Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variations in DNA synthesis as measured by tritiated-thymidine autoradiography in mammary carcinoma before and during endocrine therapy were studied in patients treated for inoperable or locally recurrent mammary carcinoma. Tumor cells were collected by aspiration biopsy and immediately expelled into the incubating solution. Cell viability was assessed by staining unfixed cells with trypan blue and fixed cells with orecin. To assess viability tritiated-uridine incorporation was used in some experiments. The same cells were identified by each method. Bilateral oophorectomy was done in 4 patients. In the 1 case in which regression followed, a 5-fold decrease in DNA-synthesis was noted 1 week after oophorectomy but at 2 weeks no cells incoporated thymidine. In the 3 patients with tumor progression the fraction of labeled cells was unchanged. For antiestrogen therapy, Tamoxifen (Nolvadex) was used. Serial needle aspirates were collected from 38 patients who received 20 mg of Tamoxifen twice daily. Complete remission followed in 7, incomplete remission in 8, stationary disease in 7, and progression in 16. DNA synthesis fell to very low values after 1-3 weeks and remained low in the 7 cases with complete regression. Tumors showing partial regression showed diminished fractions of 5-phase cells (tritiated-thymidine-labeled cells) after 1-5 weeks. In 1 instance at 72 weeks the S-phase fraction of cells was higher than initial value. Tumor value remained stationary for 40 weeks and then increased. Antiestrogen therapy was stopped at 82 weeks. In those with progressive tumor growth there was high DNA synthesis. Between 20-30% of the cells were replicating DNA. None showed decrease in the fraction of S-phase cells, and 1 showed increase. For estrogen therapy, estradiol valepianate was given im every 2 weeks. Of the 3 patients who received estrogen therapy, 2 of the tumors responded and the DNA-synthesis rapidly decreased until none was measurable after 4 weeks. S-phase values prior to endocrine therapy showed no correlation with the therapeutic response. Tumors that responded showed a decrease in the proportion of S-phase cells during the first 3 weeks. In tumors responding to encocrine therapy the decrease in tritiated-thymidine incorporation was rapid and preceded reduction in tumor size. Data suggest that 2 aspirates should be studied before therapy and repeated after 2-4 weeks in order to include the minimal proportion of S-phase cells. The patients accepted the needle biopsies well. There were no growths of carcinoma at the puncture sites. About 5 weeks must elapse before tumor response can be assessed. Determining hormone receptors in surgically removed carcinoma specimens gives much more rapid indications as to possible response to endocrine therapy.
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PMID:3H-thymidine incorporation into mammary carcinoma cells obtained by needle aspiration before and during endocrine therapy. 106 73

Spleen cells from C57BL mice bearing the syngeneic carcinoma 3LL enhanced tumor growth. Tumor growth was also enhanced by a soluble factor found in the media of cultured spleen cells from tumor-bearing animals. This factor suppressed a protective immune response of the host and was found to be a product of T-lymphocytes. Removal of B-lymphocytes and macrophages did not prevent its appearance in the culture media, whereas removal of T-lymphocytes inhibited its appearance. Similar suppressor factors were obtained from C3H mice bearing the 3LL tumor and from mice with other tumors. The suppressing factor produced after the growth of 3LL tumor also enhanced the growth of other tumors. It could act on strains incompatible with the donor of the factor-producing cells. Hence tumor growth was possibly facilitated by soluble products of T-lymphocytes that were found in spleens of tumor-bearing mice and that nonspecifically suppressed immune defense mechanisms.
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PMID:Suppressor factor secreted by T-lymphocytes from tumor-bearing mice. 108 47

The effects of specific dead tumor cell immunization and nonspecific immunostimulation with Corynebacterium parvum on the s.c. growth of the line 1 carcinoma in syngeneic BALB/c mice have been studied. Injection of heavily irradiated line ) carcinoma cells did not inhibit the transplantability or growth of the line 1 carcinoma, and in certain cases these treatments actually prolonged the period of rapid growth. This latter observation was traced to a mild inhibition of metastatic spread, which itself can slow the s.c. tumor growth. Treatment of the mice with 0.25 mg of C. parvum 7 days prior to transplant of the tumor had no effect on its growth by itself; but in combination with i.v.-injected tumor cells, which themselves had no effect on tumor growth, a 45% inhibition of tumor growth was induced. These data demonstrate that, in the weekly immunogenic line 1 carcinoma system, inhibition of s.c. transplants requires not only exposure to tumor antigens but also stimulation of the immunological reactivity.
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PMID:Specific and nonspecific stimulation of resistance to the growth and metastasis of the line 1 lung carcinoma. 110 93

A single intraperitoneal (ip) or intravenous (iv) injection of Corynebacterium granulosum into C3Hf/Bu mice shortly after subcutaneous (sc) injection of cells from a strongly antigenic syngeneic fibrosarcoma induced by 3-methylcholanthrene caused complete and lasting regressions of 100 and 70% of resulting tumors, respectively. Treatment with this bacterium sc only slightly inhibited the growth of some tumors. C. granulosum given iv to mice 3 days after the sc injection of fibrosarcoma cells caused complete regressions of 39 of 45 tumors; two iv injections with this immunostimulant given 1 month apart were no more effective than a single injection. Intralesional treatment of fibrosarcomas 8 mm in diameter induced complete regressions of tumors in 30% of the animals, whereas sc treatment contralateral to the growing tumor only slightly reduced tumor growth. Intraperitoneal growth of a fibrosarcoma was efficiently controlled (58-80% survival of mice) if C. granulosum was given ip, but not iv, 3 days after inoculation with tumor cells. Again, two injections of C. granulosum (given ip 4 days apart) were only as effective as a single injection. Treatment with C. granulosum iv at 3, 7, 14, or 21 days after sc inoculation of a weakly antigenic, spontaneously arising mammary carcinoma (MC-1) strongly inhibited tumor growth. Three complete but temporary tumor regressions were observed. The subcutaneous growth of another spontaneous mammary carcinoma (MC-2), which contained fairly strong tumor-specific antigen(s), was also significantly inhibited if C. granulosum was given 3,7, or 14 days after, but not 7 days before, tumor cell inoculation. However, pretreatment of mice with the immunostimulant significantly protected the mice against artifically induced pulmonary metastases of this tumor.
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PMID:Nonspecific Immunotherapy of Murine Solid Tumors With Corynebacterium granulosum. 112 18

Mice bearing a 3-methylcholanthrene-induced fibrosarcoma (MCAM-7) transplant in the right leg underwent surgical excision of the tumor and showed specific resistance to subsequent challenges with that identical tumor line. An in vivo response to tumor-specific antigens (MCAM-7 antigen) solubilized by hypertonic potassium chloride was measured by 24-hour footpad swelling response in mice immunized to the tumor from which the antigens were extracted. These observations suggested that the transplantable MCAM-7 fibrosarcoma could produce immunity toward the solubilized MCAM-7 tumor antigens and that this tumor immunity could be measured by footpad swelling response to injection of the solubilized antigens, an indication of cell-mediated immunity. The footpad swelling response was also minotored in relation to the extent of tumor growth. Mice received MCAM-7 tumor transplants by injection of 5 times 10-6 tumor cells and were tested for footpad swelling response at intervals following tumor transfer. A significant footpad response to injected MCAM-7 antigens was present 10 days following tumor transfer; at this time signs of tumor growth were only minimally detectable. The footpad swelling response to injected antigens disappeared by 28 days following initial tumor transfer; at this time the tumor diameters were in excess of 1.0 cm. Surgical removal of tumor at this point promptly restored footpad responses within 24 hours. Similar techniques have been applied to patients bearing adenocarcinoma of the prostate, where skin testing was substituted for the measurement of footpad swelling in animals. Seven patients with known prostatic carcinoma were given intradermal injections of soluble tumor antigens extracted from their own tumors. Three of the seven patients exhibited a cutaneous delayed type hypersensitivity response to the injected autologous tumor extracts. No positivereactions were observed in response to solubilized components of control tissues, including benign prostatic hyperplasia. The significance of the demonstrated concomitant immunity in these patients has not been resolved. However, these observations suggest that some patients bearing adenocarcinoma of the prostate can exhibit an immunologic response to specific antigens present in their own neoplasms.
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PMID:Specificity of cell membrane antigens in prostatic cancer. 113 99

Admixed spleen cells from normal animals or from animals given injections of Syrian hamster type C virus significantly potentiated the growth of the transplanted D9 lymphoma of random-bred hamsters. Potentiation was measured by an increase in incidence of tumors, a shortened latent period, and a decreased 50% tumor-producing dose of tumor cells. Intermediate doses of spleen cells (10 to 100 spleen cells per tumor cell) produced the greatest potentiation. Preincubation of admixed spleen and tumor cell suspensions in vitro was unnecessary. Immunization to isoantigens was not responsible for potentiation, since growth of a transplantable carcinoma of inbred hamsters was also facilitated by normal spleen cells. In addition, normal kidney or liver cells increased the incidence of tumors transplanted by a small number of tumor cells. Potentiation did not occur when spleen cells were injected at a site remote from the tumor cells. Since the potentiating cells might act eigher as a physical barrier to host response, or by blocking normal macrophage function, we injected charcoal with tumor cells. Simultaneous treatment with charcoal facilitated the growth of the lymphoma but not that of the carcinoma. Treatment with some doses of charcoal was also effective at distant sites. Although potentiation of tumor growth by cells or charcoal may operate through different mechanisms, these phenomena should be explored in regard to outgrowth of primary tumors, tumor immunity, or enhancement of tumor growth.
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PMID:Potentiation of hamster tumors by normal cells or charcoal. 114 24

Single and combination chemotherapy was evaluated for antitumor activity against N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT)-induced bladder carcinoma in syngeneic mice. Two hundred fifty C3H/He mice having ingested FANFT for 10 months were randomly divided into groups of 30, and the following regimens initiated: cyclophosphamide (Cy), cis-diam-minedichloroplatinum (cis-Pt-II), dactinomycin, adriamycin, Cy plus cis-Pt-II, Cy plus 5-fluorouracil, and Cy plus adriamycin. The drugs were administered for 3 weeks. Each regimen was capable of producing a significant reduction in the mean bladder weight (MBW) when compared to a groups not receiving therapy (108.3 mg). Adriamycin (MBW equal 69.5), dactinomycin (49.6), and cyclophosphamide (42.9) were the best single agents, but the greatest inhibition of tumor growth was achieved by the combination of cyclophosphamide with 5-fluorouracil (38.3) or adriamycin (37.3). These combination chemotherapeutic regimens were able to effect a significant reduction in the number of bladders with Stage C tumors. It is hoped that information gained from this new animal model which allows evaluation of many antitumor drugs within a relatively short period of time will lead to therapeutic trials in patients with locally advanced or metastatic bladder cancer.
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PMID:Single and combination chemotherapy for primary murine bladder cancer. 115 4

Several novel steroidal alpha-methylene-gamma-lactones and related derivatives have been synthesized as potential steroid alkylating antitumor agents. The synthesis of these compounds involved the convenient Reformatsky-type reaction between ethyl-alpha-(bromomethyl)acrylate and the proper steroidal ketones. In vitro assay for the cytotoxicity of these compounds against the growth of tissue culture cells originating from human epidermoid carcinoma of the larynx (H.Ep.-2) has shown significant activity. Cytotoxicity was improved at least sixfold with the introduction of lipophilic steroidal character. Preliminary in vivo tumor assay also indicated that these compounds were active against Walker 256 carcinosarcoma in rats and were inactive against both L1210 lymphoid leukemia and Ehrlich ascites carcinoma in mice. However, the simple alpha-methylene-beta,beta-dicarbethoxy-gamma-butyrolactone significantly inhibited Ehrlich ascites tumor growth.
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PMID:Antitumor agents. 16. Steroidal alpha-methylene-gamma-lactones. 115 98

Liver homogenates or extracts of liver homogenates from rats in which portacaval shunt had been performed were found to have a significant growth-promoting effect on 7,12 dimethyl (a) benzanthracene (DMBA)-produced breast carcinoma in rats. Tumor potentiation was manifested by increased incidence of animals developing tumors, increased number of tumors, and increased tumor size, when compared with animals receiving injections of shunted or control liver. These observations suggest the existence of a tumor-stimulating factor in liver from which portal blood has been completely and chronically diverted by portacaval shunt. The demonstration of tumor growth stimulating factor(s) present in shunted liver, together with previously reported observations of the modification of the growth of various types of tumors in animals with a portacaval shunt, suggests that the liver is capable of playing an important role in tumor-host interactions. The portacaval shunt appears to be useful as a technique in elucidating ways that liver function may influence tumor growth.
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PMID:Promotion of experimental breast carcinoma in rats treated with extract of liver from rats with portacaval shunt. 116 83

Local control of a mammary carcinoma in air-breathing C3H mice was enhanced by giving metronidazole before radiotherapy; When 0.5-1.0 mg metronidazole/g body weight was given ip 10 minutes before irradiation, the dose required for local control of 50% of the tumors (TCD50) was reduced by a factor of 1.37-1.38. The TCD50 was reduced by a factor of 1.48-1.50 when tumors were irradiated 30-60 minutes after 1.0 mg/g. Metronidazole alone, at a dose of 1.0 mg/g, only slightly inhibited tumor growth. The acute skin response of the leg, as determined by the radiation dose required to produce complete moist desquamation in 50% of the animals (DD50), was enhanced by a factor of 1.26 when mice were irradiated 10 minutes after a dose of 1.0 mg metronidazole/g. Clonogenic cells in the jejunal epithelium were not sensitized after metronidazole administration in either air-breathing mice or those irradiated in O2 30 pounds per square inch, but the drug appeared to exert a slight protective effect at higher doses of radiation.
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PMID:Metronidazole: effect on radiosensitivity of tumor and normal tissues in mice. 120 45


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