Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin (IL) 6 was measured in the serum of 138 patients with metastatic renal carcinoma before the initiation of IL-2 treatment. IL-6 was detectable in 66 patients with renal cancer (48%) and in only 8 of 70 normal adults (11%). Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL-6 is involved in CRP increase in these patients. The interval between diagnosis of the primary tumor and metastasis was shorter in patients with a detectable serum IL-6 and/or serum CRP level greater than 50 mg/liter. Serum IL-6 and CRP levels were higher in subgroups of patients previously defined as having a poor life expectancy according to the Eastern Cooperative Oncology Group criteria. Pretreatment concentrations of IL-6 and CRP were higher in patients who experienced progressive disease after IL-2 treatment. Patients with detectable IL-6 had a shorter survival from the beginning of IL-2 treatment than patients without circulating IL-6 (median, 8 versus 16 months). Similarly, the median survival from the beginning of IL-2 therapy of patients with CRP levels greater than 50 mg/liter was 6 months, compared to 16 months in those with CRP levels below this threshold. None of the 21 patients with serum IL-6 concentrations greater than 300 pg/ml achieved response to any of the three IL-2 regimens. This subgroup has a median survival of 5 months after IL-2 treatment and consisted of 15% of the patients in our series. These results indicate that serum IL-6 and CRP levels are adverse prognosis factors in patients with metastatic renal cell carcinoma. Serum IL-6 level could help in the selection or stratification of the patients in future IL-2 trials.
 ...
PMID:Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma. 159 90

MTP-PE in liposomes is a BRM which can be given relatively safely to patients with cancer. The maximum tolerated dose appears to be higher than the optimal dose inducing immunomodulatory effects such as cytokine induction and monocyte/macrophage activation. The most consistently induced cytokines measured in the plasma of patients a few hours after MTP-PE are TNF and IL-6. Indirect evidence supports the assumption that increased levels of TNF and IL-6 are signs of macrophage activation occurring in situ in tissues taking up liposomal MTP-PE shortly after injection. These tissues are mainly lungs, liver and spleen, as shown in 4 patients injected with radiolabelled liposomes containing MTP-PE. Assuming that activated monocytes and macrophages cannot eliminate gross tumor load, the main targets for MTP-PE are micrometastases after removal of the primary tumor. Thus, adjuvant treatment using liposomal MTP-PE in combination with chemotherapy is a major goal for the future.
 ...
PMID:MTP-PE in liposomes as a biological response modifier in the treatment of cancer: current status. 159 3

Gelatinases (GLs) belong to a family of enzymes known as matrix metalloproteinases (MMPs), which are produced by both normal and neoplastic cells. These enzymes have been implicated in tumor invasion and metastasis, although the mechanism of regulation of tumor MMP production is unknown. Since our previous studies have shown that numerous cytokines are present in the tumor microenvironment, our goal was to establish the effect of selected cytokines on GL production by both established tumor cell lines and primary cultures of head and neck squamous cell carcinoma (HNSCC). Supernatants of HNSCC cell lines SCC-25 and FADU stimulated with interleukin (IL)-1 alpha and IL-1 beta demonstrated modest induction of 92 kd GL production by zymogram analysis when compared with controls; IL-2, IL-6, and interferon-gamma had no consistent effect on MMP production. Stimulation of cell lines with tumor necrosis factor (TNF)-alpha (10(4) to 10 U/mL), however, dramatically enhanced production of 92 kd GL by both cell lines in a dose-dependent fashion, although tissue inhibitor of metalloproteinase (TIMP) expression was unaffected. Northern blot analysis showed that this enhancement of 92 kd GL occurred at the messenger RNA level. Stimulation of short-term primary tumor cultures with TNF-alpha resulted in significant enhancement of 92 kd GL expression in one of four cultures and enhancement of 72 kd GL expression in all cultures. The observed increase in GL expression by TNF-alpha suggests a role for this cytokine in the regulation of GL expression by tumor cells during invasion and metastasis.
 ...
PMID:Cytokine regulation of gelatinase production by head and neck squamous cell carcinoma: the role of tumor necrosis factor-alpha. 787 3

In the present study we evaluated the antitumor effects of recombinant human interleukin-6 (rhIL-6), expressed in Chinese hamster ovary cells, in a murine primary tumor model. We showed that treatment with rhIL-6 substantially inhibited the implantation and growth rates of CT-26 adenocarcinoma tumor cells in the rectal submucosa of syngeneic mice. This effect was achieved by injecting rhIL-6 for 7 consecutive days starting 1 day prior to tumor inoculation. No obvious antitumor effect was noted when rhIL-6 injections started 5 days after tumor inoculation. Analysis of the mechanisms by which rhIL-6 exerts its antitumor effects did not reveal a direct antitumor effect on CT-26 tumor cells or the up-regulation of major histocompatibility complex antigens on these cells. However, infiltration of lymphocytes at the tumor site was observed. Increase of carcinoembryonic antigen by IL-6 was clearly seen in human HT-29 colon carcinoma cells. The possible application of these results for adjuvant immunotherapy of selected colorectal patients and prevention of reimplantation of tumor cells disseminated during surgery is discussed.
 ...
PMID:Inhibition of CT-26 murine adenocarcinoma growth in the rectum of mice treated with recombinant human interleukin-6. 806 98

Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) was evaluated, alone or in combination with local hyperthermia (LH), for their antitumor effects in mice inoculated with B16a melanoma cells. Several tumor related parameters and other hematopoietic and immunologic parameters were evaluated 5 weeks after subcutaneous (s.c.) inoculation of tumor cells into the right limbs of C57BL/6J male mice. RhuM-CSF was administered at 20 micrograms/injection, s.c., twice a day for 5 days/week for 2 weeks beginning 6 days after tumor cell inoculation and LH (43 +/- 0.2 degrees C) was given for 30 min twice/week for 2 weeks. Combined therapy prolonged survival of mice and caused significant inhibition of tumor growth, as measured by the volume or size of primary tumor, number and size of lung metastases, and chromatin fragment (CF) formation in tumor bearing mice, while treatment with M-CSF or LH alone had less or no effect. Combined therapy also resulted in increased numbers of splenic T-lymphocytes and the ratio of T-helper/suppressor cells, restoration of natural killer (NK) cell activity, increased numbers of peritoneal macrophages and their erythrophagocytosis capacity, and increased release or production of tumor necrosis factor (TNF)-alpha, but not interleukin (IL)-1 alpha or IL-6. These results add to previous evidence that M-CSF might be a relevant therapeutic agent in combination with other therapies in the treatment of certain malignant diseases.
 ...
PMID:In vivo effects of purified recombinant human macrophage colony-stimulating factor in combination with local hyperthermia on tumor progression in B16a melanoma bearing mice. 814 92

Expression of an extended panel of cytokine genes was investigated by reverse polymerase chain reaction (PCR) in 10 freshly excised melanoma metastases infiltrated by lymphocytes (TIL). cDNA encoding for CD3-delta and tyrosinase could be amplified in all samples, confirming the presence of T lymphocytes and melanoma cells. Cytokine genes possibly transcribed by both cell types, such as GM-CSF, IL-6 and IL-10 could be amplified from 5, 2 and 2 samples respectively. In contrast, IL-1 beta and TNF-alpha mRNA were never detectable, IL-1 alpha, IL-3 and IL-7 mRNA could be observed only in one case each. Transcripts encoding for TGF-beta 1 were observed in 8 samples, while TGF-beta 2 and 3 mRNA were detectable in only 2 specimens. mRNA encoding for cytokine genes typically transcribed by antigen-stimulated T lymphocytes, such as IL-2, IL-4 and IFN-gamma were rarely or never detectable (none, none and 1 of the samples respectively). In one case, where no cytokine gene transcription was detectable at the time of surgery, we addressed the question of the antigenicity of the tumor and of the functional competence of TIL. A primary tumor cell line was generated and cultured TIL were induced to transcribe IL-2 and IFN-gamma genes by incubation with the autologous irradiated tumor cell line, but not with autologous EBV-transformed cells. In these conditions, tumor-specific cytotoxic T lymphocytes (CTL) could be generated only after 3 weekly re-stimulations. In contrast, if autologous irradiated EBV-transformed cells were added to the cultures, specific CTL could be detected after one single tumor stimulation. Thus, signs of active responsiveness in terms of lymphokine gene mRNA are seldom detectable in melanoma metastases. Tumor-specific responses, however, including IL-2 and IFN-gamma gene expression and generation of CTL can be produced in vitro from specimens in which no cytokine gene mRNA is detectable ex vivo.
 ...
PMID:The pattern of cytokine gene expression in freshly excised human metastatic melanoma suggests a state of reversible anergy of tumor-infiltrating lymphocytes. 818 65

Interleukin (IL)-7 has been evaluated for its influence, alone or in combination with local hyperthermia (LH), on B16a melanoma-bearing mice. Six- to eight-week-old C57BL/6J male mice were inoculated s.c. with 5 x 10(5) tumor cells into the left hind limb. Mice were randomly divided into four groups, and treated s.c. with IL-7 (5 ng) or saline as control, twice a day for three weeks beginning eight days after tumor inoculation. LH, using hot water circulator at 43 +/- 0.2 degrees C for 30 min, was induced to the limb with tumor twice a week for two weeks. Size of the primary tumor was measured every other day for five weeks. Mice were sacrificed five weeks after tumor inoculation. The size of the primary tumor and the number of lung metastases were reduced in mice treated either with IL-7 or LH alone. As a control for IL-7, granulocyte colony stimulating factor (G-CSF) alone had no effect on primary tumor size or number of lung metastases. The greatest antitumor effect was observed in mice treated with IL-7 in combination with LH. Survival was prolonged significantly only in mice treated with IL-7 plus LH compared with that of mice treated with saline. Decreased natural killer (NK) cell activity, number of Thy1.2 cells, and ratio of L3T4+/Lyt2+ cells were associated with tumor growth. These parameters were restored in mice treated with IL-7 plus LH. Increases in levels of IL-1 alpha, IL-6, tumor necrosis factor (TNF alpha) and interferon (IFN gamma) were associated with an increase in the survival of tumor-bearing mice treated with IL-7 and/or LH. These results suggest that changes in T-cell, NK cell and cytokines such as IL-1 alpha, IL-6, TNF-alpha and IFN-gamma in response to IL7 and/or LH might account for prolonged survival of B16a melanoma-bearing mice and that IL-7 might be useful as a potential antitumor agent combined with other therapy in certain malignant solid tumors with metastases.
 ...
PMID:Antitumor effect of interleukin 7 in combination with local hyperthermia in mice bearing B16a melanoma cells. 824 52

We investigated the anti-tumor effects of human recombinant interleukin-6 (hrIL-6) on the highly metastatic Lewis lung-carcinoma clone, D122. These cells express high-affinity IL-6 receptors at numbers comparable to the IL-6-dependent murine hybridoma B9 cells; however, IL-6 did not affect D122 cell proliferation or expression of MHC-class-I antigens in vitro. In vivo, treatment of mice bearing D122 tumors in the footpads, with a low dose of IL-6 in 3 daily injections, 4 days a week for 3 weeks, significantly decreased spontaneous metastases. However, only combined treatment of IL-6 and irradiated tumor cells resulted in almost complete protection against spontaneous metastases. Histological analysis confirmed the absence of micrometastases in most of the animals treated by this combination protocol. Analysis of the cytolytic activity of splenocytes at various time points during combined IL-6 and immunotherapy of tumor-bearing mice revealed significant and sustained lysis of the poorly immunogenic D122 carcinoma cells, while splenocytes of control mice could not lyse D122 target cells. Activation of specific immunity was also demonstrated when mice were pre-immunized with hrIL-6 and inactivated D122 cells and challenged with live carcinoma cells 10 days later. Significant growth inhibition of the primary tumor was observed.
 ...
PMID:Combined therapy with IL-6 and inactivated tumor cells suppresses metastasis in mice bearing 3LL lung carcinomas. 844 6

We compared the cytogenetic pattern of 20 different primary tumor cell cultures (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was correlated with the gain of an additional chromosome 7. Structural changes involving chromosome 5q22, the site of the GM-CSF gene, were matched with the high secretion of GM-CSF in PTCC. No such association was found for beta 2-microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc, and pan-ras. Our approach may be useful in simultaneously analyzing several factors contributing to tumor progression and may contribute to understanding the multistep development of RCC.
 ...
PMID:Comparison of cytogenetics, cytokine secretion, and oncogene expression in primary cultures of renal carcinoma cells. 926 Jun 6

The neuroendocrine system modulates the immune response through neuropeptides and neurohormones, findings which point to the existence of a neuro-endocrine-immune system regulatory axis. At the same time, there is growing evidence that the pineal gland has anti-neoplastic properties, which include the action of its principal hormone, melatonin (MLT), on the immune system through the release of cytokines by activated T-cells and monocytes. The present study was carried out on 31 patients (19 males and 12 females, age range 46-73 years) with advanced solid tumors (7 gastric, 9 enteric, 8 renal, 5 bladder, 2 prostate) who either failed to respond to chemotherapy and radiotherapy or showed insignificant responses and were therefore shifted to MLT therapy (10 mg/die orally for 3 months). We obtained blood samples just before the start of MLT administration and after 30 days of therapy. Plasma was collected in EDTA tubes on ice, immediately centrifuged at 4 degrees C and stored frozen at -80 degrees C; samples were measured by immunoradiometric assays (Medgenix-Fleurus, Belgium) for tumor necrosis factor alpha (TNF), interleukin-1, 2 and 6 (IL-1, IL-2, IL-6) and interferon gamma (IFN). We used Student's paired t-test to compare each patient's cytokine circulating levels before and after MLT administration and found a significant differences (p < 0.05). After 3 months of therapy, none of our patients displayed adverse reactions to MLT or had to discontinue treatment. Nineteen patients (61%) showed disease progression. The other 12 (39%), however, achieved disease stabilization with no further growth of either the primary tumor or of secondaries; moreover, they experienced an improvement in their general well-being, in terms of Tchekmedyian's criteria, associated with a significative decrease of IL-6 circulating levels. These findings are consistent with the hypothesis that MLT modulates immune function in cancer patients by activating the cytokine system which exerts growth-inhibitory properties over a wide range of tumor cell types. Furthermore, by stimulating the cytotoxic activity of macrophages and monocytes, MLT plays a critical role in host defence against the progression of neoplasia.
 ...
PMID:Melatonin as biological response modifier in cancer patients. 961 11


1 2 3 4 5 6 7 Next >>