Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆.

BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

[Preliminary application of endoscopic titanium clip localization combined with three-dimensional CT reconstruction in the determination of resection margin of gastric central cancer under laparoscopy].

Objective: To evaluate the accuracy of endoscopic titanium clip localization combined with CT three-dimensional reconstruction for the control of incision margin in early gastric cancer under laparoscopy. Methods: A prospective analysis was made for gastric cancer whose lesions were located in the middle of the stomach and T stage was 1 to 2 from October 2017 to January 2019 at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital. Totally 25 patients were eventually enrolled in the study. There were 17 males and 8 females aging of (63.6± 7.2) years (range: 48 to 77 years). All cases were treated with titanium clip localization under endoscope combined with CT three-dimensional (3D) reconstruction to construct a virtual panorama of gastric cavity and lesions, and to design surgical margins. Laparoscopic surgical resection was performed according to the surgical margins designed before operation. The distance from the gastric angle to the origin of the minor curvature of the incisional margin, the distance from the gastric angle to the the center of lesion and the distance of the upper incision margin were measured under three-dimensional CT reconstruction and under actual specimen. Paired t test was used to compare the three distances measured by two methods. Results: The measured distances from the gastric angle to the center of the lesion and the proximal incisional margin under 3D reconstruction CT were according to the measured values of actual specimens ((2.67±1.38) cm vs. (2.83±1.56) cm, t=1.51, P=0.14; (5.23±0.60) cm vs. 5 cm, t=1.93, P=0.07); the measured distances from the gastric angle to the origin of the minor curvature of the incisional margin under CT 3D reconstruction were different with the measured values of solid specimens ((5.94±0.94) cm vs. (6.37±0.90) cm, t=3.52, P=0.00). Conclusion: The method of titanium clip localization combined with CT 3D reconstruction can provide a feasible laparoscopic localization method and incision edge solution for T1 to 2 gastric central cancer.

Peroxisome proliferator-activated receptor delta regulates lipid droplet formation and transport in goat mammary epithelial cells.

Even though recent evidence in goat mammary epithelial cells (GMEC) suggest a role of peroxisome proliferator-activated receptor delta (PPARD) in regulating lipid homeostasis, its role is not fully understood. Our hypothesis was that PPARD regulates lipid transport processes in GMEC and, thus, plays a crucial role in regulating fat formation. The PPARD was overexpressed using an adenovirus system (Ad-PPARD) with recombinant green fluorescent protein (Ad-GFP) as the control. Results revealed that overexpression of PPARD markedly upregulated the mRNA abundance of PPARD. Compared with the control (Ad-GFP+dimethyl sulfoxide), overexpression of PPARD alone had no effect on mRNA expression of CD36, SCD1, FABP4, ACSL1, and ADRP. The cultures overexpressing PPARD with the PPARD ligand GW0742 (GW) upregulated the expression of CD36, FABP3, FABP4, ACSL1, and ADRP. Overexpression of PPARD in GMEC plus GW increased the concentration of 16:1 and 18:1-trans and was associated with upregulation of SCD1. Compared with the control (Ad-GFP+dimethyl sulfoxide), the decrease of triacylglycerol concentration coupled with upregulation of genes related to lipid droplet secretion (e.g., ADRP and ACSL1) induced by PPARD overexpression suggests a role in lipid droplet (LD) secretion. Luciferase assay revealed that GW increased the ADRP promoter activity in a dose-dependent manner. Knockdown of PPARD impaired the increase of ADRP promoter activity induced by GW, whereas GW enhanced the activity of ADRP promoter in GMEC overexpressing PPARD. Data with the ADRP 5'-flanking truncated luciferase reporter suggest a core region (-1,444 to -990 bp) response element for the induction of GW. This core region contains a known PPARG response element (PPRE) at -1,003 to -990 bp. When the PPRE was mutated, the overexpression of PPARD had no effect on ADRP promoter activity. Collectively, these results reveal a novel role for PPARD in lipid homeostasis via promoting fatty acid transport and LD formation through a mechanism of direct binding to the promoter of key genes. Hence, PPARD activity may contribute to fatty acid transport and LD formation during lactation.

[The relationship of preoperativelymphocyte-monocyte ratio and the clinicopathological characteristics and prognosis of patients with epithelial ovarian cancer].

Objective: To investigate the relationship of preoperative lymphocyte-monocyte ratio (LMR) and the clinicopathological characteristics and prognosis of patients with epithelial ovarian cancer (EOC). Methods: Clinical data of 364 cases of EOC patients with initial treatment were collected in Harbin Medical University Cancer Hospital from 2005-2011 and analyzed retrospectively.The optimal cut-off points of preoperative LMR to predict the postoperative survival period of EOC patients were determined by the establishment of receiver operating characteristic (ROC) curve. The patients were divided into low LMR group and high LMR group according to the optimal cut-off points, and the relationship of LMR and the clinicopathological factors and prognosis of EOC patients were analyzed. Results: The best cut-off point of preoperative LMR to predict the postoperative survival period of EOC patients was 3.84. The preoperative LMR of EOC patients was significantly associated with the postoperative FIGO stage, ascites and CA125 level (all P<0.05). The median follow-up time was 37 months, the median progression-free survival (PFS) time of low LMR group was 56 months, significantly shorter than 88 months of high LMR group (P<0.01). And the median overall survival (OS) time of low LMR group was 69 months, significantly shorter than 100 months of high LMR group (P<0.01). The univariate analysis showed that the postoperative FIGO stage, pathological grade, ascites, lymph node metastasis, CA125 level, adjuvant therapy, preoperative LMR were all significantly associated with PFS (all P<0.05). In addition, the age, postoperative FIGO stage, pathological grade, ascites, lymph node metastasis, CA125 level, adjuvant therapy, preoperative LMR were all significantly associated with OS (all P<0.05). Cox multivariate analysis showed that postoperative FIGO stage Ⅲ-Ⅳ, low differentiation, positive lymph node metastasis, without postoperative adjuvant therapy and LMR≤3.84were independent risk factors of PFS and OS of EOC patients (P<0.05). Conclusion: The preoperative LMR is an independent influence factor of PFS and OS of EOC patients, and can be used to evaluate the prognosis of patients with EOC.

[A screening system for anti-metastatic small-molecule compounds based on perinucleolar compartment prevalence in liver cancer cells].

Objective: To establish a screening system for anti-metastatic small-molecule compounds based on perinucleolar compartment (PNC) prevalence in liver cancer cells and to investigate its validity. Methods: Polypyrimidine tract-binding protein (PTB) monoclonal antibody was used to measure the PNC prevalence in HepG2, HepG2M, and Huh7 cells, and wound healing assay and transwell assay were used to analyze the migration and invasion abilities of hepatoma cells. HepG2M cells were used as the model for the screening of anti-metastatic small-molecule compounds, and after the treatment with the compounds A1, A4, and E696, qPCR was used to measure the expression of metastasis-related miRNAs (miR-141 and miR-200c). A one-way analysis of variance was used for comparison of data between multiple groups. Results: PTB immunofluorescence assay showed that HepG2M cells had the highest PNC prevalence, followed by Huh7 and HepG2 cells, and PNC prevalence was positively correlated with the metastasis and invasion abilities of hepatoma cells. The PNC prevalence of HepG2M cells was reduced to 22.88% ±4.61% by A1, 14.22% ± 3.05% by A4, and 26.12% ± 4.94% by E696. Wound healing assay showed that the 48-hour scratch ratio increased from 17.70% ± 3.34% to 64.50% ± 2.65%, 83.40% ± 5.10%, and 57.20% ± 3.06% (F = 171.1, P < 0.01), respectively. Transwell assay showed that the number of invasive cells was reduced from 264.33 ± 30.50 to 104.33 ± 13.50, 58.00 ± 11.00, and 111.33 ± 19.50 (F = 59.87, P < 0.01), respectively. The anti-metastatic effect of these three compounds was positively correlated with their ability to destroy PNC. A4 upregulated the expression of miR-141 and miR-200c in a dose-dependent manner, and after HepG2M cells were treated with A4 at a concentration of 5 µM, 10 µM, or 20 µM, the level of miR-141 was increased to 3.61 ± 0.78, 8.12 ± 1.15, and 18.24 ± 2.44 folds (F = 88.01, P < 0.01), respectively, and that of miR-200c was increased to 2.82 ± 0.43, 4.82 ± 0.89, and 10.74 ± 1.22 folds (F = 87.94, P < 0.01), respectively. Conclusion: The screening system for anti-metastatic small-molecule compounds based on PNC prevalence can provide an effective technical platform for research and development of anti-metastatic drugs for liver cancer.

TNFAIP8 as a predictor of metastasis and a novel prognostic biomarker in patients with epithelial ovarian cancer.

BACKGROUND: Tumour necrosis factor-α-induced protein 8 (TNFAIP8) has been recently documented in various malignancies, but its role in epithelial ovarian cancer (EOC) remains unknown. METHODS: Tumour necrosis factor-α-induced protein 8 expression was determined by real-time reverse transcription PCR and western blot analysis. Tumour tissues, consisting of serous, mucinous, endometrioid and clear cell histotypes, from 202 EOC patients (International Federation of Gynecologists and Obstetricians I-IV) who underwent primary cytoreduction were collected. Then, we examined the immunohistochemical expression of TNFAIP8 and evaluated its clinical significances. RESULTS: Tumour necrosis factor-α-induced protein 8 overexpression was significantly associated with high histologic grade (P=0.005), large residual tumour size (P=0.014), recurrence (P=0.024) and response to chemotherapy (P<0.001). Multivariate analysis showed that TNFAIP8 overexpression was independently correlated with the presence of lymph node (odds ratio (OR): 4.129; 95% confidence interval (CI): 1.491-11.435; P=0.006) and intraperitoneal metastasis (OR: 2.209; 95% CI: 1.174-4.156; P=0.014). Moreover, results revealed that the status of TNFAIP8 expression was an independently prognostic factor for both cancer-specific survival (hazard ratio (HR): 1.852; 95% CI: 1.322-2.594; P<0.001) and disease-free survival (HR: 1.724; 95% CI: 1.235-2.407; P=0.001) in patients with EOC. CONCLUSION: The present data provide evidence that TNFAIP8 predicts EOC metastasis and poor survival, highlighting its potential function as a therapeutic target for EOCs.

Involvement of the NF-κB pathway in multidrug resistance induced by HBx in a hepatoma cell line.

It is widely believed that hepatocellular cancer (HCC), especially HBV associated HCC, is highly resistant to chemotherapy. To investigate the molecular influence of HBx protein on multidrug resistance (MDR) in HCC and the potential role of the NF-κB pathway in this process. We established HBx-expressing cells by liposome-mediated transfection of the HBx into the HepG2 cell line. We found that HBx expression in HCC cells induces drug resistance against multiple drugs, a significantly lower apoptosis ratio in HepG2-HBx and HepG2.2.15 cells, compared with HepG2 and HepG2-3.1 cells (P < 0.05) after treating with 5-FU or adriamycin. And compared with the control group, the HBx-transfected cells showed a higher expression of MDR-associated and anti-apoptotic genes. Furthermore, we found that the NF-κB activity was remarkably high in the HBx-expressing cells as measured by p65 nuclear localization. In addition, the upregulated anti-apoptotic genes, Gadd45b and Survivin, in HBx-expressing HCC cells were downregulated by IMD-0354 treatment, which is the NF-κB pathway inhibitor. Taken together, these results suggest that HBx protein might be one of the causes for the occurrence of MDR in HCC, and the NF-κB pathway might be involved in this change.

Clinical efficacy of palbociclib-based therapy in women with HR+/HER2- metastatic breast cancer in the real-world setting for Chinese women: a comparison with the IRIS study.

OBJECTIVE: This retrospective study aimed to explore the clinical efficacy of palbociclib with endocrine therapy (ET) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer in real-world practice. PATIENTS AND METHODS: This retrospective study analyzed the medical records of patients to determine treatment outcomes. Progression-free survival (PFS) curves were generated using log-rank tests with the Kaplan-Meier method. Treatment outcomes in Chinese patients were compared with those in patients from the USA, Argentina, Canada, and Europe in the IRIS study. RESULTS: In total, 69 patients were included in this study. The median PFS was 12.8 months (95% confidence interval: 10.1-15.5). A longer PFS was observed for patients with bone-only metastases, no liver metastases, no previous palliative chemotherapy, no previous palliative ET, and ET sensitivity. The overall response rate was 10.1%, and the clinical benefit rate was 78.3%. Nineteen patients (27.5%) received a reduced dose of palbociclib according to the decision of their physicians. Dose reduction did not affect the clinical efficacy of the combined treatment. Compared with those in the IRIS study, Chinese patients receiving palbociclib-based treatment were younger, and they had fewer bone-only metastases and more visceral and liver metastases. The clinical benefit rate and overall response rate for Chinese patients were lower than those observed for the patients in the IRIS study. CONCLUSIONS: ET combined with palbociclib treatment was effective and well-tolerated in HR+/HER2- metastatic breast cancer patients in the real-world setting. Earlier use of palbociclib-ET was associated with more clinical benefits in HR+/HER2- metastatic breast cancer.

[Association between physical activity and risk of stroke among adults aged 40 years and above: a prospective cohort study].

Objective: To examine the effect of physical activity (PA) on the incident risk of stroke among adults aged 40 years and above. Methods: The baseline data including PA and demographic characteristics were obtained from the Adult Chronic Disease Surveillance with population representativeness in Ningbo in 2015. The follow-up data of interested health outcomes from 2015 to 2019 were retrieved from a population-based Integrated Noncommunicable Disease Collaborative Management System in Ningbo. The two databases were matched to form a queue. PA was divided into three levels of low-intensity, moderate-intensity, and vigorous-intensity according to the metabolic equivalents (METs) spent per week. Cox regression model was used to calculate the hazard ratio (HR) and 95% confidence interval. Results: A total of 3 353 subjects were included at baseline survey in 2015. Until Dec 31, 2019, there had been 31 stroke events had occurred since then, with accumulative incidence rate of 242/100 000, and an average follow-up time of (50.28±2.54) months. When adjusted for gender, age, education level, smoking status, alcohol consumption, BMI and hypertension, multivariate Cox regression analysis showed that greater PA was associated with a 37.9% reduction of incidence of stroke (HR=0.621,95%CI:0.393-0.983). Compared with those who had low-intensity PA, those who were with vigorous-intensity. PA appeared associated with a 63.1% decrease in the incidence of stroke (HR=0.369, 95%CI: 0.139-0.976). However, there was no statistical significance with moderate-intensity PA (HR=0.712,95%CI:0.323-1.569), noticed. Conclusions: Greater PA is likely to reduce the incidence of stroke. Our findings indicated that people should be encouraged to increase the PA level and developing a healthy supportive environment in the community.

Organoid of ovarian cancer: genomic analysis and drug screening.

Ovarian cancer is the most common malignant tumors of the female reproductive system, and its standard treatments are cytoreductive surgery and platinum-based adjuvant chemotherapy. Great advances have been achieved in novel treatment strategies, including targeted therapy and immunotherapy. However, ovarian cancer has the highest mortality rate among gynecological tumors due to therapeutic resistance and the gap between preclinical data and actual clinical efficacy. Organoids are a 3D culture model that markedly affects gene analysis, drug screening, and drug sensitivity determination of tumors, especially when used in targeted therapy and immunotherapy. In addition, organoid can lead to advances in the preclinical research of ovarian cancer due to its convenient cultivation, good genetic stability, and high homology with primary tumors.

[Transcriptional regulation of the human gene coding for proline-rich nuclear receptor coactivator (pnrc) by regulatory factor x (rfx1)].

PNRC (Proline-rich Nuclear Receptor Coactivator) is a novel coactivator for multiple nuclear receptors. PNRC was previously identified using bovine SF-1 (steroidogenic factor 1) as the bait in a yeast two-hybrid screening of a human mammary gland cDNA expression library. To understand the molecular mechanisms that regulate the expression of human PNRC gene, in this study, functional analysis of the 5' flanking region of the human PNRC gene revealed that the -123/+27 region is the minimal promoter of the human PNRC gene. Gel shift and ChIP analyses demonstrated the specific binding of RFX1 (Regulatory Factor X) protein to the human PNRC promoter region. In co-transfection experiments RFX1 was shown to repress promoter activity of PNRC gene in a dose-dependent manner. These results indicate that r RFX1 specifically bind to promoter region and negatively regulate the transcription of the human PNRC gene.

Interleukin 18 transfection enhances antitumor immunity induced by dendritic cell-tumor cell conjugates.

Dendritic cell (DC)-based tumor vaccine represents a promising approach to the immunotherapy of malignant tumors. We prepared a novel type of DC-based vaccine, stable conjugates of DCs and EL4 cells transduced with cDNA of OVA (E.G7). Immunization with DC-E.G7 conjugates led to generation of T helper (Th) 1 cytokine-producing cells, antigen-specific CD8(+) T cells, and strong antitumor immunity that is dependent on both CD4(+) T cells and CD8(+) T cells. To further increase the potency of the vaccine, interleukin 18-transfected DCs were used to prepare the IL18DC-E.G7 conjugates. Immunization with such conjugates significantly increased the production of Th1 cytokine-producing cells and the number of antigen-specific CD8(+) T cells, as well as stronger antitumor immunity. Furthermore, the increased Th1 cytokine production and stronger antitumor effect were not observed in mice depleted of IFN-gamma. These data indicated that DC-tumor cell conjugates are a potent tumor vaccine. Interleukin 18 can be administrated using gene-transfected cells and enhances antitumor immunity, which is mainly mediated by IFN-gamma.

Synergism between RIZ1 gene therapy and paclitaxel in SiHa cervical cancer cells.

RIZ1 is a tumor suppressor gene. The purpose of the present study was to investigate the inhibitory effect of RIZ1 gene therapy on the growth of SiHa cervical cancer cells and its synergism with paclitaxel. The expression levels of RIZ1 were examined by real-time PCR and western blotting before and after transfection of RIZ1. The effects of paclitaxel or pcDNA3.1(+)-RIZ1 alone or in combination, on the proliferation of SiHa cells were evaluated by MTT method. The inhibitory effect on the proliferation of SiHa cells was more significant in the pcDNA3.1(+)-RIZ1 combined with paclitaxel group than in the pcDNA3.1(+)-RIZ1 or paclitaxel groups (P<0.05). The expression level of RIZ1 in SiHa cells increased after treatment with paclitaxel, which indicated a synergism between them. RIZ1 gene therapy combined with paclitaxel showed stronger cell inhibition than paclitaxel alone, which indicated a synergism between them.

Pre-embedding Double-Label Immunoelectron Microscopy of Chemically Fixed Tissue Culture Cells.

Localization of specific proteins within cells at the nanometer level of resolution is central to understanding how these proteins function in cell processes such as motility and intracellular trafficking. Such localization can be achieved by combining transmission electron microscopy (TEM) with immunogold labeling. Here we describe a pre-embedding, indirect gold immunolabeling approach to localize two different proteins of interest with secondary antibodies labeled with gold particles of different sizes in cells grown on cover slips. In this protocol, the cells are immunolabeled prior to being embedded in an epoxy resin for ultrathin sectioning. The protocol also includes strategies for optimizing the balance between ultrastructure and antigen preservation, steps to minimize nonspecific antibody binding, and steps to optimize antibody penetration.

Good survival in a patient with recurrent transitional cell carcinoma of the ovary: A case report of PET-CT for detection and follow-up.

Transitional cell carcinoma (TCC) of the ovary is a rare subtype of epithelial ovarian cancer. The present study reports the case of a 55-year-old patient from The Affiliated Tumor Hospital of Harbin Medical University (Harbin, Heilongjiang, China) who underwent successful surgery for recurrence of a TCC of the ovary with rectum metastases following the initial surgery and chemotherapy. Positron emission tomography/computed tomography (PET-CT) was used in the pre-operative detection of the tumor and the post-operative follow-up of the patient. To date, the patient has experienced 8 years of disease-free survival. The aim of the present study was to convey the good survival rate of the patient following recurrent TCC of the ovary, and the role of PET-CT in detection and follow-up, in order to aid in the future selection of appropriate diagnostic methods and therapies for this disease.

Hepatic Steatosis as a Predictive Factor of Antiviral Effect of Pegylated Interferon Therapy in Patients With Hepatitis B.

BACKGROUND AND AIMS: This study sought to evaluate the impact of hepatic steatosis, a common hepatocyte change in nonalcoholic fatty liver disease, upon response to pegylated interferon (PEG-IFN) therapy in patients with chronic hepatitis B (CHB). METHODS: Eighty-nine consecutive CHB patients from the Affiliated Hospital of Hangzhou Normal University receiving 48 weeks of PEG-IFN therapy were enrolled in this study, and 56 patients were followed up for 48 weeks among subjects with completed therapy. Baseline characteristics, end-of-treatment response (ETR), and sustained viral response (SVR) to PEG-IFN therapy were evaluated. Univariate analysis and multivariate logistic regression were applied to find independent factors of hepatic steatosis and PEG-IFN treatment failure. RESULTS: Steatosis was present in 34.5% (31 of 89) of liver biopsy samples. ETR to PEG-IFN therapy was 56.17% (50 of 89) at 48 weeks, and SVR to PEG-IFN therapy was 57.6% (32 of 56) at 96 weeks. There was no significant difference in ETR between the patients with hepatic steatosis and those without hepatic steatosis at 48 weeks (P > .05), whereas SVR was higher in patients without hepatic steatosis than in those with hepatic steatosis at 96 weeks (P < .05). Multivariate analysis showed that the sustained response rate was independently associated with steatosis, fibrosis, aspartate aminotransferase, C-reactive protein, and ferritin. Hepatic steatosis was a prediction factor with the sustained response. CONCLUSIONS: Hepatic steatosis may be a predictive factor of response to PEG-IFN therapy in patients with CHB.

Effects of acute ethanol exposure on polyamine and gamma-aminobutyric acid metabolism in the regenerating liver.

Recently, it has been suggested that ethanol-induced inhibition of liver regeneration results from decreases in hepatic putrescine levels and/or increases in hepatic gamma-aminobutyric acid (GABA)ergic activity. Because putrescine can be metabolized by diamine (DAO) and monoamine (MAO) oxidases to GABA, we documented the effects of acute ethanol exposure on hepatic MAO or DAO activity following partial hepatectomy (PHx) in rats. We also documented the effects of ethanol on GABA transaminase (GABA-T), the enzyme responsible for GABA metabolism in the liver, and tissue putrescine and GABA levels. Adult, male Sprague-Dawley rats (200-250 g) were treated with either ethanol (3 g/kg) or equal volumes of saline by gastric gavage 1 h prior to a 70% PHx or sham surgery. Rats were then sacrificed (n = 5-7/group) at various times (0-72 h) post-PHx. Enzymatic activity and putrescine/GABA levels were determined by standard isotopic techniques and high-performance liquid chromatography respectively. Hepatic DAO activities in ethanol-treated rats were transiently higher than in saline-treated controls (30% increases at 6 h, p < 0.05). Hepatic MAO and GABA-T activities in acute ethanol-treated rats were essentially identical to saline-treated controls. Although hepatic putrescine levels were similar in ethanol- and saline-treated rats, hepatic GABA levels were approximately three times higher in ethanol-treated rats at 12 and 24 h post-PHx (p < 0.0001). In conclusion, the results of this study indicate that acute ethanol exposure has a limited effect on the enzymatic conversion of putrescine to GABA following partial hepatectomy in the liver. The results also indicate that increased GABAergic inhibition rather than decreased putrescine stimulation is more likely to play a role in ethanol-induced inhibition of hepatic regeneration.

[The effect of IL-2 and IL-3 gene therapy in mice on immunological recovery receiving high dose chemotherapy].

OBJECTIVE: To investigate the effect of Ad-IL-2 and Ad-IL-3 on immunological recovery. METHODS: The Ad-IL-2 and/or Ad-IL-3 were i.p. injected into C57BL/6 mice having received high dose cyclophosphamide (200 mg/kg) 24 hours before. The number and cytotoxicity, Ia antigen expression of peritoneal macrophages, the proliferation and NK cell activity of splenic cells were observed. RESULTS: After i.p. injection with Ad-IL-3, the number, cytotoxicity and Ia antigen expression of peritoneal macrophagee were increased. After i.p. injection with Ad-IL-2, the proliferation and NK cell activity of splenic cells were significantly augmented. As i.p. injection with Ad-IL-2 and Ad-IL-3 simultaneously, both the peritoneal macrophages and splenic cells were activated. CONCLUSION: Intraperitoneal injection of Ad-IL-2 and Ad-IL-3 can promote immune recovery after high dose chemotherapy.