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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor-infiltrating lymphocytes (TIL) were isolated from 17 human hepatocellular carcinomas (HCC). The proliferation of TIL cultured with recombinant interleukin-2 (rIL-2) was evaluated. We also examined prognosis in relation to TIL. Successful expansion of TIL was achieved in 16 of the 17 lesions. In 10 of the 16, TIL increased more than 100-fold. Cytotoxicity to the allogeneic HCC cell line, HC-4, was demonstrated in all 13 TIL cultures tested. Maximum cytotoxicity was noted two to four weeks after culture. No statistical difference was observed either with respect to prognosis based upon growth rate or the cytotoxicity demonstrated in vitro. The initial number of TIL per unit weight of tumor was, however, significantly greater in the group for which the prognosis was good (19.0 +/- 5.1 x 10(6) vs. 5.6 +/- 1.6 x 10(6), P < 0.05). It would appear that greater lymphocytic tumor infiltration is a prognostic marker.
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PMID:Tumor-infiltrating lymphocytes and prognosis of hepatocellular carcinoma. 133 71

Current assays for chicken interleukin-2 (IL-2) utilize mitogen-activated lymphocytes. However, very high inter-assay variability and sporadic high background proliferation limit their usefulness. In view of the above, several Marek's disease virus (MDV)-transformed T-cell lines (which grow well in a serum-supplemented medium) were tested for a response to chicken IL-2 when grown in serum-free media. Five of six lines examined showed a dose-dependent proliferative response to chicken T-cell conditioned media. One line, MDCC-CU14, was chosen for further studies. In addition to the tumor cells' dose-dependent responses to semi-purified chicken IL-2, they expressed T-cell activation antigens on the cell surface. Furthermore, the level of surface expression was enhanced on cells provided IL-2. Co-incubation of the tumor cells with monoclonal antibody INN-CH-16 (specific for an antigen on the surface of activated T-cells) and IL-2 resulted in a modulation of lymphokine-induced proliferation. Together, these data suggest that signalling mechanisms in MDV T-cell tumors are intact and that these lines can be used as an assay for chicken T-cell lymphokines. Furthermore, they provide an interesting model for the study of avian and mammalian T-cell transformation. Implications for the study of Marek's disease are also discussed.
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PMID:Marek's disease virus-transformed chicken T-cell lines respond to lymphokines. 133 53

The purpose of our study was to develop new biologic systems for the treatment or diagnosis of patients with ovarian carcinoma through expansion of T-cell lines from the tumor-infiltrating lymphocytes of patients with ovarian carcinoma in low-dose recombinant interleukin-2 in sufficient numbers for treatment and human monoclonal antibodies that recognize cell-surface tumor-associated antigen determinants on ovarian carcinoma cells. Technologic advances in tumor immunology and new data presented in relation to ovarian carcinoma were used to develop T-cell lines for the treatment of advanced ovarian carcinoma patients. Logarithmic expansion of T-cell lines was performed in a hollow-fiber bioreactor, and a pilot clinical trial was initiated to treat ovarian carcinoma patients with intraperitoneal tumor-infiltrating lymphocytes plus low-dose recombinant interleukin-2. Human hybridomas were produced by fusion of regional lymph node B cells with a heteromyeloma cell line SPATZ 4. Two ovarian carcinoma patients have been treated with tumor-infiltrating lymphocytes expanded to 1 x 10(10) to 1 x 10(11) with manageable side effects and evidence of biologic activity. Human monoclonal antibodies have been developed that recognize tumor-associated antigen determinants. Recombinant interleukin-2-expanded tumor-infiltrating lymphocytes and human monoclonal antibodies recognize different molecular entities on tumor cells and act by different mechanisms. These approaches may be complementary to one another in future treatment strategies for ovarian carcinoma.
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PMID:Novel immunologic strategies in ovarian carcinoma. 133 80

Tumor-infiltrating lymphocytes (TILs) were isolated from a subcutaneous metastasis of melanoma and cytotoxic T-cell lymphocyte (CTL) lines were obtained by sensitizing in vitro four separate aliquots of TILs with autologous tumor cells and recombinant interleukin-2. All CTL lines were predominantly WT31+, CD3+, and CD8+ and displayed a preferential cytotoxic activity against the autologous tumor. T-cell receptor (TCR) composition was analyzed by using the polymerase chain reaction with 5' variable region (V alpha or V beta)-specific primers and 3' constant (C alpha or C beta) primers. The entire repertoire of the V alpha and V beta gene families tested was present in fresh TILs and in the CTL lines, although, in the latter, consistent quantitative variations in transcripts of several V alpha and V beta occurred. CTL clones that exhibited CD3-dependent and major histocompatibility complex-restricted killing of the autologous melanoma were isolated from the four TIL cultures. TCR analysis indicated that, independently from the culture of origin, only two combinations of V alpha and V beta gene families were present in the majority of these CTL clones. These V alpha and V beta gene families were not found in a panel of CTL clones that did not lyse the autologous tumor. This study indicates that recognition of melanoma antigens can strongly select for certain types of TCR-bearing T-lymphocytes.
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PMID:Expansion of major histocompatibility complex-restricted antimelanoma cytotoxic T-cell lymphocyte clones with identical T-cell receptor from tumor-infiltrating lymphocytes. 133 45

Previously we have reported that human glial tumor cells secrete a factor(s) which suppresses the mitogen responsiveness of normal human peripheral blood lymphocytes (PBL) in a dose dependent manner. In this study we extend these observations and explore the possible mechanisms by which glioma-derived suppressor factor(s) (GSF) modulates lymphocyte reactivity. Preincubation of lymphocytes with GSF for 2 hrs induces suppression of lymphocyte mitogen responsiveness. GSF also inhibits production of interleukin-2 (IL-2) by mitogen activated human T-cells. Addition of delectinated or recombinant IL-2 to mitogen activated human T-cells in the presence of GSF does not restore the normal proliferative response of these cells. These findings suggest that GSF induces a defect in the expression of the receptor for IL-2 (IL-2R) on activated T-cells. Binding studies with radiolabeled IL-2 demonstrated that GSF suppresses and in some cases completely inhibits the expression of functional high affinity IL-2R on activated T-cells, thereby, preventing association of IL-2R with its receptor and the subsequent progression of the cell into the proliferative stage of the cell cycle. These cellular defects induced by GSF closely parallel the observed defects noted in T-cells obtained from patients with gliomas, indicating that the factors elicited from glial tumors may be responsible for the immunological deficits observed in patients with primary malignant intracranial tumors.
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PMID:Suppression of high affinity IL-2 receptors on mitogen activated lymphocytes by glioma-derived suppressor factor. 133 42

An African lioness from the Zoo of Zurich had to be euthanized because of an inoperable tumor. The serum tested negative for feline leukemia virus (FeLV) p27 antigen by enzyme-linked immunosorbent assay (ELISA) but was strongly positive for feline immunodeficiency virus (FIV) antibodies by ELISA and Western blot. When her only offspring and mate were tested for FIV, high antibody titers to FIV were also found in their serum. Lymphocytes were prepared from these two lions on different occasions and co-cultivated with specific pathogen free (SPF) cat lymphocytes in the presence of concanavalin A and recombinant human interleukin-2 (IL-2) for 6 weeks. The cell culture supernatants tested negative for Mg(2+)-dependent reverse transcriptase and FIV p24 by a double antibody sandwich ELISA throughout the culture period. Whole blood and buffy coat cells collected from these two lions were transmitted by intraperitoneal injection into two SPF cats. The two cats did not seroconvert for a period of 11 months nor could reverse transcriptase activity and FIV p24 antigen be demonstrated in the supernatant of several lymphocyte cultures. To determine the importance of lentivirus infections in zoo-kept wild felids, 124 serum samples were obtained from African lions, Indian and Siberian tigers, snow leopards, panthers, cheetahs and other wild cats from nine European zoos. In addition, serum samples collected from 12 Asiatic lions originating from Gir forest in the Indian State of Gujarat were included in this study. The sera were tested for antibodies to FIV, FeLV and feline syncytium-forming virus (FeSFV) by ELISA and Western blot using the respective viruses after gradient purification. In addition, some of the sera were also tested for antibodies to equine infectious anemia virus (EIAV) and Visna-Maedi virus (VMV). Antibodies to FIV were found in 30/53 (57%) of African lions, one of 18 tigers and one of four panthers. All other sera including those collected from the 12 Asiatic lions were negative for FIV antibodies. Some of the FIV positive lion sera had high antibody titers producing strong bands on Western blot strips even in dilutions of >> 1:1000. The Western blot pattern of the lion sera differed from that of domestic cats in that primarily p24 and to a lesser degree p17 was recognized. Antibodies to FeSFV were found in 14 animals (seven with strong, seven with intermediate, reaction). No correlation was found between FIV and FeSFV infection. Antibodies to FeLV were found in two cheetahs which later turned out to have been vaccinated with Leukocell, a FeLV vaccine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Retrovirus infections in non-domestic felids: serological studies and attempts to isolate a lentivirus. 133 98

The ability of Interleukin-2 (IL2) production, IL2 receptors expression and proliferative response by lymphocytes from 48 patients with primary lung cancer and 50 normal controls were studied. The results indicated that after lymphocytes were stimulated with PHA for 48 hours, the IL2 activity produced by lymphocytes from lung cancer patients was significantly reduced, the mean IL2 activity was only about 30% of that of normal controls, with lung cancer progression, the lymphocytes IL2 production tended to be more depressed. The lymphocytes IL2 receptors expression and proliferative response in cancer patients were also significantly decreased. Our study suggested that impaired IL2 production and IL2 receptors expression by lymphocytes from lung cancer patients may depress the IL2 dependent anti-tumor reaction in vivo.
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PMID:[A study about the ability of interleukin-2 production, interleukin-2 receptor expression by lymphocytes from patients with lung cancer]. 133 18

Treatment of human cancer with tumour-specific T lymphocytes is limited by the frequent unavailability of autologous tumour to stimulate T-cell growth and by the toxicity associated with high-dose interleukin-2 (IL-2) treatment. In the present study we demonstrate that Bryostatin 1 (B) plus ionomycin (I) can substitute for tumour antigen and activate tumour-bearing hosts' T-cells which provide long-term protection against tumour challenge after adoptive transfer. Lymphocytes obtained from the popliteal lymph nodes (DLN) draining an MCA-105 footpad sarcoma were stimulated with B/I, and then cultured for 7 days with 20 U ml-1 IL-2. This in vitro stimulation protocol consistently expanded cell numbers greater than 20-fold during 7 days. Mice given B/I-stimulated draining lymph node (DLN) cells were protected from specific i.v. tumour challenge for at least 15 weeks after adoptive transfer, even in the absence of IL-2 treatment. Tumour immunity conferred by B/I-activated DLN cells was systemic and independent of host T-cells. However, resistance to tumour challenge was lost when either CD4+ or CD8+ T-cells were depleted in vivo. These studies indicate that DLN cells activated with bryostatin 1 and ionomycin persist long-term in vivo as functional memory cells after adoptive transfer.
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PMID:Adoptive transfer of bryostatin 1-activated T cells provides long-term protection from tumour metastases. 134 Dec 64

Interleukin-2 (IL-2) treatment of cells and generation of non-major histocompatibility complex (MHC)-restricted cytotoxic cells from peripheral blood mononuclear leukocytes (PBML) was studied. Effector-target conjugate assays demonstrated that bovine PBML bound but did not lyse K562, HL60S and HL60R cells unless activated with IL-2. The magnitude of IL-2-activated killing of tumor cells as well as the magnitude of antibody-dependent cellular cytotoxicity depended on the IL-2 concentration. A short treatment (12-18 h) of effector cells with IL-2 was sufficient for development of cytotoxic activity. Withdrawal of IL-2 from the culture resulted in a reduction of cytotoxic activity that could be restored by further addition of IL-2. Cytotoxic activity of IL-2-activated populations obtained after nylon wool or Sephadex G-10 passage, and Percoll gradient centrifugation of PBML suggests that lymphokine-activated killer (LAK) cell activity in PBML is mainly mediated by a non-adherent lymphocyte lacking markers for B-cells. Positive and negative selection experiments using cell sorting confirmed these findings and demonstrated that the cell responsible for LAK cell activity in cattle belongs to a non-monocyte, non-B, CD2+ lymphocyte population. Furthermore, cytotoxic activity could not be generated in CD2+ populations enriched for cells expressing molecules equivalent to human and murine CD4 and CD8. These findings suggest that effector cells mediating non MHC-restricted cytotoxicity in cattle prevail in a population bearing a CD2+, CD4-, CD8- phenotype and that this population depends on the continuous presence of IL-2 for optimal cytotoxic function.
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PMID:Characterization and activation requirements of bovine lymphocytes acquiring cytotoxic activity after interleukin-2 treatment. 135 25

In an ongoing phase II study, 12 patients with lymphoma and HIV infection were treated with zidovudine (ZDV) and recombinant interleukin-2 (rIL-2) to evaluate if this association may produce beneficial effect on the immunologic status and the outcome of lymphoma. The protocol included daily doses of rIL-2 at 6 MIU/m2 over 5 days in c.i. per week for a total 4 courses; ZDV was associated at 600 mg/d in the period under study. An improved CD4 count, exceeding 2- to 4-fold the basal count, was obtained in patients with a basal CD4 number greater than 100/microliters accompanied by a significant increase of NK and LAK activity (p less than 0.001). From the clinical point of view the reduction of tumor manifestation was proportional to CD4 basal number; 2 patients from those with CD4 greater than 100/microliters obtained a complete remission after rIL-2 and ZVD. The p24 antigen, taken as parameter of viral replication, remained invariably negative after rIL-2 and ZDV in patients already negative and became negative in 1 patient previously positive. Our conclusion is that the association of rIL-2 and AZT is safe and useful in patients with lymphoma and HIV infection.
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PMID:Recombinant interleukin-2 (rIL-2) in acquired immune deficiency syndrome (AIDS): preliminary report in patients with lymphoma associated with HIV infection. 135 68


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