Biomedical subjects

G Parmiani

Publications and source records attributed to G Parmiani.

At least 163 records · Page 9Linked to original sources

PubMed1991

Biologic agents as modifiers of chemotherapeutic effects.

Recent papers dealing with the effect of biologic response modifiers on the therapeutic activity of anticancer drugs are reviewed. Preclinical findings indicate that both interferons and tumor necrosis factor-alpha are able to synergize with different cytotoxic drugs in increasing both tumor cytotoxicity or cytostasis in vitro and the therapeutic effect in animal models in vivo. The mechanism of such a synergy, however, has not been definitively worked out. Several clinical phase I and II trials have assessed the interactions of biologic response modifiers (mainly interferons and interleukin-2) with anticancer drugs, particularly in melanoma and renal cancer patients. Evidence of a therapeutic synergism is limited with most of the studies, indicating a lack of synergic or additive effects of the combination compared with single agents. Few phase III studies provided conflicting results. It is concluded that further studies on the combination of biologic response modifiers and chemotherapy both at preclinical and clinical levels are necessary to establish the possible synergistic or additive therapeutic effect of such a therapeutic approach.

Animals↗

PubMed1991

Adjuvant adoptive immunotherapy with IL2 and lymphocytes from tumor-bearing mice: in vitro tumor-stimulated lymphocytes are more effective than LAK cells.

In order to determine whether lymphocytes with therapeutic potential can be obtained from colon carcinoma (C26)-bearing (TB) mice, splenocytes were activated either in mixed lymphocyte-tumor cell (MLTC) cultures in the presence of 5 and 10 U/ml IL2 or 250 and 100 U/ml IL2 (LAK effectors). The therapeutic efficacy, as well as functional and phenotypic features of such lymphocytes, was then compared in an adjuvant immunotherapy setting. Comparisons of the antigenic phenotype, cytotoxic and proliferative activities, and of transcription of different cytokine genes (IFN gamma, TNF alpha, IL4, IL6) between lymphocytes activated in MLTC and LAK failed to reveal major differences. However, the in vitro lysis of C26 by MLTC-activated but not by LAK TB lymphocytes was significantly blocked by anti-T3 and anti-Lyt2 monoclonal antibodies, suggesting that a fraction of specific antitumor effectors was present in the MLTC bulk population. Moreover, the amount of IFN gamma (but not of other cytokines) produced by MLTC-derived lymphocytes after stimulation with C26 cells was shown to be 10-fold higher than that produced by LAKs. When combined with low-dose IL2 administration as an adjuvant treatment in C26-operated mice, MLTC effectors showed a higher therapeutic activity than LAKs obtained from the same pool of lymphocytes from TB donors. In the same setting, MLTC-activated lymphocytes obtained from TB or tumor-excised (TE) mice, combined with IL2, were equally effective (76 and 74% survivors, respectively, vs. 27% of the surgery control group and 26% of the group given IL2 only), whereas LAK cells from TE but not from TB animals resulted in the cure of a significant fraction of mice.

Animals↗

PubMed1991

Recombinant interferon-gamma differently affects DQA and DRA gene expression in two human melanoma clones: transcriptional and posttranscriptional regulation.

In a previous study, two human melanoma HLA class-II-negative clones have been shown to respond differently to recombinant interferon gamma (rINF-gamma). In fact, in clone 9229/18, rINF-gamma treatment led to a coordinate expression of both DR and DQ genes, whereas in clone 9229/5, a high increase in steady-state mRNA levels and cell surface antigen expression could be observed for DR but not for DQ genes. The molecular mechanism underlying such a different behavior was investigated and DQA gene regulation was studied both at the transcriptional and posttranscriptional level. Nuclear run-on experiments were performed on 9229/5 and 9229/18 clones. Treatment with rINF-gamma at 1,000 U/ml for 24 h led to a coordinate transcriptional activation of DRA and DQA genes in 9229/18 clone, whereas in clone 9229/5 it strongly augmented the rate of transcription of DRA but not DQA genes. For all class II genes studied, both melanoma clones showed a basal rate of transcription that never led to a mature cytoplasmatic mRNA. To study whether posttranscriptional mechanisms could affect DQA mRNA stability, a comparison was performed between mRNA turnover in 9229/18 cells treated with actinomycin D and actinomycin D plus cyclohexamide following rINF-gamma treatment. In the absence of protein synthesis, the t1/2 of specific DQA mRNA was largely reduced, showing that a short-lived protein is required to stabilize human DQA mRNA in melanoma cells. Our results indicate that DQA gene is subjected to a tight regulation, acting both at the transcriptional and posttranscriptional levels and that DQA and DRA genes can be differentially regulated at the transcriptional level by rINF-gamma in a melanoma clone such as 9229/5.

Base Sequence↗

PubMed1990

Local adoptive immunotherapy of advanced head and neck tumors with LAK cells and interleukin-2.

Since October 1987 a pilot phase I-II study on the effect of loco-regional injections of recombinant interleukin 2 (rIL-2) in association with LAK cells has been performed in advanced, recurrent head and neck cancer patients. Fourteen patients were treated with autologous LAKs and rIL-2 (Glaxo) given peritumorally and in the mastoid region (rIL-2 only in the latter site). LAKs (2-70 x 10(7)) + rIL-2 were injected on the first day of therapy, followed by 9 daily injections of rIL-2 only. The total daily dose of rIL-2 was escalated from 2,400 to 1.8 x 10(6) IU. Clinical evaluation was performed 30 days from the onset of therapy; 3 partial (95%, 66% and 50% reduction) and 3 minor responses were seen in the evaluated patients. All the other patients with a progressive disease after the first cycle were shifted to palliative chemotherapy. The partial responses were found in patients with a tumor burden less than 20 cm2. Cervical node metastasis did not respond to treatment. No relevant side effects occurred. These results indicate that loco-regional immunotherapy with rIL-2 and LAK cells can produce clinical responses in advanced head and neck cancer patients.

Aged↗

PubMed1990

Eradication of a disseminated mouse lymphoma by 1,3-bis(2-chloroethyl)-1-nitrosourea is immunologically mediated and accompanied by de novo generation of anti-tumor cytotoxicity.

The anti-tumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was examined in BALB/c mice bearing increasing burdens of a syngeneic lymphoma (YC8). A single i.p. injection of the drug resulted in over 75% of cures when given at day 3, 5, 7 or 10 after an i.v. inoculum of 10(4) YC8 cells. The efficacy of BCNU on mice bearing large tumor burdens (from day 5 on) was not only due to its tumoricidal activity, but was immunologically mediated. Residual tumorigenic cells could be recovered in the livers of 5-day tumor bearers (TB) up to 2 weeks after BCNU treatment and only a low percentage of cures could be achieved when BCNU was administered to nude mice. In addition, BCNU-cured mice specifically rejected a lethal YC8 challenge and their splenocytes developed anti-tumor cytotoxicity in response to in vitro stimulation with YC8 cells. During kinetic experiments a 2-week period elapsed after BCNU injection before an anti-tumor cytotoxic T-lymphocyte (CTL) response could be generated by spleen cells of BCNU-treated 5-day TB. This period was characterized by immunosuppression as evaluated from impairment in the generation of lymphokine-activated killer (LAK) cells or of allospecific primary CTL responses by spleen cells from BCNU-treated 5-day TB and BCNU-treated normal mice. LAK cells first recovered and could be generated 7 days later, whereas primary allospecific CTL responses could only be detected by day 14, concomitantly with the generation of anti-tumor cytotoxicity by 5-day TB. The development of secondary in vitro CTL responses, however, was permanently abrogated. Spleen cells from BALB/c mice immunized either with YC8 or with DBA/2 minor histocompatibility antigens and treated with BCNU 1 week after the last immunization failed to mount an in vitro CTL response to their immunizing antigen, even when the cultures were supplemented with recombinant interleukin-2.

Animals↗

PubMed1990

Modulation of multidrug resistance by verapamil or mdr1 anti-sense oligodeoxynucleotide does not change the high susceptibility to lymphokine-activated killers in mdr-resistant human carcinoma (LoVo) line.

Two sublines were derived from the colon adenocarcinoma line LoVo, the first one was sensitive (LoVo/H) and the second one was made resistant to doxorubicin (LoVo/Dx). When tested for susceptibility to lysis by different types of immune effectors, LoVo/Dx appeared more sensitive than LoVo/H to the killing of CD3+CD5+CD16-, CD3- CD16+)-enriched lymphokine activated killers (LAK) or activated macrophages. In order to check whether this effect was due to different expression of glycoprotein P170 between the two LoVo sublines (30% vs. 90% of positive cells), a pharmacological and genetic modulation of P170 was carried out in LoVo cells. Treatment of LoVo/Dx with the calcium channel blocker verpamil (VRP), strongly impaired P170 function as evaluated by reduced Dx resistance, without affecting the lysability of LoVo/Dx cells by LAKs. Moreover, the significant inhibition of P170 expression resulting from the treatment of LoVo/Dx with mdr1 anti-sense olideoxynucleotide also failed to change the high lysability of LoVo/Dx by LAKs. These results, therefore, indicate that molecules other than P170 are involved in the increased lysis of LoVo/Dx subline by immune effectors and that down-regulation of the P170 expression or function will not reduce the potential effectiveness of cancer chemo-immunotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1990

Human melanoma cells with high susceptibility to cell-mediated lysis can be identified on the basis of ICAM-1 phenotype, VLA profile and invasive ability.

Marked heterogeneity for susceptibility to lysis by autologous CTL clones and allogeneic IL-2-activated CD3- and CD3+ lymphocytes was found among 19 clones isolated from a human metastatic melanoma (Me665/2). A subset of 5 clones with the highest susceptibility to lysis had increased ICAM-1 antigen expression. Phenotype analysis for the presence of extracellular matrix receptors in the beta 1- and beta 3-integrin families revealed that the tumor clones with the highest susceptibility to lysis were also characterized by frequent expression or increased expression of multiple receptors in the beta 1 family including VLA-1, -2, -3, -4 and -6. The correlation between phenotypic markers and susceptibility to lysis, seen at the clonal level, was confirmed by selection experiments on the uncloned metastasis Me665/2. In fact, the neoplastic population surviving 3 cycles of immunoselection with IL-2-activated lymphocytes exhibited, in comparison to the unselected metastasis: (1) reduced susceptibility to lysis and (2) reduced expression of ICAM-1 and of VLA antigens. In contrast, enhanced susceptibility to lysis and up-regulation of ICAM-1, VLA-1 and VLA-3 antigens were observed on melanoma cells recovered after invading a reconstituted basement membrane. These data indicate that melanoma cells with enhanced susceptibility to cell-mediated lysis can be identified on the basis of phenotypic characteristics (ICAM-1 and VLA antigen profile) and functional features (invasive ability on reconstituted basement membranes).

Antibodies, Monoclonal↗

PubMed1990

In vivo interleukin 2-induced activation of lymphokine-activated killer cells and tumor cytotoxic T-cells in cervical lymph nodes of patients with head and neck tumors.

To study whether regional injection of recombinant interleukin 2 (rIL-2) can induce an in vivo lymphocyte activation in cervical lymph nodes (LNs) of patients with head and neck carcinoma, 12 patients, candidates for prophylactic dissection, were treated for 7-10 days prior to surgery with rIL-2, 10(5) units/day, injected in the perimastoid region. A marked induction of cytotoxic activity against allogeneic (K562 and Daudi lines) and autologous target cells (fresh spindle cell carcinomas of the tongue) was observed in lymphocytes obtained from jugular, spinal, and, to a lesser extent, submandibular LNs of all treated patients. An increase of cytotoxicity was also present in LNs contralateral to the rIL-2 injection side. On the other hand, only a borderline increase in spontaneous proliferation was detected. Moreover, in the two cases tested, a marked and apparently autologous tumor (Auto-Tu)-specific lysis was found in CD5+ lymphocytes obtained from LNs, whereas lymphokine-activated killer activity was mainly exerted by CD16+ natural killer cells. T-lymphocytes, when cultured with irradiated Auto-Tu cells and low doses of rIL-2, showed an increased Auto-Tu lysis, while cytotoxicity against allogeneic tumor cells (including K562) was not observed. These data indicate that regional injection of rIL-2 can activate lymphokine-activated killer cells from LN lymphocytes but also induce and/or expand a T-cell population expressing a restricted Auto-Tu cytotoxicity.

Aged↗

PubMed1990

Cellular immune response against autologous human malignant melanoma: are in vitro studies providing a framework for a more effective immunotherapy?

Data concerning the in vitro lymphocyte response against autologous tumors are reviewed, with a particular emphasis on melanoma. Evidence for such an immune response to tumors has been accumulating over the last 10 years through the work of several groups of investigators. Proliferative and/or cytotoxic responses are detectable in approximately 70% of patients with primary tumors, whereas the in vitro reaction with metastatic lesions is much less frequent. This response is mainly mediated by T lymphocytes obtained from peripheral blood, tumor lesions, and lymph nodes, but patients' suppressor cells and factors have been reported to inhibit such response. Clonal analysis revealed a low but consistent frequency of antimelanoma-specific T-cytotoxic and/or proliferating cells even in metastatic melanoma patients; such effectors are major histocompatibility complex restricted and use the T-cell receptor for tumor recognition of unique and, possibly, cross-reacting melanoma-restricted antigens. The chemical and genetic nature of such molecules remains to be defined. After the limited but biologically fundamental clinical responses achieved by adoptive immunotherapy with interleukin-2 and lymphokine-activated killers, T cells appear to lend themselves as crucial new effectors in adoptive immunotherapy of human cancer and, in particular, of melanoma.

Antigens, Neoplasm↗

PubMed1990

Cytokine-mediated modulation of HLA-class II, ICAM-1, LFA-3 and tumor-associated antigen profile of melanoma cells. Comparison with anti-proliferative activity by rIL1-beta, rTNF-alpha, rIFN-gamma, rIL4 and their combinations.

Nine different human melanomas and 16 clones, isolated from 2 of them, were characterized for susceptibility to rIL1-beta-, rIL4-, rTNF-alpha- and rIFN-gamma-mediated effects on proliferation and surface expression of class-II HLA (DR and DP), ICAM-1 and LFA-3 molecules and of 3 tumor-associated antigens (recognized by MAb 763.74T, 149.53 and R24). In spite of marked inter- and intra-tumor heterogeneity for susceptibility to the effects of each cytokine, the most frequent upregulation was induced on the HLA class-II antigens by rIFN-gamma and on adhesion molecules by rIFN-gamma, rTNF-alpha and rIL1-beta, while tumor-associated antigens were often down-modulated by rIFN-gamma. Tumor heterogeneity was also evident on tumor-cell proliferation with an apparent hierarchy in the frequency and extent of inhibitory effects: rIFN-gamma greater than rTNF-alpha greater than rIL1-beta = rIL4. Combinations of 2 cytokines resulted in rare and limited changes in the antigenic profile in comparison to the effects seen with single factors, while the combination of rTNF-alpha and rIFN-gamma resulted in significant synergistic antiproliferative effects on most tumor cells and clones. Taken together, these results indicate that single cytokines can profoundly affect the antigenic profile of melanoma cells, while strong tumor-growth inhibition is often achieved by combinations of 2 cytokines acting in synergism.

Antigens, Neoplasm↗

PubMed1990

T lymphocytes can mediate lysis of autologous melanoma cells by multiple mechanisms: evidence with a single T cell clone.

The specificity analysis of a CD3+, WT31+, CD8+ cytotoxic T lymphocyte (CTL) clone (CTL 49), isolated from peripheral blood lymphocytes of a melanoma patient (no. 665) after mixed lymphocyte culture with an HLA-A2+ allogeneic lymphoblastoid cell line (VSKB-LCL), revealed that CTL 49 could lyse, in addition to HLA-A2+ lines, autologous HLA-A2- melanoma (Me665/2) and K562 targets. Killing of VSKB-LCL, but not of Me665/2, could be inhibited by anti-CD3 and by anti-HLA-A2 antibodies or by modulation of the CD3 complex. Cold-target competition studies showed that K562, but not VSKB-LCL, could compete with Me665/2 for lysis by CTL 49. However, unlike K562, Me665/2 could be lysed by CTL 49 in a Ca2(+)-independent fashion in 4 h and 18 h assays. CTL 49 expressed mRNA specific for tumor necrosis factor (TNF alpha) and, to a lesser extent, for lymphotoxin (TNF beta). Exposure of the clone to anti-CD3 antibodies induced the expression of interferon(IFN)-gamma-specific mRNA. Antibodies to TNF alpha, TNF beta and IFN reduced the lysis of Me665/2, but not of K562, by CTL 49 in 18-h cytotoxic assays. Antibodies to TNF alpha and to IFN gamma almost completely inhibited the lysis seen on Me665/2 (but not on K562), in 96-h assays, by supernatants isolated from VSKB-LCL- or anti-CD3-stimulated CTL 49 cells. Taken together, these data indicate that major-histocompatibility-complex-independent lysis of autologous tumor cells and of natural killer reference targets by the same alloreactive T cell clone are activities related at the level of target recognition but distinct at the level of the lytic hit. Thus, efficient lysis of autologous tumor cells results from a complex mechanism based upon direct effector-target interaction as well as on cytokine-mediated cytolytic effects.

Calcium↗

PubMed1990

Adoptive immunotherapy of a mouse colon carcinoma with recombinant interleukin-2 alone or combined with lymphokine-activated killer cells or tumor-immune lymphocytes. Survival benefit of adjuvant post-surgical treatments and comparison with experimental metastases model.

We have used a BALB/c colonic adenocarcinoma (C-26) to evaluate the therapeutic potential of recombinant interleukin-2 (rIL-2) at high and low dosages in combination with or without lymphokine-activated killers (LAK) or tumor-specific, immune lymphocytes in either an adjuvant spontaneous or an artificial metastasis system. Most (approximately 80%) of the mice that underwent s.c. C-26 tumor excision systemic treatment with low-dose rIL-2 (3 x 10(4) U/day, i.p.) increased the survival rate to 31% as compared to 21% (not significant) in excised controls while administration of high-dose rIL-2 (8 x 10(4) U/day) led to 53% survival (P less than 0.001). Both LAK cells and C-26-tumor-immune lymphocytes given during rIL-2-treatment significantly increased the effects of rIL-2 at the low but not at the high-dose, with tumor-immune effectors resulting in the highest percentage (63%) of cures. When mice bearing 3-day artificial lung metastases of C-26 cells were treated wtih low- or high-dose rIL-2, in combination with or without LAK or tumor-immune lymphocytes, a highly significant reduction or abrogation of the number of lung foci was observed with all treatments, including those involving or tumor-immune lymphocytes alone. Assessment of survival benefit in these mice, however, showed survival prolongation, with 20% cures achieved by low-dose rIL-2 alone and up to 65% cures by LAK in combination with low-dose rIL-2. In this system of artificial metastasis high-dose rIL-2 alone increased the survival time but failed to cure the animals, and the addition of LAK was ineffective whereas that of tumor-immune lymphocytes led to 80% cure. These results suggest that tumor-immune lymphocytes are more effective than LAK when combined with rIL-2 and that caution is necessary in extrapolating findings obtained in artificial metastasis models.

Animals↗

PubMed1990

Mouse tumors are heterogeneous in their susceptibility to syngeneic lymphokine-activated killer cells and delineate functional subsets in such effectors.

We have analyzed whether lymphokine-activated killer (LAK) cells, generated from C57BL/6J (B6) spleen cells at different times after recombinant interleukin-2 (rIL-2) culture, could be heterogeneous in their ability to lyse a variety of tumor targets. When tested 3 days after exposure to 250 U/ml rIL-2 (day-3 LAK cells) a significant lysis was detected with the natural-killer(NK)-sensitive YAC lymphoma, the NK-resistant P815 mastocytoma, three different syngeneic melanomas and a syngeneic fibrosarcoma (group 1 targets), whereas no lysis was observed with a reticulum cell sarcoma, two different lymphomas or concanavalin A blasts, all of B6 origin (group 2 targets). LAK cells cultured for 5 days, however, lysed group 2 targets and showed a parallel increase of cytotoxic activity against group 1 targets. At day 7, LAK activity declined on all targets examined. In cold-target inhibition studies, the lysis of group 1 tumor targets by day-3 or day-5 LAK cells could be inhibited only by group 1 and not by group 2 unlabelled tumor cells. All group 1 tumors could effectively compete each other. Conversely, the lysis of group 2 tumor targets by day-5 LAK cells was inhibited by both group 1 and group 2 targets. These data indicate the presence of separate LAK effectors that appear to arise with different time kinetics and have different recognition structures. In vitro antibody depletion at the effector level showed that day-3 LAK cells with cytotoxic activity against group 1 tumors were ASGM1+. Day-5 LAK cells included both ASGM1+ and Lyt2+ effectors and both populations, although to a different extent, contributed to the lysis of all targets. Our results indicate that LAK cells are functionally heterogeneous. This heterogeneity is defined by their susceptible target cells and cannot be ascribed to different (Lyt2+ versus ASGM1+) lineages.

Animals↗

PubMed1990

An explanation of the variable clinical response to interleukin 2 and LAK cells.

Adoptive immunotherapy for the treatment of cancer has met with limited but, for some, encouraging success. A minority of malignant melanoma and renal cell carcinoma patients respond to therapy with interleukin 2 (IL-2) or IL-2 plus lymphokine-activated killer (LAK) cells. The mechanism of response, and the reasons for the variation within disease groups, is not clear. In this article, Giorgio Parmiani proposes that successful adoptive therapy is dependent on the recruitment of activated host antitumor T lymphocytes and suggests that this explains the greater efficacy of tumor-infiltrating lymphocytes in combating melanoma and renal cell carcinoma.

Animals↗

PubMed1990

Multiple VLA antigens on a subset of melanoma clones.

A panel of 19 melanoma clones was characterized by fluorescence activated cell sorter analysis for the expression of distinct integrin receptors in the very late activation antibody subfamily. A group of five melanoma clones (2/4, 2/14, 2/17, 2/51, and 2/60) was identified that shared coordinate expression of multiple VLA antigens. These same clones were more susceptible, in terms of lytic units, to cell-mediated lysis and also expressed the lower melanin content per cell in the panel. The data suggest that in a heterogeneous neoplastic population, distinct features such as susceptibility to cell-mediated lysis and expression of receptors for extracellular components are variables preferentially associated with cells in an early stage of differentiation.

Antigens, Neoplasm↗

PubMed1990

Role of T cells and tumour necrosis factor in antitumour activity and toxicity of flavone acetic acid.

To investigate the importance of natural killer (NK) and T cells in the inhibition of tumour growth by flavone acetic acid (FAA), colon 26 murine carcinoma was grafted subcutaneously in euthymic and athymic mice. FAA was active in euthymic but not in athymic mice (ratio between tumour weight in treated vs. control animals [T/C %], 27% and 92%, respectively). NK cell activity was increased in both mouse strains, indicating a lack of major involvement of this lymphocyte population in FAA efficacy. In euthymic mice tumour-specific T cells were activated, and after in vivo depletion of lymphocyte subpopulations (L3T4 and Lyt2), tumour inhibition by FAA was abrogated (T/C %, 88%). Antitumour efficacy of FAA was also reduced when the treatment was followed by injection of antitumour necrosis factor alpha (TNF alpha) antibodies. FAA toxicity depended on tumour weight at the time of treatment: 200 mg/kg caused 0 and 100% mortality in mice bearing tumour nodules under 50 and over 300 mg, respectively. When anti-TNF alpha antibodies were given after FAA treatment, the toxicity was greatly reduced (3/14 mice died compared with 10/15).

Adenocarcinoma↗

PubMed1990

Adoptive immunotherapeutic treatments with interleukin 2 and lymphocytes in a mouse colonic adenocarcinoma model.

This article reports the results of adjuvant immunotherapy studies carried out in an experimental tumor model system. A transplantable murine BALB/c colonic adenocarcinoma (C-26) was used to evaluate the therapeutic potential of treatment with recombinant interleukin 2 (rIL-2) at high and low dosage in combination with or without lymphokine activated killer cells (LAK) or tumor-specific immune lymphocytes, either as an adjuvant treatment in mice bearing spontaneous post-surgical metastases or in mice bearing artificial metastases. Moreover the in vivo LAK activation and circulation pattern have been examined during or after treatment. These results show that cytotoxic lymphocytes from tumor-immunized donors are more active than LAKs when given in combination with rIL-2 as an adjuvant treatment, while all treatment modalities exerted a strong but generally transient inhibition on the formation of artificial lung metastases by C-26 cells. Alteration of host lymphocyte responsiveness to rIL-2 was shown to occur in early-tumor-resected and large-tumor-bearing animals in both in vitro and in vivo experiments. Moreover, no evidence of homing or preferential localization of the adoptively transferred LAK cells to the site of tumor growth was observed.

Adenocarcinoma↗

PubMed1990

H-2 class I gene analysis in 3-methylcholanthrene-induced murine fibrosarcomas.

The objective of our study was to determine whether and how frequently MHC class I gene alterations occur in fibrosarcomas induced in BALB/c mice by the carcinogen 3-methylcholanthrene (3-MCA). Southern blot was performed to analyze the genomic organization of class I genes in a panel of twenty tumors of different immunogenic strength used at early in vivo passages. Our results rule out the presence of gross rearrangements or deletions in the H-2 class I genes of the tumors tested and indicate that the frequency of detectable class I alterations giving rise to restriction fragments length polymorphism (RFLP) should be very low.

Animals↗