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

Several preclinical and clinical studies have documented that dose or dose intensity of chemotherapeutic agents are important factors for response of patients' tumors. This finding has prompted empiric trials of certain chemotherapeutic agents in high-dose or regional administration treatment regimens. The present study was performed to identify agents that would be particularly good candidates for high-dose or regional administration regimens against particular types of tumors. Using a human tumor cloning technique, we constructed dose in vitro response lines for ten different chemotherapeutic agents against seven different histologic types of malignancies. Slopes of the lines indicated the agents with the greatest increases of in vitro response per increment in dose of the agent. Tumors against which the agents gave the steepest dose response lines included lymphoma, head and neck cancer, ovarian cancer, and small-cell lung cancer, while the dose response lines for non-small-cell lung cancer, breast cancer, and colon cancer were quite flat. Suggestions for clinical trials based on these findings include the use of high-dose melphalan for patients with lymphoma, head and neck, and ovarian cancer; the use of mitoxantrone in high-dose regimens for patients with breast cancer; high-dose cisplatin regimens for patients with small-cell lung cancer; high-dose bleomycin regimens for patients with non-small-cell lung and head and neck cancer; and regional perfusion of liver metastases from colorectal cancer with cisplatin. Prospective testing of high-dose or regional administration regimens suggested by this new model should indicate its use for prediction of the best agent to use in high-dose regimens against a particular tumor type.
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PMID:Use of in vitro dose response effects to select antineoplastics for high-dose or regional administration regimens. 243 Nov 10

A double antibody enzyme-linked immunosorbent assay (ELISA) was developed to quantitate circulating immune complexed IgA (IgA IC) in human serum. The serum panel for this study consisted of normal blood donors, benign surgery (BS), head and neck cancer (HN), nasopharyngeal carcinoma (NPC), lung cancer (LC), and colon cancer (CC) patients. Immune complexes (IC) were isolated from these sera by precipitation with 3.5% polyethylene glycol (PEG), washed and then redissolved in 0.1 M phosphate-buffered saline pH 7.2. The amount of IgA IC present were then quantified using the double antibody IgA ELISA. This assay was found to be both sensitive (26.0 ng/ml) and reproducible (intra-assay coefficient of variation 4.0%). The mean IgA IC for each cancer group tested (HN = 11.38 +/- 12.54 micrograms/ml; NPC = 13.36 +/- 17.56 micrograms/ml; LC = 17.39 +/- 13.04 micrograms/ml; CC = 26.50 +/- 4.60 micrograms/ml) were significantly elevated (P = 0.001) over both the normals (5.12 +/- 4.09 micrograms/ml) and the benign surgery controls (5.92 +/- 5.04 micrograms/ml). In addition to providing a new tumor marker the presence of high levels of IgA IC in cancer patients could provide a source of tumor-specific antibody as well as antigen and provide reagents to study immune regulation in cancer patients.
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PMID:Circulating IgA immune complexes in head and neck cancer, nasopharyngeal carcinoma, lung cancer, and colon cancer. 382 45

Human monocyte derived macrophages obtained from both normal donors and cancer patients can carry out antibody dependent cellular cytotoxicity (ADCC) to human tumor targets. The macrophages from breast and hematologic cancer patients with Stage I, II or III disease and colon cancer patients with Stage III disease killed tumor cells less effectively than the macrophages from normal donors. In contrast, the macrophages from colon cancer patients with Stage I and II disease killed the tumor targets as well as the macrophages from normal donors. Macrophages from head and neck cancer patients with Stage I and II disease killed tumor cells less effectively than the macrophages obtained from normal donors. In contrast, macrophages obtained from head and neck cancer patients with Stage III disease killed the tumor targets as well as the macrophages from normal donors. It must also be noted that individual patients did not always conform to the group pattern.
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PMID:A comparison of antibody dependent cellular cytotoxic potential in macrophages obtained from normal donors and cancer patients. 391 Aug 83

A broad phase II trial of elliptinium was conducted in 105 evaluable patients with advanced solid tumors. The drug was given as a 60-90-min i.v. infusion at a weekly dose of 100 mg/m2. Of 36 breast cancer patients, one achieved complete and six achieved partial response for an overall response rate of 19%. Responses lasted for 12-56 weeks from initiation of therapy. There was also one partial response among 21 patients with squamous cell carcinoma of the lung. No response could be obtained in 17 patients with colon cancer, 13 patients with head and neck cancer and 18 patients with a wide variety of other malignancies. Myelosuppression was minimal. Nausea and vomiting were the most frequent toxic effects. The drug also produced serious xerostomia and acute intravascular hemolysis. Asthenia was common. Other adverse reactions included fever and chills, transient neurologic and cardiovascular manifestations and renal function impairment. Additional work is needed to define optimal modes of drug administration.
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PMID:Phase II study of 9-hydroxy-2N-methylellipticinium acetate. 653 89

We have utilized a recently developed human tumor cloning system to screen for antitumor effects in vitro of a new anthracenedione derivative, Mitoxantrone. The object was to determine if the system is useful for pinpointing the types of tumors in patients which should be studied in early Phase II clinical trials. Tumors from 267 patients were placed in culture (20 different histological tumor types). One hundred seventy tumors both grew and formed enough colonies for drug sensitivity assays. Excellent in vitro antitumor activity was noted for Mitoxantrone against human adenocarcinoma of the lung, small cell lung cancer, melanoma, and biliary tree cancer. Good antitumor activity was noted against breast cancer, ovarian cancer, non-Hodgkin's lymphoma, head and neck cancer, squamous cell lung cancer, soft tissue sarcoma, gastric cancer, and hepatomas. The drug showed no in vitro activity against colon cancer. These data indicate that Mitoxantrone has a wide spectrum of in vitro antitumor activity. A comparison of these in vitro results with the results of Phase II clinical trials with the drug should allow an evaluation of the utility of the human tumor cloning system for predicting clinical antitumor activity of a new compound.
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PMID:Activity of mitoxantrone in a human tumor cloning system. 721 52

We have utilized a recently developed human tumor cloning system to screen for antitumor effects in vitro of a new anthracene derivative, CL216,942. The object was to determine whether the system is useful for pinpointing the types of tumors in patients which should be studied in early phase II clinical trials. Tumors from 684 patients were placed in culture (27 different histologic tumor types). Two hundred seventy-three tumors both grew and formed enough colonies for drug sensitivity assays. In vitro antitumor activity was noted for CL216,942 against human breast cancer, ovarian cancer, renal cancer, squamous cell, small cell and large cell lung cancer, lymphoma, acute myelogenous leukemia, melanoma, adenocarcinoma of unknown origin, adrenal cancer, gastric cancer, pancreatic cancer, and head and neck cancer. The drug definitely showed no in vitro activity against colon cancer. These data indicate that CL216,942 has a wide spectrum of in vitro antitumor activity. A comparison of these in vitro results with the results of phase II clinical trials with the drug should allow an evaluation of the utility of the human cloning system for predicting clinical activity of a new compound.
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PMID:Activity of 9-10 anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone]dihydrochloride (CL216,942) in a human tumor cloning system. Leads for phase II trials in man. 730 32

Discovered by Isaac and Lindemann as a substance able to induce a biological interference among viruses and host cells, interferon appeared to include three main antigenic classes: alpha, beta and gamma. There is a large variety of actions exhibited by different types of interferon and among them it is possible to distinguish an antiviral, antineoplastic, immunomodulatory or hormonal activity. Many years ago, the antiviral action seemed to be relative to some cellular membrane disorders, but later other mechanisms were stressed. Among them, it is worth describing the transcription and transduction of antiviral proteins like the oligoadenilsinthetase and proteinphosphokinase, able to cause the viral RNA breackage. The antineoplastic action is exerted by direct and indirect mechanisms. Direct mechanisms include an antiproliferative activity and the induction to cellular differentiation whereas the indirect ones involve the enhancement on tumor cell surfaces of some tumor associated antigens included in the I class of MHC system. The immunomodulatory action is exerted by the stimulation of macrophages, T cells and Killer cells cytotoxic activity. The list of viral diseases sensitive to interferon treatment includes condiloma acuminata, herpes zoster, chronic B and C hepatitis and Kaposi sarcoma AIDS-related. High proportions of overall response rate were observed among interferon treated patients with condiloma acuminata (80-100%). The use of interferon in the treatment of herpes zoster achieved good results regarding a shorter duration of the time spent to induce the chest pains and cutaneous symptoms disappearance when compared with that relative to other antiviral drugs. Results obtained in the treatment of chronic B and C hepatitis regard the disappearance of viral replication serological markers and the improvement of histological and enzymatic pattern. The effectiveness of interferon in the therapy of Kaposi sarcoma is demonstrated by the reduction of cutaneous symptoms and recurrent infectious diseases incidence. The use of interferon in treatment of solid tumors seems to play secondary role and, at any rate, to be adjuvant to chemotherapy. The administration of beta interferon as therapy of breast cancer seems to increase the estrogens and progesterone concentration in the neoplastic tissue and so it aims to improve the sensitivity to the tamoxifen treatment. The addition of interferon alpha both to 5-FU and cis-platinum seems to improve the proportion of overall response rate respectively in the treatment of colon cancer and head and neck cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Update on the use of interferons in clinical practice]. 758 95

Phase III randomized clinical trials have greatly contributed to our understanding of the pathobiology of neoplastic disease and, particularly, to therapeutic progress. However, randomized Phase III studies are no better than or are critically dependent on Phase I and Phase II studies for positive therapeutic leads that are compelling enough to test in the Phase III arena. The variables involved in the series of randomized trials that led to the curative treatment of acute lymphocytic leukemia also resulted in an understanding of the principles of cancer therapy in therapeutic research. These principles, when applied to Hodgkin's disease in non-Hodgkin's lymphoma, testis cancer, childhood solid tumors, and others, resulted in a substantial cure rate for those diseases. However, for the adult epithelial common solid tumors, a second strategy, adjuvant chemotherapy, was required This has resulted in a 20% reduction in mortality in patients with node positive and node negative breast cancer. Tamoxifen has been similarly effective in patients with postmenopausal breast cancer. In colon cancer, adjuvant chemotherapy with fluorouracil plus levamisole has decreased mortality to a comparable degree. New agents, modulations, combination chemotherapy, and biotherapeutics are being addressed to the adjuvant situation which has proven effective in a variety of neoplastic diseases. A third strategy is neoadjuvant chemotherapy. This involves the use of chemotherapy first for patients with solid tumors, designed to down-stage the primary tumor thus making it more susceptible to less radical surgery and to organ- or limb-sparing procedures in osteogenetic sarcoma and in head and neck cancer. For example, neoadjuvant chemotherapy has not resulted in an increased survival as compared with the appropriate control but has allowed for important quality-of-life contributions, such as limb-sparing and radical surgery-sparing procedures. In addition to new agents and combination chemotherapy, dose is a critical variable. This is most evident clinically in the transplantation arena. Comparative studies recently completed, for example, in patients with adjuvant breast cancer and with acute leukemia indicate that dose is a significant factor in tumor control.
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PMID:Randomized clinical trials and other approaches in clinical research. 795 73

In humans, tumor necrosis factor (TNF) treatment has been associated with characteristic changes in circulating white blood cell populations (leukopenia followed by leukocytosis) and increased cell-surface expression of integrins. A similar pattern of effects on leukocytes occurs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF treatment. To determine whether these effects were caused directly by TNF or as a result of secondary CSF release, G-GM-, and M-CSF levels were measured after TNF infusion (9.6 x 10(6) U/mg protein; < 5.0 endotoxin U/mg protein) in cancer patients during two phase I trials of TNF. One patient with aggressive fibromatosis was treated with TNF alone (200 micrograms/m2, days 1-5 every third week) and 10 patients (four colon cancer, four head and neck cancer; one melanoma; one sarcoma) received mitomycin C (15 mg/m2, day 1) followed by TNF (60-180 micrograms/m2, days 1-3) every sixth week. All treatments were given IV, mitomycin C over 5 minutes and TNF over 2 hours. Serum samples were collected at times 0 (before mitomycin C and TNF) and 1, 2, 4, 6, 12, and 24 hours after TNF initiation on day 1 and at similar times on subsequent treatment days. M-CSF samples were analyzed by radioimmunoassay (RIA) and G-CSF and GM-CSF by ELISA. The mean baseline M-CSF levels in normal control subjects (n = 12) was 158.4 +/- 36.2 (SD) U/mL, and in pretreatment cancer patients (n = 10) 235.7 +/- 60.9 U/mL (p = 0.004, Wilcoxon test). M-CSF levels increased 4 hours after TNF initiation (mean 354.7 +/- 96.3 U/mL; p = 0.020), remained elevated at 6 hours (305.6 +/- 45.4 U/mL; p = 0.004, Wilcoxon signed-rank test), and subsequently declined. This pattern was seen in all patients treated with TNF, whether treatment was TNF alone or TNF with mitomycin C. In patients treated with mitomycin C and TNF, G-CSF levels increased at 4 hours after TNF initiation (mean 3886 +/- 2009 pg/mL; p = 0.004), remained elevated at 6 hours (mean 2140 +/- 1131 pg/mL; p = 0.004), and subsequently declined. GM-CSF levels were not measurable before or after treatment with TNF. The changes in all three endogenous cytokines were not temporally related to the previously described leukopenia and integrin upregulation on circulating leukocytes and, therefore, appear to be unrelated to this event. However, release of endogenous G-CSF and M-CSF under the influence of TNF does temporally coincide with the previously described leukocytosis, suggesting a possible role for these endogenous cytokines in the release of bone marrow cellular stores.
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PMID:Tumor necrosis factor administration is associated with increased endogenous production of M-CSF and G-CSF but not GM-CSF in human cancer patients. 853 92

Gemcitabine (GEMZAR) is a novel nucleoside analogue with activity in a range of preclinical models both in vitro and in vivo. It is highly schedule dependent, with weekly x3 every 4 weeks being the recommended schedule for phase II/III studies. Early phase II trials identified activity against non-small-cell lung cancer and pancreatic cancers, tumour types for which gemcitabine has a licence for treatment in many countries. However, the preclinical models indicated that gemcitabine may be active against many other human solid tumours. In phase II studies, activity has been identified against breast cancer, both as a single agent and in combination. In bladder cancer, impressive single-agent activity of gemcitabine has also been seen, as well as in combination with cisplatin, initially in MVAC and platinum failures but more recently as first-line therapy both as a single agent and combined with cisplatin. Anti-tumour activity has also been seen in patients with ovarian cancer, head and neck cancer, small-cell lung cancer and cervical cancer, with minimal activity in renal carcinoma, prostate and colon cancer. In view of the excellent side-effect profile and the potential for gemcitabine to inhibit DNA repair after exposure to DNA-damaging agents, further developments of gemcitabine will include its use in combination chemotherapy and combined modality schedules.
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PMID:The role of gemcitabine in the treatment of other tumours. 971 87


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