Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spirogermanium (NSC 192965) is a new metallic investigational anticancer drug of novel heterocyclic structure. Although its mode of action has not been fully elucidated, it appears that spirogermanium is not a phase or cell cycle specific drug and inhibits DNA, RNA and protein synthesis, the protein synthesis being the most susceptible to this agent. Spirogermanium has shown cytotoxic activity in vitro against several human tumor cell lines at concentrations (1 micrograms/ml) that were also found toxic to the cultured rat neurons. Although spirogermanium has no effect on normal bone marrow colony forming cells in mice, dogs, or man, it has revealed cytotoxic activity in vitro against human myeloid leukemia cell line K 562 at clinically achievable concentrations. These in vitro findings, indicating selective cytotoxic activity against leukemic cells suggest this drug as a candidate for clinical studies in acute and chronic leukemias. Spirogermanium has revealed activity in vivo against intraperitoneally implanted Walker 256 sarcoma, 13762 mammary adenocarcinoma, and 11095 prostatic carcinoma in rats, but no antitumor activity in vivo was found in the murine tumors used in the past by the NCI screen (L 1210 and P 388 leukemia, B 16 melanoma, Lewis lung carcinoma). Spirogermanium is remarkable for its lack of bone marrow toxicity confirmed in preclinical toxicology and clinical studies; moderate, predictable, and reversible CNS toxicity is dose-limiting. Activity in malignant lymphoma, ovarian cancer, breast cancer, large bowel cancer, and prostatic cancer was reported in the clinical studies. The drug is currently under clinical investigation against the wide spectrum of solid tumors and malignant lymphomas. The dose of 80-120 mg/m2, given by 60' infusion three times a week, is currently used and tolerated in Phase II clinical studies. The recently introduced five days continuous infusion schedule has been also under clinical investigation and the doses of 250-300 mg/m2/day are recommended for Phase II studies. Of interest are results reported in this paper of spirogermanium in vitro preferential activity against the resistant strains of Plasmodium falciparum at clinically achievable concentrations suggesting this drug as a possible new antimalarial agent of novel structure.
 ...
PMID:Spirogermanium: a new investigational drug of novel structure and lack of bone marrow toxicity. 667 70

Clonogenic tumor cells from fresh biopsies of human cancers were cultivated in vitro and tested for sensitivity by continuous exposure to pharmacologically achievable concentrations of either of two highly purified human leukocyte interferon subtypes (IFN-alpha A and IFN-alpha D) prepared by recombinant DNA methods. The interferons were compared on a weight basis at concentrations of 0.4 and 4.0 ng/ml (equivalent to 80 and 800 units of interferon activity for IFN-alpha A and 2.0 and 20 units for IFN-alpha D). Inhibition of tumor colony-forming units (50% of control or less) was observed in 38.1% of the 273 tumors tested against IFN-alpha A, and in 16% of the 71 tumors tested against IFN-alpha D. Of the tumor types with at least ten samples tested against IFN-alpha A, the percentage of cases exhibiting inhibition was as follows: melanoma (51.7%), lung cancer (50%), myeloma (33.4%), ovarian cancer (33.9%), sarcoma (33.3%), adenocarcinoma of unknown primary (30.4%), breast cancer (28%), acute leukemia (30.8%), and renal cancer (23%). More marked inhibition (30% of control or less) was observed in 18.7% of all tumors tested against IFN-alpha A. Of 60 melanomas tested, 18 (30%) exhibited marked in vitro inhibition of growth with IFN-alpha A. Although a smaller number of tumors (71) were tested against IFN-alpha D on a weight basis, it appeared, in general, to be slightly less active than IFN-alpha A (p less than 0.01), and only 8% of tumors tested exhibited marked inhibition over the same dosage range of interferon. Comparison of the dose-response curves for the 68 tumors tested simultaneously against both interferons did not reveal marked interpatient differences in the inhibition curves, although IFN-alpha D was slightly less active overall. Tumors exhibiting at least 50% inhibition of tumor colony formation also proved to be sensitive to a significantly larger number of cytotoxic drugs (tested simultaneously) than the tumors not inhibited with interferon (p less than 0.0001 for IFN-alpha A). We conclude that the in vitro clonogenic assay may aid in targeting tumor types most likely to exhibit interferon sensitivity and assist in case selection for entry into clinical trials with cloned interferons.
 ...
PMID:Effects of cloned human leukocyte interferons in the human tumor stem cell assay. 668 47

4'-0-tetrahydropyranyladriamycin hydrochloride (THP-ADM) is a new anthracycline derivative. The antitumor activity of THP-ADM was tested on 51 human tumor samples representing ten different tumor types in in vitro colony assay method. Tested tumors were: 26 cases of ovarian cancer, 8 cases of breast cancer, 6 cases of colorectal cancer, 3 cases of endometrial cancer, 2 cases each with gastric cancer and sarcoma, and another 4 cases. An in vitro colony assay was done in soft agar as described by Hamburger & Salmon. The criteria for in vitro sensitivity was defined as a 70 percent or greater reduction in the number of colonies after a 1-h exposure to drugs. The selected concentrations of THP-ADM for assay were 0.05, 0.5, and 1.0 micrograms/ml. The sensitivity rates for THP-ADM in each dose were: 0.05 micrograms/ml (7/19, 37%), 0.5 micrograms/ml (10/51, 20%), and 1.0 micrograms/ml (12/19, 63%). In vitro sensitivity of adriamycin (0.04 micrograms/ml) was simultaneously tested in 49 cancer patients. Five out of 25 ovarian cancer patients (20%) showed responses to adriamycin and an overall response rate was 12% (6/49). These data indicate that THP-ADM has an antitumor activity against various cancers and it is comparable to that of adriamycin.
 ...
PMID:Activity of 4'-0-tetrahydropyranyladriamycin hydrochloride (THP-ADM) in a human tumor cloning system. 668 22

A phase II trial was conducted to determine the clinical activity of amsacrine (m-AMSA) in patients with heavily pretreated solid tumors, myeloma, and lymphoma at the University of Arizona Cancer Center. Additionally, m-AMSA was evaluated at other Southwest Oncology Group institutions in breast cancer, myeloma, melanoma, and oat cell cancer of the lung. At a dose of 120 mg/m2 given iv every 28 days, 12 partial responses were observed in 221 patients evaluable for response. Some antitumor activity was observed in breast cancer (four responses of 65 patients), non-Hodgkin's lymphoma (three of nine), Hodgkin's disease (two of five), and sarcoma (two of 15). A partial response was also documented in one of two patients with cervical cancer. Among the 135 patients treated at the University of Arizona who were extensively evaluated for toxic effects, only myelosuppression and anemia were seen in a significant number of patients. At this dose and schedule, 29% of patients developed leukopenia of less than 3000 cells/mm3, 16% developed a thrombocytopenia of less than 100,000 cells/mm3, and 29% had an acute fall in hemoglobin of greater than or equal to 2 g/100 ml. In addition, two patients suffered grand mal seizures which were not clearly drug-related. These results suggest that further study of m-AMSA in lymphoma, sarcoma, and cervical cancer is warranted.
 ...
PMID:Phase II evaluation of amsacrine (m-AMSA) in solid tumors, myeloma, and lymphoma: a University of Arizona and Southwest Oncology Group Study. 668 99

In the medical literature we found published four cases of irradiation induced chondrosarcoma of the scapula. We present a fifth one and report about a 63 year old female patient. She underwent a left radical mastectomy for breast cancer. Pre- and postoperatively a local irradiation of 140,00 Gy was applied. After a disease free interval of 18 years a large tumor in the left scapula was histologically confirmed as a chondrosarcoma. All criterias of Cahan for an irradiation induced sarcoma are fulfilled.
 ...
PMID:[Radiation-induced chondrosarcoma of the scapula following mastectomy]. 669 77

Lonidamine, a substituted indazole carboxylic acid with unique effects on cellular respiration, was studied in 27 patients with advanced malignancies. Of the 18 evaluable patients, 5 had small-cell lung cancer, 3 had non-small-cell lung cancer, 3 sarcoma, 2 breast cancer, and 5 other tumour types. All but 1 had had extensive prior treatment. A partial response was seen in 1 patient with metastatic synovial sarcoma, and tumour growth inhibition was demonstrated in 2 other cases. The major toxicity encountered was myalgia (66.6%) which was incompletely ameliorated by prednisone and required dose reduction in 2 patients and cessation of drug in 3. Other toxicities included auditory changes, anorexia, nausea and vomiting, diarrhoea, skin sensitivity, and conjunctivitis. No added toxicity was seen, when Lonidamine was combined with other chemotherapeutic agents. No correlation between Lonidamine dose and serum lactate levels was seen, although 4 patients showed a progressive increase in lactate levels over time, thought to be related to their increasing tumour burden. 5 patients demonstrated a dramatic fall in serum testosterone levels 4-8 weeks after starting Lonidamine which was accompanied by an increase in luteinizing hormone levels in 3 patients. In summary, modest antitumour activity was demonstrated in 3 patients; moderate toxicity was seen in most patients, but was usually tolerable. Further studies of Lonidamine are warranted in less heavily treated patients, alone or in combination with other chemotherapeutic agents.
 ...
PMID:Phase II evaluation of Lonidamine in patients with advanced malignancy. 671 99

In the Radiology Clinic of our hospital at present more than 2000 patients have been under surveillance using carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) as markers. The available results have indicated that a combination of both parameters may be applicable in monitoring therapy and in the surveillance thereafter in a variety of cancer sites. It was advantageous to utilize a common index derived from the CEA and TPA serum values after natural logarithmic transformation. Hence, discrimination could be achieved between patients without evidence of disease, and those with progressive disease, eg, in breast cancer with a probability of 95%. The following probabilities were established in 10 other tumor sites: colorectum, 96%; seminoma, 94%; lung, 93%; prostate and bladder, 90%; hypernephroma, 87%; sarcoma, 86%; thyroid, 84%; melanoma, 83%; head and neck, 77%; female genitals, 76%. CEA alone was not applicable in some localized tumors, such as seminoma, melanoma, hypernephroma, and sarcoma. Also, in monitoring patients under chemotherapy, it was established in the follow-up of different cancer sites that TPA was superior to CEA. A concordance with the clinical efficacy of the chemotherapy was found for TPA in 94%, for CEA in 54%, and for both markers in 52%. Thus, as a typical proliferation antigen, TPA appeared to react with a greater sensitivity than CEA on the cytostatic effect of chemotherapy.
 ...
PMID:Combined use of carcinoembryonic antigen and tissue polypeptide antigen in oncologic therapy and surveillance. 688 93

Karyotype of a fibroblastic SH-1 cell line derived from a human mammary sarcoma had 86 (80-92) chromosomes including 6 (4-7) markers, and a various number of double minutes. There were generally even numbers (e.g., 2, 4, etc.) of chromosomes in 17 intact and 3 common marker chromosomes. The t(3;14) and del(14), which had 2 each per s cell genome, were probably formed by the balanced translocation between nos. 3 and 14. Three other markers were single and contained a partial or entire no. 1. The presence of these latter markers was often accompanied by the decrease in the number of the intact no. 1, indicating that no. 1 was the only chromosome actively engaged in rearrangements during this stage of karyotypic diversification. Of the no. 2 and 7q that were over-represented on the per cell level, the 7q had a similar observation from many other solid tumors found in this and other laboratories. In contrast, none of the under-represented chromosomes had the concordant changes consistent to other tumors, although the frequent involvement of no. 9 in the chromosome rearrangements was seen in some human heteroploidies.
Breast Cancer Res Treat 1981
PMID:Karyotype analysis of a human mammary sarcoma explant in vitro. 695 56

Of 1,014 human solid tumors of various histologic types, 690 (68%) showed evidence of colony formation within 2 to 4 weeks. Tumors which grew particularly well were colon carcinoma (104/175), melanoma (134/155), lung carcinoma (62/85), breast cancer (100/140), ovarian carcinoma (50/67), and sarcoma (72/122). Histologic examination indicated that the colony-forming cells retained functional and morphologic features similar to those of the original tumor. Plating efficiencies varied between 0.01% and 0.2%, and the numbers of colonies observed formed a direct linear correlation with the number of cells plated. Recovery of viable tumor cells was increased when enzymatic tumor dissociation was used rather than a mechanical method. A simplified, supplemented medium resulted in improved cloning efficiencies when compared to previously reported methods (Hamburger and Salmon, 1977 b).
 ...
PMID:Cloning of human solid tumors in soft agar. 716 Sep 42

Human tumor stem cell assay is an in vitro colony-forming technique. Double soft agar layers are used for culture tumor cells and cell lethality is judged by the numbers of colony formation in this assay. Single-cell suspension made from various malignant materials in cancer patients is placed in culture after exposing to various anticancer agents for one hour and incubated for two weeks. Antitumor effects of various anticancer agents against individual patients are evaluated by % inhibition of colony formation. Of 57 tumor specimens 42 (74%) formed at least five colonies per plate (per 0.5 x 10(6) cells). The colony-forming rates of various malignancies are as follows: breast cancer 14/15 (93%), ovarian cancer 8/10 (80%), stomach cancer 5/13 (38%), sarcoma 4/5 (80%), lung cancer 1/4 (25%), colon cancer 3/3, each of pancreas cancer, leukemia and primary unknown adenocarcinoma 2/2, malignant lymphoma 1/1. The median plating efficiency (number of colonies/number of nucleated cells plated) is 0.02% (range: 0.001-0.3%). High correlation between human tumor stem cell assay results and response of an individual patient's tumor to chemotherapy is reported by Salmon and Von Hoff. Human tumor stem cell assay is useful tool for the high prediction of chemosensitivity response.
 ...
PMID:[Human tumor stem cell assay]. 718 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>