Targeted inhibition of myeloid-derived suppressor cells in the tumor microenvironment by low-dose doxorubicin to improve immune efficacy in murine neuroblastoma / 中华医学杂志(英文版)

BACKGROUND@#High agglomeration of myeloid-derived suppressor cells (MDSCs) in neuroblastoma (NB) impeded therapeutic effects. This study aimed to investigate the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin (DOX) to enhance immune efficacy in NB.@*METHODS@#Bagg albino (BALB/c) mice were used as tumor-bearing mouse models by injecting Neuro-2a cells, and MDSCs were eliminated by DOX or dopamine (DA) administration. Tumor-bearing mice were randomly divided into 2.5 mg/kg DOX, 5.0 mg/kg DOX, 50.0 mg/kg DA, and control groups (n = 20). The optimal drug and its concentration for MDSC inhibition were selected according to tumor inhibition. NB antigen-specific cytotoxic T cells (CTLs) were prepared. Tumor-bearing mice were randomly divided into DOX, CTL, anti-ganglioside (GD2), DOX+CTL, DOX+anti-GD2, and control groups. Following low-dose DOX administration, immunotherapy was applied. The levels of human leukocyte antigen (HLA)-I, CD8, interleukin (IL)-2 and interferon (IFN)-γ in peripheral blood, CTLs, T-helper 1 (Thl)/Th2 cytokines, perforin, granzyme and tumor growth were compared among the groups. The Wilcoxon two-sample test and repeated-measures analysis of variance were used to analyze results.@*RESULTS@#The slowest tumor growth (F = 6.095, P = 0.018) and strongest MDSC inhibition (F = 14.632, P = 0.001) were observed in 2.5 mg/kg DOX group. Proliferation of T cells was increased (F = 448.721, P < 0.001) and then decreased (F = 2.047, P = 0.186). After low-dose DOX administration, HLA-I (F = 222.489), CD8 (F = 271.686), Thl/Th2 cytokines, CD4+ and CD8+ lymphocytes, granzyme (F = 2376.475) and perforin (F = 488.531) in tumor, IL-2 (F = 62.951) and IFN-γ (F = 240.709) in peripheral blood of each immunotherapy group were all higher compared with the control group (all of P values < 0.05). The most significant increases in the aforementioned indexes and the most notable tumor growth inhibition were observed in DOX+anti-GD2 and DOX+CTL groups.@*CONCLUSIONS@#Low-dose DOX can be used as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering immune efficacy in NB.

Tracking in vivo migration and distribution of antigen-specific cytotoxic T lymphocytes by 5,6-carboxyfluorescein diacetate succinimidyl ester staining during cancer immunotherapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Killing of targeted tumors during adoptive cell transfer therapy is associated with cytotoxic T lymphocyte (CTL) numbers, immunophenotype, tumor-specificity, and in vivo residence time, migration, and distribution. Therefore, tracing in vivo persistence, migration, and distribution of CTLs is important for cancer immunotherapy.</p><p><b>METHODS</b>Optimal staining concentration for CTL proliferation was determined by cell counting kit-8 (CCK-8) assay and killing efficiencies of CTLs or carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled melanoma antigen-specific cytotoxic T lymphocytes (CFSE-CTLs) for malignant melanoma cells in vitro were compared. Additionally, CFSE-CTLs were intravenously transfused to mice receiving B16 melanoma, and their residence time, migration, and distribution in vivo were observed by measuring fluorescence intensities of CFSE-CTLs per gram of tissue (%FI/g) in various tissues and analyzing tumor/non-tumor (T/NT) values. Anti-tumor effects of transferred CTLs and correlation between %FI/g and D-value of tumor size were analyzed.</p><p><b>RESULTS</b>Five-micromolar CFSE was optimal for labeling CTLs with minimal cytotoxicity. No significant difference occurred between CTLs and CFSE-CTLs for tumor cell killing (P = 0.849) or interleukin-2 (P = 0.318) and interferon-γ (P = 0.201) levels. Distribution of CTLs in vivo varied with time. A negative correlation between %FI/g in tumors and D-value of tumor sizes by Spearman correlation analysis was observed. CTLs were recruited to and killed tumors from 6 hours to 3 days after cell infusion. CTLs were observed up to three weeks later in the tumor, liver, kidneys, and spleen; this was related to the abundant blood supply or the nature of immune organs.</p><p><b>CONCLUSIONS</b>CCK-8 assay is a novel method to select optimal CFSE staining concentrations. Fluorescence intensity of transferred CTLs reflects their killing efficiency of tumors. CFSE fluorescent markers can trace in vivo CTL persistence, migration, and distribution because of its stability, long half-life, and low toxicity.</p>

The role of PD-ECGF and VEGF in proliferative and involuted mechanism of the infantile capillary hemangiomas / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the relation between the expressions of PD-ECGF and VEGF and the evolution of capillary hemangioma, so as to provide theoretical basis for treatment.</p><p><b>METHODS</b>Fourty cases with capillary hemangioma, proved by pathologic method, were randomly selected and divided into proliferative (n=22) and involuted groups (n=18), according to the Mulliken standard. 8 specimens from 8 children with prepuce operation were used as control group. All the specimens were fixed, embedded and underwent HE staining. The expression of PD-ECGF, VEGF and CD34 in endothelial cells were detected by immunohistochemistry. The microvessel-density (MVD) was also calculated. The results were analyzed by SPSS12.0.</p><p><b>RESULTS</b>The positive expression rates of PD-ECGF and VEGF were 95.45% (21/22) and 86.36% (19/22) in proliferative hemangioma, 77.78% (14/18) and 66.67% (12/ 18) in involuted hemangioma, 37.50% (3/8) and 37.50% (3/8) in normal skin. MVD in proliferative and involuted hemangioma and normal skin was 93.68 +/- 20.56, 51.94 +/- 20.73 and 17.50 +/- 5.30, respectively. There was a significant difference in PD-ECGF expression and MVD between the proliferative and involuted groups, or between the hemangioma and control groups (P < 0.05). The VEGF was significantly different between the proliferative and involuted groups, or between the proliferative and control groups (P < 0.05), but not between the involuted and control groups (P > 0.05). The expression of VEGF, PD-ECGD and MVD showed a positive relationship.</p><p><b>CONCLUSIONS</b>PD-ECGF and VEGF have a synergetic effect in the proliferation of micro-vessels. PD-ECGF may enhance the activity of thymidine phosphorylase. They play an important role in the proliferation and involution of hemangioma.</p>

Laparoscopic splenectomy: color Doppler flow imaging for preoperative evaluation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Laparoscopic splenectomy (LS) is currently the standard approach for resection of a normal-sized spleen. However, this method becomes technical challenge in cases of splenomegaly due to intraoperative hemorrhage. A complete understanding of the splenic vessel anatomy is important to facilitate the difficult laparoscopic procedure. In this retrospective study, we examined the role of color Doppler flow imaging (CDFI) in splenic vessel anatomy and evaluated its value for LS.</p><p><b>METHODS</b>Forty-eight patients who underwent splenectomy for various hematologic and autoimmune disorders from May 2004 to December 2007 were enrolled in this study. Twenty-three patients underwent preoperative CDFI examination that included examination of the anatomic type of splenic pedicle, the adjacent relationship between the splenic vessel and pancreas, and spleen size (CDFI group). In the remaining 25 patients, ultrasonic inspections of the splenic vessel were not performed (non-CDFI group). Laparoscopic splenectomies in the CDFI group were performed in accordance with the information provided by the preoperative CDFI in each patient. In the non-CDFI group, LS was performed according to the conventional method. In the CDFI group, the constituent ratios of the above-mentioned parameters by CDFI were compared with those recorded during LS using the chi square test. The effectiveness of the technique on surgery in both groups was compared with an independent sample Student's t test.</p><p><b>RESULTS</b>All laparoscopic splenectomies in both groups were performed successfully. However, 2 cases in the non-CDFI group were converted to LS with the assistance of micro-incision because the branches of the splenic vein were inadvertently torn. Two anatomic types of splenic pedicle and four different adjacent relationships between the splenic vessel and pancreas were detected by CDFI. About 80% of spleens fit the criteria of megalosplenia. There were no statistically significant differences between the constituent ratios of the parameters by CDFI and those by intraoperative telerecording in the CDFI group (chi(2) = 0.383, 1.072, 0.119, P = 0.536, 0.784, 0.730). However, statistically significant differences were observed in the operative time ((158.70 +/- 42.51) minutes vs (200.65 +/- 47.89) minutes, P = 0.003), intraoperative blood loss ((55.87 +/- 17.36) ml vs (101.83 +/- 62.21) ml, P = 0.001), and recovery time of gastrointestinal function ((24.39 +/- 8.88) hours vs (30.60 +/- 9.45) hours, P = 0.024) between the groups.</p><p><b>CONCLUSIONS</b>The individual operative route and schedule can be successfully determined on the basis of various kinds of reproducible anatomic frameworks of the spleen provided by preoperative CDFI. This technique facilitates the surgical procedure, shortens the operative time, reduces intraoperative blood loss and decreases the risk of LS in splenomegaly cases.</p>

Factors of Serumal Estrogen Increasing in Infant with Hemangiomas and Its Relationship with Tumors' Proliferation / 实用儿科临床杂志

Objective To explore the factors of high level of serum estradiol(E2)in infant with hemangiomas and its relationship with tumors' proliferation.Methods The levels of serumal estradiol of 25 proliferative hemangiomas and 15 oblique inguinal hernias with same ages 1 day preoperation and 3 days postoperation were tested by chemiluminescence enzymatic immune method.The expressions of estrogen receptors(ER)in 25 tumors and 15 normal skin tissue were tested by immunohistochemical method.Results The levels of E2 of preoperation were ob-viously higher than that of postoperation in hemangiomas and control group(Pa0.05).The expression of ER in tumors was significantly higher than that in normal skin tissue(P

Pingyangmycin Treating Infantile Proliferating Capillary Hemangiomas in 30 Children / 实用儿科临床杂志

Objective To explore the microcosmic mechanism of pingyangmycin treating infantile proliferating capillary hemangiomas so as to find the optimal method for hemangiomas′ treatment.Methods Sixty samples of infantile proliferating hemangiomas were divided into control group(30 cases,aged from 2 days to 6 months) and experimental group(30 cases,aged from 2 to 6 months).Pingyangmycin was made into emulsion and smeared on the surfaces of the leision in experimental group with 3 times every day as well as only matrix in control group.The specimens were resected on d7,then made into pathological slices and electron microscope slices in order to observe the cells microcosmic structure changes and ultrastructure changes.Furthermore,the apoptotic indexes of two groups were detected by the molecular biology method(TUNEL test).Results The number of apoptotic cells were lower in control group(apoptotic index 18.87?13.67)but higher apparently in experimental group(apoptotic index 29.52?15.33).The difference between two groups was significant(t=2.842 P

Pingyangmycin emulsion inducing apoptosis in infantile proliferating capillary hemangiomas / 中华整形外科杂志

<p><b>OBJECTIVE</b>To insight whether PYM emulsion induces apoptosis more rapidly in proliferating capillary hemangiomas so as to find the optimal method for hemangiomas' treatment.</p><p><b>METHODS</b>Thirty volunteers of infantile proliferating hemangiomas were divided into control group (15 cases) and mediational group (15 cases). PYM was made into emulsion and smeared on the surfaces of the lesion in mediational group with 3 times every day as well as only matrix in control group. The specimens were resected on day 7, then made into pathological slices and electron microscope slices in order to observe the cells microcosmic structure changes and ultrastructure changes. Furthermore , the apoptotic index of two groups were detected by the molecular biology method (TUNEL test ).</p><p><b>RESULTS</b>The number of apoptotic cells were lower in control group (AI 9.693 +/- 4.948) but higher apparently in mediational group (AI 39.373 +/- 15.927). The difference between two groups was significant (t = 6.893, P < 0.01) .</p><p><b>CONCLUSIONS</b>PYM emulsion can effectively accelerate apoptosis in infantile proliferating capillary hemangiomas . The mechanism is supposed to related to the blockage of cell cycle and activation of apoptotic signal transduction pathway.</p>

A seven-year follow-up analysis on prognosis factors of stroke patients / 中华流行病学杂志

<p><b>OBJECTIVE</b>To describe survival conditions of patients with stroke and to analyze the factors associated with survival, a seven-year follow-up study was carried out.</p><p><b>METHODS</b>From Nov. 1995 to Dec. 1996, 189 stroke patients were selected in the Department of Neurology, General Hospital, Tianjin Medical University. Cases were followed up since the onset of stroke. Data collected would include case history, illness and survival conditions. Kaplan-Meier methods were used for survival description. Cox regression was used for prognostic factors analyses.</p><p><b>RESULTS</b>A total number of 82 patients had been dead during the period of study and among them,58 cases died from stroke. The survival rate was 79.86% in one year, 65.46% in three years and 57.46% in seven years. Factors with statistical significance that associated with survival would include: age (RR = 1.065, P < 0.001), physical exercises before stroke (RR = 0.308, P<0.001), hypertension history (RR = 1.785, P < 0.05) and stroke history (RR =2.493, P < 0.001) while factors associated with severity of the illness were: area of cerebral lesion, conditions when discharged from the hospital, rehabilitative treatment of post-discharge and recurrence. We also found that social-psychical factors as rehabilitative confidence, repression, negative event, support from relatives and friends were related to survival of stroke.</p><p><b>CONCLUSIONS</b>Histories on hypertension, stroke and brain injury condition were related to the rate survival on stroke. Patients persisting physical exercises before stroke had better prognosis. The survival rate of patients with recurrence was lower than those without while social psychic factors might be related to survival.</p>

Risk factors of lung cancer in Tianjin / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the risk factors of lung cancer in Tianjin and to provide evidence for further monitor there of.</p><p><b>METHODS</b>A case-control study involving interviews with 193 new cases and 259 controls aged 30 - 76 years was carried out. Structured questionnaires were used to collect information on general condition, living environment, living style, disease and family history, etc. Logistic regression model univariate and multivariate analysis were used to pick out the significant lung cancer risk factors.</p><p><b>RESULTS</b>By monovariate analysis, risk factors such as smoking, passive smoking, drinking, history of malignancy in family and occupation were found. By multivariate analysis, smoking, passive smoking, higher body mass index (BMI) and average income and living space per capita ten years earlier were ascertained, their operations research (OR) values were 3.302, 1.193, 1.003, 1.067 and 0.913.</p><p><b>CONCLUSION</b>Smoking and passive smoking are independent risk factors of lung cancer. Monthly income per person and living space per person 10 years earlier are associated with elevated risk of lung cancer. Higher body mass index has protective effects on lung cancer risk.</p>