Search PubMed⌕ Search

Biomedical subjects

N Hunter

Publications and source records attributed to N Hunter.

246 records · Page 14Linked to original sources
PubMedDate not supplied

Antitumor and antimetastatic activity of the differentiating agent N-methylformamide in murine tumor systems.

N-Methylformamide (NMF), a cell-differentiating agent, was assessed for its antitumor activity against a fibrosarcoma (FSA), a hepatocarcinoma (HCA-I) and a mammary carcinoma (MCA-K), syngeneic to C3Hf/Kam mice. Tumors were grown as solitary tumors in the leg or as artificial or spontaneous micrometastases in the lung. NMF, at a dose of 300 mg/kg, was administered i.p. daily for 6 to 18 days. NMF slowed the growth of FSA and HCA-I tumors and totally inhibited the growth of the MCA-K tumor. However, the effect was transient; tumors resumed their pretreatment growth rate upon cessation of the treatment. Histologically, MCA-K tumors treated with NMF (300 mg/kg daily for six days) underwent considerable cell depopulation and reduction in mitotic activity. The number of artificial metastases, as well as the incidence and the number of spontaneous metastases, were markedly reduced by NMF. This resulted in a prolongation of the survival of mice that had artificial metastases of MCA-K tumor. The in vitro clonogenicity of MCA-K, but not of FSA or HCA-I cells, was reduced. However, in vivo reduction of MCA-K cell clonogenicity was minimal, if any. Thus, NMF is effective in restricting the growth of both solitary tumors and metastases, but the degree of response is highly dependent on tumor type.

Animals↗
PubMedDate not supplied

Concomitant development of granulocytosis and enhancement of metastases formation in tumor-bearing mice.

The experiments reported here show concomitant development of granulocytosis and enhancement of metastasis formation in C3Hf/Kam mice bearing NFSA fibrosarcoma. Both phenomena developed at approximately 2 weeks after s.c. transplantation of tumor cells, at a time when the tumor was approximately 10 mm in diameter. The number of granulocytes in the blood doubled approximately every 3.5 days, reaching about 30 times control levels shortly before the death of the mice. The magnitude of the metastasis enhancement formation by i.v. injection of tumor cells was three to four times the control value. Mice bearing NFSA had a significant increase in the number of endogenous CFUs. Plasma from NFSA-bearing mice and medium from cultured NFSA cells stimulated in vitro growth of granulocyte and macrophage colonies from normal bone marrow cell precursors, and induced granulocytosis upon i.v. injection into normal mice. This shows that NFSA tumor secretes factor(s) with potent granulopoietic activity. Injection of plasma from tumor-bearing animals followed by i.v. injection of NFSA cells did not lead to the enhancement of metastasis, implying that granulocytosis might be rather concomitant manifestation than a causative factor of the enhancement of metastasis formation. Importance of granulocytosis as a paraneoplastic manifestation during tumor growth is discussed.

Agranulocytosis↗
PubMedDate not supplied

Effectiveness of AMSA alone or in combination with radiation on murine fibrosarcoma pulmonary nodules.

The cytotoxic effects in vivo of 4'-(9-acridinylamino) methanesulfon-m-anisidide (AMSA), radiation or both modalities in combination on murine fibrosarcoma (FSa) cells grown as pulmonary tumors were determined. Fourteen days following the i.v. injection of viable FSa cells, recipient mice developed between 100 and 150 visible pulmonary nodules. At that time, tumor-bearing animals were exposed to either single or combined modality treatments, as well as single and fractionated dose regimens. Animals were sacrificed 1 hour after the last treatment. Tumor nodules were excised, made into a single cell suspension and separated on the basis of cell size by centrifugal elutriation. Flow microfluorometry (FMF) was used to determine the cell-cycle parameters and the relative synchrony of the separated populations, as well as the percentage contamination by normal diploid cells in each of the tumor cell populations. Known numbers of viable cells from each elutriator fraction were injected into recipient mice to determine their colony-forming efficiency (CFE). Surviving fractions were determined by comparing the CFEs of treated FSa cells from each of the separated elutriator fractions with those of appropriate untreated controls. Following a single i.v. dose of AMSA (30 mg/kg), populations of cells enriched in S phase were the most sensitive. When a single dose of AMSA was combined with a single dose of radiation (100 rad), there was a marked schedule dependence with the more effective sequence, especially if a 12 hour interval was chosen between doses, being AMSA followed by irradiation. No schedule dependence was observed if both modalities were combined and administered under a fractionated protocol of four fractions of AMSA (5 mg/kg per fraction) and four fractions of radiation (300 rad per fraction). Under these conditions the greatest reduction in CFE was in cell subpopulations most enriched in S and G2 + M phase cells.

Aminoacridines↗
PubMedDate not supplied

Studies on the antitumor activities of pyrimidinone-interferon inducers. Part 2. Potentiation of antitumor resistance mechanisms.

In continuation of studies on antitumor activities of pyrimidinone interferon inducers, we report here that 2-amino-5-bromo-6-mF-phenyl-4(3H)-pyrimidinone (ABmFPP) is similarly effective to 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP) in its ability to reduce the number of metastatic nodules of a spontaneous fibrosarcoma (NFSa) and a spontaneous mammary carcinoma (MCa-K) in the lungs of C3Hf/Kam mice. Both compounds were more effective when given to mice prior to, rather than after, intravenous transplantation of tumor cells. In studies on the mechanism of the antitumor activity of pyrimidinones, 2-amino-5-iodo-6-phenyl-4-pyrimidinone (AIPP) was used in addition to ABPP and ABmFPP. These agents were capable of activating peritoneal macrophages that thus became capable of lysing in vitro 3T12 transformed cells but not syngeneic BALB/c embryo fibroblasts. Also, these agents were capable of augmenting significantly the natural killer (NK) cell activity in the spleen of C3Hf/Kam mice. Spleen cells from treated mice admixed to NFSa cells inhibited in vivo tumor take of these cells when the admixture was injected subcutaneously. Pyrimidinones were also effective against the development of NFSa nodules in the lungs of T-cell deficient mice implying that the presence of T-cells is not a prerequisite for the induction of antitumor activity by these agents. A further observation was that pyrimidinone compounds reduced the metastasis formation enhancing effect of cyclophosphamide. Therefore, pyrimidinone interferon inducers exhibit an appreciable antimetastatic activity mediated through antitumor resistance mechanisms involving activation of macrophages and stimulation of NK-cells.

Animals↗
PubMedDate not supplied

Treatment with cortisone plus heparin or hexuronyl hexoaminoglycan sulfates of murine tumors and their lung deposits.

Heparin, cortisone, and combination of these two drugs were used for treatment of solitary tumors and artificial lung metastases of the fibrosarcoma NFSA and the mammary carcinoma MCA-K in C3Hf/Kam mice. Heparin reduced the number of artificial metastases of both tumors, but it did not affect the s.c. growth of these tumors. Conversely, cortisone reduced both the number of artificial metastases and the growth rate of s.c. tumors. The effect of cortisone was not further influenced by heparin. Cortisone showed a tendency for causing enhancement of spontaneous metastases. In addition, two heparin analogs, hexuronyl hexoaminoglycan sulfates were studied against MCA-K solitary tumors and their spontaneous metastases. They were ineffective when given alone, and they did not influence the effect of cortisone on the s.c. tumor growth. However, they slightly reduced the cortisone-induced enhancement of spontaneous metastases.

Animals↗
PubMedDate not supplied

Metastatic properties of murine sarcomas and carcinomas. I. Positive correlation with lung colonization and lack of correlation with s.c. tumor take.

The spontaneous metastatic properties of six sarcomas and seven carcinomas syngeneic to C3Hf/Kam mice were investigated and the correlation between spontaneous metastasis, the lung colony forming efficiency (LCFE) of i.v. injected tumor cells, and s.c. tumor take was determined. The incidence and number of spontaneous metastases in the lung were determined in mice that had primary tumors in the leg removed 17 to 120 days earlier, depending on tumor type. There was a significant positive correlation between spontaneous metastasis and LCFE when all 13 tumors were compared, but the significance was lost when carcinomas and sarcomas were considered separately. No significant correlation between spontaneous metastasis and the s.c. tumor take was observed. Also, no correlation was found between LCFE and the s.c. tumor take of carcinomas, but there was a strong inverse relationship between these two properties of sarcomas. The number of cells shed from primary tumors was estimated and found to be more extensive in tumors with higher metastatic properties. Thus, in general, highly metastatic tumors were characterized by a high LCFE and a significant cell shedding. Furthermore, LCFE was greatly increased by treatment of animals with cyclophosphamide and by admixing heavily irradiated tumor cells to viable cells, implying that local environmental factors are important in determining the establishment of tumor cell clonogens into metastasis.

Adenocarcinoma↗
PubMedDate not supplied

Protective effects of WR-2721 against radiation-induced injury of murine gut, testis, lung, and lung tumor nodules.

WR-2721 (S-2-(3 aminopropylamino) ethylphosphorothioic acid) has been investigated for its ability to protect gut, lung, and testis, as well as fibrosarcoma (FSa) tumor nodules, in the lungs of mice from gamma-radiation injury. This compound greatly protected jejunum and testis epithelial cells. FSa micrometastases in the lung were protected to a lesser extent than jejunum and testis. Conversely, WR-2721 was not able to protect the lung against radiation-induced enhancement of tumor metastases formation generated by intravenously injected FSa cells.

Amifostine↗
PubMedDate not supplied

In vivo transfer of antitumor activity by peritoneal exudate cells from mice treated with C. parvum.

We have investigated whether peritoneal exudate cells (PEC) from C. parvum (CP) treated (C3Hf/Bu mice could transfer in vivo the resistance against a syngeneic fibrosarcoma (FSa). Inhibition of tumour development and prolongation of survival of recipients were observed when CP-activated PEC were admixed with FSa cells before their intraperitoneal (ip) or subcutaneous (sc) injections into normal mice. The antitumour activity increased with the increase of the ratio of effector to target cells. Heat killed CP-PEC were unable to transfer the resistance. Also, pretreatment of recipients with 600 rads whole body irradiation (WBI) substantially reduced the efficacy of CP-PEC. Reconstitution of WBI mice with mixed normal spleen and lymph node cells, or spleen cells alone, or bone marrow cells did not restore the antitumor activity of transferred CP-PEC. In fact, reconstituted mice showed a further reduction of transferred antitumor resistance. CP-PEC activity was also inhibited in sc transfer experiments when normal PEC, spleen cells, T-cells or even fetal fibroblasts were admixed with tumor cells and CP-PEC. Possible reasons for the failure of WBI recipients to be fully protected by transferred CP-PEC are discussed.

Animals↗
PubMedDate not supplied

Radiosensitivity of irradiated mouse skin to a second course of single and multifractionated irradiation. I. Early skin reaction.

Six or 12 months after a single or multifractionated gamma ray irradiation of the skin from the hind legs of mice, the response of the skin to the test dose in single or multi-fractionated (4-16) exposures was studied, using an early skin reaction as an endpoint. The pre-irradiated skin was relatively radioresistant compared to the previously untreated control skin in either dorsal or ventral sides of the legs. The variation in the skin sensitivity depending on the site of irradiation is also discussed for the pretreated and the untreated skin.

Animals↗
PubMedDate not supplied

Visual cell profiles for quantitation of premalignant cells in sputum: a preliminary report.

Visual cell profiles were used to analyze the distribution of atypical bronchial cells in sputum specimens from cigarette-smoking volunteers, cigarette-smoking asbestos workers and cigarette-smoking uranium miners. The preliminary results of these sputum visual cell profile studies have demonstrated distinctive distributions of bronchial cell atypias in progressive patterns of squamous metaplasia, mild, moderate and severe atypias and carcinoma, similar to those the authors have previously reported using cell image analysis techniques to determine an atypia status index (ASI). The information gained from this study will be helpful in further validating this ASI and subsequently achieving the ultimate goal of employing cell image analysis for the rapid and precise identification of premalignant atypias in sputum.

Age Factors↗