G-CSP基因治疗对大剂量化疗后结肠癌小鼠中性粒细胞数量和功能的影响

中性粒细胞作为一种重要效应细胞在机体抗肿瘤过程中发挥重要的作用。为了探讨G-CSF基因治疗及大剂量化疗后对荷瘤小鼠中性粒细胞的影响以及G-CSF基因治疗后中性粒细胞在抗肿瘤中所起的作用,我们对G-CSF基因治疗后荷瘤小鼠中性粒细胞的数量和功能进行了研究。结果发现,G-CSF基因治疗与重组G-CSF(rhG-CSF)注射疗法相比,能更明显地提高结肠癌小鼠中性粒细胞的数量、中性粒细胞的吞噬功能、杀伤C-26细胞的活性以及分泌IL-1、TNF、NO水平。对大剂量化疗后的结肠癌小鼠,仍能明显提高中性粒细胞数量、吞噬功能、杀伤C-26结肠癌细胞的活性以及分泌IL-1、TNF、NO水平。表明G-CSF基因治疗比rhG-CSF注射疗法更有效地纠正并提高由于大剂量化疗后引起的外周血中性粒细胞的降低,增强中性粒细胞的杀伤活性,促进中性粒细胞分泌IL-1等细胞因子,发挥直接或间接的抗肿瘤作用。     

G-CSF基因治疗对大剂量化疗后结肠癌小鼠中性粒细胞数量和功能的影响

中性粒细胞作为一种重要效应细胞在机体抗肿瘤过程中发挥重要的作用。为了探讨G-CSF基因治疗及大剂量化疗后对荷瘤小鼠中性粒细胞的影响以及G-CSF基因治疗后中性粒细胞在抗肿瘤中所起的作用．我们对G-CSF基因治疗后荷瘤小鼠中性粒细胞的数量和功能进行了研究。结果发现．G-CSF基因治疗与重组G-CSF(rhG-CSF)注射疗法相比．能更明显地提高结肠癌小鼠中性粒细胞的数量、中性粒细胞的吞噬功能、杀伤C-26细胞的活性以及分泌IL-1、TNF、NO水平。对大剂量化疗后的结肠癌小鼠．仍能明显提高中性粒细胞数量、吞噬功能、杀伤C-26结肠癌细胞的活性以及分泌IL-l、TNF、NO水平。表明G-CSF基因治疗比rhG-CSF注射疗法更有效地纠正并提高由于大剂量化疗后引起的外周血中性粒细胞的降低．增强中性粒细胞的杀伤活性．促进中性粒细胞分泌IL-1等细胞因子．发挥直接或间接的抗肿瘤作用。     

联合自杀基因与IL-2基因转移疗法的抗肿瘤效果及其抗肿瘤免疫应答的诱导作用

单用自杀基因疗法或单用细胞因子基因疗法抗肿瘤效果不理想,本研究中我们观察了大肠杆菌胞嘧啶脱胺酶(CD)基因与白细胞介素2(IL-2)基因联合转移对荷瘤小鼠的治疗效果及其对抗肿瘤免疫的诱导作用。复制荷瘤小鼠模型后在荷瘤部位注射表达CD基因的重组腺病毒(AdCD)及表达小鼠IL-2基因的重组腺病毒(AdIL2),并连续10天、每天1次腹腔注射5氟胞嘧啶(5FC)对荷瘤小鼠进行治疗。结果表明,AdCD/5FC/AdIL2联合基因治疗能显著抑制荷瘤小鼠皮下肿瘤的生长,并明显延长其生存期(P<0.01)。联合基因治疗组小鼠肿瘤细胞发生明显的坏死,瘤内及瘤周有大量的炎性细胞浸润,瘤内CD4~ 和CD8~ T细胞明显增加,脾细胞NK和CIL杀伤活性明显高于单用AdCD/5FC、对照病毒AdLacZ/5FC或PBS组。实验结果表明,联合应用自杀基因与细胞因子基因治疗可更有效诱导机体的抗肿瘤免疫反应,从而更显著地抑制荷瘤小鼠肿瘤的生长。     

单克隆抗体MGb2和LAK细胞的协同抗胃癌作用

本研究探讨了成纤维细胞介导的G-CSF基因疗法联合应用IL-2基因疗法及时对小鼠I期肾癌的治疗作用。经NIH3T3-IL-2基困疗法．NIH3T3-G-CSF基因疗法单独治疗后的荷瘤小鼠存话期明显延长，而经以上两者联合治疗后的荷癌小鼠存活期的延长更为明显，且有75％荷瘤小鼠长期存活。对经G-CSF基因疗法及IL-2基因疗法联合治疗后的荷瘤小鼠体内抗肿瘤免疫功能的检测表明，经治疗后第14天，荷瘤小鼠睥脏明显增大，睥脏淋巴细胞数量明显增多；肿瘤局部的常规病理检查可见数量较多的嗜酸性粒细胞浸润。荷瘤小鼠睥细胞NK活性、经诱导后的LAK话性及CTL，杀伤活性均明显升高，小鼠腹腔巨噬细胞杀伤活性在NIH3T3-IL-2基因疗法治疗组升高．而在NIH3T3-G-CSF基因疗法组未见明显升高。以上结果表明．联合应用成纤维细胞介导的G-CSF基因疗法与IL-2基因疗法可因对小鼠体内抗肿瘤免疫功能的联合增强作用而取得更佳的抗肿瘤效果。     

重组腺病毒介导γ-干扰素基因对小鼠结肠癌腹腔转移模型的实验治疗作用

背景与目的：肿瘤细胞靶向的细胞因子基因治疗是肿瘤治疗领域的研究热点。γ干扰素通过多种机制发挥抗肿瘤免疫的作用。本研究探讨利用γ-干扰素（IFN-γ）基因治疗对大肠癌的预防和治疗作用。方法：利用BALB／C小鼠成瘤的小鼠结肠癌CT26细胞株制备小鼠结肠癌腹腔转移瘤模型，用携带鼠IFN-γ基因的重组缺陷型腺病毒AdIFN-γ进行治疗，同时利用携带LacZ（β—galactosidase）基因的腺病毒AdLacZ和PBS（phosphate—buffered saline）作空白对照，检测经基因治疗后小鼠体内IFN-γ基因的表达情况、脾脏的细胞毒性T淋巴细胞（CTL）活性变化、肝转移的发生及荷瘤小鼠的生存期。结果：经IFN-γ基因治疗后，与对照组相比，治疗组小鼠血清中IFN-γ表达量明显增加（P〈0．01），脾脏的CTL活性明显增强（P〈0．05），肿瘤生长受到抑制，肝转移的发生率明显下降，荷瘤小鼠的存活期明显延长。结论：利用IFN-γ基因治疗大肠癌具有明显的疗效，并对其肝转移具有一定的预防作用。     

重组腺病毒抗小鼠移植瘤生长

目的:研究携带细胞因子基因hIL-2、hTNF-a的重组腺病毒对小鼠移植瘤生长抑制作用。方法:将分别携带有hIL-2基因、hTNF-a基因的重组腺病毒感染人肺腺癌Anip973细胞系,应用ELISA试剂盒检测转染后的细胞IL-2、TNF-α的分泌量;通过肿瘤局部注射重组腺病毒的方法观察其在小鼠体内的抗肿瘤作用。结果:转基因的肿瘤细胞生长能力、克隆形成率等无明显变化。24h细胞培养上清IL-2的分泌量为50pg/2×105细胞,TNF-α的分泌量为20pg/2×105细胞。体内实验表明注射重组腺病毒后小鼠肿瘤生长缓慢,体积明显小于对照组(P<0.05),存活期显著延长。结论:瘤内注射重组腺病毒具有明显抗肿瘤作用。     

联合应用成纤维细胞介导的G-CSF基因疗法及IL-2基因疗法对肿瘤的治疗作用

本实验观察了成纤维细胞介导的G-CSF基因疗法对大剂量化疗后造血功能损伤小鼠的恢复作用。结果发现:接受G-CSF基因治疗的实验小鼠外周血白细胞尤其是中性粒细胞降低程度明显减弱,恢复速度明显加快;并可明显促进血小板的恢复,但作用较缓;其脾脏和骨髓CFU-GM、CFU-MK、CFU-S水平显著地高于对照组,表明成纤维细胞介导的G-CSF基因疗法可显著降低大剂量化疗后造血损伤程度,并明显加速受损的造血功能的恢复。     

A-LAK/IL-2局部应用抗肿瘤作用的研究

目的观察A-LAK和NA-LAK的体外生长与增殖,研究A-LAK/IL-2局部注射的体内抗肿瘤作用.方法绘制A-LAK和NA-LAK生长曲线.小鼠体内作A-LAK/IL-2抗肿瘤治疗实验.结果A-LAK在培养第10天时达到增殖高峰增加16.08倍,而NA-LAK增殖高峰在第7天仅增加3.36倍.体内实验表明,A-LAK/IL-2肿瘤旁局部注射与全身应用相比,能明显抑制肿瘤生长,延长动物存活期(P＜0.05).结论A-LAK具有增殖倍数高,抗瘤活性强的特点,局部注射是强于静脉给药的给药途径.     

腺病毒介导的胞嘧啶脱氨酶自杀基因联合IL-2基因疗法的肿瘤治疗作用及免疫机理分析

目的以腺病毒作为载体，将大肠杆菌胞嘧啶脱氨酶（ＣＤ）基因与小鼠ＩＬ－２基因联合转移，研究其体内抗肿瘤作用及免疫机理。方法小鼠皮下接种黑色素瘤Ｂ１６Ｆ１０细胞后３天，肿瘤局部注射表达ＩＬ－２的重组腺病毒ＡｄＩＬ－２和表达ＣＤ的重组腺病毒ＡｄＣＤ，然后连续１０天给予５－氟胞嘧啶（５－Ｆｃ）３００ｍｇ／ｋｇ进行治疗。结果联合治疗组荷瘤小鼠皮下肿瘤结节的生长明显受到抑制，小鼠存活期明显长于ＡｄＩＬ－２、ＡｄＣＤ／５－Ｆｃ、ＡｄｌａｃＺ／５－Ｆｃ或ＰＢＳ组。经联合治疗后，小鼠脾细胞的ＮＫ活性和ＣＴＬ杀伤活性明显增强；肿瘤瘤体内ＣＤ４、ＣＤ８细胞浸润增加；肿瘤细胞表达Ｈ－２Ｋｂ和Ｂ７－１分子明显增加。结论联合应用自杀基因和ＩＬ－２基因治疗，一方面可以明显抑制荷瘤小鼠肿瘤生长，另一方面可以提高机体对肿瘤细胞免疫应答，增加机体的抗肿瘤作用，是肿瘤基因治疗中一条行之有效的途径。     

5-FC/CD 自杀基因疗法结合热休克蛋白-多肽复合物瘤苗治疗小鼠黑色素瘤的研究

 目的　研究 5 -氟尿嘧啶 /胞嘧啶脱氨酶 (5 FC/ CD)基因疗法与热休克蛋白 -多肽复合物 (HSP- PC)瘤苗免疫疗法联合抗肿瘤效果。方法　将携带 CD基因的重组腺病毒注射到小鼠黑色素瘤体内 ,腹腔注射 5 - FC,同时皮下接种 HSP70 - PC。结果　经联合治疗后 ,70 %荷瘤小鼠肿瘤体积缩小、消退 ,小鼠存活期延长 ,肿瘤组织明显坏死 ,炎症细胞、CD+4 及 CD+8T细胞浸润明显。结论5 - FC/ CD基因疗法结合 HSP- PC瘤苗免疫疗法抗小鼠黑色素瘤作用显著 ,具有临床应用前景。     

Lifestyle Factors Including Diet and Leukemia Development: a Case-Control Study from Mumbai,India

In India, among males, leukemia rates vary across the country. The present unmatched hospital-based casecontrolstudy conducted at Tata Memorial Hospital included subjects registered between the years 1997-99.There were 246 leukemia cases and 1,383 normal controls. Data on demographics, lifestyle, diet and occupationhistory were recorded. Cigarette (OR=2.1) and bidi smoking (OR=3.4) showed excess risk for leukemia. Oddsratios were 3.9 for fish-eaters, 0.40 for chilli eaters, 1.5 for milk drinkers and 0.60 for coffee drinkers, comparedto non-drinkers/eaters. However, neither exposure to use of pesticides nor cotton dust showed any excess riskfor leukemia.     

Malignant Neoplasm Prevalence in the Aktobe Region of Kazakhstan

An oncopathological state assessment was conducted among adults, children and teenagers in Aktobe region for 2004-2013. Overall the burden of mortality was in the range of 94.8-100.2 per 100,000 population, without any obvious trend over time. Ranking by pathology, the highest incidences among women were registered for breast cancer (5.8-8.4), cervix uteri (2.9-4.6), ovary (2.4-3.6) and corpus uteri, stomach, esophagus, without any marked change over time except for a slight rise in cervical cancer rates. In males, the first place in rank was trachea, bronchus and lung, followed by stomach and esophagus, which are followed by bladder, lymphoid and hematopoietic tissues pathology. Agian no clear trends were apparent over time. In children, main localizations in cancer incidence blood (acute lymphocytic leukemia, lymphosarcoma, acute myeloid leukemia, Hodgkin’s disease), brain and central nervous system, bones and articular cartilages, kidneys, and eye and it’s appendages, in both sexes. Similarly, in young adults, the major percentage was in blood and lymphatic tissues (acute myeloid leukemia, acute lymphocytic leukemia, Hodgkin’s disease) a significant percentage accruing to lymphosarcoma, lymphoma, other myeloid leukemia and hematological malignancies as well as tumors of brain and central nervous system, bones and articular cartilages. This initial survey provides the basis for more detailed investigation of cancer epidemiology in Aktobe, Kazakhstan.     

Estimation of the Projections of the Incidence Rates,Mortality and Prevalence Due to Common Cancer Site in Isfahan,Iran

Background: Accurate statistics on the cancer burden are essential, both for purposes of research and forsetting priorities in healthcare management. So that in vast countries with partial registration coverage, suchas Iran, local data are more useful. We here estimated the incidence, prevalence and mortality time trend offour major cancer site, lung, stomach, breast and prostate, over the period 2001-2010 and provided short-rangeprojections to 2015 in Isfahan. Materials and Methods: Estimates were derived by applying the mortality-incidenceanalysis method, a back-calculation approach to estimate and project incidence, prevalence and mortality ofchronic degenerative disease, starting from knowledge of mortality and relative survival information. Results:Age adjusted incidence, mortality and prevalence rates in Isfahan exhibited a clear upward trend for all four sitesduring the period 2001-2015, with marked increasees in prostate and breast predicted for the future. Differencein incidence trends between males and females might be attributable to the difference in risk factors specificto certain cancer sites, with smoking being the main risk factor. Conclusions: In this study, males and femalesdisplayed an increasing pattern for incidence and mortality rate over the entire study period until 2015. Thisinformation can be used as basis for planning healthcare management and allocating recourses in public health.     

Costing of a State-Wide Population Based Cancer Awareness and Early Detection Campaign in a 2.67 Million Population of Punjab State in Northern India

Background: Punjab state is particularly reporting a rising burden of cancer. A ‘door to door cancer awareness and early detection campaign’ was therefore launched in the Punjab covering about 2.67 million population, wherein after initial training accredited social health activists (ASHAs) and other health staff conducted a survey for early detection of cancer cases based on a twelve point clinical algorithm. Objective: To ascertain unit cost for undertaking a population-based cancer awareness and early detection campaign. Materials and Methods: Data were collected using bottom-up costing methods. Full economic costs of implementing the campaign from the health system perspective were calculated. Options to meet the likely demand for project activities were further evaluated to examine their worth from the point of view of long-term sustainability. Results: The campaign covered 97% of the state population. A total of 24,659 cases were suspected to have cancer and were referred to health facilities. At the state level, incidence and prevalence of cancer were found to be 90 and 216 per 100,000, respectively. Full economic cost of implementing the campaign in pilot district was USD 117,524. However, the financial cost was approximately USD 6,301. Start-up phase of campaign was more resource intensive (63% of total) than the implementation phase. The economic cost per person contacted and suspected by clinical algorithm was found to be USD 0.20 and USD 40 respectively. Cost per confirmed case under the campaign was 7,043 USD. Conclusions: The campaign was able to screen a reasonably large population. High to high economic cost points towards the fact that the opportunity cost of campaign put a significant burden on health system and other programs. However, generating awareness and early detection strategy adopted in this campaign seems promising in light of fact that organized screening is not in place in India and in many developing countries.     

Protective Effect of Tomato Juice Against Mouse Skin Carcinogenesis

The anticarcinogenic effect of tomato juice, a natural source of antioxidants and other chemopreventive /antimutagenic agents, was studied in a skin carcinogenesis model in mice. The possible mode of action was alsoinvestigated. Oral administration of tomato juice afforded protection from development of skin tumour and increasedlife expectancy which may be attributed to the combined action of a number of chemical compounds with cancerchemopreventive properties present in tomato. The protective role may be associated with a decreased level of lipidperoxides noted in the tomato treated group and modulation of host detoxification enzymes. Exposure to the carcinogenresulted in a depression of the liver enzymes- glutathione-S-transferase (GST), glutathione peroxidase (GPx) andsuperoxide dismutase (SOD). Oral administration of tomato juice resulted in significant activation of all these enzymes(p<0.001). These results suggest a preventive role of tomato juice during carcinogenesis which is mediated possiblyby their modulatory effects on biotransformation enzymes and the detoxification system of the host.     

Awareness of cervical cancer and HPV vaccination and its affordability among rural folks in Penang Malaysia

Introduction: As the second most common cancer in women worldwide, cervical cancer causes major health and economic burdens. Recent introduction of HPV immunization program locally has been encouraging but vaccine uptake remains poor. In addition, no study has been conducted to explore the people’s awareness and knowledge on cervical cancer, HPV and its vaccine in a rural setting in Malaysia after the inception of the HPV vaccination program. Objective: This study was conducted to determine the awareness of cervical cancer, HPV vaccination and its affordability among people in a rural area in Malaysia. Method: A cross-sectional study was conducted among 116 participants in a village in Penang. All consenting female villagers aged 13 years and above, and males who were married were interviewed using a questionnaire. Results: Most participants (88.8%) had heard of cervical cancer, however only 29.3% and 42.2% of them had heard of HPV and HPV vaccination respectively. Only 5.2% knew the actual market price for the vaccine. They were willing to pay an average of RM 96.7 (USD $27.7) for the full course of vaccination if it is not given to them for free, whereas the market price is RM1200 (USD $342.85). Conclusion: Awareness among the Malaysian population in a rural setting on HPV and HPV vaccination is low. Educating the public on the infection can help control the illness. Cost of the HPV vaccine is a serious barrier to the success of the vaccination program in Malaysia.     

Cancer Incidence and Mortality Data in Aktobe,West Kazakhstan, 2000-2010

The article provides an assessment of the dynamics of cancer incidence and mortality in the territory ofAktobe city for the period 2000-2010. The most common cancers were found in the lungs, stomach, esophagusand breast throughout the period, with slight increase in colon cancer and decrease in esophageal cancer beingapparent. In an attempt to cast light on effects of environmental pollution, the authors also compared data ontotal emissions of chemicals into the air. While preliminary, the findings provide a basic picture of cancer burdenin this industrialised city in Kazakhstan which should be followed up by more comprehensive monitoring.     

Effect of homeopathic medicines on transplanted tumors in mice.

Ultra low doses used in homeopathic medicines are reported to have healing potential for various diseases but their action remains controversial. In this study we have investigated the antitumour and antimetastatic activity of selected homeopathic medicines against transplanted tumours in mice. It was found that Ruta graveolens 200c and Hydrastis canadensis 200c significantly increased the lifespan of Ehrlich Ascites Carcinoma and Dalton's Lymphoma Ascites induced tumour-bearing animals by 49.7%, and 69.4% respectively. Moreover there was 95.6% and 95.8% reduction of solid tumour volume in Ruta 200c and Hydrastis 200c treated animals on the 31st day after tumour inoculation. Hydrastis 1M given orally significantly inhibited the growth of developed solid tumours produced by DLA cells and increased the lifespan of tumour bearing animals. Some 9 out of 15 animals with developed tumors were completely tumour free after treatment with Hydrastis 1M. Significant anti-metastatic activity was also found in B16F-10 melanoma-bearing animals treated with Thuja1M, Hydrastis 1M and Lycopodium1M. This was evident from the inhibition of lung tumour nodule formation, morphological and histopathological analysis of lung and decreased levels of gamma-GT in serum, a cellular marker of proliferation. These findings support that homeopathic preparations of Ruta and Hydrastis have significant antitumour activity. The mechanism of action of these medicines is not known at present.     

Cancer Notification at a Referral Hospital of Kermanshah,Western Iran (2006-2009)

Background: Cancer is a major public health problem and the leading cause of mortality in both males andfemales in developed and developing countries. The incidence of cancer is gender dependent. Among Iranians,it is the third cause of death. Materials and Methods: The information recorded in the files of all patients (7,695individuals) pathologically diagnosed with cancer in Imam Reza referral hospital of Kermanshah University ofMedical Sciences during the four year period of 2006-2009 were reviewed and analyzed using SPSS statisticalsoftware package version 16.0. Results: Around 61.6% of reported cancer cases were males and 38.4% werefemales. The most prevalent reported malignant tumors occurred at the age group of 70-79 years in males andin females these tumors were presented in the ages of 60-69 years. The most prevalent cancers among studiedpatients were gastrointestinal (GI) cancers with a frequency of 22.9% [gastric 10.7%, colorectal 6.9%, andesophageal 6%]. The second, third and forth prevalent cancers were blood at 16.4%, lung 13.5% and bladder12.8%, respectively. In males the cancers of GI (25.6%) were the most prevalent followed in order of frequencyby bladder (18%), blood (17.6%), lung (17.4%) and prostate (6.8%) . In females the most frequent recordedcancer was breast (24.1%) followed in order of frequency by GI (20.5%), blood (14.4%), lung (7.3%), uterus(6.2%) and ovary (5.1%) . Breast cancer was the most prevalent cancer (27%) in the age group of 40-49 years.Conclusions: The present study provides frequency data for various types of cancers in both males and femalesfrom a referral hospital of Kermanshah that are comparable with some reports from other areas of the country.