Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors studied 68 patients suffering from breast cancer, with or without lymph node metastasis, who underwent surgery and antitumour therapy (CMF). Twenty-three patients were treated using CMF and 1.5 mg/kg of thymostimulin, 24 with CMF and 1 mg/kg of thymostimulin and lastly, 21 subjects received anti-tumour therapy with CMF alone. Thymostimulin was administered every day for a week prior to surgery; subsequently, it was administered on alternate days for a week and then twice a week for 3 months. The blastogenesis of immunocompetent cells was evaluated. During thymostimulin treatment a higher rate of 3HTdR captation (p < 0.005) by cells stimulated with ConA + IL-2 was observed; these levels tended to increase after 3 weeks and reached statistically significant levels after 3 months of treatment; no significant changes were observed in those patients treated with CMF alone. In addition, the cytotoxic activity of monocytes and NK cells against K-562 cells and against short-lasting cell lines derived from breast carcinoma was also studied. It was observed that this activity increased significantly (p < 0.002) following thymostimulin treatment; this increase was greater in subjects treated with 1.5 mg/kg compared to those treated with 1 mg/kg, but the difference was not statistically significant. The study also evaluated the presence of IL-2 receptors (Tac): thymostimulin treatment for 3 months led to the appearance of receptors, although in restricted numbers, on non-stimulated cells. After IL-2 stimulation, the percentage of cells with Tac receptors increased significantly (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of immunostimulating therapy on the immunocompetent system in breast carcinoma. 129 46

The metastatic non-small cell lung cancer (NSCLC) still remains an untreatable disease, and the role played by chemotherapy has yet to be defined. The new immunotherapeutic strategies, such as interferon and IL-2, seem to be also less effective, since they generally determine only a stabilisation of disease. On the basis of previous experimental results suggesting a synergistic action between IL-2 and the pineal neurohormone melatonin (MLT), a study was started to evaluate the clinical efficacy and toxicity of a neuroimmunotherapeutic combination consisting of IL-2 plus MLT as a first line therapy in metastatic NSCLC. The study included 20 patients (adenocarcinoma: 10; epidermoid cell carcinoma: 7; large cell carcinoma: 3). MLT was given orally at a dose of 10 mg day-1 at 8.00 pm every day, starting 7 days before the onset of IL-2 administration. IL-2 was given subcutaneously at a dose of 3 x 10(6) IU m-2 every 12 h for 5 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In responder patients or in those with stable disease, a second cycle was given after a rest-period of 21 days. A partial response was achieved in 4/20 (20%) patients. Ten other patients had a stable disease (50%), whereas the last six patients progressed. Toxicity was low in all cases. This study shows that the neuroimmunotherapeutic therapy with IL-2 and the pineal hormone MLT may represent a new effective and well tolerated treatment in metastatic NSCLC, with results comparable to those obtained with chemotherapy, but with an apparent lower biological toxicity.
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PMID:Biological and clinical results of a neuroimmunotherapy with interleukin-2 and the pineal hormone melatonin as a first line treatment in advanced non-small cell lung cancer. 132 55

Previous in vitro and in vivo studies have shown a synergism between interferon (IFN) and 5-fluorouracil (5-FU) against different tumor cell lines. In the present study we report that the combination of IFN-alpha and 5-FU has a significant effect not only on the inhibition of tumor cell growth but also on the regulation of natural killer cell-mediated cytotoxicity (NK-CMC). The addition of 5-FU to effector cell population neither affects NK cell activity nor activation of NK cells by IFN or by interleukin (IL)-2. However, pretreatment of target cells with 5-FU increased their susceptibility to NK activity and abolished the protective effect induced by IFN against NK-CMC. This dual effect of IFN-alpha and 5-FU was found to be applicable to target cells of different origins including a cervical carcinoma cell line (ME-180), a hairy cell leukemia-like cell line (Eskol), a CML cell line (K-562) and a primary culture of AIDS-related Kaposi's sarcoma cells. Similar results were found with IL-2 treatment of Eskol cells but not other cells. Combination of IL-2 with 5-FU resulted in enhancement of the sensitivity of the cells to NK activity and abolished the protection against NK-CMC. Based on these results we propose that the combination of IFN-alpha and 5-FU not only has a direct growth inhibitory effect on tumor cells but also has a regulatory role on the immunological arm of the NK-CMC. Moreover, since the combination gave the same pattern of response in different tumor cells, both NK-sensitive and NK-resistant, this combination treatment may be a candidate for clinical trials in various types of tumors.
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PMID:A dual anti-tumor effect of a combination of interferon-alpha or interleukin-2 and 5-fluorouracil on natural killer (NK) cell-mediated cytotoxicity. 137 Feb 57

This study examined the production of an immunosuppressive factor by the KB and H191 human oral squamous carcinoma cell lines. Conditioned media (CM) from both cell lines markedly inhibited mitogen- and alloantigen-induced proliferation of normal human and rat peripheral blood lymphocytes. By contrast, the proliferation of an exponentially-growing fibroblast cell line remained unchanged by CM. The immunosuppressive factor appeared to act after lymphocyte commitment as indicated by continued blast cell formation, the failure of CM to suppress resting lymphocytes and the fact that CM caused maximum inhibition of lymphocyte proliferation 72 h after the addition of PHA. The addition of exogenous IL-2 did not counteract lymphocyte suppression. Inclusion of indomethacin and isoniazid during cell culture did not significantly alter the degree of suppressive activity. Mycoplasma contamination was absent and CM did not act directly with the thymidine or mitogen. The factor was heat stable at 50 degrees C, acid labile and had a molecular weight in excess of 300 kDa. The results demonstrate that human oral squamous carcinoma cell lines produce an immunosuppressive factor that may have a role in tumour evasion of the host immune response.
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PMID:Production of a suppressor of lymphocyte proliferation by two human oral carcinoma cell lines. 138 28

The effects of the i.v. administration of endotoxin (6.25-50 micrograms/mouse on day 13 after tumor implantation) in mice treated orally with lysozyme hydrochloride (100 mg/kg on days 5-12 from tumor implantation) were examined using Lewis lung carcinoma in the C57Bl mouse and MCa mammary carcinoma of CBA mice. On primary tumor growth, endotoxin alone causes a dose-dependent and statistically significant reduction with a nadir on day +2 from endotoxin treatment. Combined with lysozyme, endotoxin causes an effect independent of the dose used, corresponding to the effect caused by endotoxin alone at the dose of 25 micrograms/mouse. No tumor regression was recorded in any of the treated groups. Endotoxin is virtually devoid of effects at the metastatic level. In the same conditions, lysozyme causes a reduction of primary tumor growth and a more pronounced inhibition of lung metastasis formation as expected from its already reported effects. The antitumor activity of endotoxin, unlike lysozyme, can be ascribed to tumor hemorrhagic necrosis due to tumor necrosis factor (TNF) production, as determined in tumor homogenates. Endotoxin does not increase the antitumor effects in mice treated with lysozyme, as expected from the data obtained with the more immunogenic SA1 sarcoma, although lysozyme increased the mitogenic response to ConA of ex vivo isolated splenocytes, in vitro cultured in the presence of IL-2.
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PMID:Effects of endotoxin in mice bearing solid metastasizing tumors and treated with lysozyme hydrochloride. 140 79

Cytokines have recently appeared to be effective in the palliative therapy of neoplastic effusions. The present study was carried out to evaluate the efficacy and the tolerability of an intracavitary injection of IL-2 in patients with neoplastic effusion due to solid tumors. The study included 14 patients with cytologically positive effusion (pleura, 11; peritoneum, 2; pericardium, 1). Tumor histotypes were: mesothelioma, 5; non-small cell lung cancer, 3; breast cancer, 2; ovarian cancer, 2; cervix carcinoma, 1; unknown primary tumor, 1. The efficacy was evaluated according to the criteria of Paladine et al. (Cancer 38: 1903, 1976). An objective response was achieved in 10/14 (71%) patients (4 CR, 6 PR), with a median duration of 4 months (range, 2-8). No important toxicity was seen. This preliminary study showed that low dose IL-2 given intracavitarily is an effective and well-tolerated therapy in patients with neoplastic effusions.
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PMID:Intracavitary administration of interleukin-2 as palliative therapy for neoplastic effusions. 152 3

In order to determine the growth factor requirements of hairy cell leukemia (HCL) cells, we studied the in vitro effects of tumor necrosis factor (TNF), interleukin (IL) 1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, B-cell growth factor (BCGF), GM-CSF, PHA-stimulated lymphocyte-conditioned media (CM), and 5637 bladder carcinoma CM on HCL cells obtained from spleens of patients with HCL. Mononuclear cells from a normal donor, obtained at post-traumatic splenectomy, served as a control. TNF prolonged the survival of HCL cells obtained from five different HCL patients when compared to cells cultured in control media alone, although cell proliferation could be demonstrated in only two of the five. HCL cells stained negative for the Epstein-Barr nuclear antigen (EBNA) both before and after 4 weeks in culture. BCGF, 5637 CM, and PHA-stimulated lymphocyte CM also prolonged the survival of HC25 and HC56 cells, although not to the same degree as TNF. Cells cultured in BCGF, however, stained positive for EBNA. None of the other recombinantly produced or purified cytokines prolonged the survival of the leukemic cells. With the exception of IL-2, none of the growth factors studied prolonged the survival of purified normal spleen (NS) cells over a 4-week period of time when compared to NS cells incubated in media alone. TNF prolonged the survival of HC25 cells in a dose-dependent manner, and a highly purified antibody to TNF abrogated the effects of TNF. HC25 cells incubated in the presence of control media alone did not constitutively produce TNF mRNA; however, incubation of the cells in the presence of TNF for 48 h induced the cells to express TNF message. We conclude that TNF is important in prolonging the survival of HCL cells, and thus may be important in the pathogenesis of this disease.
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PMID:Tumor necrosis factor, but not other hematopoietic growth factors, prolongs the survival of hairy cell leukemia cells. 156 38

To study the effect of hepatectomy on the growth of liver tumor, Shionogi Carcinoma 42, a mammary tumor, was transplanted into the liver of mice which had undergone 40% hepatectomy. The liver tumor and the number of pulmonary metastases in hepatectomized mice were significantly larger than those in nonhepatectomized mice. Responses to lectins and IL-2, subpopulations, and cytotoxicity to YAC-1 and P815 cells of splenocytes were assessed to evaluate immunological status. At the initial phase after hepatectomy and tumor transplantation into the remaining liver, NK activity transiently increased, and function of B and T cells, especially of helper T cells, decreased, while B-cell function recovered beyond normal levels in a later phase. These results suggest that liver may play an important immunological role and that the immunological modification after hepatectomy may be responsible for the accelerated growth of liver tumor. Accordingly, some adjuvant immunotherapy may be recommended for the prevention of recurrence after hepatectomy for liver tumor.
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PMID:Hepatectomy accelerates the growth of transplanted liver tumor in mice. 160 May 23

The correlation between the presence and absence of HLA Class II antigen and stromal lymphocyte infiltration in cervical cancer tissue was analyzed immunohistologically. The correlation was also studied in relation to the prognosis of patients with cervical carcinoma. Immunohistological staining was performed with a monoclonal antibody differentiating monomorphic determinants of HLA-DR and an antibody (HU-30) differentiating HLA-DR1/2, one of the polymorphic determinants, in 36 patients with cervical carcinoma. Infiltrating lymphocytes were identified immunohistologically with various monoclonal antibodies, and the following results were obtained: 1) Twenty-six (72.2%) of the 36 patients were evaluated as positive for HLA-DR1/2 from the reaction with HU-30. 2) Cancer cells from 21 (80.8%) of the 26 patients were HLA-DR positive, while those from 5 (19.2%) were HLA-DR negative. 3) Cancer cells from 12 (46.2%: group A) of the 21 patients were also positive for HLA-DR1/2, while those from 9 (34.6%) were negative for the determinant. 4) There was no patient whose stromal lymphocytes were negative for HLA-DR1/2 and whose cancer cells alone were positive for the determinant. Thus, there was a total of 14 patients (53.8%: group B) whose cancer cells were negative for HLA-DR. 5) The lymphocytes that infiltrated the area surrounding the cancer lesion were mainly T cells, with Leu-3a cells (helper/inducer T cell) more abundant than Leu-2a cells (suppressor/cytotoxic T cell). 6) Infiltration of T cells, the subgroup and IL-2-receptor-positive cells was greater in group A than in group B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunohistological study on HLA class II antigen expression and lymphocyte infiltration in cancer tissues of the uterine cervix]. 160 58

Killer cell activity against Shope carcinoma cells was not detected in PBL nor in spleen cells from tumor-bearing B/J rabbits, but was induced by in vitro culture of these cells in the presence of IL-2 and X-irradiated carcinoma cells. HTLV-I-transformed killer cell lines were successfully obtained by the culturing of PBL from an HTLV-I-infected and tumor-bearing Chbb:HM rabbit. These killer cells included large cells with azurophilic granules in the cytoplasm and with a reniform nucleus, thus resembling large granular lymphocytes. The killer activity was similar against the Vx2K cell line from a random-bred rabbit and SCB cell lines from an B/J rabbit, suggesting the absence of MHC restriction.
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PMID:Killer cell lines against Shope carcinoma cells in rabbits. 165 41


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