Prognostic importance of systemic inflammation and insulin resistance in patients with cancer: a prospective multicenter study.

BACKGROUND: Systemic inflammation and insulin resistance (IR) are often associated with poor prognosis in cancer. This study aimed to investigate the prognostic value of surrogate systemic inflammation and IR indices in patients with cancer. METHODS: This multicenter prospective study included 5,221 patients with cancer, with a mean age of 59.41±11.15 years, of whom 3,061 (58.6%) were male. The surrogate IR indices included low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LHR) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/ HDL-c) ratio, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and fasting triglyceride glucose (TyG). Prognostic receiver operator characteristic (ROC) curves and C-indices were used to select a better surrogate IR index in patients with cancer. The prognostic value of the indicators was evaluated using univariate and multivariate survival analyses. RESULTS: In this study, the median survival time of patients was 44.5 (40.5-51.4) months, and the overall mortality in the 12-month period was 1,115 (53.7%), with 196 mortality events per 1,000 patient-years of patients' follow-up. The prognostic ROC curve and C-index suggested that the prognostic value of LHR was better than that of the other IR indices. The multivariate-adjusted hazard ratios (HRs) for overall survival (OS) were higher in patients with high C-reactive protein (CRP) (HR, 1.51; 95% confidence interval [CI]: 1.38-1.65) and high LHR (HR, 1.20; 95% CI: 1.06-1.37), respectively. The mortality rate of patients with both high CRP and LHR was 1.75-fold higher than that of patients with both low CRP and LHR. CONCLUSION: Both CRP and LHR showed good survival predictions in patients with cancer. CRP combined with LHR can improve the predictive power of patients with cancer.

[Judging the postoperative lymph node metastasis of esophagus cancer patients with pN0 stage by detecting MTA1 protein expression].

OBJECTIVE: To investigate the feasibility for judging the postoperative lymph node metastasis of esophagus cancer patients with pN0 stage by detecting the protein expression of metastasis-associated protein 1 (MTA1). METHODS: Immunohistochemistry was used to detect the expression of MTA1 protein in lymph node of esophageal squamous cell carcinoma (ESCC) with pN0 stage. RESULTS: (1) There were no significant differences in age, gender and differentiation among the lymph node metastasis (P > 0.05), but not with pT stage (P < 0.05; χ(2) = 13.29). (2) There were no significant differences among the expression of MTA1 protein and age, gender and differentiation (P > 0.05), but not with differentiation and pT stage (P < 0.05; χ(2) = 18.61). Both stages pT1b and pT3 had higher expression of MTA1 protein than stage pT1a (P < 0.05; χ(2) = 25.54). (3) The curve of lymph node metastasis showed that the patients with no/lower MTA1 protein expression had a lower metastasis rate than those a higher MTA1 protein expression (P < 0.05; χ(2) = 16.63). (4) The results of multivariate analysis confirmed that T status and MTA1 protein over-expression were independent risk factors for pN0 stage ESCC. CONCLUSION: Detecting MTA1 protein expression is helpful for judging the lymph node metastasis of ESCC patients with pN0 stage. And its over-expression may used as a guide in the decision-making of postoperative adjuvant therapy.

A Novel Inflammation and Insulin Resistance Related Indicator to Predict the Survival of Patients With Cancer.

Background: Systemic inflammation and insulin resistance (IR) are closely related in patients with cancer. However, there is no relevant indicator that combines inflammation and IR to predict patient prognosis. Therefore, this study aimed to develop and validate a novel inflammation- and IR-related marker in patients with cancer. Methods: The total cohort of this study included 5221 patients with cancer, and the training and validation cohorts were randomized in a 7:3 ratio. C-reactive protein (CRP) and fasting triglyceride glucose (TyG) were used to reflect patients' inflammation and IR status, respectively. The CRP-TyG index (CTI) was composed of CRP and TyG. The concordance (C)-index, receiver operator characteristic (ROC) curve, and calibration curve reflected the prognostic predictive power of CTI. Univariate and multivariate survival analyses predicted the prognostic value of CTI in patients with cancer. Results: The C-indices of CTI in patients with cancer were 0.636, 0.617, and 0.631 in the total, training, and validation cohorts, respectively. The 1-, 3-, and 5-year ROC and calibration curves showed that CTI had a good predictive ability of survival in patients with cancer. Meanwhile, patients with high CTI had a worse prognosis compared to patients with low CTI (total cohort: hazard ratio [HR] = 1.46, 95% confidence interval [95% CI] = 1.33-1.59; training cohort: HR = 1.36, 95% CI = 1.22-1.52; validation cohort: HR = 1.73, 95% CI = 1.47-2.04]. Conclusion: The CTI is a useful prognostic indicator of poor prognosis and a promising tool for treatment strategy decision-making in patients with cancer.

Association of systemic inflammation and low performance status with reduced survival outcome in older adults with cancer.

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

Lycoris wulingensis, a dwarf new species of Amaryllidaceae from Hunan, China.

Lycoris wulingensis S.Y. Zhang, a new species from Hunan Province (central South China), is described and illustrated. This new species is a fertile diploid plant and its karyotype is 2n = 22. It is most similar to L. × haywardii in morphology, but the latter is a hybrid species and distributed in East China and the plant is much larger. Amongst the original species, L. wulingensis is similar to L. radiata, but differs from it in its flowers being rose-red (vs. red) and stamens and tepals are nearly the same length (vs. stamens significantly longer than tepals).

Association of Systemic Inflammation and Overall Survival in Elderly Patients with Cancer Cachexia - Results from a Multicenter Study.

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality. PATIENTS AND METHODS: This multicenter cohort study included 746 EPCC (age >65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria. RESULTS: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (<25.03) had a worse overall survival (OS) than patients with high ALI (≥25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590-2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups. CONCLUSION: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.

Geriatric Nutrition Risk Index: Prognostic factor related to inflammation in elderly patients with cancer cachexia.

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown. METHODS: This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group <91.959) according to the optimal cut-off value of the ROC curve. The calibration curves were performed to analyse the prognostic, predictive ability of GNRI. Comprehensive survival analyses were utilized to explore the relationship between GNRI and the overall survival (OS) of EPCC. Interaction analysis was used to investigate the comprehensive effects of low GNRI and subgroup parameters on the OS of EPCC. RESULTS: In this study, a total of 2560 patients were diagnosed with cancer cachexia, including 746 cases of EPCC. During the 3.6 year median follow-up, we observed 403 deaths. The overall mortality rate for EPCC at 12 months was 34.3% (95% CI: 62.3% to 69.2%), and resulting in rate of 278 events per 1000 patient-years. The GNRI score of EPCC was significantly lower than those of young patients with cancer cachexia (P < 0.001). The 1, 3, and 5 year calibration curves showed that the GNRI score had good survival prediction in the OS of EPCC. The GNRI could predict the OS of EPCC, whether as a continuous variable or a categorical variable. Particularly, we also found that low GNRI score (<91.959) of EPCC had a worse prognosis than those with a high GNRI score (≥91.959, P = 0.001, HR = 1.728, 95% CI: 1.244-2.401). Consistent results were observed in the tumour subgroups of gastric cancer and colorectal cancer. Notably, similar results were observed in the sensitivity analysis. In the subgroup analysis, the low GNRI has a combined effect with age (<70 years) on poor OS of EPCC. The results of the prognostic risk model found that the lower the GNRI score, the greater the prognostic risk score, and the greater the risk of death in EPCC. CONCLUSIONS: For the first time, this study found that the GNRI score can serve as an independent prognostic factor for the OS of EPCC.

Association Between Systemic Inflammation and Malnutrition With Survival in Patients With Cancer Sarcopenia-A Prospective Multicenter Study.

OBJECTIVE: Systemic inflammation and malnutrition are correlated with cancer sarcopenia and have deleterious effects on oncological outcomes. However, the combined effect of inflammation and malnutrition in patients with cancer sarcopenia remains unclear. METHODS: We prospectively collected information on 1,204 patients diagnosed with cancer sarcopenia. the mean (SD) age was 64.5 (11.4%) years, and 705 (58.60%) of the patients were male. The patients were categorized into the high advanced lung cancer inflammation index (ALI) group (≥18.39) and the low ALI group (<18.39) according to the optimal survival cut-off curve. We selected the optimal inflammation marker using the C-index, decision curve analysis (DCA), and a prognostic receiver operating characteristic curve. Univariate and multivariate survival analyses were performed to determine the prognostic value of the optimal inflammation indicator. We also analyzed the association between inflammation and malnutrition in patients with cancer. RESULTS: The C-index, DCA, and prognostic area under the curve of ALI in patients with cancer sarcopenia were higher or better than those of neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). The prognosis for patients in the low ALI group was worse than that of patients in the high ALI group [HR (95%CI) = 1.584 (1.280-1.959), P < 0.001]. When the ALI was divided into quartiles, we observed that decreased ALI scores strongly correlated with decreased overall survival (OS). Patients with both a low ALI and severe malnutrition (vs. patients with high ALI and well-nourished) had a 2.262-fold death risk (P < 0.001). Subgroup analysis showed a significant interactive association between the ALI and death risk in terms of TNM stage (P for interaction = 0.030). CONCLUSIONS: The inflammation indicator of the ALI was better than those of the NLR, PNI, SII, and PLR in patients with cancer sarcopenia. Inflammation combined with severe malnutrition has a nearly 3-fold death risk in patients with cancer sarcopenia, suggesting that reducing systemic inflammation, strengthening nutritional intervention, and improving skeletal muscle mass are necessary.

Immunosuppressive effect of IDO on T cells in patients with chronic hepatitis B*.

AIM: Recently indoleamine 2,3-dioxygenase (IDO) has drawn considerable attention as a mechanism of immune regulation. Our study was to observe the role of IDO in immune tolerance of chronic hepatitis B (CHB), so as to provide a novel approach for reestablishment of active immunity. METHODS: Peripheral venous blood samples were taken from 50 CHB patients and HBV viral load, T lymphocyte subsets as well as the mRNA, protein and activity of IDO were detected. The correlations between HBV viral load, T lymphocyte subsets and IDO were statistically analyzed. Blood samples from 50 healthy people were tested as a control group. RESULTS: In CHB patients, the mRNA, protein and activity of IDO were all significantly more than those in control group (mRNA:[2.11 +/- 0.615] x 10(3) vs. [0.143 +/- 0.026] x 10(3); protein: 0.22 +/- 0.06 vs. 0.02 +/- 0.0017; activity: 26.07 +/- 8.12 vs. 4.98 +/- 1.65; P < 0.05) and IDO mRNA was positively correlated with HBV viral load (r = 0.502, P < 0.001) and alanine aminotransferase (ALT) (r = 0.65, P < 0.01). Furthermore, IDO mRNA, protein and activity were negatively correlated with CD4(+) T cells (r = -0.622, -0.682, -0.549 respectively, P < 0.05), CD8 (+) T cells (r = -0.487, -367, -294 respectively, P < 0.05) and the ratio of CD4/CD8 (r = -0.426, -0.533, -0.397 respectively, P < 0.05). CONCLUSION: IDO closely correlates with HBV viral load and is responsible for immunotolerance against HBV. Suppression of IDO could be a novel approach to break tolerance in CHB.

DeepMRMP: A new predictor for multiple types of RNA modification sites using deep learning.

RNA modification plays an indispensable role in the regulation of organisms. RNA modification site prediction offers an insight into diverse cellular processing. Regarding different types of RNA modification site prediction, it is difficult to tell the most relevant feature combinations from a variant of RNA properties. Thereby, the performance of traditional machine learning based predictors relied on the skill of feature engineering. As a data-driven approach, deep learning can detect optimal feature patterns to represent input data. In this study, we developed a predictor for multiple types of RNA modifications method called DeepMRMP (Multiple Types RNA Modification Sites Predictor), which is based on the bidirectional Gated Recurrent Unit (BGRU) and transfer learning. DeepMRMP makes full use of multiple RNA site modification data and correlation among them to build predictor for different types of RNA modification sites. Through 10-fold cross-validation of the RNA sequences of H. sapiens, M. musculus and S. cerevisiae, DeepMRMP acted as a reliable computational tool for identifying N1-methyladenosine (m1A), pseudouridine (Ψ), 5-methylcytosine (m5C) modification sites.

Effects of rapamycin in liver transplantation.

BACKGROUND: Rapamycin is a potent new immunosuppressant with a mechanism of action that is distinct from that of calcineurin inhibitors, but few clinical data on rapamycin in liver transplantation are available. Hence it is necessary to evaluate the efficacy and side-effects of rapamycin-based immunosuppression in liver transplant patients. METHODS: We retrospectively analysed 39 liver transplantation patients who took rapamycin as an immunosuppressant. This series consisted of 28 patients with hepatocellular carcinoma, 9 patients with chronic fulminant hepatitis, and 2 patients with end-stage liver cirrhosis. Eight patients used rapamycin for monotherapy, and 31 used rapamycin-based immunosuppression. In the 31 patients, 7 patients used rapamycin instead of mycophenolate mofetil to treat acute rejection. RESULTS: In the 28 patients with hepatocellular carcinoma, the one-year survival rate was 67% without any tumor recurrence. The acute rejection in 7 patients was relieved in 1-2 weeks after the administration of rapamycin. All the 8 patients who received rapamycin monotherapy survived for at least 6 months and liver function tests and biopsy showed nothing abnormal. Jaundice in 8 patients with chronic rejection was reduced sharply after use of rapamycin. CONCLUSIONS: Rapamycin given alone or in conjunction with calcineurin inhibitors appears to be an effective primary immunosuppressant regimen for orthotopic liver transplantation patients. Further studies are warranted to evaluate the efficacy and side-effect profile of rapamycin in liver transplant patients.

[Effects on lymphangiogenesis and angiogenesis of lung cancer with antisense oligonucleotides of vascular endothelial growth factor C].

OBJECTIVE: To investigate the effects on lymphangiogenesis and angiogenesis of orthotopic implantation of lung cancer in nude mice with antisense oligonucleotides of VEGF-C. METHODS: The model in nude mice was established with orthotopic implantation for the human lung cancer cell line A549. Thirty nude mice were randomized into three groups: PBS control group, sense oligonucleotides control group and antisense oligonucleotides group (AODN group). After treatments were completed, the expression of VEGF-C and lymphatic microvessel density (LMVD) and microvessel density (MVD) of lung cancer were detected by RT-PCR,Western Blot and immunohistochemistry. RESULTS: The expression of VEGF-C in AODN group was inhibit significantly (P < 0.05). The LMVD in AODN group was decreased significantly (P < 0.1). Though the MVD in AODN group was also decreased, but there were no significant differences compared with control groups (P > 0.05). CONCLUSIONS: The antisense oligonucleotides of VEGF-C can inhibit the expression of VEGF-C in nude mice of orthotopic implantation of lung cancer. It could inhibit the lymphangiogenesis.

Establishment of hepatocellular carcinoma multidrug resistant monoclone cell line HepG2/mdr1.

BACKGROUND: The multidrug resistance (MDR) associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell (HCC) patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1. METHODS: The 4.5-kb mdr1 cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCI-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein (Pgp) in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated. RESULTS: The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of mdr1 cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were (59.7 +/- 7.9)% and (12.28 +/- 2.09)%, respectively, compared with (16.9 +/- 3.2)% and (3.07 +/- 1.06)% in HepG2 cells. In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours. CONCLUSION: The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the experimental basis of MDR research.

Prognostic significance of osteopontin in acute myeloid leukemia: A meta-analysis.

Osteopontin (OPN) has been investigated in the field of tumor research for several years. However, the prognostic role of OPN overexpression in acute myeloid leukemia (AML) remains controversial. A meta-analysis of four studies, including a total of 492 patients, was performed to determine the association of OPN with overall survival (OS) in AML patients. The random-effects model of Der Simonian and Laird was used to synthesize data; hazard ratio (HR) with its 95% confidence interval (CI) was used as the effect size estimate. It was observed that serum-based OPN was inversely correlated with OS and the difference was statistically significant (HR=1.83; 95% CI: 1.43-2.35; P<0.001). Experimental findings indicate that OPN overexpression is associated with a poor prognosis in AML and may be of prognostic value for AML stage and metastasis.

Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla.

Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness, cerebrovascular diseases, and nervous disorders in China. Previously, the neuro-protective activities of the alkaloids from U. rhynchophylla were intensively reported. In current work, three new indole alkaloids (1-3), identified as geissoschizic acid (1), geissoschizic acid N 4-oxide (2), and 3ß-sitsirikine N 4-oxide (3), as well as 26 known analogues were isolated from U. rhynchophylla. However, in the neural stem cells (NSCs) proliferation assay for all isolated compounds, geissoschizic acid (1), geissoschizic acid N 4-oxide (2), isocorynoxeine (6), isorhynchophylline (7), (4S)-akuammigine N-oxide (8), and (4S)-rhynchophylline N-oxide (10) showed unexpected inhibitory activities at 10 µM. Unlike previous neuro-protective reports, as a warning or caution, our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U. rhynchophylla, while the structure-activity relationships of the isolated compounds were discussed also.

Intramuscular hepatitis B immune globulin combined with lamivudine in prevention of hepatitis B recurrence after liver transplantation.

BACKGROUND: Combined hepatitis B immune globulin (HBIg) and lamivudine in prophylaxis of the recurrence of hepatitis B after liver transplantation has significantly improved the survival of HBsAg positive patients. This study was undertaken to evaluate the outcomes of liver transplantation for patients with hepatitis B virus (HBV). METHODS: A retrospective chart analysis and a review of the organ transplant database identified 51 patients (43 men and 8 women) transplanted for benign HBV-related cirrhotic diseases between June 2002 and December 2004 who had survived more than 3 months. HBIg was administered intravenously during the first week and intramuscularly thereafter. RESULTS: At a median follow-up of 14.1 months, the overall recurrence rate in the 51 patients was 3.9% (2/51). The overall patient survival was 88.3%, and 82.4% after 1 and 2 years, respectively. A daily oral dose of 100 mg lamivudine for 2 weeks before transplantation for 10 patients enabled 57.1% (4/7) and 62.5% (5/8) of HBV-DNA and HBeAg positive patients respectively to convert to be negative. Intramuscular HBIg was well tolerated in all patients. CONCLUSION: Lamivudine combined with intramuscular HBIg can effectively prevent allograft from the recurrence of HBV after liver transplantation.

[An experimental study of recombinant adenovirus microsphere carrying antisense multidrug resistance-associated protein gene for reversing MRP of hepatocellular carcinoma in vitro].

OBJECTIVE: To conduct an in vitro study on the effect of recombinant adenovirus microsphere encapusulated antisense MRP (as-mrp) for use in the gene therapy to overcome drug resistance in hepatocellular carcinoma. METHODS: Recombinant adenovirus microsphere encapusulated as-mrp was transfected into hepatocellular carcinoma multidrug resistance cells HepG2/ADM, the fluorescence intensity of transfected cells were observed at 48 hours and 120 hours after transfection. in vitro drug sensitivity was measured by MTT assay; the resistant index of andromycin resistant variants was determined by drawing the cell dosage reaction curves. The levels of MRP mRNA expression were detected by RT-PCR and the ratio of MRP mRNA/beta-actin was detected. Intracelluar rubidomycin (DNR) concertration was examined by flow cytometry (FCM). RESULTS: More than 90% of the HepG2/ADM cells could be transfected when microspheres being 10 mg. Adv microsphere inhibited the expression of mRNA in HepG2/ADM and enhanced the sensitivity of HepG2/ADM to chemotherapeutic drug. CONCLUSION: Recombinant adenovirus microsphere encapusulated as-mrp could effectively reverse HepG2/ADM cells, which would provide an experimental basis for the methods of reversing the multidrug resistance in human hepatocellular carcinoma.

JAK2 inhibitor TG101348 overcomes erlotinib-resistance in non-small cell lung carcinoma cells with mutated EGF receptor.

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are responsive to EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, NSCLC patients with secondary somatic EGFR mutations are resistant to EGFR-TKI treatment. In this study, we investigated the effect of TG101348 (a JAK2 inhibitor) on the tumor growth of erlotinib-resistant NSCLC cells. Cell proliferation, apoptosis, gene expression and tumor growth were evaluated by diphenyltetrazolium bromide (MTT) assay, flow cytometry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, Western Blot and a xenograft mouse model, respectively. Results showed that erlotinib had a stronger impact on the induction of apoptosis in erlotinib-sensitive PC-9 cells but had a weaker effect on erlotinib-resistant H1975 and H1650 cells than TG101348. TG101348 significantly enhanced the cytotoxicity of erlotinib to erlotinib-resistant NSCLC cells, stimulated erlotinib-induced apoptosis and downregulated the expressions of EGFR, p-EGFR, p-STAT3, Bcl-xL and survivin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of TG101348 and erlotinib induced apoptosis, inhibited the activation of p-EGFR and p-STAT3, and inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo. Our results indicate that TG101348 is a potential adjuvant for NSCLC patients during erlotinib treatment.

Infections during induction therapy of protocol CCLG-2008 in childhood acute lymphoblastic leukemia: a single-center experience with 256 cases in China.

BACKGROUND: Infections remain a major cause of therapy-associated morbidity and mortality in children with acute lymphoblastic leukemia (ALL). METHODS: We retrospectively analyzed the medical charts of 256 children treated for ALL under the CCLG-2008 protocol in Beijing Children's Hospital. RESULTS: There were 65 infectious complications in 50 patients during vincristine, daunorubicin, L-asparaginase and dexamethasone induction therapy, including microbiologically documented infections (n = 12; 18.5%), clinically documented infections (n = 23; 35.3%) and fever of unknown origin (n = 30; 46.2%). Neutropenia was present in 83.1% of the infectious episodes. In all, most infections occurred around the 15 th day of induction treatment (n = 28), and no patients died of infection-associated complications. CONCLUSIONS: The infections in this study was independent of treatment response, minimal residual diseases at the end of induction therapy, gender, immunophenotype, infection at first visit, risk stratification at diagnosis, unfavorable karyotypes at diagnosis and morphologic type. The infection rate of CCLG-2008 induction therapy is low, and the outcome of patients is favorable.

Experimental study on inhibition effects of the XAF1 gene against lung cancer cell proliferation.

OBJECTIVE: To investigate the effect of high expression of XAF1 in vivo or in vitro on lung cancer cell growth and apoptosis. METHODS: 1. The A549 human lung cancer cell line was transfected with Ad5/F35 - XAF1, or Ad5/ F35 - Null at the same multiplicity of infection (MOI); (hereinafter referred to as transient transfected cell strain); XAF1 gene mRNA and protein expression was detected by reverse transcription polymerase chain reaction (RT- PCR) and Western blotting respectively. 2. Methyl thiazolyl tetrazolium (MTT) and annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis before and after infection of Ad5/F35 - XAF1 with Western blotting for apoptosis related proteins, caspase 3, caspase - 8 and PARP. 3. After the XAF1 gene was transfected into lung cancer A549 cells by lentiviral vectors, and selected by screening with Blasticidin, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were applied to detect mRNA and protein expression, to establish a line with a stable high expression of XAF1 (hereinafter referred to as stable expression cell strain). Twenty nude mice were randomly divided into groups A and B, 10 in each group: A549/ XAF1 stable expression cell strain was subcutaneously injected in group A, and A549/Ctrl stable cell line stable expression cell strain in group B (control group), to observe transplanted tumor growth in nude mice. RESULTS: The mRNA and protein expression of XAF1 in A549 cells transfected by Ad5/F35 - XAF1 was significantly higher than in the control group. XAF1 mediated by adenovirus vector demonstrated a dose dependent inhibition of lung cancer cell proliferation and induction of apoptosis. This was accompanied by cleavage of caspase -3, -8, -9 and PARP, suggesting activation of intrinsic or extrinsic apoptotic pathways. A cell strain of lung cancer highly expressing XAF1 was established, and this demonstrated delayed tumor growth after transplantation in vivo. CONCLUSION: Adenovirus mediated XAF1 gene expression could inhibit proliferation and induce apoptosis in lung cancer cells in vitro; highly stable expression of XAF1 could also significantly inhibit the growth of transplanted tumors in nude mouse, with no obvious adverse reactions observed. Therefore, the XAF1 gene could become a new target for lung cancer treatment.