevisiae rad6 mutant. There is a larger subgroup with reduced DNA repair capacity that is likely to be at increased cancer risk. The authors investigated Hrad6B expression in lung cancer. An attempt was made to determine the influence of Hrad6B expression on clinicopathological features for patients with lung cancer who had undergone surgery. Expression of Hrad6B messenger RNA was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 110 lung carcinomas and adjacent histological non-malignant lung samples from patients for whom follow-up data were available using LightCycler. The Hrad6B/glyceraldehydes-3-phosphate dehydrogenase (GAPDH) mRNA expression was significantly decreased in the lung cancer tissue (4.078+/-5.674) as compared with the non-malignant lung tissue (10.495+/-12.976, p<0.001). There was no relationship between Hrad6B/GAPDH expression and age, clinical stages, T-status, N-status, and pathological subtypes in lung cancer tissues. Hrad6B/GAPDH mRNA levels in males (3.521+/-4.280) and in females (6.420+/-8.167) were significantly different (p=0.0443) in lung cancer tissues, but not in non-malignant lung tissues. Heavy smokers had a slight non-significant tendency (p=0.0857) towards lower Hrad6B/GAPDH mRNA levels (3.453+/-4.743) in their lung cancer tissues as compared with light or non-smokers. Thus decreased Hrad6B mRNA expression might be a biomarker for decreased DNA repair capacity and the dysfunction of Hrad6B might play a role in the tobacco-related oncogenesis of lung cancer.

Aged↗