PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “MAMMARY NEOPLASMS, EXPERIMENTAL”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed1988

Towards an idiotype vaccine against mammary tumors. Induction of an immune response to breast cancer-associated antigens by anti-idiotypic antibodies.

Previously we have reported on the production of two sets of human monoclonal antibodies reacting with mouse mammary tumor virus (MMTV) and human mammary tumor virus (HuMTV) cross-reacting antigens. B11 is a monoclonal IgG generated by the human-human hybridoma technique using axillary lymph node of breast cancer patients. 4.6/6 is a monoclonal IgG established by the mouse-human hybridoma procedure using peripheral blood lymphocytes of a healthy investigator working with the breast cancer cell line T47D which secretes HuMTV antigens. Two anti-idiotypic (Id) antibodies were produced by immunizing rabbits with B11 or 4.6/6. Following exhaustive adsorption on unrelated human-Ig, fetal calf serum and purification on B11 or 4.6/6 affinity columns, the anti-Id antibodies were shown to react specifically with their respective Id. The binding of these anti-Id antibodies to the respective Id was specifically inhibited by prior incubation of the Id with MMTV and/or HuMTV antigens. Rabbit anti-B11 and rabbit anti-4.6/6 anti-Id antibodies were employed to immunize female C3Heb mice. Following immunizations, humoral and cellular immune responses to MMTV-related antigens could be demonstrated. The sera of the mice contained anti-MMTV antibodies and delayed-type hypersensitivity was specifically expressed when irradiated cells of the Mm5MT line (which carry surface MMTV antigens) were injected. Our results support the notion that anti-Id antibodies harboring the internal image can immunize animals against tumor cells bearing on their surface viral-associated antigens.

Animals↗
PubMed1997

Massive mammary gland infection and pregnancy-dependent mammary tumor development in mice infected neonatally with mouse mammary tumor virus (SW) but not in mice infected as adults, despite a dramatic local response.

Mouse mammary tumor virus (MMTV) (SW) caused a high incidence (65%) of pregnancy-dependent adenocarcinomas in BALB/c(SW) mice infected as newborns by suckling their mothers' milk. These tumors were type B adenocarcinomas which developed early, at about 1 year of age. Uninfected breeding females and those infected at an age of 8 weeks by injection of virus had the same low incidence of malignant tumors (13%), and the tumors developed later (at approx. 23-24 months). The low incidence of tumors in adult-infected mice was correlated with partial infection of the mammary glands, and delayed transmission of MMTV(SW) to the offspring. Although the virus was rapidly disseminated in both types of infection, the responses of neonatally infected and adult-infected mice to MMTV(SW) infection and viral superantigen (vSAG) presentation were different. Activation by and presentation of the vSAG was impaired in mice infected neonatally, and tolerance induction by clonal deletion was delayed. Local activation was dramatic in mice infected as adults and clonal deletion followed rapidly. Although interaction between B and T cells is needed for completion of the virus life cycle and viral amplification, the strong local immune response to MMTV(SW) in adult-infected mice limits mammary gland infection, and protects them against mammary tumor development.

Adenocarcinoma↗
PubMed2001

Impairment of mammary lobular development induced by expression of TGFbeta1 under the control of WAP promoter does not suppress tumorigenesis in MMTV-infected transgenic mice.

It has previously been shown that transgenic female mice expressing TGFbeta1 under control of regulatory elements of the whey-acidic protein (WAP) gene were unable to lactate. This was due to the increased apoptosis of the cells committed to the lobular-lactogenic phenotype. Our goal was to determine whether the expression of WAP-TGFbeta1 transgene could inhibit MMTV (mouse mammary tumor virus) tumorigenic activity in the mammary gland. It is well known that the infection with this virus produces focal hyperplastic secretory nodules (HANs) and, some variants can also induce ductal pregnancy-dependent lesions (plaques). In either case, MMTV infection leads ultimately to the appearance of malignant mammary tumors. The results shown herein demonstrate that TGFbeta1 expression in the secretory mammary epithelium does not suppress mammary tumorigenesis in MMTV infected mice. Although MMTV infected WAP-TGFbeta1 transgenic females displayed a strong impairment of lobule-alveolar development, carcinogenesis induced by any of the four MMTV variants used herein proceeded unabated. WAP-TGFbeta1 tumors that showed a strong expression at the WAP promoter, appeared later and grew more slowly than their wild-type counterparts. Transgenic females also had a lower incidence of HANs and plaques. Our study suggests that the epithelial target cells for tumorigenic mutations are probably progenitor cells that are not susceptible to the apoptotic effect of TGFbeta1. Alternatively, their daughters cells that display the secretory phenotype and could be more involved in the formation of premalignant lesions continue to die due to the expression of the transgene.

Animals↗
PubMed2005

Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice.

A prominent phenotype of plasmin deficiency in mice is reduced metastasis in the MMTV-PymT transgenic breast cancer model. Proteolytically active plasmin is generated from inactive plasminogen by one of 2 activators, uPA or tPA. We now find that uPA deficiency alone significantly reduces metastasis >7-fold in the MMTV-PymT model. We studied a cohort of 55 MMTV-PymT transgenic mice, either uPA-deficient or wild-type controls. Tumor incidence, latency, growth rate and final primary tumor burden were not significantly affected by uPA deficiency. In contrast, average lung metastasis volume was reduced from 1.58 mm(3) in wild-type controls to 0.21 mm(3) in uPA-deficient mice (p = 0.023). Tumor cell dissemination to brachial lymph nodes was also reduced from 53% (28/53) in wild-type controls to 31% (17/54) in uPA-deficient mice (p = 0.032). Mice without plasminogen display a severe pleiotropic phenotype. By comparison, spontaneous phenotypes are modest in uPA-deficient mice, probably because they still have active tPA. We show that metastasis is strongly and selectively decreased in uPA-deficient mice, suggesting that uPA-directed antimetastatic therapy would be efficacious and have limited side effects.

Animals↗
PubMed1975

Studies of genetic transmission of mammary tumour virus by C3Hf mice.

By radioimmunoassay (RIA) mammary tumour virus (MTV) antigens were detected in individual milk samples of C3Hf mice, (female BALB/c X male C3Hf)F1 mice and (female C3Hf X male BALB/c)F1 mice; milk samples of BALB/c mice were negative. In the segregating backcross I population, female BALB/c X male (female BALB/c X male C3Hf) viral antigens were found in the milk of 93 out of 169 mice (55%). In the Bc II population (daughters of Bc I mothers and BALB/c fathers) two groups were distinguished. In the first group, derived from positive Bc I mothers, 55 out of 110 mice (50%) had detectable levels of viral antigens in the milk. In the second group, progeny of negative Bc I mothers, 1 mouse out of 47 was positive. These data are consistent with the assumption that one dominant gene is responsible for the presence of viral antigens in the milk of C3Hf mice. This gene (Mtv-1) seems to be linked with the albino locus situated on chromosome 7; the recombination percentage was about 29. In the first experiment with Bc I mice a significant difference was found between the tumour ages of the mice with virus-positive milk and of the mice with virus-negative milk: all mice (18) with viral antigens in the milk developed mammary tumours at an age ranging from 7 to 18 months, whereas in only 7 out of 16 mice with virus-negative milk were mammary tumours found before the age of 21 months. Viral antigens were detectable (by RIA) in the tumours of mice of both subgroups; however, the amounts (mU/mg tumour) were significantly lower in the tumours derived from mice with virus-negative milk. Although MTV-L of C3Hf mothers could be transmitted to BALB/c mice by foster-nursing, viral antigens could not be detected in milk samples collected prior to the third lactation period; thus an influence on the data of extrachromosomally transmitted MTV-L is unlikely.

Age Factors↗
PubMed1977

Genetic transmission of mammary tumour virus by GR mice.

By immunodiffusion assay (ID-test) milk samples of mice of several strains and of F1-hybrids of the GR strain were tested for the presence of mammary tumour virus (MTV) antigens. The results clearly demonstrated that the presence of viral antigens in the milk of the first lactation period is restricted to mice harbouring endogenous MTV-GR. Viral antigens were detectable in about 50% of the milk samples collected during the first (occasionally the second) lactation periods of mice of the segregating backcross I (Bc I) populations: DBAfX(DBAfXGR), AKRX(AKRXGR), BALB/cX(BALB/cXGR) and C57BLX(C57BLXGR), indicating that one dominant gene is responsible for the presence of viral antigens in the milk of GR mice. The proposed gene symbol is Mtv-2. Milk samples from female mice of three different Bc II populations were tested for the occurrence of viral antigens. In the first Bc II: [BALB/cX(BALB/cXGR)]XBALB/c 33 out of 51 mice, descending from ID-positive mothers, had ID-positive milk and only one out of 71 mice, which were the progeny of ID-NEGATIVE Bc I mothers, was ID-positive. These results may be influenced by the MTV transmitted extrachromosomally via the milk of the mother. The two other Bx II populations were derived from Bc I fathers, either [BALB/cX(BALB/cXGR)] or [(BALB/cXGR)XBALB/c] f and BALB/c females. The results obtained with these Bc II populations suggested that 6 Bc I fathers were heterozygous for Mtv-2. Since the segregation ratio (60:29) in the Bc II population (progeny of these 6 Bc I male) deviates significantly from the expected 1:1 ratio, one may assume extrachromosomal transmission of MTV via the seminal fluid of the father to the progeny. A close correlation was found between the presence of MTV antigens in the milk and the occurrence of both early mammary tumours after hormone treatment and spontaneous mammary tumours before the age of 13 months. These results suggest that the early appearance of mammary tumours in the GR strain and the early expression of MTV antigens in the milk appear to be controlled by the same genetic factors.

Animals↗
PubMed1977

Factors interfering with cellular immunological responses to the murine mammary tumor virus in tumor-bearing mice.

T-cell-enriched spleen cell fractions from BALB/c mice bearing virally induced mammary tumors become unresponsive with progressive tumor growth in the lymphocyte blastogenesis test, using purified mammary tumor virus (MTV) as an antigen. reactivity can be restored by mild trypsinization or extensive washing of the cells. When reactive cells from mice immunized with MTV were incubated with the wash fluid of the initially unresponsive cells. MTV-specific blastogenesis was inhibited. Washings of normal cells had no such effect. Leukocytes from tumor-bearing mice also become unresponsive to MTV in the leukocyte adherence inhibition (LAI) assay. Trypsinization or extensive washing does not restore reactivity. However, such treatment of reactive cells from immunized animals abolishes a positive reaction in the LAI assay, using MTV as an antigen. The washings of spleen cells from tumor-bearing mice inhibit the reactivity of leukocytes from immunized animals. Sera from these mice could block the reaction in both cellular immunological tests. The inhibiting factors appeared early after the onset of tumor growth. By means of the Sepharose bead immunofluorescence assay it was established that wash fluid and sera with blocking activity contain MTV antigens as well as anti-MTV antibodies.

Animals↗
PubMed1977

Development of a congeneic line of the GR mouse strain without early mammary tumours.

Based on the previous observation that Mtv-2 controls the appearance of pregnancy-dependent mammary tumours and the early expression of mammary tumour virus (MTV)-antigens in the milk, an attempt was made to develop a congeneic GR line, without this locus, by introducing genetic material of the C57BL/10 strain. The cross-intercross system was used for this purpose. The mice of the even-numbered generations were selected for the absence of the Mtv-2 locus with the early maammary tumour (EMT) test and during the later cycles with the immunodiffusion (ID) test for MTV-antigens in the milk. After six cycles of cross-intercross, brother-sister mating was started with mice selected for the absence of Mtv-2. After two brother-sister matings the milk-transmitted MTV was eliminated by foster-nursing. Of the foster-nursed subline 233 mice (16 of the first, 118 of the second and 99 of the third generation) were tested for the presence of Mtv-2 with one or two of the following three methods: (1) ID-test, (2) EMT-test and (3) by examination of the development of spontaneous mammary tumours in breeding females. The tests were negative in 226 mice. This indicates that Mtv-2 was absent in nearly all mice of the congeneic subline. The positive reactions in the seven other tested mice were weaker than that observed in the GR strain and in GR mice foster-nursed by BALB/c. The presence of the Mtv-2 gene in the seven positive mice of the congeneic line is doubtful. With the ID test, viral antigens were detectable in 50% of the milk samples from the first lactation period of mice of the segregating backcross I population [GR congeneic X (GR congeneic X GR)], indicating a one-gene difference between the congeneic GR line and the progenitor GR strain.

Animals↗
PubMed1978

Early detection of tumor-specific antibodies to mammary carcinoma.

BALB/cfC3H female mice which develop mammary tumor virus (MTV)-induced mammary tumors possess not only serun antibodies directed against virus-associated antigens which are expressed on mammary tumor cells but also antibodies directed against antigenic specificities which are unique to each tumor. The possible range of unique specificities is considerable; a survey of serum samples from 18 tumor-bearing females revealed only two which reacted with a tumor-unique specificity of another isologous MTV-induced mammary tumor. A retrospective study revealed that in multiparous females, the serum activity against tumor-unique antigenicity could be detected 1 to 4 months before the tumor was grossly visible. On the other hand, in virgin females, the serum activity was detectable only when the tumor was visible. On the basis of this difference in time of origin of reactivity, we speculate that the mechanism of tumor formation in parous females may involve a longer preneoplastic or latent neoplastic period than in virgin females; in the latter the change from normal to overtly neoplastic appears to be more abrupt.

Animals↗
PubMed1978

Induction of mammary tumors in C57BL/HAAG female mice by a low oncogenic mammary tumor virus.

Mammary tumor virus (MuMTV)-negative mouse substrain C57BL/Haag foster-nursed by strain DD becomes a line with a moderately high incidence of mammary tumors occurring in the females at a late age. Electron microscopy revealed B particles in the tumors, providing additional evidence for the propagation and transmission of DD-MuMTV in C57BL/HaagfDD. Since both albino strains DD and RIII originated in Europe, develop pregnancy-dependent mammary tumors, carry black and agouti genes (cc, BB, AA), and therefore may be related, evidence is presented which suggests that the two naturally occurring MuMTVs from DD and RIII may also be related, and that they may share a common origin.

Animals↗
PubMed1979

Idiopathic mammary tumors in BALB/c mice.

A colony of BALB/c mice consisting of two sublines with a high incidence of mammary tumors was examined for the presence of a mammary tumor virus (MuMTV). The mammary tumor incidences in the two sublines were 18% and 35% at average tumor age 19-20 months. Over a period of 8 years, their milk at third to tenth lactations were monitored for the presence of MuMTV antigen,and the milk and tumors were examined for the presence of B particles. Neither antigen nor B particles were found. Milk and tumor extracts from the higher mammary tumor lines were also assayed for MuMTV bioactivity by intraperitoneal inoculation of weanling C57BL, BALB/c, and RIIIf females. No response was obtained, except possible in RIIIf. Both the MuMTV antigen incidence and the tumor incidence in inoculated RIIIf mice were somewhat elevated over controls. The question remains unanswered as to whether there is an active MuMTV in our colony of tumor-bearing BALB/c mice and, if there is, whether it is associated with B particles.

Animals↗
PubMed1979

Tumour-related antigen specificities associated with 3-methylcholanthrene-treated rat embryo cells.

Rat embryo cells were treated in vitro for 18 h with 10 micrograms/ml 3-methylcholanthrene (MCA). Syngenetic male rats were immunized with several inocula of treated cells to prepare antisera which were screened for membrane immunofluorescence reactivity against panels of established chemically-induced syngeneic rat tumours. Three separate antiserum pools raised against MCA-treated cells reacted with certain chemically-induced tumours, whereas antisera to control (DMSO-treated) cells were completely negative. The reactions observed were reproducible and highly specific for particular target tumours. Absorption studies indicated that each antiserum contained antibodies to several different antigens, present on different tumours. Antiserum prepared against extranuclear membrane from MCA-treated cells, rather than intact MCA-treated cells, was negative. This suggests that the antibody responses were directed against antigens arising subsequently to MCA treatment and injection into syngeneic hosts. It is postulated that carcinomgen treatment results in the acquisition of multiple neoantigens among a treated cell population, which represent an early change in a sequence of events leading to malignant transformation.

Animals↗