Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TAM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed2003

[In vivo effect of Shu-Gan-Liang-Xue decoction on estrogen].

OBJECTIVE: To observe the in vivo effect of traditional chinese medicine (TCM) Shu-Gan-Liang-Xue (SGLX) decoction on estrogen in vivo in mice. METHODS: Mice were randomly divided into control, tamoxifen (TAM), SGLX and SGLX + TAM groups. After SGLX decoction had been given to mice for 21 days, the serum hormone level of mice was tested by radioimmunological method, uterine weight index was obtained by uterine weight divided by body weight. Endometrial change was pathologically observed. RESULTS: SGLX decoction reduced the level of serum estrogen more than the control with significant difference (P < 0.001). Uterine weight index was more lowered in the SGLX group than the control giving a difference but not significant. The endometrium in the SGLX group showed no change when compared with that of the control, but the SGLX + TAM group showed slightly more endometrial hyperplasia than the TAM group. CONCLUSION: SGLX decoction, having synergistic effect on TAM, can reduce serum hormone level and alleviate the endometrial hypertrophy side effect of TAM.

Animals↗
PubMed2004

[Correlation between expression of vascular endothelial growth factor-C in tumor-associated macrophages and lymphatic metastasis in oral cancer].

BACKGROUND & OBJECTIVE: Previous study shows that both vascular endothelial growth-C (VEGF-C) and tumor-associated macrophages (TAMs) are related to lymphatic metastasis. This study aimed to explore the correlation between the expression of VEGF-C in TAMs and lymphatic metastasis in human oral squamous-cell carcinoma (OSCC). METHODS: After immunohistochemical staining, light microscope was used for counting macrophages and automated image analysis quantification was used to determine VEGF-C expression,which was reflected by positive index (PI). In addition,the double staining was also used to determine VEGF-C expression in TAMs. RESULTS: VEGF-C expression was higher in lymphatic metastasis group (PI=12.169+/-2.778) than in no-metastasis group (PI=8.498+/-2.674, P< 0.05). TAMs counts was related to VEGF-C expression in OSCC (r=0.370, P< 0.05). The result of double staining indicated that macrophage with positive VEGF-C expression accounted for about 22.8% of the total. CONCLUSION: Not only tumor cells but also TAMs secrete the VEGF-C in OSCC, and TAMs may play a major role in peritumoral lymphatic neoangiogenesis and lymphatic metastasis.

Antigens, CD↗
PubMed1992

Differential effects of estrogen and antiestrogen on transforming growth factor gene expression in endometrial adenocarcinoma cells.

While antiestrogens are useful agents in the treatment of breast cancer, the usefulness of these agents in the treatment of endometrial cancer remains controversial. There is some concern that the currently available antiestrogens may have partial agonist activity in uterine tissue. To better understand the mechanisms by which estrogens and antiestrogens modulate growth of endometrial adenocarcinoma cells, we have compared the effects of 17-beta estradiol and three antiestrogens, 4-hydroxytamoxifen (OH-TAM), ICI 164384, and LY 117018 on proliferation and transforming growth factor (TGF) mRNA accumulation in two human endometrial adenocarcinoma cell lines. In HEC-50 cells, neither estradiol nor anti-estrogens had any effect on cell proliferation or TGF mRNA abundance under estrogen-depleted culture conditions [basal medium containing 1% twice charcoal-treated fetal bovine serum (ctFBS)] or in the presence of estrogen (basal medium containing 5% fetal bovine serum). At very high concentrations, both estradiol and OH-TAM caused a small decrease in HEC-50 cell proliferation in medium containing 5% serum. In contrast, the antiestrogens had different effects on Ishikawa cells, depending upon the culture conditions. In medium containing 5% fetal bovine serum, the antiestrogens inhibited cell proliferation and significantly decreased TGF-alpha mRNA abundance and TGF-alpha secretion. OH-TAM was more potent than the other antiestrogens. Under these culture conditions, estradiol had no effect on cell proliferation or TGF-alpha mRNA levels but increased TGF-alpha secretion. In medium supplemented with 1% ctFBS, estradiol increased cell proliferation and TGF-alpha mRNA (2.72-fold, P less than 0.005) and TGF-alpha secretion (700 +/- 156 versus 250 +/- 23 pg/10(6) cells/24 h, P less than 0.05), whereas OH-TAM, which also stimulated cell proliferation, reduced TGF-alpha mRNA abundance (P less than 0.05) but had no significant effect on TGF-alpha secretion. Under these conditions, ICI 164384 and LY 117018 had no effect on either cell proliferation or TGF-alpha expression. Estradiol treatment decreased, whereas OH-TAM increased, epidermal growth factor receptors in Ishikawa cells. Both estradiol and the antiestrogens decreased TGF-beta 1 mRNA abundance when cells were grown in media containing 1% ctFBS. In summary, the response of human endometrial adenocarcinoma cells to estrogen and antiestrogens varied between cell lines and was dependent upon the culture conditions used. In addition, OH-TAM, unlike the other two antiestrogens tested, had growth-stimulating effects on Ishikawa cells.

Adenocarcinoma↗
PubMed2006

Microvessel density, VEGF expression, and tumor-associated macrophages in breast tumors: correlations with prognostic parameters.

Angiogenesis plays an important role in tumor growth, metastasis, and prognosis. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen and acts on the angiogenic stimulation of human neoplasias. In infiltrative ductal carcinoma (IDC), VEGF expression is correlated with high vascularity. Tumor-associated macrophages (TAMs) contribute to tumor proliferation, progression and angiogenesis and have a complex role in tumor biology. In this study, the correlations between microvessel density (MVD), VEGF expression, and TAMs and their relations to clinicopathological parameters such as tumor size, metastatic lymph node, mitotic activity index (MAI) and tumor grade were investigated in 48 cases of IDC and 30 infiltrative lobular carcinoma (ILC) cases. MVD showed a significant positive correlation with TAMs, VEGF, metastatic lymph nodes, tumor size and grade in IDC (P < 0.001). In ILC, MVD and tumor size were positively correlated (P = 0.003), while MVD was not correlated with VEGF, TAMs, MAI, metastatic lymph nodes, and grade. These findings are suggestive of angiogenesis stimulation in IDCs by VEGF, driving the macrophages into the tumor area. MVD and TAMs were found to be important prognostic factors in IDCs. On the other hand, however, VEGF did not contribute to angiogenesis in ILCs, and MVD and TAMs did not have any prognostic significance. These results suggest the involvement of factors not related to VEGF in the angiogenesis of lobular carcinoma.

Adult↗
PubMed1989

Sequential hormone therapy with medroxyprogesterone acetate for 7, 12-dimethylbenz [alpha] anthracene-induced rat mammary tumors.

Two types of sequential hormone therapy with medroxyprogesterone acetate (MPA) were examined in female 93 Sprague--Dawley (SD) rats with 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced mammary tumors. Estradiol (E2) priming induced progesterone receptors (PgR) in most cases and, after induction of PgR, MPA often showed an augmented antitumor effect. For this reason, E2 priming + MPA had a more marked antitumor effect on DMBA tumors than MPA alone. Tamoxifen (TAM) (0.1 mg/kg) priming induced PgR more frequently than TAM (0.4 mg/kg) priming. Furthermore, treatment with TAM priming (0.1 mg/kg) + MPA showed a more marked antitumor effect than with TAM priming (0.4 mg/kg) + MPA or MPA alone. In the above two priming therapies with MPA, the latter is more practical for the clinical treatment of breast cancer than the former because the mechanism of action of E2 is usually thought to show tumorigenic activity on breast cancer, while the mechanism of action of TAM is thought to show an antitumor effect. It is suggested that the sequence of administration of MPA after TAM priming may be favorable for the treatment of breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Organ preference of metastasis. The role of organ-specifically modulated endothelial cells.

Many cancers display characteristic organ colonization patterns that do not fit simple, anatomical-mechanical trapping theories of tumor cell dissemination. Organ preferences of metastatic spread appear to be mediated partly by the selective attachment of tumor cells to organ-specific, microvascular endothelium. To study these tumor cell-endothelial cell interactions in an efficient and reproducible manner, we have designed a novel in vitro assay system wherein endothelial cells isolated from large vessels (e.g., aorta) can be modulated to assume phenotypic traits of organ-specific, microvascular endothelium. Modulation is achieved by growing bovine aortic endothelial cells (BAEC) on organ-specific matrix components, termed tumor attachment modulators (TAMs). Using monolayers of modulated BAEC in a tumor attachment assay, we show here that tumor cells which metastasize to a given organ, have a significantly higher binding affinity for BAEC grown on TAMs of the preferred, metastasized organ, than they have for BAEC grown on TAMs of any other organ not colonized by these tumor cells. Lung-metastatic tumor cells (R3230AC-MET, B16-F10) adhere preferentially to BAEC monolayers grown on lung-specific TAMs, whereas liver-metastatic tumor cells (RAW117-H10, M5076) selectively adhere to BAEC grown on liver-specific TAMs. In contrast, nonmetastatic tumors cells (R3230AC-LR, RBTCC-1, 647V) show no such adhesion preferences. Preferential tumor cell adherence is increased by growing BAEC for prolonged periods on organ-specific TAMs. Metastatic preference and organ distribution are mediated, at least in part, by urea-extractable endothelial cell surface components that are regulated by the extracellular matrix.

Adenocarcinoma↗
PubMed1986

Role of tumor-associated macrophages in lung cancer.

The percentage of tumor-associated macrophages recovered (TAMR) and antitumoral activity of tumor-associated macrophages (TAM) were examined in 77 patients with resectable primary lung cancer. TAM was obtained by plastic adherence following trypsinization. TAMR increased from Stage I to Stage II and decreased in Stage III. It also increased in N1 as compared with N0 and N2 but was unrelated to tumor size. However, the cytostatic activity of TAM declined with advance in stage of the disease and an increase of tumor size, but it was relatively unaffected by the presence of metastasis to regional lymph nodes. There was no correlation between TAMR and the recurrence rate; however, cytostatic activity of TAM was correlated significantly with the prognosis of totally resected cases. TAMR and cytostatic activity of TAM tended to be lower in palliatively resected cases. These results suggest that the assessment of the antitumor activity of TAM, but not merely TAMR, may give prognostic information for lung cancer patients.

Adenocarcinoma↗
PubMedDate not supplied

Effects of aminoglutethimide plus hydrocortisone on the genital tract of postmenopausal women with advanced breast cancer. A clinical and cytologic survey.

In this study we compared the effects of either Aminoglutethimide (AGL) or Tamoxifen (TAM) therapy on the genital tract of postmenopausal women with advanced breast cancer. Thus, 15 patients treated with AGL, and 10 patients treated with TAM underwent gynaecological examination, during which vaginal smears were taken. All smears were reviewed in blind by one pathologist for determination of karyopycnotic indices (KI). Under TAM, no significant clinical abnormality was observed, except in one patient who had a small (histologically benign) endocervical polyp, easily removed during the examination. As reported by others, smears made under TAM therapy were generally characterized by high KI, indicating that an hormonal, estrogen-like stimulation remained present in these patients. On the contrary, most women under AGL had some evidence of vulvovaginal atrophy, which was unvariably associated with low KI on smears. Among the latter, four had severe dystrophic lesions consisting of leukoplasia (1), kraurosis (2) or lichen sclerous and atrophicus (1). It is therefore recommended not to neglect the systematic practice of gynaecological examination in patients with advanced breast cancer under endocrine therapy. These observations also indicate that AGL and TAM exert entirely opposite effects on the vaginal mucosa, which is a very sensitive estrogen-target tissue. In good agreement with former endocrine studies, AGL acts as a potent suppressor of estrogens resulting in severe mucosal atrophy. On the contrary, TAM seems nearly always to display some agonistic hormonal stimulation.

Adult↗
PubMed1985

The immunological basis of tumor rejection: the absolute dependence of the effector arm on sensitized T cells after chemoimmunotherapy of a murine sarcoma.

The mechanisms of tumor rejection were investigated by using a therapeutic model system involving treatment of C57BL/6J (B6) mice bearing the syngeneic MCA/76-9 or the unrelated MCA/76-64 sarcomas with cytoxan and tumor-sensitized T lymphocytes. Separated tumor-associated T lymphocytes (TAL) and tumor-associated macrophages (TAM) isolated from the regressing tumors 8 to 10 days after combination therapy expressed relatively specific cytotoxicity in vitro, whereas the unseparated tumor-associated cells (TAC), consisting of a mixture of TAL and TAM, expressed nonspecific cytotoxicity. TAM-mediated cytotoxicity was not dependent on the presence of TAL, as shown by T cell depletion of TAM or TAC cultures with the use of monoclonal anti-Thy-1 or anti-Lyt-2 antibody and complement. In contrast, the nonspecific cytotoxicity was dependent on the presence of T cells. In vivo assays using the Winn test failed to confirm certain aspects of the in vitro data. Without exception, the TAC inhibited tumor growth in an immunologically specific manner, having no effect on the growth of the unrelated B6 sarcoma. T cell depletion completely abrogated in vivo cytotoxicity. Specificity of tumor growth inhibition was confirmed in a bystander experiment in which TAC were mixed with both tumor cell types and were injected into recipient B6 mice. Tumors grew under these conditions, but the tumor that grew consisted only of those tumor cells toward which TAC cytotoxicity was not specifically directed. A bioassay indicated that the specifically immune antitumor effects at the site of regression were initiated between days 3 and 7 after combination therapy. By days 7 and 9, few tumorigenic stem cells could be detected at the tumor site. However, T cell depletion of the TAC isolated on days 8 to 10 resulted in enhanced tumor growth when the depleted TAC were injected into recipient mice. The conclusions reached were that tumor rejection was absolutely dependent on T cell participation at the tumor site, and that if TAM were involved, they required the presence of TAL and did not express nonspecific antitumor cytotoxicity. Indeed, the accelerated tumor growth seen in the absence of TAL suggested the possibility that TAM were growth stimulatory.

Animals↗
PubMed1985

Hormonal therapy of human endometrial adenocarcinoma in a nude mouse model.

The hypothesis that 17 beta-estradiol or tamoxifen (TAM) can potentiate clinical response of endometrial cancer treated with progestin was tested in an ovariectomized nude mouse system, using a sex steroid receptor-positive and a receptor-negative human endometrial carcinoma. Animals were divided into three groups: control; 17 beta-estradiol-treated; and TAM-treated. When tumors of a group reached about 1 cm in diameter, subgroups were given either 0.9% NaCl solution (saline) or medroxyprogesterone acetate (MPA). The receptor-negative tumor grew rapidly in all three groups, and several animals were dead before or during progestin treatment. The growth rate of receptor-containing carcinoma was significantly increased in TAM-treated mice compared to controls (p less than 0.02) but significantly less than that in 17 beta-estradiol-treated animals (p less than 0.01). Endometrial carcinoma in 17 beta-estradiol-saline-treated animals continued to grow rapidly, and all animals were dead by 11 weeks. The growth of tumors in the 17 beta-estradiol-progestin group was suppressed at 11 weeks, and some of these animals lived 20 weeks. Administration of progestin to TAM-exposed animals resulted in a remarkable regression of the tumor compared to TAM-saline-treated group. The growth rate of tumors in control animals (no implants) was unaffected by progestin treatment. We conclude that, in this nude mouse model, treatment with TAM and MPA is superior to MPA alone, or 17 beta-estradiol plus MPA for sex steroid receptor-positive endometrial carcinoma.

Adenocarcinoma↗
PubMed1984

Structural requirements for the pharmacological activity of nonsteroidal antiestrogens in vitro.

The structure-activity relationships of a tamoxifen (TAM) (Z-1-(4- beta-dimethylaminoethoxyphenyl)1,2-diphenylbut-1-ene) series have been investigated. The tamoxifen derivatives were assayed in vitro by their modulation of estradiol (E2)-stimulated prolactin synthesis in primary cultures of dispersed rat pituitary gland cells. Monohydroxylation of TAM in position 4 of the stilbene ring system was found to be the optimal substitution for binding to the estrogen receptor [relative binding affinity (RBA) = 234] and to inhibit E2 (1 nM)-stimulated prolactin synthesis (IC50 7 nM) by pituitary cells in primary culture. Substitution in positions 3 and 4 to form a catechol did not decrease affinity for the estrogen receptor (RBA = 252), and potency as an antiestrogen was maintained in the prolactin assay (IC50 20 nM) as long as oxidation of the catechol was prevented. All of the hydroxylated derivatives of tamoxifen tested were estrogen antagonists; however, removal of the alkylaminoethoxy side chain from TAM produced a full estrogen agonist with low potency (20 nM). In contrast, removal of the side chain from 4-hydroxytamoxifen (4-OH TAM) produced a partial agonist. A structural analogue of 4-OH TAM, 3-[beta-dimethylaminoethoxy]-11-ethyl-12-(4-hydroxyphenyl)5,6- dihydrodibenzo[a,e]-cyclooctene (7c) had a decreased potency (IC50 16 nM) compared with 4-OH TAM (IC50 4 nM in the same experiment) as an estrogen antagonist. If the side chain was changed from a dimethylaminoethoxy to glyceryl, antagonist activity was reduced (IC50 0.8 microM). An allyl side chain produced a compound with no antiestrogenic activity at concentrations up to 1 microM. An adaptation of Belleau's macromolecular perturbation theory is suggested to explain the interaction of agonists, antagonists, and partial agonists at the ligand binding site of the estrogen receptor.

Animals↗
PubMed1993

Inhibition of oxidative stress in HeLa cells by chemopreventive agents.

12-O-Tetradecanoylphorbol-13-acetate (TPA)-mediated oxidative stress in HeLa cells and its inhibition were studied by fluorometric measurement of H2O2 and by 3H-postlabeling of the oxidized bases 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and 5-hydroxymethyl-2'-deoxyuridine (HMdU). TPA treatment (10 fmol/cell) caused approximately 7-fold increase in H2O2 levels (0.1 nmol TPA/ml), and 5-10-fold increase in 8-OHdG and HMdU (10 nmol TPA/ml). Naturally occurring compounds [caffeic acid phenethyl ester (CAPE), (-).epigallocatechin gallate (EGCG), penta-O-galloyl-beta-D-glucose (PGG) and sarcophytol A (Sarp A)] and the anticancer drug tamoxifen (TAM) were tested as potential chemopreventive agents. These agents dose-dependently inhibited TPA-induced H2O2, 8-OHdG and HMdU. The doses required for a 50% decrease in H2O2 were approximately 2.5 microM for TAM; 5 microM for CAPE, EGCG and PGG; and 75 microM for Sarp A. TAM and PGG (10 microM), EGCG (25 microM), and CAPE (50 microM) abolished TPA-mediated H2O2 production, even below the normal cellular levels. TAM (2.5-20 microM) decreased TPA-mediated HMdU and 8-OHdG formation 2-29 times. Maximum inhibition occurred at 20 microM TAM, which caused an approximately 95% decline in HMdU and 8-OHdG. CAPE was effective at 0.5-50 microM. CAPE (25 microM) decreased 8-OHdG 95%, and HMdU 58%, while Sarp A (250 microM) reduced 8-OHdG by 93% and HMdU by 78%. EGCG (1-25 microM) and PGG (1-10 microM) inhibited of 8-OHdG and HMdU dose-dependently. However, higher doses (50 and 100 microM) decreased the efficacy of that inhibition. Of those agents tested, TAM appears to be the most and Sarp A the least effective. Our results point to these 5 compounds as being potential chemopreventive agents, which at very low doses decrease the tumor promoter-mediated oxidative processes.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

[Adjuvant endocrine therapy for breast cancer].

As reported by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) in Lancet (1992), the 10-year relapse-free survival or overall survival was significantly better in the tamoxifen (TAM) treatment group than in the control group in both node-positive and -negative groups. Adjuvant TAM treatment works better on patients over 50 years of age. Adjuvant TAM treatment for over 2 years is more effective than less than that time. Some reports demonstrated that long-term TAM treatment caused an increase in the circulating estrogen levels of premenopausal patients. This increase blocked the antitumor effect of TAM in a dose dependent fashion in our animal models. Similar results were obtained in toremifene or TAT-59 in our animal models. These results show that antiestrogens are more effective for postmenopausal than premenopausal women. LH-RH agonist or aromatase inhibitor may be a promising adjuvant endocrine agent of breast cancer. Combination therapy of TAM and LH-RH agonist, or LH-RH agonist and aromatase inhibitor will be an effective new adjuvant endocrine therapy for breast cancer. The combination of endocrine therapy and biological response modifiers, or of endocrine therapy with vitamin D3 will be clinically used in the future.

Animals↗
PubMed1994

Transformation by Raf and other oncogenes renders cells differentially sensitive to growth inhibition by a dominant negative c-jun mutant.

In NIH3T3 cells expressing active Raf-1 protein serine/threonine kinase (PSK) c-jun expression is constitutive while c-fos expression is attenuated. This alteration prompted us to determine whether oncogene transformation would render cells differentially sensitive to growth inhibition by a dominant negative mutant of c-jun, TAM 67. Growth inhibition was observed in three types of assays: (1) transfection of TAM 67 into cells stably transformed by a variety of oncogenes, (2) cotransfection of TAM 67 with oncogene expression plasmids into NIH3T3 cells and (3) titration of oncogene-expressing retroviruses on cells stably expressing TAM 67. The results clearly demonstrate that Raf-1 dependent oncogenes, which include receptor protein tyrosine kinases (PTKs)-, intracellular PTKs- and Ras-derived genes share the Raf phenotype of constitutive c-jun expression, attenuated c-fos induction, and high sensitivity to growth suppression by TAM 67. Additionally, the intracellular PSK oncogene, mos and the nuclear oncogenes c-myc, c-fos, and SV40 T antigen were TAM 67-sensitive for transformation. This universal pattern of altered growth regulation in oncogene transformed fibroblast cell lines highlights the potential usefulness of c-jun based inhibitors for control of tumor cell growth.

3T3 Cells↗
PubMed1993

[Systemic adjuvant chemo-endocrine therapy after breast conservation treatment for breast cancer].

The majority of patients who have undergone breast conserving surgery proved to be node-negative. Node-negative breast cancer has a fairly good prognosis, achieving a 10 year disease-free survival rate of 88%. Patterns of recurrence and relapse in node-negative cases are characterized by a higher ratio of hematogenous metastases after relatively longer disease-free intervals. Such cases have been considered the best indications of systemic adjuvant therapy. Postoperative adjuvant trials using cyclophosphamide (CPA) and/or tamoxifen (TAM) were conducted at the Aichi Cancer Center Hospital, and the following results were obtained concerning adjuvant treatment for early-stage (node-negative or stage I) breast cancer; (1) In the post-menopausal group, CPA and/or TAM administration was recommended as the treatment of choice. (2) In the postmenopausal group, TAM was evaluated as the key drug. After TAM alone or TAM plus CPA administration, an improvement in the disease-free survival rate was expected. (3) After administration of CPA alone in the postmenopausal group, there were no demonstrable benefits. On the contrary, adverse effects were suspected. (4) The risk of contralateral breast cancer was reduced to two-thirds when TAM was administered as an adjuvant therapy.

Breast Neoplasms↗
PubMed1993

Tamoxifen-induced increase in the potential doubling time of MCF-7 xenografts as determined by bromodeoxyuridine labeling and flow cytometry.

The anti-estrogen tamoxifen (TAM) is widely used in the therapy of human breast cancer. Shown to induce a G1 transition delay in vitro, the kinetic effects of TAM on breast carcinoma cells growing as tumor xenografts in nude mice have been less well characterized. In this study, we demonstrate a significant increase in the tumor potential doubling time (Tpot) and decrease in the labeling index (%LI) of estradiol (E2)-stimulated MCF-7 xenografts following TAM treatment or E2 deprivation. MCF-7 tumor pieces were transplanted s.c. into nude mice supplemented with Silastic capsules containing E2. After 2-4 weeks, animals were randomized to continued E2 treatment, E2 and TAM treatment, or E2 deprivation. At times ranging from 0 to 23 days after treatment, animals were given injections of bromodeoxyuridine and tumors excised for kinetic analysis. Using flow-cytometric techniques, the Tpot and %LI were estimated for all tumors. Seven independent experiments were performed and data pooled for statistical analysis. At the time of hormonal manipulation, E2-stimulated tumors had a volume doubling time of 5 days, a Tpot of 2.3 days, and a %LI of 23%. Continued E2 treatment resulted in only minimal changes in Tpot and %LI over the remainder of the observation period. Treatment with TAM resulted in a slowing of tumor growth (tumor doubling time, 12 days), a significant (P < 0.001) increase in Tpot to 6.6 days, and a decrease in %LI to 8% by 23 days posttreatment. E2 deprivation resulted in a cessation of tumor growth and similar changes in Tpot and %LI to 5.3 days and 10%, respectively (P < 0.001). In contrast to previous reports, these data demonstrate that TAM treatment and E2 deprivation both significantly decrease tumor cell proliferation in MCF-7 xenografts.

Animals↗
PubMed1996

Isolation of a cosmid clone corresponding to an inv(21) breakpoint of a patient with transient abnormal myelopoiesis.

Transient abnormal myelopoiesis (TAM) is a leukemoid reaction occurring occasionally on Down syndrome (DS) newborn infants. It has been hypothesized that "disomic homozygosity" in 21-trisomic cells plays an important role in the genesis of TAM, and the putative TAM gene was suggested to be mapped at a 21q11 region. We encountered a DS-associated TAM infant with a 47,XY,inv(21)(q11.1q22.13),+inv(21)(q11.1q22.13) karyotype. On the basis of another presumption that in this patient the putative TAM gene is disrupted by the break, we tried to isolate a breakpoint DNA. FISH analysis with cosmid clones corresponding to various sequence-tagged-site (STS) markers mapped at around 21q11.1-q11.2, we confirmed that the proximal breakpoint of the inv(21) was located between two STSs, G51E07 and D21S215, the latter locus being consistent with the previous tentative mapping. After construction of a cosmid contig encompassing between the two markers, we have isolated a cosmid clone corresponding to the proximal breakpoint of the inversion. This breakpoint was located near a previously identified duplicated region that is homologous to the sequence at 21q22.1. The isolated cosmid clone is useful for analysis of other TAM patients and for a search for a transcript at or flanking the breakpoint.

Adult↗
PubMed1997

Tumor growth inhibition, apoptosis, and Bcl-2 down-regulation of MCF-7ras tumors by sodium phenylacetate and tamoxifen combination.

We demonstrated previously the antitumoral and antiproliferative effects of sodium phenylacetate (NaPA) on malignant breast epithelial MCF-7ras cells and its lack of toxicity. The present in vivo protocols were as follows: (1) a control group; (2) a NaPA-receiving group (450 mg/kg) through s.c. osmotic pumps (ALZA Corp.) for 2 weeks, followed by 2 weeks with no treatment; and (3) a tamoxifen (TAM)-receiving group (20 mg/kg two times per week). The second group was further divided as follows: (a) a group receiving same doses of NaPA; (b) a TAM-receiving group; and (c) a group receiving both NaPA and TAM. Although tumors treated by TAM alone (group 3) showed progressive regrowth after 6 weeks, indicating an escape from antiestrogen inhibition, the TAM-administered group, following 2 weeks of NaPA pretreatment (group 2b), showed significant tumor regression of about 40% after 8 weeks. This effect was amplified to over 60% (P < 0.001) by simultaneous administration of the two drugs (group 2c). The last group displayed about 30% apoptotic-like nuclei, together with lower proliferation index, and less tumor vascularization, as compared to less than 5% terminal deoxytransferase-mediated dUTP-X nick end labeling-positive nuclei, highly vascularized tumors, in the TAM-treated group. Furthermore, in vitro administration of 4-OH-tamoxifen induced a Bcl-2 up-regulation in MCF-7ras cells, which was completely abolished by NaPA pretreatment. The combination of NaPA and OHT induced significant cell differentiation with cell cycle accumulation in the G0-G1 phase.

Adenocarcinoma↗