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At least 163 records · Page 9Linked to original sources
PubMed1985

Lymphokine-activated tumor inhibition in vivo. I. The local administration of interleukin 2 triggers nonreactive lymphocytes from tumor-bearing mice to inhibit tumor growth.

CE-2 is a chemically induced tumor of low immunogenicity in syngeneic BALB/c mice. Nylon wool columns eluting lymphocytes from the spleen of mice bearing clinically evident (5-mm mean diameter) CE-2 tumors (CE-2 TB lymphocytes) do not react with CE-2 cells in vitro, nor are they able to affect their growth in vivo in a Winn-type neutralization assay at 5:1 lymphocyte:tumor cell ratio. However, they become able to inhibit CE-2 tumor growth when 20 U of interleukin 2 (IL 2) in 0.4 ml are injected daily for 10 days at the challenge site. In contrast, mice injected with CE-2 cells and IL 2 only display tumor takes and growth that are not significantly different from those in controls challenged with CE-2 cells alone. This lymphokine-activated tumor inhibition (LATI) is not a peculiarity of the CE-2 tumor-host combination, because different tumors can be inhibited in this way and various TB lymphocytes can initiate it. In these experiments, IL 2-rich 25,000 to 30,000 m.w. fractions were obtained routinely from the culture supernatants of a clone of EL-4 thymoma stimulated with phorbol myristic acetate. Equally active IL 2-rich preparations were obtained from rat spleen cells stimulated with concanavalin A, or from MLA 144 gibbon lymphosarcoma spontaneously releasing IL 2. Treatment of CE-2 TB lymphocytes with various antibody and C, with 2000 rad gamma-irradiation, or fractionation on Percoll density gradients suggested that radioresistant functions of Thy-1.2+, Lyt-1.2+, Lyt-2.2- and of asialo GM1+ cells are independently involved in LATI induction. These lymphocytes inhibit tumor growth by recruiting the radiosensitive effector mechanisms of the recipient mice required for ultimate tumor destruction. CE-2 tumor inhibition by LATI leaves a specific delayed-type hypersensitivity and an immunologic memory, resulting in rejection of a second lethal CE-2 challenge in a significant number of mice.

Adenocarcinoma↗
PubMed2002

Aberrations of the hSNF5/INI1 gene are restricted to malignant rhabdoid tumors or atypical teratoid/rhabdoid tumors in pediatric solid tumors.

The hSNF5/INI1 gene, which encodes a subunit of the SWI/SNF family of chromatin-remodeling complexes and is located at 22q11.2, has been reported as a tumor suppressor gene inactivated in malignant rhabdoid tumors (MRTs). We analyzed this gene in varieties of pediatric solid tumors including MRTs, using the reverse transcription-polymerase chain reaction (PCR) and PCR-single strand conformation polymorphism method. We found 5 homozygous deletions, 2 truncated mutations, one missense mutation, and one silent mutation of the hSNF5/INI1 gene in 7 MRT cell lines, and one homozygous deletion, one microdeletion, one splicing acceptor site mutation, and one absence of expression in 7 fresh tumor tissues of MRT and atypical teratoid (AT)/rhabdoid tumors (RTs). Homozygous deletions were also found in one (KYM-1) of 8 rhabdomyosarcoma (RMS) cell lines. To investigate characteristics of the KYM-1 cell line, we have established KYM-1 tumors in nude mice into which KYM-1 cells were transplanted. Notably, we found that MyoD1, known as a marker for RMS, was not expressed in the KYM-1 cell line as well as MRT cell lines and fresh tumors. Histopathologic, cytogenetic, and molecular studies of the KYM-1 cell line and KYM-1 tumors in nude mice have revealed that this RMS cell line should be MRT rather than RMS. RMS-carrying aberrations of the hSNF5/INI1 gene should be reevaluated. No aberrations of this gene were found in the other 34 cell lines or 80 fresh tumor specimens except the single nucleotide polymorphisms in the 3' noncoding region. These results suggest that alterations of the hSNF5/INI1 gene were restricted to MRTs or AT/RTs in pediatric solid tumors.

Adult↗
PubMed1993

Identification of colon-tumor-associated antigens by T-cell lines derived from tumor-infiltrating lymphocytes and peripheral-blood lymphocytes from patients immunized with an autologous tumor-cell/bacillus Calmette-Guérin vaccine.

Tumor immunity developing as a response to an autologous colon-tumor/bacillus Calmette-Guérin (BCG) vaccine appears to be associated with induction of CD4+ helper T cells, implied by the observation that vaccine efficacy is associated with major histocompatibility complex class-II molecule expression on the vaccine tumor cells. Therefore, in an attempt to identify colon-tumor-associated antigens responsible for conferring immunity, we examined and compared the proliferative responses of peripheral-blood lymphocytes (PBL) from patients immunized with the autologous tumor/BCG vaccine to T-cell lines cloned expanded from colon-tumor-infiltrating lymphocytes to 5 antigens isolated on the basis of their reactivity by colon-tumor-reactive human monoclonal antibodies. Enzymatically dissociated colon tumors provided a source for establishment of cloned T-cell lines, tumor cell lines propagated in vitro or in vivo as nude-mouse xenografts and EBV-transformed B-cell lines used as antigen-presenting cells. Of 104 different T-cell lines tested, only 3 proliferated in response to CTAA 28A32-46K, and I to the CTAA28A32-32K antigen. In contrast, PBL from 64% of patients immunized with the autologous colon-tumor/BCG vaccine responded to the CTAA 28A32-32K antigen. This antigen is related to a family of calcium- and phospholipid-binding placental proteins termed annexins. Since proliferative responses developed to this antigen after vaccination in 64% of individuals, this antigen may be an important common colon-tumor-associated rejection antigen.

Animals↗
PubMed1993

Transfer of tumor immunity by both CD4+ and CD8+ tumor infiltrating T lymphocytes activated in vivo by IL-2 therapy of tumor bearing mice.

DBA/2 mice were inoculated i.p. with syngeneic SL2 lymphoma or P815 mastocytoma on day 0 and treated i.p. with 20,000 units IL-2/day on day 10-14. This treatment is curative for 70-90% of the tumor bearing mice. Peritoneal cells and/or spleen cells were isolated from responding mice at the last day of IL-2 therapy. The in vivo antitumor activity of these cells was tested in Winn Assays (i.p.) and by adoptive transfer (i.v.) into mice injected s.c. with tumor previously. Peritoneal exudate cells isolated on day 14 (PEC14) from mice cured of SL2 tumor were highly effective in Winn Assays. Up to 5 x 10(7) SL2 cells could be eliminated in naive mice when injected i.p. together with 2 x 10(7) PEC14. Adoptive transfer (i.v.) of PEC14, without the addition of IL-2, into mice s.c. injected with SL2 tumor cells 1 or 3 days earlier, also prevented outgrowth of the tumor cells. T cells isolated from the spleens were less effective. Only at E:T ratios of 100:1 and 10:1 was tumor outgrowth inhibited. The adoptive transfer of PEC14 resulted in a long lasting immunity of the recipient mice. Furthermore, it was shown that depletion of both the CD8+ and CD4+ T cells from the suspensions used in the transfer studies, resulted in a significant decrease of tumor inhibition. However, the effect was not abrogated completely. PEC14 isolated from IL-2-treated DBA/2 mice cured of P815 tumor, protected naive mice against P815 tumor at E:T ratio 20:1. Adoptive transfer (i.v.) of these PEC14 into mice bearing s.c. P815 did not have an antitumor effect. In conclusion, low dose i.p. IL-2 therapy predominantly induces locally both CD4+ and CD8+ T cells with a strong antitumor activity in vivo. The potency of the IL-2-induced immunity seems related to the type of tumor used.

Animals↗
PubMed2006

Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity.

The proteasome inhibitor, bortezomib, and the histone deacetylase inhibitor, depsipeptide (FK228), up-regulate tumor death receptors. Therefore, we investigated whether pretreatment of malignant cells with these agents would potentiate natural killer (NK)-mediated tumor killing. NK cells isolated from healthy donors and patients with cancer were expanded in vitro and then tested for cytotoxicity against tumor cell lines before and after exposure to bortezomib or depsipeptide. In 11 of 13 (85%) renal cell carcinoma cell lines and in 16 of 37 (43%) other cancer cell lines, exposure to these drugs significantly increased NK cell-mediated tumor lysis compared with untreated tumor controls (P < 0.001). Furthermore, NK cells expanded from patients with metastatic renal cell carcinoma were significantly more cytotoxic against autologous tumor cells when pretreated with either bortezomib or depsipeptide compared with untreated tumors. Tumors sensitized to NK cell cytotoxicity showed a significant increase in surface expression of DR5 [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-R2; P < 0.05]; in contrast, surface expression of MHC class I, MIC-A/B, DR4 (TRAIL-R1), and Fas (CD95) did not change. The enhanced susceptibility to NK cell killing was completely abolished by blocking TRAIL on NK cells, and partially abolished by blocking DR5 on tumor cells. These findings show that drug-induced sensitization to TRAIL could be used as a novel strategy to potentiate the anticancer effects of adoptively infused NK cells in patients with cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Failure of B7.1-modified tumor to evoke full activation of CD8+ tumor-infiltrating lymphocytes in the central nervous system: prevention of parental tumor growth in the subcutaneous environment.

OBJECT: It is well known that the central nervous system (CNS) is an immunologically privileged site. To characterize CD8+ tumor-infiltrating lymphocytes (TILs) recovered from the CNS, the authors compared these cells with TILs recovered from subcutaneous tissue by using a B7.1 gene-modified tumor implantation model. METHODS: The authors established a B7.1 gene-modified EL4 murine lymphoma cell line (EL4-B7.1) and implanted the cells into the CNS to observe the duration of tumor-free survival. Although EL4-B7.1 cells were completely rejected in a subcutaneous implantation model, 40% of animals died after the CNS implantation (all animals in which the parent tumor was implanted died within 16 days). Therefore, the authors isolated TILs from each implantation site and analyzed the expressions of activation antigens CD25 and CD69 by performing the anti-CD8 magnetic beads separation method and flow cytometric analysis. After implantation of the parent tumor, there was no difference in the number of TILs from each site (CD25 1.7-3.2%, CD69 21.9-34.3%). After implantation of the B7.1-modified tumor, the CD25-expressing TIL population from the subcutaneous site was 4.68 times higher than that from the CNS site (17.8% compared with 3.8%). Based on these findings, the authors used a mitomycin C-treated EL4-B7.1 subcutaneous vaccination with various protocols. Vaccination before tumor challenge was sufficient to prevent the development of the tumor. For animals with established tumor, the vaccination protocol was able to prolong host survival (p = 0.0053). CONCLUSIONS: The data clearly demonstrate that the CNS environment fails to activate CD8+ TILs fully. These are the first data indicating in detail a difference between CD8+ TILs from the CNS and those from other sites based on a B7.1-modified tumor model.

Animals↗
PubMed1993

Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines.

Metastatic renal cell carcinoma (RCC), like melanoma, belongs to the small group of human tumors in which partial or complete remission has been observed in some patients after treatment with various forms of immunotherapy. In contrast to melanoma, CTL showing MHC-restricted lysis of RCC have not been easily found among tumor-infiltrating lymphocytes (TIL). This has led to the suggestion by some that responses to immunotherapy are mediated predominantly by non-MHC-restricted effector cells. We have characterized an MHC-restricted, CD8+ CTL line obtained from an uncloned TIL population of a primary RCC using a low concentration of rIL-2; in fact, these CTL represented a majority of the short-term cultured TIL population. The CTL lysed autologous tumor cells but not normal kidney cells or target cells sensitive to non-MHC-restricted effector cells. In contrast, lymphokine-activated killer (LAK) cells grown in a high concentration of rIL-2 from the patient's PBL lysed autologous tumor and normal kidney cells in addition to several allogeneic tumors. The TIL could be expanded optimally using an autologous tumor line retrovirally transduced with the human cDNA encoding IL-2. TIL were 20-fold more potent than LAK cells in eliminating the IL-2 expressing tumor cells in vitro. The cultured TIL utilized a restricted number of V alpha gene families, suggesting that they may recognize only a limited number of MHC-peptide complexes presented by autologous tumor cells. HLA-A2 was identified as an MHC restriction molecule for presentation of one tumor-derived peptide to these CTL. Only some allogeneic HLA-A2 RCC tumors were lysed. Sequencing of the second and third exons of the HLA-A2 alleles of these cells revealed that both heterogeneity in MHC and peptide availability influenced CTL recognition. These studies demonstrate that some RCC express common antigenic determinants that can be recognized by MHC-restricted CTL and open the possibility of defining the nature of RCC-derived peptides, which, combined with HLA-A2, can generate specific immune responses.

Antibodies, Monoclonal↗
PubMed1997

IL-12-induced tumor regression correlates with in situ activity of IFN-gamma produced by tumor-infiltrating cells and its secondary induction of anti-tumor pathways.

Administration of recombinant interleukin-12 (rIL-12) into CSA1M fibrosarcoma-bearing mice results in complete regression of growing tumors. This tumor regression is associated with massive lymphoid cell infiltration to tumor sites and is completely blocked by injection of anti-interferon-gamma (IFN-gamma) monoclonal antibody (mAb). We investigated whether anti-IFN-gamma mAb exerts its suppressive effect on tumor regression by blocking the IL-12-induced lymphoid cell migration to tumor sites or by inhibiting the secondary effects of IFN-gamma produced by infiltrating cells. Injection of anti-IFN-gamma mAb to CSA1M-bearing mice before IL-12 treatment prevented the induction of tumor regression, whereas this treatment affected only marginally the infiltration of lymphoid cells to tumor masses. In accordance with this, IFN-gamma mRNA was expressed inside tumor masses by infiltrating cells after IL-12 therapy irrespective of whether anti-IFN-gamma mAb was injected. However, anti-IFN-gamma mAb treatment almost completely abrogated the in situ expression of inducible nitric oxide synthase (iNOS) as well as IFN-inducible protein-10 (IP-10) genes as examples of IFN-gamma-inducible genes. Immunohistochemical analyses also revealed that the expression of iNOS protein was completely inhibited by anti-IFN-gamma injection. These results suggest that the implementation of in situ IFN-gamma activity and its secondary induction of anti-tumor pathways such as iNOS and IP-10 expression are important processes in the IL-12-induced tumor regression.

Animals↗
PubMed2005

Functional endogenous cytotoxic T lymphocytes are generated to multiple antigens co-expressed by progressing tumors; after intra-tumoral IL-2 therapy these effector cells eradicate established tumors.

Tumors contain many antigens that may be recognized by the immune system. It is not known whether these antigens, and the epitopes within these antigens, can all be recognized by the anti-tumor immune response or if such responses are restricted to a few dominant epitopes. Effector function of endogenous cytotoxic T lymphocytes (CTL) generated during tumor progression has previously been assessed by indirect, ex vivo assays, which often focused on a single antigen. Therefore, we evaluated the endogenous in vivo CTL response to multiple neo tumor antigens using murine Lewis lung carcinoma tumor cells transfected with ovalbumin or a polyepitope construct. Both express multiple MHC class I-restricted epitopes. Ovalbumin contains a known hierarchy of epitopes for given MHC molecules, whilst the polyepitope expresses a number of dominant epitopes. We show that as tumors progress, potent effector CTL are generated in vivo that are restricted to dominant epitopes; we did not see the responses to subdominant or cryptic epitopes. Our data show that the CTL recognizing tumor antigens vary in their lytic capacity, as the CTL responding to two of the four epitopes were particularly potent killers. The presence of these effector CTLs did not prevent tumor growth. However, intra-tumoral IL-2 treatment altered the potency, but not the hierarchy, of these CTL such that they mediated tumor regression. These results have implications for immunotherapy protocols.

Animals↗
PubMed2003

Intra-tumoral injection of CpG results in the inhibition of tumor growth in murine Colon-26 and B-16 tumors.

Direct tumor injections of CpG (ODN #1826) into murine tumors markedly suppressed the tumor growth and increased the survival of the mice. Tumor growth was reduced by 60-67% in Colon Tumor 26 (CT-26) and B-16 melanoma tumors treated with CpG as compared to untreated one. In CT-26 and B-16 tumors treated with CpG, the average survival of the animals were prolonged to 26 and 28 d as compared to 16 and 18 d in control respectively. Long-term surviving animals in CT-26 tumor groups were also protected from a subsequent injection of a lethal dose of tumor cells. In the present study, effect of CpG was mediated through CD8+ T cells, as their depletion resulted in the abrogation of the therapeutic effects of the CpG. It suggests that direct tumor injection might be a simple means of achieving a clinical response in cancer patients.

Animals↗
PubMed1977

Immune surveillance against virus-induced tumors and nonrejectability of spontaneous tumors: contrasting consequences of host versus tumor evolution.

Spontaneous tumours are defined as tumors that develop in the absence of all experimental interference. In contrast to the widely documented, strong rejection reactions against most virus-induced tumors, spontaneous tumors evoke little or no detectable rejection reaction in intact or preimmunized syngeneic hosts. The difference can be viewed in relation to the contrasting natural history of the two conditions. Spontaneous tumors evolve in several steps, as a fule. "Tumor progression" is a microevolutionary process at the level of the somatic tissue where successive clonal variants replace each other. Each new variant gains the upper hand due to its greater independence of some restricting host mechanism. Independence of immune restrictions must be part of this process. Host selection for immune resistance apparently plays no major role here, presumably because most of the naturally occurring tumors arise after the host has passed the peak of its reproductive period. Protection against the oncogenic effects of ubiquitous tumor viruses is, on the other hand, the result of host selection for immune mechanisms favoring prompt rejection of virus-transformed cells. This is neither synonymous with nor related to protection against the viral infection per se, which is frequently successful and usually quite harmless. A certain relationship can be perceived between the degree of viral ubiquity and the strength of immune protection against the corresponding tumor cells. Natural selection for host recognition of commonly occurring, virally induced changes in neoplastic cell membranes can be surmised to occur, at least in part, by the fixation of appropriate immune responsiveness (Ir) genes. The role of Ir genes for tumor recognition can be approached by the genetic analysis of the F1 hybrid resistance effect. Unresponsiveness to spontaneous tumors may be overcome by target-cell modification, e.g., by chemical coupling, somatic cell hybridization, or viral "xenogenization".

Animals↗
PubMed1990

Mechanism of antitumor activity of tumor necrosis factor alpha with hyperthermia in a tumor necrosis factor alpha-resistant tumor.

Cells from a radiation-induced fibrosarcoma (RIF-1) are exceedingly resistant to tumor necrosis factor alpha (TNF-alpha) in vitro. We tested whether the addition of mild hyperthermia (42.5 degrees C, 30 minutes) could enhance TNF-alpha activity against RIF-1 tumors growing in syngeneic hosts (C3H mice). TNF-alpha was administered intratumorally. Tumor cell killing essentially was not measurable following TNF-alpha, hyperthermia, or a combination of the two. Single-modality treatments also had no effect on tumor growth delay or on the x-ray dose (given 24 hours after the primary treatment) required to sterilize 50% of the tumors. The combination of TNF-alpha and hyperthermia, however, resulted in a marked increase in tumor doubling time and a highly significant reduction in the x-ray dose required to sterilize the tumors. Syngeneic lymph nodal lymphocytes and blood leukocytes did not appear to mediate the action of TNF-alpha on RIF-1 cells in vitro. Necrosis and hemorrhage were the most prominent histopathological alterations in the treated tumors. Electron microscopic studies 6 hours after therapy showed increased damage to capillary endothelial cells and accumulation of neutrophils in the capillaries of tumors treated with TNF-alpha with or without heat, suggesting that neutrophils may mediate the endothelial cell injury. These observations indicate a greater than additive tumoricidal effect of TNF-alpha with hyperthermia. Furthermore, they support the concept that the interaction between the two agents damages the vasculature, compromising the microcirculation and ultimately causing ischemic tumor necrosis.

Animals↗
PubMed2007

Prognostic value of tumor architecture, tumor-associated vascular characteristics, and expression of angiogenic molecules in pancreatic endocrine tumors.

PURPOSE: It is difficult to predict the biological behavior of pancreatic endocrine tumors (PETs). Our aim was to evaluate the prognostic significance of certain variables in PETs. EXPERIMENTAL DESIGN: The following variables were examined in 37 patients with PETs and then compared with other clinicopathologic characteristics: histologic tumor structure; microvessel density (MVD) measured by three different methods, including a unique method involving calculation of solid area MVD; endothelial proliferation; and the immunohistochemical expression of vascular endothelial growth factor-A and CXC chemokine CXCL-12. Intratumoral vascular structures were analyzed by double immunofluorescence using 30-microm-thick sections. RESULTS: The presence of focal and intensive solid growth of tumor cells (large solid nests; P = 0.003), low solid area MVD (P = 0.002), a high endothelial cell proliferation index (EPI; P = 0.005), and high expression of CXCL-12 in PET cells (P = 0.018) were significant unfavorable prognostic indicators. The predominant structure of the overall tumor histology and the expression of vascular endothelial growth factor-A did not separate aggressive PETs. In areas of focal solid growth, tumor-associated blood vessels had obviously low MVD and high EPI, and their structures were poorly formed with highly abnormal features, in comparison with other areas. High expression of CXCL-12 in tumor cells was significantly associated with variables representing tumor growth, hematogenous tumor spread, low MVD, high EPI, and the presence of large solid nests. CONCLUSIONS: This study has provided novel findings on the prognostic features of tumor architecture and tumor-associated angiogenesis in PETs. CXCL-12 is the first candidate molecule in association with neoangiogenesis in PETs.

Adolescent↗
PubMed1992

Effect of thrombin treatment of tumor cells on adhesion of tumor cells to platelets in vitro and tumor metastasis in vivo.

Seven different tumor cell lines (human melanoma SK MEL 28; hamster melanoma HM29; murine melanomas B16F10 and amelanotic melanoma B16a; human colon carcinoma HCT8; murine colon carcinoma CT26; and murine Lewis lung carcinoma) were treated with thrombin at 0.5-1 unit/ml and examined for their ability to bind to adherent platelets; HM29 was studied for its ability to bind to fibronectin and von Willebrand factor; CT26, B16F1, B16F10, and B16a were studied for their ability to form pulmonary metastasis after i.v. injection of thrombin-treated tumor cells; CT26 was studied for its ability to grow s.c. Five of 7 thrombin-treated tumor cell lines increased their adhesion to adherent platelets 2-to 3-fold. HM29 increased its adherence to fibronectin and von Willebrand factor 2- to 3-fold. CT26, B16F1, B16F10, and B16a increased experimental pulmonary metastasis 10- to 156-fold. Thrombin-treated CT26 cells demonstrated 2-fold greater growth in vivo after s.c. injection. The mechanism of enhanced adhesion of thrombin-treated tumor cells to platelets required the platelet integrin GPIIb-GPIIIa since it could be inhibited by agents known to block adhesion of ligands to GPIIb-GPIIIa (monoclonal antibody 10E5, tetrapeptide RGDS, disintegrin Albolabrin); as well as a "GPIIb-GPIIIa-like" structure on tumor cells since it could be inhibited by treatment of thrombin-treated tumor cells with 10E5 and RGDS. The thrombin effect on tumor cells was optimum at 1 h of incubation with thrombin, did not require active thrombin on the tumor cell surface, and did not require protein synthesis (not inhibited by cycloheximide). Thus, thrombin-treated tumor cells markedly enhance pulmonary metastasis. It is suggested that this may be secondary to thrombin-induced enhanced adhesion as well as growth of tumor cells.

Animals↗
PubMed1998

Cytogenetic alterations in eight mammary tumors and tumor-suppressor gene p53 mutation in one mammary tumor from dogs.

OBJECTIVE: To identify mutations in canine mammary tumors. ANIMALS: 10 tumor-bearing dogs. PROCEDURE: Culture of neoplastic cells originating from mammary tumors was performed, and trypsin-G banding was used for cytogenetic investigations. The same tumors were subjected to molecular genetic screening by use of DNA extraction, polymerase chain reaction, DNA elution, and DNA sequencing for ras oncogenes and the p53 tumor suppressor gene. RESULTS: A broad spectrum of chromosome aberrations was observed, including trisomies, reciprocal translocations, and structural and numerical X-chromosome alterations and deletions. Molecular genetic analysis revealed a tumor suppressor p53 gene mutation in codon 249 of exon 7 in one instance. Interestingly, analyzed mammary tumors were free of mutations in N-ras, K-ras and H-ras, exons 1 and 2. CONCLUSIONS: Chromosome alterations are wide-spread in canine mammary tumors, but no ras family mutations were detected in tumors from these 10 dogs. CLINICAL RELEVANCE: Knowledge about chromosome, oncogene, and tumor suppressor gene damage could be helpful for diagnosis and prognosis of neoplastic diseases in dogs.

Adenocarcinoma↗
PubMed1997

HLA-A2402-restricted and tumor-specific cytotoxic T lymphocytes from tumor-infiltrating lymphocytes of a child with Wilms' tumor.

The existence of specific immunity against pediatric tumors is not well studied. We report here the CD3+CD4-CD8+ cytotoxic T lymphocyte (CTL) line established from tumor-infiltrating lymphocytes (TIL) of a 3-mo-old child with Wilms' tumor. This CD3+CD4-CD8+ CTL line showed cytotoxicity against the HLA-A2402+ tumor cells including the autologous tumor, adenocarcinomas from various organs (colon, stomach, lung, and ovary), and an esophageal squamous cell carcinoma. No other cell lines examined, including HLA-A2402- tumors, K562 cells, or HLA-A2402+ normal cells were lysed by this CTL line. This CTL line recognized an HLA-A2402- ovarian adenocarcinoma transfected with HLA-A2402 cDNA. These results suggest the existence of HLA-A2402-restricted and tumor-specific CTL at the tumor site of a child with Wilms' tumor.

Base Sequence↗
PubMed2001

Molecular cloning of pituitary tumor transforming gene 1 from ovarian tumors and its expression in tumors.

Pituitary tumor transforming gene 1 (PTTG1) recently cloned from human testis is a potent oncogene and is highly expressed in all the tumors analyzed to date. However, primary structure of PTTG1 and the cell types that express PTTG1 in tumors remained undescribed. We have used the reverse transcriptase-polymerase chain reaction technique to clone PTTG1 from ovarian tumors. Nucleotide sequencing of the PTTG1 cDNAs from various ovarian tumors showed identity with that of the human testis PTTG1. To determine the cell types that express PTTG1 in normal and tumor tissues, we performed in situ hybridization using digoxigenin-labeled cRNA as a probe. Our studies revealed a high level of expression of PTTG1 mRNA in both seminomatous and non-seminomatous testicular tumors; epithelial, sex-cord and stromal cell, and germ cell tumors of the ovary; and invasive ductal, ductal in situ and infiltrating ductal carcinoma of the breast. In normal tissues, expression of PTTG1 mRNA was very low or undetectable except in testis, where PTTG1 mRNA was found to be localized to spermatocytes and spermatids. Tumors that expressed high levels of PTTG1 mRNA also exhibited high levels of expression of basic fibroblast growth factor (bFGF), suggesting a correlation between PTTG1 and bFGF expression, and further suggesting that the PTTG1 protein may be involved in tumor angiogenesis and mitogenesis.

Amino Acid Sequence↗
PubMed1975

Different responses of lymphoid cells from tumor-bearing as compared to tumor-immunized mice when sensitized to tumor specific antigens in vitro.

Lymphoid cells from spleen and lymph nodes of BALB/c mice were sensitized in vitro by cocultivation with cells from syngeneic methylcholanthrene-induced sarcomas. The donor mice were either immunized in vivo by tumor transplantation followed by excision ("tumor-excised mice") or were carrying a progressively growing tumor ("tumor-bearing mice"). The cell-mediated immune response of the sensitized cells was compared by a 36-hr microcytotoxicity assay. Lymphoid cells from tumor-excised mice were cytotoxic when tested after 3 days and also after 6 days of sensitization in vitro. Lymphoid cells from tumor-bearing mice were cytotoxic to cells of the tumor borne when tested after 3 days in culture. However, the cytotoxic effect was lost after 6 days of contact with the sensitizing tumor in vitro. Preliminary data suggest that the cultured lymphoid cells of tumor-bearing mice which have lost cytotoxicity, can suppress the reactivity of in vitro sensitized lymphoid cells from tumor-excised mice.

Animals↗