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Biomedical subjects

B M Boman

Publications and source records attributed to B M Boman.

At least 55 records · Page 3Linked to original sources
PubMed1987

A randomized study of two schedules of copovithane in patients with advanced colorectal carcinoma.

Copovithane (BAY i 7433), a copolymer of 1,3-bis(methylaminocarboxyl)-2-methylenepropanecarbamate and N-vinyl pyrrolidone, has antitumor activity in vitro and in vivo. The mechanism of this polymer is unknown. Thirty patients with advanced colorectal carcinoma with measurable tumors were treated in an open randomized study with two schedules of copovithane (schedule A: 6 g/m2 i.v. over 30 min daily for 5 consecutive days and repeated every 3 weeks; schedule B: 10 g/m2 i.v. over 30 min once a week until progression, unacceptable toxicity, or up to 18 months). Fifteen patients received copovithane on a weekly schedule, and 15 patients received it on an intermittent schedule. None of the patients on either schedule achieved a complete or partial remission. Copovithane was ineffective against colorectal carcinoma by both schedules selected in this study.

Antineoplastic Agents↗
PubMed1986

Phase II study of spirogermanium in patients with advanced colorectal carcinoma.

Twenty one evaluable patients with advanced colorectal carcinoma were treated with continuous infusion of spirogermanium at a median daily dose of 150 mg/m2 (range 120-210) for five consecutive days every 14 days. Treatments were accomplished by using outpatient infusion devices. Fifteen patients had not received any prior radiation therapy, immunotherapy, or chemotherapy. Nineteen patients were previously untreated with chemotherapy. Five patients had received prior immunotherapy with copovithane and only two patients had received radiation therapy prior to spirogermanium therapy. None of the patients achieved a complete or partial remission. Minor tumor regressions were observed in two patients, both were less than 12 weeks in duration. The major toxicities included nausea and vomiting and neurologic side effects; however, the toxicity was completely reversible. Spirogermanium is not effective in the treatment of patients with advanced colorectal carcinoma.

Adult↗
PubMed1984

Carcinoma of the anal canal. A clinical and pathologic study of 188 cases.

Among 188 patients presenting with carcinoma of the anal canal the predominant cell types were squamous cell (56%) and nonkeratinizing basaloid (35%). Thirteen patients who had predominantly small (less than or equal to 2 cm) and only superficially invasive squamous cell lesions were treated with local excision, and although one required later abdominal perineal (AP) resection for local recurrence, all were apparently cured. Local excision should be preferred as initial treatment for such lesions. One hundred eighteen patients with squamous cell and nonkeratinizing basaloid carcinomas were primarily treated with AP resection. The operative mortality rate was 2.5%. Among 114 patients who survived surgery and had adequate follow-up, 40% developed recurrent disease, and 71% have survived 5 or more years. Pathologic staging based on depth of tumor invasion and regional nodal involvement was strongly predictive of survival as was tumor histology with progressively poorer survival rates from low-grade squamous cell to high-grade squamous cell to nonkeratinizing basaloid types. Tumor size was inversely related to prognosis and was strongly associated with stage. Squamous cell anal carcinoma was dominantly a local disease with approximately 70% of patients presenting with tumor apparently limited to the bowel wall, only 20% with regional node involvement and only 2% with distant metastasis. Even among those patients who recurred after AP resection approximately 80% had all known disease still limited to the pelvic area. Corresponding figures for nonkeratinizing basaloid tumors were 50 percent presenting limited to the bowel wall, 30% with regional nodes, 20% with distant metastasis, and 60% with initial recurrence limited to the pelvis. Among the 13 patients studied with small cell anal carcinoma, the authors found the disease to be very virulent either initially presenting with or rapidly evolving into diffuse dissemination. Only one of the seven patients who could be treated surgically survived 5 years. As is true for small cell carcinomas primary to other sites, this neoplasm should be regarded as a systemic disease. With these findings as a foundation, possible future strategies for management of anal carcinoma are discussed.

Adult↗
PubMed1984

Topography of protein kinases and phosphoproteins in the plasma membrane of 3T3 cells.

The plasma membrane of 3T3 cells contains at least two different endogenous cyclic AMP-dependent protein kinase systems. One catalyzes the phosphorylation of endogenous protein substrates, i.e., PP24 and PP14, whereas the other catalyzes the phosphorylation of exogenous substrates. In this paper the topography of these cyclic AMP-dependent phosphorylation systems is described. The results show that the kinases which phosphorylate only exogenous substrates are primarily localized to the outer plasma membrane surface whereas the endogenous cyclic AMP-dependent protein kinase and its two endogenous substrates are localized to the cytoplasmic plasma membrane surface. The data also establish that neither the cytoplasmically orientated kinase nor its substrates has a transmembrane orientation even though factors acting on the outer plasma membrane can affect these proteins. This suggests that functional modulation of the cytoplasmically localized cyclic AMP-dependent phosphorylation system can be mediated by a transmembrane regulatory mechanism. The importance of determining the topography of such plasma membrane phosphorylation systems is emphasized by recent studies which show that neoplastic transformation can be mediated at least in part by protein kinases and/or phosphoproteins which are localized on the cytoplasmic surface of the plasma membrane.

Animals↗
PubMed1983

Cell cycle and cyclic AMP-dependent phosphorylation of plasma membrane proteins p14 and p24: defects in smooth surface transformed cells.

Two proteins which are localized to the cytoplasmic surface of the plasma membrane, p14 and p24, undergo cyclic AMP-dependent phosphorylation in rapidly growing nontransformed murine embryo cells. In this cell system, growth arrest in the G1 phase of the cell cycle induced by growth factor deprivation is associated with the reversible loss in ability to phosphorylate these substrates. By contrast, Simian virus 40 and methylcholanthrene transformed cells show both defective G1 growth control and defects in their ability to phosphorylate p14 and p24 under all tested growth conditions. These data suggested a correlation between defects in the physophorylation of p14 and p24 and defects in the ability of transformed cells to G1 growth arrest. The results of the current studies by contrast show that 3T3 T proadipocytes which have been transformed by the smooth surface tumorigenesis method show different characteristics. They retain the ability to G1 growth arrest in serum-deficient medium. They show cyclic AMP-dependent phosphorylation of p14 and p24 during exponential growth. They do not, however, down regulate p14 and p24 phosphorylation in association with G1 growth arrest. These observations suggest that neoplastic transformation is not necessarily associated with absolute defects in the ability to phosphorylate p14 and p24. Rather, the results of the current study suggest that the inability to modulate the cyclic AMP-dependent phosphorylation of plasma membrane p14 and p24 proteins during the G1 phase of the cell cycle may be more tightly associated with neoplastic transformation.

Adipose Tissue↗
PubMed1983

Cell surface characteristics of proadipocytes growth arrested at the predifferentiation GD state. Defects associated with neoplastic transformation.

The differentiation of murine proadipocytes is preceded by growth arrest at a specific state in the G1 phase of the cell cycle, designated GD. The GD arrest state has been shown to be distinct from other G1 arrest states, including those induced by serum or growth factor deprivation, designated GS, and by nutrient deprivation, designated GN. Defects in the control of growth arrest at GD have also been correlated with carcinogenesis. In this study we have analyzed the cell surface characteristics of nontransformed proadipocytes at various states in the G1 phase of the cell cycle by scanning electron microscopy. The results show that abundant cell surface microvilli, 2.0 to 4.0 micrometer long and 0.2 to 0.4 micrometer in diameter, develop when proadipocytes are cultured in medium that induces GD arrest but not when they are cultured under conditions that induce GS or GN arrest. The results also show that initiated and transformed proadipocytes fail to develop prominent cell surface microvilli when cultured in differentiation-promoting medium; they also fail to GD arrest and differentiate.

Adipose Tissue↗
PubMed1980

Manganese and magnesium dependent properties and inner plasma membrane surface localization of guanylate cyclase from murine plasmocytoma cells.

The particulate fraction from murine plasmocytoma cells contained 90 per cent of the total guanylate cyclase activity. Triton X-100 produced a 6 fold stimulation of guanylate cyclase activity in plasma membrane enriched fractions obtained by zonal centrifugation. Isolated inside out (10) vesicles contained 9 times more activity than rightside out (RSO) vesicles. This difference was abolished by Triton X-100 treatment of the vesicles indicating that the catalytic site of guanylate cyclase is located on the inner face of the plasma membrane. Kinetic studies of membranous guanylate cyclase showed that optimal activity was found with manganese. Only 20 per cent of this activity was obtained with magnesium. The Km for GTP with magnesium (1.4 mM) was about 7 fold greater than with manganese (0.2 mM). Positive cooperativity was obtained in both cases and the Hill coefficients were 1.8 for manganese and 1.6 for magnesium. Physiological concentrations of ATP were found to inhibit both manganese and magnesium supported activities indicating a possible regulatory mechanism for this nucleotide in vivo.

Animals↗
PubMedDate not supplied

Development of cross-resistance to tamoxifen in raloxifene-treated breast carcinoma cells.

Selective estrogen receptor modifiers (SERMs) are used chronically in the treatment of breast cancer and osteoporosis but some patients become resistant, at which point second-line SERMs are considered as options. Because the use of SERMs is increasing and breast cancer is so common, we tested the hypothesis that treatment with SERMs can induce cross-resistance to other SERMs. We used three cultured breast carcinoma cell lines (MCF-7, ZR-75-1, and T47D) which are estrogen-receptor-positive (ER+) and are prone to developing resistance to hormonal treatment. Cell lines were exposed to increasing doses of raloxifene. Raloxifene-resistant clones were selected and tested for cross-resistance to tamoxifen. Compared to untreated cells, raloxifene-resistant clones showed an increased IC50 (reduced potency) of about 15,000-fold with no apparent change in maximal inhibition of cell growth. These same raloxifene-resistant clones were also about 15-fold more resistant to the growth-inhibiting effects of tamoxifen. While the resistance to tamoxifen is considerably less marked (1000-fold less), it is large enough to raise the question as to whether patients who become resistant to raloxifene will benefit by switching to tamoxifen or vice versa.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Expression of the gene coding for the light chain of calpactin I (annexin II) in cell lines DiFi, HT-29, and WI-38.

Calpactin I (annexin II) light chain gene messages were expressed in the DiFi and HT-29 human colon cancer cell lines, as well as in the diploid lung fibroblast cell line WI-38. However, expression of an approximately 1.0 kb transcript was stronger in DiFi and HT-29 cells than in WI-38 cells. The moderate to strong expression of such transcripts in DiFi and HT-29 cells indicates that the calcium binding protein, calpactin I, may be abundant in colon carcinoma cells. Calpactin I is the major substrate of pp60v-src, a tyrosine-specific protein kinase encoded by v-src, whose cellular homologue c-src also codes for a tyrosine kinase (pp60c-src), known to be activated in colon carcinomas and in cell lines derived from them (including HT-29). Abundance of calpactin I in such cells is consistent with the possibility that activation of the pp60c-src tyrosine kinase contributes to the origin of human colon cancers.

Annexins↗
PubMedDate not supplied

A study of chromosome 6 allele loss in human colorectal carcinomas.

Matched normal/tumor DNA pairs from patients with sporadic and hereditary (FAP = familial adenomatous polyposis) colorectal carcinoma were examined for tumor-specific allele loss on chromosome 6 using cDNA probes for the avian myeloblastosis viral oncogene homologue (MYB on 6q22-q23), the estrogen receptor (ESR on 6q24-q27), and for the alpha polypeptide of human chorionic gonadotropin (CGA on 6q14-q21). No chromosome 6 allele loss was observed at these gene loci among 22 colorectal carcinomas examined, although such losses were relatively frequent (37.5% of informative individuals) at the D17S28 locus on chromosome 17. These results are consistent with karyological studies and indicate that chromosome 6 allele loss from colorectal carcinomas may occur less frequently than previously reported.

Adenomatous Polyposis Coli↗
PubMedDate not supplied

Characterization of beta-adrenergic receptors in DiFi and HT-29 cells.

The beta-adrenergic receptors present in two human colorectal adenocarcinoma cell lines were characterized by measuring specific binding of [125I]-cyanopindolol (CYP). Whole, cultured, DiFi (derived from a familial adenomatous polyposis [FAP] patient) and HT-29 cells were used in radioligand binding assays. Scatchard analysis of specific 125I-CYP binding gave KDS of 38.6 +/- 5.7 pM in DiFi cells and 54 +/- 9.1 pM in HT-29 cells. However, binding site density (Bmax) in the DiFi cells was greater than that in HT-29 cells. In DiFi cells, the kinetically determined KD was similar to that calculated from Scatchard analysis. Studies in DiFi cells of the displacement of specific 125I-CYP binding by nonselective (propranolol), beta 1-selective (metoprolol and atenolol), and beta 2-selective (ICI 118-551) antagonists revealed only a single class of beta 2-adrenergic receptors. This provides the first evidence that colorectal adenocarcinoma cell lines contain beta-adrenergic receptors and shows that only beta 2-adrenergic receptors are present in DiFi cells. Mechanisms possibly affecting beta-adrenergic-receptor expression in such cells are discussed in relation to colon carcinogenesis.

Adenocarcinoma↗
PubMedDate not supplied

Growth effects of tamoxifen on Lovo colon carcinoma cells and cultured cells from normal colonic mucosa.

The growth effects of tamoxifen (TAM) were studied using normal and malignant colonic epithelial cells. Addition of TAM (0.8 to 10 microM) to cultured normal human colon epithelial cells and Lovo colon adenocarcinoma cells produced a dose response decrease in growth of 42 to 76%. Histamine (1 to 10 microM) did not affect cell growth and did not negate the TAM effect. Calmodulin (2 micrograms/ml) totally blocked growth inhibitory effects of a calmodulin antagonist, trifluoperazine (10 microM), but did not block the TAM inhibitory effect. These data suggest that antiestrogen binding sites (AEBS) may play an important role in the growth-inhibitory effects of TAM on colon cells. Competition with estrogen and antagonism with histamine or calmodulin do not appear to be significant in this regard.

Adenocarcinoma↗