Possibilities for the spread of alpha-fetoprotein and heterologous antibodies in mother and fetus during transplacental carcinogenesis]

The study of distribution of J125 labelled homologous alpha-fetoproteins (AFP) and heterologous antibodies (anti-AFP) in rats indicated some differences in the level of radioactivity of organs and tissues in animals, depending on age, especially in kidneys and large intestine. In normal pregnancy AFP passes through the placenta in both directions, but in rather less relative amounts from the fetus to mother. No labelled AFP was found in the amniotic fluid of fetuses 5 hours after its injection to pregnant mice. Anti-ATP injected in normal pregnant mice failed to pass through the placental barrier to the fetus, and radioactivity 5 hours following the injection was detected neither in fetal tissues nor in the amniotic fluid. After transplacental exposure of fetuses to methyl nitrosurea the labelled AFP was found in the amniotic fluid, while anti-AFP-both in fetal tissues and the amniotic fluid.     

Selective suppression of t-cell activity in tumor-bearing mice and its improvement by lentinan,a potent anti-tumor polysaccharide

The cellular site of immunosuppression in Ehrlich tumor-bearing mice was analysed with particular reference to the T- and B-cell activities. The B-cell activity as measured by the anti-dinitrophenyl (DNP) antibody responses to DNP-thymus-independent carriers (TID) was not impaired in tumor-bearing mice as compared with normal mice, whereas the anti-DNP antibody responses to DNP-thymus-dependent carriers (TD) and the development of helper T-cell activity to TD were markedly suppressed in tumor-bearing animals or mice pretreated with cell-free cancerous ascitic fluid. The selective suppression of T-cell response was not mediated by the generation of suppressor cell activity toward TD, which may depress the manifestation of developed helper T-cell activity. A marked suppression of T-cell response was observed when the animals were inoculated with tumor cells or injected with cancerous ascitic fluid prior to antigenic stimulation, but not when the animals were rendered tumor-bearing by such treatments after the immunization. The suppression of T-cell activity in both sarcoma 180 tumor-bearing mice and cell-free Ehrlich cancerous ascitic fluid-treated mice was prevented by treatment with lentinan, a potent anti-tumor polysaccharide. The applicability of this experimental system to the search for immunopotentiators relevant to tumor immunotherapy is discussed in the light of the preventive effect of lentinan on the suppression of T-cell response in tumor-bearing animals.     

An oncofetal 60-kilodalton protein in the plasma of tumor-bearing and carcinogen-treated rats

A M_r 60,000 protein, detected by its ability to induce the release of RNA from isolated nuclei, is present in the plasma of tumor-bearing and carcinogen-treated rats, together with low amounts of 2 messenger RNA transport proteins identified earlier in normal cells. The M_r 60,000 protein has been identified in tumor cell cytoplasm and in amniotic fluid, but does not appear to cross the placental barrier. Significant amounts of the M_r 60,000 oncofetal protein appear in the plasma of carcinogen-treated rats within a few weeks of treatment. It may be the fetal form of the adult messenger RNA transport proteins.     

Protection against MOPC-315 plasmacytoma by immunization with C-type particle preparations.

Mice were given injections of C-type particles extracted from the ascitic fluid of plasmacytoma-bearing mice. These particles, extracted from MOPC-315 tumor-bearing mice and injected into BALB/c mice, protected them against challenge with MOPC-315 tumor cells. The protection was dependent upon tumor cell dose; 66% survival was observed with a lethal dose of tumor cells. No protection was observed against challenge with another plasmacytoma (S13). Attempts to protect mice against S-13 plasmacytoma by immunizing them with C-type particles originating from S-13 tumor-bearing mice were unsuccessful.     

Hepatic transport of gluconeogenic substrates during tumor growth in the rat

Hepatic gluconeogenic substrates (alanine, lactate, and glycerol) transport have been studied in liver plasma membrane vesicles from rats bearing the ascitic tumor Yoshida AH-130 hepatoma. Hepatic alanine uptake was increased in membrane vesicles from tumor-bearing animals as compared with those isolated from non-tumor-bearing controls. Although no changes were observed in relation with K_M (2.19 and 2.10 mM for control and tumor groups, respectively), the presence of the tumor caused a clear increase in V_max (3.07 and 5.04 nmol alanine/mg protein, respectively). The time course of lactate uptake showed no differences between the tumor-bearing animals and their corresponding controls. Both time course and kinetic experiments showed that liver glycerol uptake was due to passive diffusion and therefore cannot contribute to explain the enhanced utilization of this hepatic gluconeogenic substrate during tumor growth. The results suggest that hepatic alanine uptake may be an important factor accounting for its increased utilization for glucose synthesis in tumor-bearing rats.     

Metabolism and DNA damage induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in fetal tissues of the Syrian golden hamster

The nicotine derived N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent respiratory tract carcinogen in adult Syrian golden hamsters. In this study, the metabolism and genotoxicity of NNK was investigated in fetal hamster trachea and lung tissues. Fetal lung and tracheal explants were cultured in vitro with [5-3H]NNK, and metabolites released into the culture medium were assayed by high-performance liquid chromatography-scintigraphy. Activation of NNK by alpha-carbon hydroxylation and deactivation by pyridine N-oxidation increased from Day 12 to 15 of fetal development. In lung tissues, at Day 12 of fetal development, carbonyl reduction of NNK to 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol was the major metabolic pathway. When adult and fetal lung explants were cultured in vitro with [methyl-3H] NNK, explant DNA was methylated at the O6- and N-7 guanine sites. When hamsters were injected i.p. with NNK (0-200 mg/kg) on Day 14 of gestation, chromosome aberrations were observed in epithelial cells established from lung and tracheal explant outgrowths. Most aberrations in lung and tracheal cells were of chromatid types. High frequency of chromatid exchange was observed in tracheal cells. After injection of NNK (200 mg/kg) to 14-day pregnant hamsters, NNK was detected in lung (0.39 +/- 0.16 nmol/mg), placenta (0.72 +/- 0.48 nmol/mg protein) and amniotic fluids (34.07 +/- 7.62 nmol/ml). These results demonstrated that NNK can cross the placental barrier in pregnant hamsters and be activated to genotoxic intermediates in tracheal and lung tissues and suggest that NNK is a transplacental carcinogen in this species.     

Identification of linoleic and arachidonic acids as the factors in hyperlipemic blood that increase [3H]thymidine incorporation in hepatoma 7288CTC perfused in situ

Tumor growth and the incorporation of [3H]thymidine into tumor DNA in vivo are increased about 3 times in adult rats (greater than 250 g) after 1 to 2 days of starvation or the induction of diabetes with streptozotocin. These tumor growth responses require hyperlipemia and are reversed by refeeding or insulin treatment, respectively. They do not occur in young tumor-bearing rats (less than about 150 g) that lack appreciable fat stores. A direct relationship between the increased rates of both [3H]thymidine incorporation and tumor growth and host hyperlipemia suggests that tumor cell renewal in vivo in fed rats is limited by substances that are present in hyperlipemic blood. In this study we used a procedure for perfusion of solid tumors in situ to measure the sensitivity of tumor [3H]thymidine incorporation to hyperlipemic blood and to identify the rate-limiting substances. Tissue-isolated Morris hepatomas (7288CTC) growing in young or adult Buffalo rats were perfused with blood from donor rats. Hyperlipemic blood for perfusion was obtained from 2-day starved tumor-bearing (Buffalo) or non-tumor-bearing (Buffalo or Lewis) rats. At the end of the perfusions the tumors were labeled with a pulse of [3H]thymidine (2 microCi/g estimated tumor wet weight). [3H]Thymidine incorporation in tumors growing in fed adult rats was increased from 80 +/- 5 (SD) dpm/micrograms DNA at zero time (before perfusion) to 209 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Tumors growing in fed or starved young rats showed similar responses, and hyperlipemic blood from non-tumor-bearing rats was as effective as hyperlipemic blood from tumor-bearing rats. Perfusion of tumors growing in starved rats with normolipemic blood from fed adult rats decreased [3H]thymidine incorporation from 211 +/- 13 dpm/micrograms DNA before perfusion to 68 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Cells, plasma, and plasma subfractions from hyperlipemic blood were reconstituted to whole blood using plasma, cells, and whole blood, respectively, from fed rats and the mixtures were perfused into tumors growing in fed adult rats. Mixtures containing hyperlipemic plasma, lipid extracts (ethanol:acetone, 1:1) of hyperlipemic plasma, or albumin from hyperlipemic plasma increased tumor [3H]thymidine incorporation. Free fatty acid concentrations were increased about five times in hyperlipemic plasma and perfusion of tumors with normolipemic blood containing added linoleic and arachidonic acids increased [3H]thymidine incorporation. Blood mixtures containing palmitic, stearic, and oleic acids were inactive.(ABSTRACT TRUNCATED AT 400 WORDS)     

Embryonic antigens associated with chemically induced colon carcinomas in rats

Blood lymphocytes of multiparous, pregnant Wistar/Furth rats were cytotoxic to plated cells derived from chemically induced rat colon carcinomas as well as to fetal kidney, fetal liver and fetal colon cells, but not to normal adult rat colon mucosa cells. Blood lymphocytes and lymph-node cells from rats bearing colon carcinomas induced by two different chemical carcinogens were consistently cytotoxic to fetal colon cells but never cytotoxic to fetal kidney, fetal liver, or normal adult rat colon mucosa cells. Sera from multiparous, pregnant rats always (4/4 experiments) blocked the cytotoxicity of lymphocytes from colon-carcinoma-bearing rats against fetal colon target cells, but less frequently (2/4 tests) inhibited the cytotoxicity of these lymphocytes against colon carcinoma target cells. Sera from colon carcinoma bearers blocked the cytotoxicity of lymphocytes from colon tumor bearers on either colon carcinoma or fetal colon target cells. When assayed with colon carcinoma target cells exposed to lymph-node cells from colon-tumor-bearing rats, the blocking activity of sera from multiparous, pregnant rats could be absorbed out by treatment with colon carcinoma and fetal gut cells, but not by polyoma-virus-induced sarcoma, normal colon mucosa, fetal kidney, or whole embryo cells. Blocking activity could be recovered from low pH eluates of the colon carcinoma and fetal gut cells. In 2/3 absorption experiments the ability of sera from multiparous, pregnant rats to block cytotoxicity of lymphocytes from colon tumor bearers incubated with fetal colon target cells was abolished by absorption of the sera with colon carcinoma, fetal gut, fetal kidney and whole embryo cells, but not by absorption with polyoma-virusinduced sarcoma cells or with normal colon mucosa cells. These results indicate that (1) embryonic antigensgare immunogenic in multiparous, pregnant rats; (2) chemically induced colon carcinomas in rats share at least a partial antigenic identity with a wide spectrum of fetal tissues; and (3) a more particular antigenic cross-reactivity exists between the colon carcinomas and fetal gut, reflecting the presence of fetal organ-specific antigens.     

Stimulation of tumor growth in adult rats in vivo during acute streptozotocin-induced diabetes

The effects of acute diabetes mellitus on the growth of Morris hepatoma 7288CTC and Jensen sarcoma were studied in fed, young (less than 200 g), and adult (greater than 250 g) rats. Animals were matched for tumor size and growth; the rates of tumor growth were the same in fed, young and adult nondiabetic rats. Diabetes was induced by the i.v. injection of streptozotocin (65 mg/kg total body weight) into tumor-bearing rats and changes in arterial blood nutrient concentrations were compared to changes in the rates of tumor growth and DNA synthesis. In young rats acute diabetes did not increase the blood concentrations of the fat store-derived nutrients and did not increase the rate of tumor growth. In adult rats, however, acute diabetes raised the arterial blood free fatty acid, glycerol, triglyceride, and ketone body concentrations to high levels and increased the rate of tumor growth about three times over that observed in untreated rats. Progress curves for the mobilization of host fat stores and for incorporation of [methyl-3H]thymidine into tumor DNA during the onset of diabetes showed that these activities were closely correlated in adult rats. Both processes began to increase 2 to 4 h after streptozotocin treatment, reached an initial peak at 12 to 16 h, decreased to a low point at 18 to 20 h, and then increased again to the new steady state after 23 to 24 h. The results indicate that the rate of tumor growth in rats in vivo is limited by the availability of a substance(s) present in the hyperlipemic blood of adult diabetic rats. The tight relationship between host lipolysis and tumor growth suggests that the substance(s) is derived from host fat stores.     

磁流体对肝癌细胞的凋亡诱导研究及联合紫杉醇对大鼠肝癌的抑制作用

不同浓度的磁性纳米颗粒作用于肝癌HepG2细胞后,检测其凋亡情况,并电镜观察细胞形态变化。制备抗肿瘤靶向药物紫杉醇白蛋白磁性纳米颗粒（MAG-TAX-NP）,将其联合碘化油治疗大鼠肝癌,观察治疗效果。方法:化学共沉淀法制备磁流体,将其作用于HepG2细胞,流式细胞仪检测细胞凋亡情况。电镜观察磁微球作用于肝癌HepG2细胞后的形态学变化。用乳化-超声-加热固化法制备紫杉醇磁性纳米颗粒。建立大鼠肝癌模型,将荷瘤大鼠30只随机分为5组,除空白对照组外,分别将碘化油﹑碘化油紫杉醇﹑碘化油纳米磁流体、碘化油紫杉醇白蛋白磁性纳米颗粒各0.2 mL注入其余4组大鼠肝固有动脉内。紫杉醇用量为5mg/kg体重,肝肿瘤区外加磁场,14d后处死大鼠,取肝肿瘤组织称重,计算各组抑瘤率。结果:证实了磁流体可诱导肝癌HepG2细胞凋亡。电镜下可见肿瘤细胞吞噬磁流体后细胞内形成凋亡小体,细胞裂解增加。大鼠肝癌模型中除空白对照组外,其余各组的抑瘤率分别为43.2%、51%、57.4%、87.4%。结论:磁微球可诱导肝癌HepG2细胞凋亡。碘化油紫杉醇白蛋白磁性纳米颗粒局部栓塞可抑制肿瘤生长,较其他组具有更强的抑瘤效果。随着深入研究,磁流体有望成为治疗肿瘤的方法,紫杉醇白蛋白磁性纳米颗粒可作为临床紫杉醇药物治疗肝癌的新剂型。      

Tumor Growth-Promoting Effect of Immunosuppressive Substance in Mice

The effect of immunosuppressive (IS) substance obtained from cancerous ascitic fluid on tumor growth and host immunity in plasmacytoma X5563-bearing C3H/He mice is described. IS substance given in three injections, before and after tumor inoculation caused: (a) enhanced tumor growth, (b) marked reduction in survival times, (c) inhibition on Con-A response of spleen cells. Depressed natural killer (NK) activity was observed in normal and tumor-bearing mice treated with IS substance. The data presented here suggest that IS substance suppresses both humoral and cellular immunoresponsiveness and tumor cells evade immune surveillance or immunologically mediated removal.     

Fate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in pregnant and newborn C57BL mice

Whole-body autoradiography of pregnant C57Bl mice injected intravenously with the tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), indicated that NNK and/or its metabolites can diffuse through the placenta and reach the fetal tissues. During the last days of gestation, nasal, pulmonary and hepatic tissues develop the enzymatic capacity to activate NNK to alkylating species which bind covalently to cellular macromolecules. Within 4 h of the injection, a considerable proportion of NNK metabolites present in the fetal tissues are excreted in the amniotic fluid via the fetal urinary tract. Incubation of tissue slices with NNK indicated that the nose, the lung and the liver of 13-day-old fetuses could reduce NNK to 4-(methylnitrosamino)-1-(3-pyridyl)butan -1-ol (NNA1), but could not activate NNK by alpha-carbon hydroxylation. However, these activating enzymes were competent in 18-day old fetuses, and the activities increased during the first six days of life. The results provide evidence that NNK could exert genotoxic effects transplacentally and in newborn mice.     

The antitumor effect of an extract of human umbilical cord

The study was concerned with the evaluation of effect of the extract of a human fetal organ, the umbilical cord, on development and growth of such transplantable tumors as Ehrlich's ascites tumor, sarcoma 37, sarcoma 180 and Zajdela's hepatoma as well as of dimethylbenzanthracene- and benzo(a)pyrene-induced cancer. In a subgroup of animals who had been vaccinated once or twice prior to inoculation of cells, a significant inhibition of growth of tumors of all the histologies except sarcoma 180 was observed alongside with a decrease in tumor incidence and partial resorption of ascitic fluid. Preliminary vaccination of rats interfered with dimethylbenzanthracene- and benzo(a)pyrene-induced carcinogenesis reducing tumor incidence and assuring longer latent period and slower progression of cancer.     

p53腺病毒注射液联合得力生对H22腹水瘤的作用

目的:探讨p53腺病毒注射液(Ad-p53)联合中药得力生治疗腹水瘤的作用。方法:建立H22肝癌腹水瘤昆明小鼠模型,建模48h后分组给予Ad-p53、得力生及两药联用。用药1周后检测体重、腹围、腹水量、腹水瘤细胞计数,流式细胞仪测定瘤细胞凋亡百分比以及细胞周期情况。结果:Ad-p53、得力生单用组,除体重以外的上述指标与对照组比较均有统计学差异(P<0.05),析因分析两药联用也有统计学差异(P<0.05)。结论:腹腔注射Ad-p53、得力生均可抑制H22细胞生长并减少腹水形成,Ad-p53与中药得力生联合腹腔内给药对治疗腹腔转移癌有协同作用。     

Primary melanoma of the ovary in a 25 year old primigravida--a case report

A 25 year old primigravida with edema of the left foot and fetal distress during 36 weeks gestational period underwent an emergency lower segment cesarian section (LSCS). During surgery ascites and a left ovarian tumor with omental seedlings were observed. Cytopathology of the ascitic fluid, histopathology of the ovarian tumor and the omental seedlings showed features of a malignant melanoma, further confirmed at electron microscopy. Considering the age of the patient and the intra-abdominal restriction of metastasis of the neoplasms this tumor appeared to be a primary melanoma of the ovary. This case is reported since there is no reference to a pure melanoma of the ovary occurring in a young primigravida in the literature.     

Nafoxidine possesses antitumor activity against an ascitic hepatoma

Nafoxidine an antiestrogen is shown to possess antitumor activity against the Zajdela ascitic hepatoma. Nafoxidine prolonged the survival time of the rats injected with the tumor cells; complete regression of the tumor was observed when rats bearing a 3-day-old tumor were injected with this compound. Nafoxidine (Naf) also showed cytotoxic effects against the hepatoma cells in vitro. Naf competed with the binding of labelled estradiol to the tumor cells.     

Metastatic melanoma in pregnancy: risk of transplacental metastases in the infant.

PURPOSE: Although metastases to the fetus via the placenta are rare, melanoma is the most common culprit. When it occurs, maternally derived melanoma metastasis in the infant is almost invariably fatal. PATIENTS AND METHODS: This article reviews current guidelines for placental evaluation in pregnant women with metastatic melanoma and presents surveillance recommendations for their infants. Comprehensive literature reviews were performed on melanoma in pregnancy and melanoma metastasis to the placenta and fetus. The use of interferon alfa in the pediatric population was also reviewed. A comprehensive search of the MEDLINE database (1966 to 2002) was performed. Articles were reviewed and additional references were obtained from the bibliographies. Translation of non-English articles was performed, and authors of previous publications were contacted. RESULTS: Eighty-seven patients with placental or fetal metastasis were identified. Twenty-seven occurrences were attributed to melanoma (31%). The fetus was affected in six of 27 melanoma patients (22%), with five of six infants dying of disease. The use of high-dose interferon alfa adjuvant therapy in pediatric patients has not been reported. CONCLUSION: The placentas of women with known or suspected metastatic melanoma should be carefully examined grossly and histologically by pathologists. With placental involvement, fetal risk of melanoma metastasis is approximately 22%. Neonates delivered with concomitant placental involvement should be considered a high-risk population. The risk-benefit ratio of adjuvant treatment for a potentially affected infant should be carefully weighed.     

Detection of a cell proliferation-inhibiting factor in the cell-free ascitic fluid of intraperitoneal mouse tumors

Three cell-free ascitic fluids: MCG3AF, P815AF and SL2AF were obtained from mice injected with MCG3, P815 and SL2 tumor cells, respectively. These ascitic fluids were tested in culture with different normal and tumor mouse cells showing an inhibitory effect on 3H-thymidine and 3H-uridine uptake. The MCG3AF, selected for further study, was tested with a larger number of mouse tumor cell lines and also with normal mouse and human cells. This ascitic fluid inhibited 3H-thymidine and 3H-uridine uptake in all cases. The cell proliferation-inhibiting factor(s) (CPIF) detected in MCG3AF was found to be thermostable and nondialyzable. Further biochemical analysis showed that CPIF is a lipid but with no relationship with very low-density lipoproteins.     

Role of the thymus and T-cells in slow growth of B16 melanoma in old mice

Clinical observations suggest that tumors grow more slowly in aged subjects. To investigate the influence of age on tumor growth, we injected the same number of cultured B16 melanoma cells into C57BL/6 mice of various ages. B16 melanoma cells, inoculated s.c., grew more slowly in old (18-20-month-old) as compared to young (6-8-week-old) mice. In young tumor-bearing mice there was a significant increase in the number and the proliferative response to phytohemagglutinin and concanavalin A of splenic T-cells as compared to old tumor-bearing animals. There was no difference in the response of B-lymphocytes from old and young tumor-bearing mice to lipopolysaccharide. The positive association between T-cells and the rate of tumor growth was also suggested by the slower growth of melanoma cells in thymectomized or thymectomized and anti-theta antiserum-treated young mice. Finally, the age-associated difference in tumor growth could be transferred by spleen cells from old or young mice to thymectomized and lethally irradiated syngeneic young animals. Young mice with rapidly growing B16 melanoma tumors have increased numbers and proliferative responses of thymic-derived lymphocytes. It is likely that T-cells or their products facilitate the growth of B16 tumor cells.     

Amino acid profiles in tumor-bearing and pair-fed nontumor-bearing malnourished rats

To investigate the metabolic and organ changes accompanying growth of a malignant tumor, ten male Fisher 344 rats weighing 150 to 200 g were inoculated subcutaneously with 10(6) viable MCA sarcoma cells (tumor-bearing). Ten other rats (controls) were similarly inoculated with saline. Both groups were allowed food and water ad libitum. An additional ten rats (pair-fed) were inoculated with saline and fed the same mean daily food intake as the tumor-bearing rats. Thirty-five days after inoculation the rats were killed by exsanguination. Livers, spleens, and tumors were weighed, and amino acid profiles and biochemical parameters were measured. Liver and spleen weights in tumor-bearing rats were significantly greater than control rats (P less than 0.05 and P less than 0.01, respectively). Liver weight in pair-fed rats was significantly less than control rats (P less than 0.01), but spleen weight was greater (P less than 0.01). Amino acid profiles of tumor-bearing rats and pair-fed rats were different from each other and from those of control rats. Branched-chain amino acids were lowest in tumor-bearing rats and significantly different from control and pair-fed rats. Lysine was significantly higher (P less than 0.01) and arginine significantly lower (P less than 0.05) in tumor-bearing rats compared with control rats. These different plasma amino acid profiles and changes in serum biochemistry of cachectic tumor-bearing rats compared with malnourished pair-fed rats suggest specific tumor effects on host metabolism not mediated solely by anorexia.