大豆异黄酮对MMTV-erbB-2 转基因小鼠乳腺肿瘤中MMP-2 和TIMP-2 表达影响的研究

目的:利用MMTV-erbB-2转基因小鼠,探讨食物中大豆异黄酮对MMTV-erbB-2转基因小鼠乳腺肿瘤发生发展的影响。方法:选择健康雌性MMTV-erbB-2转基因小鼠60只,随机分为实验组(自鼠龄四周起喂养含有大豆异黄酮的豆饲料和对照组(喂养不含大豆异黄酮的普通饲料)。观察两组小鼠生长情况,观察各组小鼠乳腺肿瘤的发病率和潜伏期、记录肿瘤生长情况,并通过HE染色观察其病理类型,免疫组织化学染色SP法检测各组小鼠乳腺癌组织及正常乳腺组织中MMP-2和TIMP-2的表达并分析其关系。结果:豆饲料干预组,普通饲料干预组小鼠乳腺肿瘤的发瘤率分别为36.7%,66.7%,豆饲料干预组小鼠乳腺肿瘤发瘤率与对照饲料干预组相比明显降低,差异有统计学意义(P<0.05)。小鼠肿瘤多生长在第2-3对乳腺上,两组小鼠乳腺肿瘤最大平均直径及潜伏期相比较差异无统计学意义。两实验组小鼠乳腺肿瘤组织经HE染色后全部确定为乳腺癌组织。两实验组小鼠乳腺肿瘤组织中MMP-2和TIMP-2表达均高于正常乳腺组织,差异有统计学意义(P<0.05),MMP-2和TIMP-2在乳腺肿瘤组织中表达呈负相关,在正常乳腺组织中表达无相关性。MMP-2在豆饲料干预组,普通饲料干预组小鼠乳腺肿瘤组织中的阳性率分别为83.3%,73.9%,各实验组阳性率相比较差异无统计学意义(P=0.888);TIMP-2在豆饲料干预组,普通饲料干预组小鼠乳腺肿瘤组织中的阳性率分别为33.3%,43.5%,各实验组阳性率相比较差异无统计学意义。结论:大豆异黄酮能抑制MMTV-erbB-2转基因小鼠乳腺肿瘤的发生,但其对小鼠乳腺肿瘤的作用与MMP-2及TIMP-2的表达无明显相关,具体机制尚待进一步研究。     

Effect of ALS or ATS administration on tumor formation in two-stage skin carcinogenesis

Summary When given during initiation, antithymocyte serum (ATS) increased tumor incidence by 83%, increased the number of tumors per animal from 2.6 to 4.2, and caused a decrease in the latent period to appearance of the first tumor by 27% as compared to animals receiving only 9,10-dimethylbenzo(a)anthracene (DMBA) as initiating agent and phorbolmyristateacetate (TPA) as promotor. The effect of ATS when given during promotion was less pronounced: tumor incidence was increased by 50% and the average number of tumors per animal was 3.1. Antilymphocyte serum (ALS) given during initiation caused an increase in tumor incidence by 33% and the average number of tumors was 3.1 per animal. When ALS was given during promotion the effect on tumor formation was neglibible, i.e., 52 tumors were observed in 21 animals, as against 48 tumors in 18 DMBA/TPA-treated animals.     

地舒单抗联合免疫检查点抑制剂治疗实体瘤骨转移临床疗效及安全性

摘要 目的：探究地舒单抗联合免疫检查点抑制剂治疗实体瘤骨转移临床疗效及安全性。方法：选择2020年7月~2022年11月南通市肿瘤医院收治的60例实体瘤骨转移患者为本次研究对象,分为两组：观察组,n=18,对照组,n=42。对照组开展伊班膦酸+替雷利珠单抗治疗,观察组开展替雷利珠单抗+地舒单抗治疗。比较治疗效果、骨密度水平、骨相关事件、相关指标及安全性。结果：观察组治疗控制率为82.86 %,对照组治疗控制率为54.76 %,观察组更高（P＜0.05）;治疗前,观察组及对照组的右足SOS变化比较无差异（P＞0.05）,治疗后,与治疗前相比,观察组及对照组均升高,且观察组更高（P＜0.05）;观察组骨相关事件发生率为22.22 %,对照组为50.00 %,观察组发生率更低（P＜0.05）;治疗前,匹兹堡睡眠质量指数（PSQI）、焦虑及抑郁自评表（SAS）、（SDS）、日常生活能力评价表（ADL）评分,观察组及对照组比较无差异（P＞0.05）,治疗后,与治疗前比较,观察组及对照组各指标水平均降低,且观察组更低（P＜0.05）;观察组不良反应率为44.44 %,对照组不良反应率为52.38 %,观察组及对照组比较（P＞0.05）。结论：地舒单抗联合免疫检查点抑制剂治疗可有效提升实体瘤骨转移的治疗效果,提升骨密度,降低骨不良事件风险,改善患者心理及生理指标,促进日常生活能力的有效提升,且安全性较高。     

Administration of ethylnitrosourea to neonate hamsters increases growth and frequency of SV40-induced fibrosarcomas

The in vivo interaction between the chemical carcinogen ethylnitrosourea (ENU) and the oncogenic simian virus 40 (SV40) was studied. Inbred newborn Syrian golden hamsters were injected subcutaneously with SV40 (5 x 10(6) plaque-forming units), ENU (0.5% solution, 125 or 25 mg/kg body wt), or equal mixtures of the two. Animals that received SV40 and ENU developed more tumors (100% vs 52%) within a shorter latent period (10 weeks vs 18 weeks) than animals that received SV40 alone. Animals given SV40 and ENU showed increased mortality and increased metastatic tumors (54.2% vs 30.8%) compared with those given SV40 alone. The SV40 and ENU group also exhibited multiple (greater than 10 nodules) pulmonary metastases (33.3% vs 7.7%) and metastases in multiple organs (12.5% vs 0%) compared with animals injected with SV40 alone. No difference in primary tumor size, histology, and SV40 T-antigen content was detected between SV40- and SV40/ENU-induced tumors. Four weeks after SV40 or SV40 plus ENU treatment, animals were challenged intradermally with 2.7 x 10(6) SV40-transformed hamster cells. Five weeks after challenge, 89.5% of the animals treated with SV40 and ENU and 45.4% of animals treated with SV40 developed tumors at the challenge site. Newborn animals given SV40 and ENU developed larger tumors at the challenge site (P less than 0.002) than newborns treated with SV40 alone. Thus, administration of ENU to hamsters during the neonatal stage of development produced a long-lasting systemic effect that enhanced tumor development by transplanted SV40-transformed hamster cells.     

Tumor growth and antibodies after RSV-challenge in normal chickens and in chickens congenitally infected with avian leukosis virus.

Normal chickens and chickens congenitally infected with an avian leukosis virus (ALV) of antigenic subgroup A were challenged with strains of Rous sarcoma virus (RSV) of two different antigenic subgroups (B and C) and tumor induction and growth as well as humoral antibody to viral envelope antigen (VEA) and tumor-specific surface antigen (TSSA) were measured. There was no effect of congenital ALV infection on RSV tumor incidence or latent period but the growth rate and size of the tumors were much higher in congenitally infected birds as compared to controls. Whereas most tumors in the RSV-challenged normal birds regressed, tumors in ALV-infected birds grew progressively. There were no striking differences in the number of birds in either group in the incidence of anti-TSSA or anti-VEA antibodies nor did the presence of either type of antibody reflect the tumor status of the host.     

Modelling of ovarian tumors in rats

The investigation of ovary tumours induced by different methods has revealed their highest frequency (75%) and shortest latent period (4 months) when the ovaries were transplanted into the spleen. The incidence of ovary tumours induced by carcinogens, androgen, subtotal castration and irradiation accounted for 14-28%. Histological picture of the ovary tumours (granulosa cell tumours, granulosa-thecoma, luteoma) was identical in all the experimental groups.     

Antitumor immunologic reactivity in the relatively early period after cryosurgery: Experimental studies in the rat

An experimental investigation was performed on antitumor immunity in the relatively early postoperative period after cryosurgery, using a metastasizing rat's mammary tumor, MRMT-1. Two weeks after its inoculation, surgical excision of the tumor, cryosurgery, surgical excision plus inoculation with freezing-thawing produced vaccine, or surgical excision plus fasting for 72 hr was performed, and postoperative follow-up was done on incidences of metastases, those of metastatic death, etc. Specific immunologic reactivity was examined in the surgical excision (SE) and cryosurgery (CR) groups.The FTV and fasting groups showed more metastatic deaths as compared with the SE group. The CR and SE groups did not differ significantly from each other in incidences of lung and lymph node metastases.Specific footpad reactivity at 2 and 3 weeks after treatment was lower in the CR group than in the SE group.Winn's neutralization assay showed an inhibition of tumor growth at 1 and 3 week(s) after treatment both in the SE and in the CR groups, the inhibitory effect tending to be lower in the latter.Inactivated serum obtained at 1 week after treatment showed a facilitation of tumor growth in the SE group and a tendency of tumor suppression in the CR group, showing a significant difference between them.A mild reduction in antitumor immunity seen in the relatively early postoperative period following cryosurgery probably was not due to a blocking effect by superfluous antigens. Rather it was considered to be due to activation of suppressor cells, consequent on cryosurgical stress, and/or slow and steady absorption of antigens.     

Chloramphenicol and dextramycin, inhibitors of mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene]

In noninbred rats chloramphenicol and its optical isomer dextramycin diminished the blastomogenic effect of 7,12-dimethylbenz(a)anthracene on mammary glands. The protective effect was shown by a decreased tumor incidence at all periods of observation and an increase in the life span of rats and in the case of dextramycin this action consisted in a prolongation of the latent period of tumor emergence.     

Evidence that treatment with vaccinia melanoma cell lysates (VMCL) may improve survival of patients with stage II melanoma

Summary A total of 80 patients with melanoma metastases in regional lymph nodes were treated by i.d. injections with a vaccine prepared from a vaccinia virus-infected allogeneic melanoma cell line; 39 patients have been followed for a 2-year period. Interim results from comparison of the treated group with 151 historical controls treated without the vaccine from September 1978 to December 1981 at the same institution and 56 non-randomized concurrent controls suggest that survival was significantly prolonged in the vaccinated group. At the 2-year period overall survival was 75% in the treated compared to 57% in the historical control group. Subset analysis showed a greater apparent benefit of vaccine therapy among patients who had metastases detected at the time of treatment of the primary melanoma (synchronous metastases), while therapy appeared less effective in patients with metastases detected at some time after treatment of the primary (delayed metastases). In the latter only those with one lymph node appeared to benefit from the treatment whereas in patients with synchronous metastases patients with three or more nodes as well as one node appeared to have improved survival. The survival rates at 2 years for treated patients with synchronous metastases in one, two, three or more lymph nodes was 100%, 83% and 79% respectively compared with that of 82%, 86% and 47% respectively in the equivalent control groups. Survival rates in treated patients with delayed metastases in one, two, three or more lymph nodes was 70%, 70% and 65% compared with 47%, 42% and 35% in the equivalent control groups. Treatment and control groups appeared well matched for a number of known prognostic features, including number and size of involved nodes, sex and thickness of primary tumor. Multivariate analysis indicated the effect of treatment was independent of these factors. Despite the empiricism of this approach the present results suggest that this form of therapy warrants further evaluation in a randomized controlled trial.     

Effect of differential housing in mice on natural killer cell activity, tumor growth, and plasma corticosterone.

Various forms of stress have been shown to alter natural killer (NK) cell activity and tumorigenesis; however, few studies have measured these two variables simultaneously. Isolation of mice was utilized as a model of stress by which to study NK cell activity and pulmonary metastatic response following a tumor challenge. Male C3H mice were group or individually housed for 3 weeks, after which CIRAS 3 fibrosarcoma tumor cells or the tumor vehicle was injected intravenously (tail vein), NK cell activity, pulmonary metastasis, and plasma corticosterone were measured 1, 7, and 21 days following tumor cell inoculation. Individually housed mice, irrespective of tumor or vehicle condition, had a higher NK response on Day 1 relative to group-housed animals (P less than 0.001). By Day 21, tumor condition, rather than housing, was the major significant factor affecting NK activity (P less than 0.001). Nevertheless, individually housed, tumor-injected mice still had higher NK activity compared with the other treatment groups on Day 21. No effect of housing condition was present for the incidence of pulmonary metastases or frequency of metastases in affected animals. Plasma corticosterone levels generally increased over the study period, with no housing or injection effects at Days 1 and 7. Individually housed, vehicle-injected mice had higher corticosterone levels at Day 21 (P less than 0.01). These data suggest that in response to housing condition, NK cell activity differs in tumor-bearing mice and vehicle controls. Furthermore, CIRAS 3 pulmonary tumor formation is not affected by differences in NK activity consequent to housing condition. Plasma corticosterone does not appear to be a major in vivo regulator of NK activity in this experimental tumor system. Finally, the interpretation of housing effects on NK activity and plasma corticosterone levels depends on the temporal window in which sampling occurs.     

Late appearance of resistance to tumor rechallenge following cryosurgery: A study in an experimental mammary tumor of the rat

Resistance to tumor challenge following surgical and cryosurgical eradication of the tumor was studied, using an experimental mammary tumor of the rat, MRMT-1. It was revealed that rejection rate of the challenged tumor increased gradually following cryosurgery and reached its peak at 10 weeks after cryosurgery. No such phenomenon was observed after surgical excision of the tumor. Decreased incidence of lymph node metastases and decreased tumor weights in “take” cases also suggested an increased immunological activity against the tumor at 10 weeks after cryosurgery.     

Evaluation of adjuvant chemotherapy in patients with colorectal cancer in Primorsko-Goranska and Istarska County--a twenty years retrospective study

Colorectal cancer is the second most common malignant disease in developed countries, with about one million new cases worldwide every year, accompanied with high mortality rate. We examined the survival rate and recurrence (occurrence of distant metastases and/or local recurrence) of patients with colorectal cancer in Primorsko-Goranska and Istarska County who received adjuvant chemotherapy, compared to those who did not in the period since 1980. until 1999. This study involves 483 patients with colorectal cancer stages II and III of Primorsko-Goranska and Istarska County, which were underwent curative resections of colorectal cancer at the Clinical Hospital Centre Rijeka, and then treated with chemotherapy (288) or without Chemotherapy (195). We analyzed the five year survival rate and the recurrence of malignant disease in the adjuvant treatment group in comparison with not treated group with chemotherapy, depending on the stage of disease, degree of histological differentiation, patient age and location of cancer (colon or rectum). After follow-up of 60 months died 44.79% (129/288) of patients who received chemotherapy and 53.33% (104/195) of patients who did not receive chemotherapy. The relative risk of death (from any cause) in chemotherapy-treated group versus the group without chemotherapy was 0.82 (p < 0.008). Recurrence of malignant disease in the chemotherapy group was 38.54% (111/288), and in the group without chemotherapy was 46.15% (90/195). The relative risk of recurrence of malignant disease in the chemotherapy group versus the group without chemotherapy was 0.78 (p < 0.001). There was no difference in treatment efficacy regard to the localization of the tumor, but there were differences in efficiency with respect to disease stage, grade and age. Chemotherapy with 5-fluorouracil and leukovorin ameliorate the survival and reduces recurrence and distant metastases in patients with colorectal cancer stages II and III.     

Adjuvant liver perfusion in colorectal cancer: initial results of a clinical trial.

Fifty consecutive patients with colorectal cancer but no evidence of secondary deposits in the liver were included in an ongoing controlled clinical trial of adjuvant liver perfusion aimed at reducing the incidence of hepatic metastases. All patients had their primary tumour resected in the standard way. Twenty-six of the patients served as controls, and 24 received fluorouracil, 1 g daily, as a continuous infusion into the portal venous system during the first seven days after operation. The patients were matched for age, sex, and site and stage of the disease. The immediate postoperative mortality and morbidity did not differ significantly between the two groups. During the follow-up period (mean duration 15.5 months), however, six deaths occurred in the control group and only one in the perfusion group. At necropsy four of the controls had multiple liver metastases. Two of the surviving controls developed evidence of liver metastases, and two had a local recurrence. No patient in the perfusion group developed evidence of hepatic metastases. These initial results suggest that adjuvant portal venous perfusion with fluorouracil may reduce the incidence of liver metastases in colorectal cancer.     

唑来膦酸延缓骨转移癌放射治疗的临床研究

目的以帕米膦酸二钠为对照,研究唑来膦酸对延缓骨转移癌放射治疗事件发生的临床疗效。方法对118例骨转移癌患者,随机分为病例组60例,对照组58例,以疼痛持续加重,X线或CT证实骨转移病灶进展或有可能导致病理性骨折而行放射治疗为观察终点,研究唑来膦酸延缓骨转移癌放射治疗事件出现时间的临床疗效。结果近期止痛有效率和获益率在唑来膦酸组分别为55.36%,65.18%;帕米膦酸组为35.19%,44.44%,P<0.05;放疗事件发生率在唑来膦酸组为34.21%,帕米膦酸钠组为54.28%,P>0.05;发生放疗事件中位时间在唑来膦酸组为121天,帕米膦酸钠组为189天,P=0.041。结论唑来膦酸近期止痛的临床有效率、获益率和总体骨相关事件(SRE)危险性降低的比例均高于帕米膦酸二钠。     

神经导航下经胼胝体-穹窿间入路切除丘脑胶质瘤的临床应用价值分析

目的:探讨神经导航系统辅助下经胼胝体-穹窿间入路手术切除丘脑胶质瘤的临床应用价值。方法:选择2016年2月至2018年9月我院收治的丘脑胶质瘤患者60例为研究对象,以其中采用神经导航系统辅助下的经胼胝体-穹隆间入路显微切除丘脑胶质瘤的30例患者作为实验组,另外30例采用常规手术切除的患者作为对照组。分析和比较两组手术情况、治疗效果及并发症的发生情况。结果:治疗后,实验组手术时间、住院时间均比对照组明显缩短,术中出血量及术中引流量显著少于对照组(均P0.05);实验组肿瘤全切除率高于对照组,次全切除率及部分切除率均低于对照组(P0.05);实验组并发症发生率(20.0%)显著低于对照组(53.3%)(P0.05)。结论:与常规手术相比,神经导航系统辅助下经胼胝体-穹窿间入路切除丘脑胶质瘤能显著缩短手术时间,减少术中出血量及术后引流量,显著提高丘脑肿瘤全切除率,并降低术后并发症的发生率。     

The induction of liver tumors by 239Pu citrate or 239PuO2 particles in the Chinese hamster

The influence of radiation dose distribution on the frequency of 239Pu-induced liver tumors was evaluated in the Chinese hamster. Different concentrations of 239Pu citrate 239PuO2 particles of known sizes were injected intravenously via the jugular vein. About 60% of the injected 239Pu citrate was deposited in the liver and 40% in the bone. The 239Pu citrate was rather uniformly distributed throughout the liver parenchyma. Injected plutonium oxide particles were taken up by the reticuloendothelial system with 90% of the body burden deposited in the liver. The 239PuO2 particles were localized in the Kupffer cells and produced nonuniform dose distributions that were dependent on particle size. There was an activity- and dose-dependent increase in the incidence of total liver parenchymal cell tumors following injection with either plutonium particles or citrate. For animals that received 14.0-, 2.7-, 0.3-, and 0.04-Gy dose to liver from 239Pu citrate the cumulative tumor incidence was 39, 32, 5, and 0%, respectively. Animals that were injected with the 0.24 micron 239PuO2 particles had doses of 42.0, 7.2, and 0.8 Gy to the liver and tumor incidences of 34, 26, and 5%, respectively. Plutonium citrate also produced hemangiosarcomas of the liver and tumors in bone and bone marrow. The latent period for liver tumor appearance in animals exposed to 239Pu citrate or 239PuO2 particles increased as the injected activity decreased. For animals injected with a similar total activity (7.4 Bq/g), the lifetime cumulative liver tumor incidence was similar for animals exposed to either 239Pu citrate (32%) or 239PuO2 (26%). There was little effect of particle size on liver tumor incidence. These data indicate that, in Chinese hamster liver, local radiation dose distribution is less important in altering tumor incidence than injected activity or average dose. However, the more uniform irradiation from 239Pu citrate administration was more effective in cancer production than the nonuniform irradiation from 239PuO2 particles.     

Influence of octreotide and tamoxifen on tumor growth and liver metastasis in N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancer in Syrian hamsters

In prospective clinical trials single octreotide therapy or combined therapy with tamoxifen has improved the quality of life and survival time in patients with pancreatic cancer. In this study we analyzed the influence of octreotide and tamoxifen on tumor growth and liver metastases in chemically induced pancreatic adenocarcinoma in Syrian hamsters. Octreotide alone and the combined therapy (octreotide/tamoxifen) decreased the incidence of macroscopic pancreatic carcinomas as well as the number and size of liver metastases. The combined therapy showed no superior effect to octreotide alone. Furthermore, there was no difference between the tamoxifen and the control group.     

Endobronchial Metastases in Breast Carcinoma

In a consecutive series of 1,628 patients with breast carcinoma, six cases of endobronchial metastases were diagnosed for an incidence of 0.4 percent. The median latent interval from the diagnosis of the primary carcinoma until the time of diagnosis of endobronchial metastases was 21 months. Endobronchial metastases can be the initial manifestation of recurrent cancer and can present with no abnormalities shown on x-ray films of the chest. Because of similar symptomatology, the diagnosis of endobronchial metastases may be confused with a central bronchogenic carcinoma but the histological appearance could differentiate the two entities. Local treatment with radiation therapy is usually inadequate and patients should also be treated with some form of systemic treatment such as chemotherapy. The median survival after the diagnosis of endobronchial metastases was 13 months.     

阿托伐他汀钙片治疗急性冠脉综合征的临床疗效

目的:探讨阿托伐他片汀治疗急性冠脉综合征(ACS)的临床疗效。方法:选择2013年3月至2013年12月我院收治的156例ACS患者,按随机字数表法分为实验组和对照组各78例,两组均采取常规治疗,实验组在此基础上加用阿托伐他汀钙片,对照组则用辛伐他汀滴丸。对比两组治疗效果及心血管事件发生率。结果:两组治疗后总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、血清高敏C反应蛋白(hs-CRP)、纤维蛋白原(Fg)和尿酸水平均明显下降,且实验组下降更明显,比较差异均有统计学意义(P0.05);治疗期间实验组心血管事件发生率率为8.97%(7/78),显著低于对照组的24.36%(19/78),比较差异均有统计学意义(P0.05)。结论:阿托伐他汀片治疗ACS的临床效果优于辛伐他汀滴丸,能有效降低心血管事件的发生,值得的临床推广。     

Direct evidence for the role of LGL in the inhibition of experimental tumor metastases

The role of NK cells in the control of the metastatic spread of tumor cells was studied. Rats pretreated with rabbit anti-asialo GM1 (anti-asGM1) serum exhibited a diminished ability to destroy circulating MADB106 mammary adenocarcinoma cells, which in turn caused an increased incidence of experimental pulmonary metastasis. The anti-asGM1 treatment caused a selective inhibition of NK activity without detectable effect on T cell-mediated immunity, and overall had no effect on the cytotoxic activity or numbers of alveolar macrophages (alv.M phi) or monocytes. The suggestion of a role for NK cells in resistance to metastases from the MADB106 tumor cells was confirmed by the adoptive transfer of 5 X 10(6) highly purified large granular lymphocytes (LGL) into NK-depressed animals 2 hr before tumor challenge. This transfer of LGL, highly enriched in NK activity, partially or fully restored the ability of these rats to inhibit the development of pulmonary metastases. This ability to adoptively transfer resistance to metastases appeared to be confined to the LGL population, because transfer of the same number of mature peripheral blood T cells had no effect on tumor development. These results provide the first unequivocal evidence that LGL, with high NK activity, are involved in in vivo resistance to tumors, particularly in the elimination of potentially metastatic tumor cells from the circulation and capillary beds.