thioguanine-anhydrous and Adenocarcinoma

Topics: Adenocarcinoma; Alkylating Agents; Antineoplastic Agents; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Fluorouracil; Humans; Lung Neoplasms; Methotrexate; Mitomycins; Nitrosourea Compounds; Thioguanine; Vinblastine; Vincristine

To evaluate a combination of thioguanine, procarbazine, dibromodulcitol, CCNU (CCNU), fluorouracil, and hydroxyurea (TPDC-FuHu), designed to improve the efficacy of CCNU, in the treatment of recurrent metastatic brain tumors.. One hundred fifteen patients with progressive or recurrent metastatic brain tumors that failed to respond to surgery and/or radiation therapy were enrolled onto a multicenter prospective study between 1989 and 1995. Patients received TPDC-FuHu in a repeated cycle every 6 weeks until recurrence or until they completed six courses.. Ninety-seven patients were assessable at the end of the study. Forty-eight had lung cancer (39 non-small-cell [NSCLC] and nine small-cell [SCLC]), 28 had breast cancer, nine had melanoma, and 12 had adenocarcinoma of different origins (three colon, two kidney, one bladder, one stomach, and five of unknown origin). The response and stable disease (SD) rate (overall response rate) was 52%, 66%, 60%, and 22% in patients with NSCLC, SCLC, breast cancer, and melanoma, respectively. Median time to progression (MTP) was 12, 26, 12, and 6 weeks, respectively, for the four groups. Side effects were mild to moderate in the majority of patients. Severe myelosuppression (grade 4) occurred in only 11% of the patients.. TPDC-FuHu chemotherapy is an active treatment against recurrent brain metastases from breast cancer and SCLC, and to a lesser extent from NSCLC. This regimen is well tolerated and has acceptable toxicity.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Disease Progression; Female; Fluorouracil; Humans; Hydroxyurea; Lomustine; Lung Neoplasms; Male; Middle Aged; Mitolactol; Procarbazine; Prospective Studies; Thioguanine

In order to redefine the effectiveness of 5-fluorouracil (5-FU) as palliative therapy in patients with metastatic colorectal carcinoma, and to compare the effectiveness of 6-thioguanine (6-TG) with that of 5-FU, we studied 176 patients with metastatic colorectal carcinoma in a randomized prospective trial (SEG 79G1268 ). The pretreatment performance status of all patients was greater than 50% (ambulatory), and there was an equal distribution of patients with favorable pretreatment characteristics into each of the treatment regimens. Complete responses were only seen to 5-FU, but were obtained in only 3% of instances. The overall complete plus partial response rates were not different for 5-FU (8%) versus 6-TG (3%), or for patients who had shown prior progression on chemotherapy and who then received 6-TG in a nonrandomized fashion (7%). The time to tumor progression on each of the treatment programs was similar, 1.0 months. Survival was also similar in each regimen in the randomized study (6.3 months for 5-FU versus 7.9 months for 6-TG). However, survival was only 4.8 months for patients with previously drug-resistant tumors treated with 6-TG in the nonrandomized arm. In 16 patients failing 6-TG who then received 5-FU, there were no objective responses. Similarly, in patients failing 5-FU on this study who then received 6-TG, there were no responses in nine patients. Dose-limiting toxicity was observed in 40% to 51% of patients, and consisted of myelosuppression, vomiting, or diarrhea. It is concluded that 5-FU is a minimally effective agent in a very small number of patients with metastatic colorectal carcinoma. The drug 6-TG is equally ineffective in this setting. Alternative treatment programs to the systemic use of 5-FU should be considered in patients requiring palliative chemotherapy.

Topics: Adenocarcinoma; Bone Marrow; Clinical Trials as Topic; Colonic Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Male; Middle Aged; Prospective Studies; Random Allocation; Rectal Neoplasms; Thioguanine; Vomiting

In a randomized multi-institutional trial of the Eastern Cooperative Oncology Group, 316 patients with advanced measurable colorectal adenocarcinoma were treated with a weekly schedule of 5-fluorouracil given orally and intravenously with oral-5-fluorouracil in combination with cyclophosphamide or 6-thioguanine, or with oral Methyl CCNU administered once every eight weeks. On failure or progression, 133 protocol patients crossed-over to a secondary therapy, while 116 other patients previously treated with 5-fluorouracil off protocol were randomized to treatment with Methyl CCNU or B-2'-deoxythioguanosine. Response rates among patients who had received no prior chemotherapy were 18% to oral 5-FU, 15% to intravenous 5-FU and to MeCCNU, 12% to 5-FU and 6-thioguanine and 5% to cyclophosphamide and 5-FU, with little activity (3% response rate) in crossover or previously treated patients. Treatment with 5-FU, particularly oral 5-FU was associated with the least drug-related toxicity. Hematologic toxicity was greatest with Methyl CCNU, but was no more frequent in previously treated than in untreated patients. A tendency toward cumulative bone marrow depression was noted. 5-FU was effective only in ambulatory patients, whereas responses among non-ambulatory patients were seen only in the group treated with Methyl-CCNU.

Topics: Adenocarcinoma; Antineoplastic Agents; Bone Marrow; Clinical Trials as Topic; Colonic Neoplasms; Cyclophosphamide; Deoxyguanosine; Drug Therapy, Combination; Female; Fluorouracil; Humans; Male; Neoplasm Metastasis; Rectal Neoplasms; Semustine; Thioguanine; Thionucleosides

Pancreatic adenocarcinoma is one of the malignancies that is highly resistant to therapy and among the leading causes of cancer-related death. Several factors may influence pancreatic cancer resistance, and expression of ATP-binding cassette transport proteins is one of the major mechanisms of drug resistance. Members of this family's C-branch, also referred to as multidrug resistance-associated proteins (MRPs), might be of particular interest because they are able to efflux nucleoside analogs used in the treatment of pancreatic cancer. Expression of MRP1, MRP3, MRP4, and MRP5 in human pancreas and pancreatic carcinoma has been reported. However, contributions of MRPs to chemoresistance of pancreatic cancer are not fully understood. MRP5 mRNA expression in pancreatic adenocarcinoma cell lines correlated significantly with cellular sensitivity to 5-fluorouracil (5-FU) (r = 0.738, p < 0.05). Long-term treatment with 5-FU increased expression of MRP5 by 2.4-fold and was associated with significant drug resistance [IC(50) values for control and 5-fluorouracil (5-FU)-resistant Patu-T cell lines were 11.3 ± 5.3 and 33.2 ± 6.9 μM, respectively (p < 0.05)]. Consequently, overexpression of MRP5 in Colo-357 cells resulted in significantly reduced accumulation of 5-FU related radioactivity and 5-FU cytotoxicity. Knockdown of MRP5 significantly increased cellular cytotoxicity of 5-FU to Patu-02 cells and enhanced accumulation of radioactivity related to 5-FU and its metabolites. Our results suggest that MRP5 is expressed and functionally active and contributes to variable sensitivities of pancreatic adenocarcinoma cell lines to 5-FU. Further investigations using models that resemble human pancreas tumors are necessary to prove a causative relation between expression and activity of MRP5 and tumor resistance to 5-FU.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Fluorouracil; Gene Knockdown Techniques; Humans; Multidrug Resistance-Associated Proteins; Pancreas; Pancreatic Neoplasms; RNA; RNA Interference; Tumor Cells, Cultured

Pterocarpans, the second group of natural isoflavonoids, have received considerable interest on account of their medicinal properties. These drugs are employed as antitoxins, but display antifungal, antiviral and antibacterial properties as well. Erybraedin C and bitucarpin A are two new structurally related pterocarpans recently purified and characterized. Bitucarpin A differs from erybraedin C for the absence of a prenyl group in 5' position and the presence of a methoxylate hydroxyl group in 7, 4' positions. These compounds proved not to be clastogens in human lymphocytes per se but displayed anticlastogenic activity against mytomicin C and bleomycin C. Here we extended the study of their antiproliferative and apoptosis-inducing mechanism on human cell lines. Two human adenocarcinoma cell lines, LoVo and HT29, as examples of slow-growing solid tumors, proficient and deficient in mismatch repair system (MMR), p53 and Bcl-2, were used to evaluate the cytotoxicity of the drugs and their effects on the cell cycle, measured by flow cytometry. Erybraedin C similarly affects the survival of HT29 (MMR +/+, p53 -/- and Bcl-2 +/+) and LoVo (MMR -/-, p53 +/+ and Bcl-2 -/-) cells (LD(50): 1.94 and 1.73 microg/ml, respectively). By contrast, bitucarpin A exhibits a differential cytotoxicity in the cell lines (LD(50): 6.00 microg/ml, HT29, and 1.84 microg/ml, LoVo). The cell cycle distributions of the LoVo and HT29 cells treated with erybraedin C lacked a specific checkpoint arrest, whereas they underwent a characteristic sub-G(1) peak, time- and drug-concentration dependent. So that apoptotic process induced by erybraedin C in both adenocarcinoma cell lines is independent of cell cycle arrest and of phenotypic status of the cells as well. By contrast, bitucarpin A affects cell cycle progression on both cell lines, inducing a transient block in G(0)/G(1) along 24-96 h, and induces apoptosis with a cell density and treatment time dependency. Similar results were obtained with the positive control drug etoposide. The programmed cellular death on human adenocarcinoma cell lines may be efficiently activated, via a topoisomerase II poison pattern, by erybraedin C, the drug containing regio-specific hydroxyl and prenyl groups. The apoptotic effect induced by the methoxylated bitucarpin A proved to be conditioned by cell density and required higher dose (5-fold-LD(50)) and longer treatment time. The present study provides evidences that erybraedin C may act as a potent gro

Topics: Adenocarcinoma; Apoptosis; Cell Division; Cell Line, Tumor; Colonic Neoplasms; DNA-Binding Proteins; Dose-Response Relationship, Drug; Etoposide; Fabaceae; Humans; MutS Homolog 3 Protein; Pterocarpans; Structure-Activity Relationship; Thioguanine; Tumor Suppressor Protein p53

Loss of DNA mismatch repair is a common finding in hereditary non-polyposis colon cancer as well as in many types of sporadic human tumours. We compared the effect of loss of DNA mismatch repair on drug sensitivity as measured by a clonogenic assay with its effect on the ability of the same drug to enrich for mismatch repair-deficient cells in a proliferating tumour cell population. Mixed populations containing 50% DNA mismatch repair-deficient cells constitutively expressing green fluorescent protein and 50% mismatch repair-proficient cells were exposed to different chemotherapeutic agents. 6-Thioguanine, to which DNA mismatch repair-deficient cells are known to be resistant, was included as a control. The results in the cytotoxicity assays and in the enrichment experiments were concordant. Treatment with either carboplatin, cisplatin, doxorubicin, etoposide or 6-thioguanine resulted in enrichment for mismatch repair-deficient cells, and clonogenic assays demonstrated resistance to these agents, which varied from 1.3- to 4.8-fold. Treatment with melphalan, paclitaxel, perfosfamide or tamoxifen failed to enrich for mismatch repair-deficient cells, and no change in sensitivity to these agents was detected in the clonogenic assays. These results identify the topoisomerase II inhibitors etoposide and doxorubicin as additional agents for which loss of DNA mismatch repair causes drug resistance. The concordance of the results from the two assay systems validates the enrichment assay as a rapid and reliable method for screening for the effect of loss of DNA mismatch repair on sensitivity to additional drugs.

Topics: Adenocarcinoma; Antineoplastic Agents; Carboplatin; Cell Separation; Cisplatin; Colorectal Neoplasms; Cyclophosphamide; DNA Repair; DNA, Neoplasm; Doxorubicin; Enzyme Inhibitors; Etoposide; Humans; Melphalan; Paclitaxel; Tamoxifen; Thioguanine; Tumor Cells, Cultured; Tumor Stem Cell Assay

Loss of DNA mismatch repair has been described in a number of tumour types such as colorectal adenocarcinoma and leads to microsatellite instability. This may have clinical relevance due to mismatch repair defects altering chemosensitivity towards certain classes of anti-tumour agent. This study has examined microsatellite instability of eight murine colon adenocarcinoma tumour models induced by 1,2-dimethylhydrazine. Four microsatellite regions were examined suggesting that four of the tumour models exhibit a low level of microsatellite instability. Loss of heterozygosity was found in 5/8 tumours, suggesting that allelic loss may be a relatively common step in the carcinogenesis of these tumour models. Three of the allelic losses involved the D11MIT4 locus which is situated very close to the p53 tumour suppressor locus. Four tumour models are routinely cultured in vitro and these were used to examine whether there was any association between microsatellite instability, mutant frequency and chemo-sensitivity of these tumour models, comparing them with four human adenocarcinoma cell lines of known mismatch repair status. Two cell lines (MAC26 and MAC16) were found to be more chemoresistant towards cisplatin but not 6-thioguanine. No association was found between microsatellite instability and chemosensitivity for either the human or mouse cell lines.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Animals; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinogens; Cisplatin; Colonic Neoplasms; Disease Models, Animal; DNA Repair; DNA, Neoplasm; Drug Screening Assays, Antitumor; Humans; Loss of Heterozygosity; Mice; Microsatellite Repeats; Mutation; Thioguanine; Tumor Cells, Cultured

Loss of DNA mismatch repair is a common finding in many types of sporadic human cancers as well as in tumors arising in patients with hereditary nonpolyposis colon cancer. The effect of the loss of DNA mismatch repair activity on sensitivity to a panel of commonly used chemotherapeutic agents was tested using one pair of cell lines proficient or deficient in mismatch repair due to loss of hMSH2 function and another due to loss of hMLH1 function. 6-Thioguanine and N-methyl-N'-nitro-N-nitrosoguanidine, to which these cells are known to be resistant, were included in the panel as controls. The results were concordant in both pairs of cells. Loss of either hMSH2 or hMLH1 function was associated with low level resistance to cisplatin, carboplatin, and etoposide, but there was no resistance to melphalan, perfosfamide, 5-fluorouracil, doxorubicin, or paclitaxel. The results are consistent with the concept that the DNA mismatch repair proteins function as a detector for adducts produced by 6-thioguanine, N-methyl-N'-nitro-N-nitrosoguanidine, cisplatin, and carboplatin but not for melphalan and perfosfamide. They also suggest that these proteins play a role in detecting the DNA damage produced by the binding of etoposide to topoisomerase II and propagating signals that contribute to activation of apoptosis.

Topics: Adaptor Proteins, Signal Transducing; Adenocarcinoma; Antineoplastic Agents; Carboplatin; Carrier Proteins; Cisplatin; Colorectal Neoplasms; Cyclophosphamide; DNA Adducts; DNA Damage; DNA Repair; DNA-Binding Proteins; DNA, Neoplasm; Doxorubicin; Drug Resistance, Neoplasm; Endometrial Neoplasms; Etoposide; Female; Fluorouracil; Humans; Melphalan; Methylnitronitrosoguanidine; Mutagenesis; MutL Protein Homolog 1; MutS Homolog 2 Protein; Neoplasm Proteins; Nuclear Proteins; Paclitaxel; Proto-Oncogene Proteins; Thioguanine; Tumor Cells, Cultured

PANC02 is a unique experimental animal tumor that fails to respond significantly to any known clinically active antitumor agent. In this regard, the murine ductal adenocarcinoma resembles its human counterpart. To study the mechanism for its intrinsic resistance to 6-thioguanine (TG), we compared the metabolism of the drug in PANC02 and a reference, TG-sensitive adenocarcinoma, CA-755. In comparison with CA-755, PANC02 cells were approximately 6 times less sensitive to TG and CHO cells were 80 times less sensitive in tissue culture. Nevertheless, the incorporation of TG into the DNA of these three cell lines was approximately equal at the lowest concentrations capable of reducing cloning efficiency by 50%, i.e., 3.0-3.8 pmol (dthioGMP)/nmol (dGMP). In mice bearing bilateral implants of CA-755 and PANC02, only CA-755 responded to TG treatment. At various doses used on various schedules, the incorporation of TG into CA-755 DNA readily achieved that observed to be cytotoxic to the cells in vitro, whereas the incorporation into the DNA of PANC02 tumor cells did not. Although the biochemical basis for the poor incorporation of TG into the DNA of PANC02 in vivo is not known, this factor appears to explain the refractoriness of PANC02 as compared with CA-755 to this antitumor antimetabolite.

Topics: Adenocarcinoma; Animals; Cell Division; Drug Resistance; Male; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Pancreatic Neoplasms; Thioguanine

A rapid decrease in expression of the oncogene c-myc has been associated with the induction of differentiation of HL-60 human leukemia cells. In this manner, the treatment of a hypoxanthine phosphoribosyltransferase (HPRT)-deficient HL-60 variant (HL-60/var) with 6-thioguanine (TG) was accompanied by lower c-myc mRNA levels. This occurred in the absence of 6-thioguanosine 5'-monophosphate (TGMP) synthesis and without alterations in cellular nucleotide pool sizes. Paradoxically, inhibition of c-myc expression in the wild type HL-60 (HL-60/wt) cell, which is only weakly induced to differentiate by TG, was 5-fold more sensitive to the thiopurine (IC50 = 35 microM). Furthermore, inosine, which blocks the formation of TGMP and enhances the extent of differentiation of HL-60/wt cells, decreased the sensitivity of c-myc expression in the HL-60/wt to TG. These actions of TG and inosine on c-myc were also observed in the human colon carcinoma cell line COLO 320, further dissociating some of the effects of TG on c-myc expression from granylocytic differentiation. The hematopoietic granulocyte-macrophage colony stimulating factor (GM-CSF) elevated c-myc expression and antagonized the actions of TG on c-myc in the HL-60 cells. GM-CSF more readily antagonized the inhibitory action of TG in the HL-60/var cell line when compared to the HL-60/wt cells, restoring c-myc levels to that of the untreated controls. Hence, TG inhibited c-myc expression by two distinct mechanisms in cells which express high levels of the oncogene: a TGMP-dependent, differentiation-independent process with an IC50 of 35 microM, and a TGMP-independent action with an IC50 of 175 microM that was associated with induction of differentiation and was reversed more readily by GM-CSF.

Topics: Adenocarcinoma; Cell Division; Colonic Neoplasms; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leukemia, Promyelocytic, Acute; Proto-Oncogene Proteins c-myc; Proto-Oncogenes; Ribonucleotides; RNA; Thioguanine; Tumor Cells, Cultured

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytosine; Daunorubicin; Humans; Ileal Neoplasms; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Thioguanine

A 6-thioguanine-resistant (TgR) variant of the metastatic mammary tumor 13762 was found to be very immunogenic. This TgR variant was nontumorigenic and nonmetastatic, whereas the parent 13762 cell line is very tumorigenic and metastatic in normal syngeneic animals. The TgR variant was tumorigenic in irradiated animals. The mechanism of the hosts' immune rejection of this TgR variant was investigated. A 51Cr-release cytotoxic cell assay was used to assess lymphocyte cell-mediated cytotoxicity (CMC) of tumor-draining lymph nodes and spleens from animals injected with tumor cells. In a secondary CMC response of splenic T cells from animals injected with TgR cells, there was a much stronger response as compared to animals injected with 13762 cells. This strong cytotoxic T cell response was short-term and correlated to the host rejection of TgR cells. Previously, we selected revertant cell lines (TgRrev, TgRrevM) from the TgR variant line that were more metastatic and tumorigenic. The revertant cell lines induced a lower CMC response than the TgR line, but a higher response compared to the parent 13762 line. The poor CMC response from 13762 tumor-bearing animals was investigated and appeared to be due to a suppressor T cell response.

Topics: Adenocarcinoma; Animals; Cell Line; Cytotoxicity, Immunologic; Drug Resistance; Female; Genetic Variation; Mammary Neoplasms, Experimental; Rats; Rats, Inbred F344; T-Lymphocytes; Thioguanine

The relationship between immune complex (IC) formation and tumor cell metastatic potential was investigated in rats inoculated in the footpad with parental 13762 mammary adenocarcinoma cells or 6-thioguanine-resistant (TGR) variant cells. These cell lines are either highly metastatic (13762), nonmetastatic (TGR), or occasionally metastatic ( TGRrev , TGRrevM ). The 13762 TGR rat tumor model thus provides the opportunity to examine host immune responses to tumor cells of different phenotypes, but derived from the same parent tumor line. IC levels were low in 13762 tumor-bearing rats. In contrast, animals with TGR tumors had high levels of ICs in their sera, while animals bearing TGRrev and TGRrevM tumors had intermediate levels of ICs. In this rat tumor model system, IC formation is inversely related to the metastatic potential of the tumor lines.

Topics: Adenocarcinoma; Animals; Antigen-Antibody Complex; Cell Line; Drug Resistance; Female; Mammary Neoplasms, Experimental; Neoplasm Metastasis; Rats; Rats, Inbred F344; Thioguanine

Topics: Adenocarcinoma; Animals; Ethyl Methanesulfonate; Mammary Neoplasms, Experimental; Mast-Cell Sarcoma; Methylnitronitrosoguanidine; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mutagens; Ouabain; Thioguanine

A 6-thioguanine resistant (TGR) variant of the highly tumorigenic and metastatic mammary adenocarcinoma cell line 13762 was obtained. This variant was no longer tumorigenic or metastatic in normal syngeneic rats but did grow as a primary tumor in irradiated animals. Our results suggest that the TGR cell line was rejected by an irradiation-sensitive immunological mechanism. Although the TGR cells produced primary tumors in irradiated animals, there was no evidence of the extensive metastasis seen with the 13762 cells. This apparent inability to metastasize was confirmed by injecting the TGR cells intravenously. Whereas the 13762 cells produced large numbers of metastatic lung foci, there was no evidence of lung metastasis with the TGR cells, even in irradiated animals. Revertant cells for the 6-thioguanine-resistant phenotype were still non-tumorigenic and non-metastatic in normal rats, suggesting that 6-thioguanine resistance is not associated with the altered tumorigenic phenotype. From the TGR variant, cell lines were selected with an increased ability to produce tumors in normal rats. Although some of these revertants were capable of producing limited lung metastases in normal animals, extensive metastases were always seen when the cells were injected into irradiated animals. Differences between the 13762 and the TGR variants were also found in their ability to produce plasminogen activator. The TGR cells released far less plasminogen activator in culture than the 13762 cells. This could be a contributing factor in their different metastatic potentials.

Topics: Adenocarcinoma; Animals; Cell Line; Dose-Response Relationship, Drug; Drug Resistance; Female; Immunosuppression Therapy; Mammary Neoplasms, Experimental; Neoplasm Metastasis; Plasminogen Activators; Rats; Rats, Inbred F344; Thioguanine

Consecutive studies were undertaken in advanced colorectal adenocarcinoma, comparing two different schedules of the combination methyl-CCNU, 6-thioguanine, and 5-fluorouracil in 89 patients. The two schedules exhibited similar efficacies, with a combined complete and partial remission rate of 17%, a median response duration of 36+ weeks, and a median survival of 53+ weeks. Significant symptomatic benefit was seen in 52% of patients. Toxicity was predominantly hemopoietic and gastrointestinal, being acceptable overall, with only minor qualitative differences between the two protocols. These triple-drug regimens exhibit response rates and survival patterns comparable with those reported for other multidrug combinations and some single agents. It would appear that major improvements in the management of advanced-stage disease must await the availability of more efficacious agents used alone or in combination.

Topics: Adenocarcinoma; Adult; Aged; Colonic Neoplasms; Drug Therapy, Combination; Female; Fluorouracil; Humans; Male; Middle Aged; Nitrosourea Compounds; Rectal Neoplasms; Semustine; Thioguanine

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Cyclophosphamide; Drug Therapy, Combination; Fluorouracil; Heparin; Humans; Infusions, Parenteral; Lung Neoplasms; Male; Methotrexate; Middle Aged; Thioguanine; Vincristine

Topics: Adenocarcinoma; Animals; Autoradiography; Azaguanine; Cell Line; Cell Survival; Chromosomes; Clone Cells; Ethyl Methanesulfonate; Genes; Genetic Complementation Test; Hybrid Cells; Hypoxanthine Phosphoribosyltransferase; Methylnitronitrosoguanidine; Mice; Mice, Inbred C3H; Mutation; Polyploidy; Temperature; Thioguanine

Topics: Adenocarcinoma; Alkanesulfonates; Animals; Autoradiography; Azaguanine; Carbon Radioisotopes; Cell Line; Cell-Free System; Clone Cells; Drug Resistance; Genes; Genetic Complementation Test; Hybrid Cells; Hypoxanthines; Mice; Mice, Inbred C3H; Mutagens; Mutation; Nitrosoguanidines; Pentosyltransferases; Thioguanine

Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Cyclophosphamide; Cytotoxicity Tests, Immunologic; Dactinomycin; Drug Therapy, Combination; Female; Immunity, Cellular; Male; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred DBA; Mitomycins; Neoplasm Recurrence, Local; Neoplasm Transplantation; Thioguanine; Transplantation, Homologous

Topics: Adenocarcinoma; Animals; Antigen-Antibody Reactions; Antineoplastic Agents; Cortisone; Cyclophosphamide; Dactinomycin; Drug Synergism; Female; Immunity, Cellular; Lymphocytes; Mammary Neoplasms, Experimental; Mice; Mitomycins; Streptonigrin; Thioguanine; Zymosan

Topics: Adenine; Adenocarcinoma; Buffers; Carbon Isotopes; Guanine; Hydrogen-Ion Concentration; Hypoxanthines; In Vitro Techniques; Kinetics; Mercaptopurine; Neoplasms, Experimental; Nucleotides; Purines; Thioguanine; Transferases

Topics: Adenine; Adenocarcinoma; Animals; Azaserine; Carbon Isotopes; Cell Line; Feedback; Hypoxanthines; Mercaptopurine; Methotrexate; Neoplasms, Experimental; Nucleotides; Phosphotransferases; Purines; Sarcoma 180; Thioguanine

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Body Weight; Carcinoma, Ehrlich Tumor; Chemical Phenomena; Chemistry; Female; Formamides; Injections, Intraperitoneal; Leukemia, Experimental; Mice; Organ Size; Sarcoma 180; Thioguanine; Time Factors

Topics: Adenocarcinoma; Animals; Chromatography, Paper; DNA, Neoplasm; Mercaptopurine; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Thioguanine

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carbon Isotopes; DNA; DNA, Neoplasm; Mice; Neoplasms, Experimental; Pharmacology; Research; RNA; RNA, Neoplasm; Thioguanine

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cattle; Chromatography; Deoxyguanosine; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Metabolism; Mice; Neoplasms, Experimental; Nucleosides; Pharmacology; Research; Sulfhydryl Compounds; Thioguanine; Thionucleosides; Ultraviolet Rays

Topics: Adenocarcinoma; Alopecia; Antineoplastic Agents; Azaserine; Carcinoma, Squamous Cell; Diarrhea; Drug Eruptions; Drug Therapy; Geriatrics; Guanine; Leukopenia; Nausea; Neoplasms; Stomatitis; Thioguanine; Thrombocytopenia; Toxicology

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Mercaptopurine; Mice; Neoplasms; Neoplasms, Experimental; Research; Sarcoma 180; Thioguanine; Toxicology

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Chemistry, Pharmaceutical; Deoxyguanosine; DNA; DNA, Neoplasm; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Metabolism; Mice; Nucleosides; Pharmacology; Research; RNA; RNA, Neoplasm; Thioguanine; Thionucleosides

Topics: Adenocarcinoma; Antimetabolites; Antineoplastic Agents; Chemical Phenomena; Chemistry; Mercaptopurine; Pharmacology; Purines; Research; Sulfhydryl Compounds; Thioguanine

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Leukemia L1210; Nucleosides; Research; Sarcoma 180; Thioguanine