Human Sulfatase-1 Improves the Effectiveness of Cytosine Deaminase Suicide Gene Therapy with 5-Fluorocytosine Treatment on Hepatocellular Carcinoma Cell Line HepG2 In Vitro and In Vivo / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human sulfatase-1 (Hsulf-1) is an endosulfatase that selectively removes sulfate groups from heparan sulfate proteoglycans (HSPGs), altering the binding of several growth factors and cytokines to HSPG to regulate cell proliferation, cell motility, and apoptosis. We investigated the role of combined cancer gene therapy with Hsulf-1 and cytosine deaminase/5-fluorocytosine (CD/5-FC) suicide gene on a hepatocellular carcinoma (HCC) cell line, HepG2, in vitro and in vivo.</p><p><b>METHODS</b>Reverse transcription polymerase chain reaction and immunohistochemistry were used to determine the expression of Hsulf-1 in HCC. Cell apoptosis was observed through flow cytometry instrument and mechanism of Hsulf-1 to enhance the cytotoxicity of 5-FC against HCC was analyzed in HCC by confocal microscopy. We also establish a nude mice model of HCC to address the effect of Hsulf-1 expression on the CD/5-FC suicide gene therapy in vivo.</p><p><b>RESULTS</b>A significant decrease in HepG2 cell proliferation and an increase in HepG2 cell apoptosis were observed when Hsulf-1 expression was combined with the CD/5-FC gene suicide system. A noticeable bystander effect was observed when the Hsulf-1 and CD genes were co-expressed. Intracellular calcium was also increased after HepG2 cells were infected with the Hsulf-1 gene. In vivo studies showed that the suppression of tumor growth was more pronounced in animals treated with the Hsulf-1 plus CD than those treated with either gene therapy alone, and the combined treatment resulted in a significant increase in survival.</p><p><b>CONCLUSIONS</b>Hsulf-1 expression combined with the CD/5-FC gene suicide system could be an effective treatment approach for HCC.</p>

Survival without common toxicity criteria grade 3/4 toxicity following second-line treatment with pemetrexed for nonsquamous non-small cell lung cancer in Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The efficacy of pemetrexed in the second-line treatment of Chinese patients with advanced non-small cell lung cancer (NSCLC) has been shown to be similar to that of docetaxel in a recent study; additionally, pemetrexed was associated with much better safety and toxicity profiles. Here, the survival without common toxicity criteria grade 3/4 toxicity (SWT) data from a post hoc analysis of this recent prospective NSCLC study in Chinese patients is reported. This post hoc analysis differs from the main study; it focuses on the nonsquamous population to align with the current approval for pemetrexed in China.</p><p><b>METHODS</b>A total of 154 patients with nonsquamous NSCLC received either pemetrexed (500 mg/m(2) intravenously (IV)) or docetaxel (75 mg/m(2) IV) on day 1 of 21-day cycles. SWT was analyzed using Kaplan-Meier and univariate Cox methods.</p><p><b>RESULTS</b>Patients treated with pemetrexed had a longer median SWT than patients treated with docetaxel (7.4 months versus 1.2 months; unadjusted hazard ratio = 0.59, 95% confidence interval (CI): 0.41-0.84; P = 0.003). At 12 and 18 months, the SWT event-free probability for pemetrexed patients (18 months: 24.5%, 95%CI 13.9%-36.6%, vs. 12.3%, 95% CI 4.8%-23.6%) was greater than that for docexatel patients (12 months: 37.3%, 95% CI 26.5%-48.0%, vs. 23.3%, 95% CI 14.4-33.4). The progression-free survival without common toxicity criteria grade 3/4 toxicity (PFS-WT) was also statistically significantly longer for patients treated with pemetrexed than patients treated with docetaxel (1.9 months vs. 1.1 months, P = 0.002).</p><p><b>CONCLUSIONS</b>Chinese patients with nonsquamous NSCLC disease treated with pemetrexed had improved SWT beyond 6 months than those receiving docetaxel. This analysis supports a benefit-to-risk profile that favors pemetrexed over docetaxel in the second-line treatment of Chinese nonsquamous NSCLC patients.</p>

Analysis of prognostic factors in patients with locoregional recurrence of esophageal carcinoma after curative treatment / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this paper was to evaluate the treatment outcome of multimodal treatment for 196 patients with locoregional recurrent esophageal cancer after curative treatment and to determine the prognostic factors of recurrence.</p><p><b>METHODS</b>One hundred and ninety six patients with locoregional recurrent esophageal cancer curatively treated in our hospital were included in this study. Kaplan-Meier method was used to analyze the survival rate. Log rank test was used to evaluate the difference between the groups. Multivariate survival analysis was conducted using a Cox proportional hazard regression model with a backward stepwise procedure.</p><p><b>RESULTS</b>The overall 1-, 2- and 3-year survival rates were 29.8%, 5.9% and 4.0%, respectively, with a median survival time of 8.0 months. The univariate analysis showed that ECOG PS, the interval between initial treatment and recurrence, the regimens of initial treatment and retreatment were independent prognostic factors. The multivariate analysis showed that the regimens of initial treatment and retreatment were independent prognostic factors. Retreatment methods significantly influenced the survival. The median survival time of chemoradiotherapy, radiation therapy alone, chemotherapy alone, EGFR-TKI and best supportive care were 13.0, 7.0, 6.0, 4.0 and 3.0 months, respectively (P = 0.000).</p><p><b>CONCLUSIONS</b>The prognosis of patients with locoregional recurrent esophageal cancer after curative treatment is poor. The main prognostic factors are the regimens of initial treatment and retreatment. Multimodal treatment including radiotherapy and chemotherapy may improve the long-term survival of the patients.</p>

Anti-tumor and apoptotic effects in vitro and in vivo of a traditional Chinese medicine prescription / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Zhongfei Mixture (ZM), a traditional Chinese medicine, exploited from the clinical experience, has mainly been used for the treatment of advanced lung cancer since it was produced in 1983. However, little research has been conducted on its anti-tumor mechanism. In this study, we aimed to investigate the anti-tumor and apoptotic effects of ZM in vitro and in vivo.</p><p><b>METHODS</b>The growth inhibition effect of ZM on A549 cells was evaluated by MTT assay. Morphological observation and clone forming tests were performed to determine the effect of ZM on cell viability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. In addition, the in vivo anti-proliferation activity of ZM was evaluated using mice bearing Lewis lung carcinoma. Further, the apoptosis of cells in tumor tissue was determined by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and the expression of Ki-67 protein in tumor tissues was analyzed by En-Vision immuno-histochemistry staining.</p><p><b>RESULTS</b>ZM exerted an obvious inhibitory effect on proliferation of A549 cells. It arrested A549 cells in G(2)-M phase and induced apoptosis. Compared with 3.02% and 5.32% in control group, the percentages of cells arrested in G(2)-M phase were 19.20% and 19.58% in 7.94 mg/ml ZM treated A549 cells at 24 hours and 48 hours. Moreover, the apoptosis rate increased from 0.18% to 18.01% after ZM treatment for 48 hours. ZM also significantly inhibited tumor growth in the tumor-implanted mice. Compared with saline control group, the effects of ZM showed significant tumor growth inhibition (P < 0.05). Furthermore, ZM could down-regulate the expression of Ki-67 in tumor tissue in mice bearing Lewis lung carcinoma.</p><p><b>CONCLUSIONS</b>Our results indicated that ZM has notable anti-tumor effect and the effects of ZM in moderate dose groups were superlative both in vitro and in vivo. The possible mechanism of ZM might be associated with arresting cell cycle in G(2)-M phase as well as down-regulating Ki-67 expression in tumor tissues.</p>

Clinical study on toxicity-attenuation effect of Yiguan Decoction in treatment of non-small cell lung cancer with NP protocol of chemotherapy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the toxicity-attenuation effect of Yiguan Decoction (YGD) in treatment of non-small cell lung cancer (NSCLC) with NP protocol of chemotherapy.</p><p><b>METHODS</b>Ninety-two NSCLC patients were randomly assigned to two groups equally, the control group given only NP protocol of chemotherapy and the treated group given the same protocol of chemotherapy plus YGD. Hepatic function, T-cell subgroup and NK cell were examined, and quality of life (QOL) was evaluated with scoring by Karnofsky performance status (KPS), Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) and Special Scale for lung cancer (EORTC LC13) issued by European Organization for Research and Treatment of Cancer.</p><p><b>RESULTS</b>The effects on all the above-mentioned indexes in the treated group were better than those in the control group after 42 days of treatment (P <0.05).</p><p><b>CONCLUSION</b>YGD could not only reduce the side and toxic effects caused by NP protocol of chemotherapy in NSCLC patients but also improve their QOL.</p>

Clinical observation on treatment of radiation pneumonia by Qingjin Runfei Decoction combined with hormone and antibiotic / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the curative effect of Qingjin Runfei Decoction (QRD) combined with hormone and antibiotic in treating radiation pneumonia (RP).</p><p><b>METHODS</b>Patients were randomly assigned to two groups, the control group (51 cases) treated with hormone and antibiotic and the treated group (53 cases) with the above therapy plus QRD. The curative effects on RP, quality of life (QOL), chest radiography and TCM symptoms were observed.</p><p><b>RESULTS</b>The curative effects on the above items in the treated group were all significantly better than those in the control group (P < 0.05).</p><p><b>CONCLUSION</b>QRD could enhance the effects of hormone and antibiotic in treating RP, as well as improve QOL of the patients.</p>

Clinical research on nourishing yin and unblocking meridians recipe combined with opioid analgesics in cancer pain management / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the analgesic effects of Nourishing yin and Unblocking meridians Receipe (NUR) combined with opioid analgesics in managing cancer pain.</p><p><b>METHODS</b>All the patients enrolled were differentiated as of yin deficiency and meridian blocked syndrome type of TCM. Forty-one of them in the treated group were treated with NUR combined with opioid analgesics, while 43 of them in the control group were given opioid analgesics alone with successive 14 days as one treatment course for both groups.</p><p><b>RESULTS</b>The indexes of the treated group were superior to those in the control group as to the degree of pain-relieving, the therapeutic effect of analgesia, the occurrence frequency of cancer pain every day and its duration each time, the analgesic initial time, and the quality of life.</p><p><b>CONCLUSION</b>NUR combined with opioid analgesics in cancer pain management was more effective than opioid analgesics alone.</p>

Effect of Supportan on nutritional status and immune function of late-staged gastric cancer patients undergoing chemotherapy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Supportan, an enteral nutrition (EN) specific for tumor patients, on the nutritional status and immune function of late-staged gastric cancer patients undergoing chemotherapy.</p><p><b>METHODS</b>Sixty-six late-staged gastric cancer patients undergoing chemotherapy were randomly divided into EN group (n=33) and control group (n=33). During chemotherapy, the patients in EN group received Supportan and the patients in the control group received basic diet. On the 14th day before chemotherapy and after chemotherapy, nutritional status and cell immune indicators were evaluated.</p><p><b>RESULTS</b>As for nutrition indicators, there were no significant differences in EN group before and after chemotherapy (P > 0.05). Total protein, hemoglobin, prealbumin and transferrin significantly decreased after chemotherapy compared with those before chemotherapy in the control group (P< 0.01). The levels of CD4(+), CD8(+) T cells and CD4/CD8 were significantly increased, and NK cells, serum levels of IL-1, IL-6 were significantly decreased after chemotherapy in EN group (P< 0.01). The levels of IL-6 and TNF-alpha were significantly higher after chemotherapy than those before chemotherapy in the control group(P< 0.01). Curative effects of immune nutrition in EN group were superior to that in the control group, however, the differences were not statistically significant. The incidences of nausea, vomiting and marrow inhibition in Supportan group was lower compared with those in the control group, but with no significant difference.</p><p><b>CONCLUSION</b>Supportan can prevent malnutrition of the late-staged gastric cancer patients undergoing chemotherapy, and improve immune function and alleviate adverse effects of chemotherapy.</p>

Establishment of human multidrug-resistant lung carcinoma cell line (D6/MVP) / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish human multidrug-resistant lung carcinoma cell line (D6/MVP) with its characteristics studied.</p><p><b>METHODS</b>Intermittent administration of high-dose MMC, VDS and DDP (MVP) was used to induce human lung carcinoma cell line (D6) to a multidrug-resistant variety (D6/MVP). MTT assay was used to study the multidrug resistance of D6/MVP to multianticarcinogen. Flow cytometry was used to study the cell cycle distribution and the expression of P-gp, multidrug resistance-associated protein (MRP) and GSH/GST.</p><p><b>RESULTS</b>1. D6/MVP was resistant to many anti-tumor agents, with the IC(50) 13.3 times higher and the drug resistance 2 - 6 times higher than D6, 2. The multiplication time of D6/MVP was prolonged and the cell number of S-phase decreased while that of G1- and G(2)-phase increased and 3. The expression of P-gp and MRP was enhanced significantly (96.2% vs 51.7%), but the expression of GSH/GST kept stable.</p><p><b>CONCLUSION</b>D6/MVP is a multidrug-resistant cell line possessing the basic characteristics of drug-resistance.</p>