Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory cytokines are able to facilitate the homing of transferred lymphocytes, tumor cell lysis through induction of adhesion molecules, also able to reduce tumor cell susceptibility to LAK cells by increasing tumor cell class I antigen. Investigation with 12 cell lines suggested that promotion of lysis by ICAM-1 was more responsible than protection by (allogeneic) class I Ags (Fig. 1). PBMC were cultured in anti-CD3 coated flasks with rIL-2. CD3+ cells dominated until day 7, decreased thereafter with CD4+. CD8+ and CD16+ increased (Fig. 2). Strong cytotoxicity obtained in some cultures correlated well with CD16+, contributing exclusively among several variables to the activity estimation in multiple regression analysis (Fig. 4). Among 6 cases, in which 2 or more cycles of transfer was done, 1 was prophylaxis of recurrence, in 2 of 3 advanced metastasis cases in which cells were transferred as BRM in the course of chemotherapy, survival of half a year was obtained in good QOL with suppressed disease and adequate level of PBL number. In 2 other cases, inflammation eliciting local treatments were combined. In the case 4, three large liver metastasis from colon cancer which resisted topical ethanol injection and chemotherapy, responded to the transfer with reduced lesions to 1/8 (Fig. 8). In the case 5, abdominal metastasis from colon cancer were removed, liver metastasis were injected of ethanol, and cells were transferred. Responses were obtained to immunotherapy in a certain degree, while never to any chemotherapy.
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PMID:[Adoptive immunotherapy using immobilized anti-CD3 mAb-activated autologous lymphocytes: the strong cytotoxicity was supported by CD16+ cells which proliferated in prolonged cultures]. 146 25

Nineteen patients with metastatic liver tumor (9 of gastric cancer, 5 of colon cancer, 2 of pancreatic cancer, one each of mammary cancer, cholecystic cancer, carcinoid of biliary tract) and one patient with primary liver cancer were treated by endogenously induced LAK therapy consisting of transhepatic arterial infusion with ADM or MMC for induction therapy and OK-432 and rIL-2 (TGP-3) for immunotherapy. The following results were obtained. 1) Clinical response for liver tumor showed no CR but 8 cases of PR, for an overall response rate of 42.1%. 2) Reduced tumor marker value was noted in 76.5% cases, and 50% survival term became 349 days after the therapy. 3) Many CD4 and CD8 positive mononuclear cells had infiltrated around liver tumor after therapy by immuno-histochemical staining of surface marker. 4) NK activity of peripheral blood lymphocytes was markedly reduced soon after the therapy and continued for about 4-7 days, while in cases of combined subcutaneous administration with OK-432, NK activity showed only a slight decrease.
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PMID:[Significance of antitumor effects and immunological response on endogenously induced LAK therapy for primary or metastatic liver tumor]. 153 Feb 92

The initial site of disease relapse was identified for 79 patients with metastatic renal cell cancer (RCC), melanoma, colon cancer, or non-Hodgkin's lymphoma (NHL), who had achieved partial or complete responses to one of five IL-2-based immunotherapy regimens. The initial site of relapse was evenly distributed between pre-existing sites of disease (33%), new sites of disease (38%), or both (29%). There was no difference in the distribution of recurrences between patients with partial or complete responses. Fifty-one patients with prior complete or partial responses were retreated with additional IL-2-based therapy following tumor progression. Five of 51 patients retreated following relapse developed new partial responses. There were no complete responses. Three patients with NHL were retreated with IL-2 and LAK cells and all achieved a second response, while only 2 of 48 patients with other histologic diagnoses reresponded. It is concluded that after a partial or complete response to IL-2-based immunotherapy, patients who relapse do so equally at new and pre-existing sites of disease. A response to retreatment following tumor progression may be attained in patients with NHL, while a new response is unlikely for patients with melanoma and RCC.
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PMID:Relapse after response to interleukin-2-based immunotherapy: patterns of progression and response to retreatment. 179 Jan 45

The antibody-dependent cellular cytotoxicity (ADCC) properties of a murine monoclonal antibody (MAb), designated D612 (IgG2a), which reacts with human colon carcinomas, was studied using normal human peripheral blood lymphocytes (PBMNC). Although the level of ADCC of PBMNC with D612 varied among different donors, it was 20 to 30 times higher than the lytic activity of control cultures containing isotype-matched control MAb. Incubation of PBMNC with recombinant interleukin-2 (IL-2) resulted in a 2- to 5-fold augmentation in the cytotoxicity of effector cells exposed to MAb. This augmentation was apparent after subtracting nonspecific cellular cytotoxicity from the total cytotoxicity mediated by activated effector cells in the presence of D612. Optimal stimulation of specific ADCC with IL-2 appeared after 24 hr of culture in 500 U/ml of IL-2, resulting in a 3.8 +/- 1.7 fold increase in lytic units. However, stimulation of ADCC was also evident at 10 U/ml of IL-2. Furthermore, antibody dose titrations with untreated and IL-2 activated effectors showed that the threshold dose of MAb needed for efficient ADCC was reduced by 200-fold with IL-2. Depletion of FcR gamma III-positive lymphoid cells markedly reduced D612 ADCC, demonstrating the participation of NK/LAK cells in D612-mediated ADCC. Low levels of ADCC activity were found associated with adherent cells, either untreated or following their activation with gamma-interferon, while D612 was most active with non-adherent effectors. The specificity and ADCC properties of the D612 MAb suggest that it should be considered as a candidate for immunotherapy of colon cancer, particularly when used in combination with IL-2 plus LAK cell treatment.
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PMID:Lymphokine-activated killer cell cytotoxicity against human colon carcinomas enhanced by monoclonal antibody D612. 212 77

In order to examine the quality of life with immunotherapy, a survey was conducted on 17 advanced gastric or colon cancer patients receiving LAK immunotherapy and on 10 patients receiving EAP chemotherapy as a control. Performance status of patients at the time of treatment was similar between the groups. Many patients on EAP therapy complained of severe side effects, such as loss of hair, nausea and vomiting, and appetite loss. None of the patients on LAK therapy complained of such effects on the contrary, favorable effects were found. Appetite increased in some patients and tenderness of the liver disappeared in others. As for the continuance of the treatment, two thirds of EAP patients declined, and all LAK patients replied in the affirmative. The data suggest that LAK immunotherapy is better than EAP chemotherapy from the standpoint of the quality of life.
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PMID:[Immunotherapy and quality of life]. 234 1

Adoptive immunotherapy of malignant diseases was tried using LAK cells induced from peripheral blood lymphocytes with recombinant IL-2 (TGP-3) and fresh human plasma. The cytotoxicity of autologous and mixed cultured allogeneic LAK cells reached maximum after two weeks, and after 7 to 10 days of incubation, respectively. The necessary dose of IL-2 combined with LAK cells was 1000 or 2000 units for maintenance and enhancement of LAK activity, which did not cause any lethal side effect, i.e., capillary permeability leak syndrome. A clinical effect was observed in cases of carcinomatous pleural effusion of colon cancer, pulmonary metastases from breast cancer and rhabdomyosarcoma, and pulmonary, hepatic and abdominal wall metastases from squamous cell carcinoma of the epipharynx. The only side effect observed was fever. No pathological reaction occurred after frequent injection of allogeneic LAK cells. The most important problem to be solved is how to induce a large amount of LAK cells.
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PMID:[Adoptive immunotherapy of malignant disease using LAK cells]. 326 Apr 66

The patient was an 82-year-old female with a 32-month clinical course after right hemicolectomy for ascending colon cancer. Serum carcino embryonic antigen (S-CEA) increased about 38 ng/ml, and metastatic spleen tumor was recognized by abdominal CT and MRI. To induce endogenous LAK, intra-arterial immunochemotherapy with cyclophosphamide (CPM) and OK-432 was performed. Three days after CPM administration, peripheral white blood cells decreased. Recovery from this CPM side effect was achieved with granulocyte colony-stimulating factor (G-CSF). LAK activity of peripheral blood lymphocytes increased from 3% to 17%. Then intra-arterial immunochemotherapy was continued for 7 months, after which the tumor size increased but the S-CEA level remained under 40 ng/ml.
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PMID:[A case of metastatic splenic tumor treated with intra-arterial immunochemotherapy to induce endogenous LAK cell]. 769 May 34

The effects of prothymosin alpha1 (Pro alpha1) in combination with interleukin-2 (IL-2) on peripheral blood lymphocytes from 50 colorectal tumor patients at different stages were studied with respect to immunocytotoxicity, adhesion to cultured SW620 colon carcinoma cells, secretion of cytokines and expression of adhesion and surface marker molecules. On average, the patients showed lower natural killer (NK) cell activity than healthy donors, which was associated with a lower adhesion capacity to the tumor target cells. The NK cell activity of the patients was inversely related to the tumor stage. The generation of lymphokine(IL-2)-activated killer (LAK) cell activity was found to be comparable on lymphocytes from healthy individuals and patients and was not correlated to tumor stage. Pro alpha1 stimulated patients' LAK cell activity only, primarily at the early stage (Dukes A/B). The Pro alpha1 effect was associated with an increased adhesion of lymphocytes to tumor target cells and an increased secretion of the deficient IL-2-induced IFN gamma secretion. No significant effects on the low level of TNF alpha secretion was noted. By flow cytometry, Pro alpha1 in combination with IL-2 augmented the expression of the NK cell markers CD56, CD16/56, the subset CD3/16/56 and CD25 on lymphocytes of the patients. In contrast, Pro alpha1 was equally effective by increasing the expression of CD18 and CD11a on lymphocytes from the patients and from normal controls. In conclusion, Pro alpha1, in combination with IL-2, can partially normalize lymphocyte deficiencies of colon cancer patients in vitro. This potential might provide an experimental basis for applying Pro alpha1 or related thymic peptides in selected immunotherapies against colorectal tumors.
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PMID:Interleukin-2-activated killer cell activity in colorectal tumor patients: evaluation of in vitro effects by prothymosin alpha1. 929 4

IL-2-activated killer lymphocytes (LAK cells) secrete inflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNFalpha) that can induce nitric oxide (NO) synthesis. We evaluated whether LAK cells could activate NO synthesis in human cancer cells. LAK cells and their culture supernatants induced NO synthesis in DLD-1 colon cancer cells in a dose-dependent manner. NO synthesis was inhibited completely by blocking antibodies to IFN-gamma, demonstrating a key role for this LAK cell cytokine in regulating NO synthesis. The addition of TNFalpha antibodies resulted in partial inhibition. Induction of iNOS mRNA and protein expression in DLD-1 cells was detected. Endogenous NO production inhibited DLD-1 cell proliferation and induced apoptosis, processes that were inhibitable by the NO synthase inhibitor N(G)-monomethyl-l-arginine. Our study has identified a novel, non-contact-dependent LAK cell cytotoxic mechanism: induction of growth inhibition and programmed cell death due to endogenous NO synthesis in susceptible human cancer cells.
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PMID:Cytokines secreted by lymphokine-activated killer cells induce endogenous nitric oxide synthesis and apoptosis in DLD-1 colon cancer cells. 1100 6