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D N Danforth

Publications and source records attributed to D N Danforth.

At least 19 recordsLinked to original sources
PubMed2004

All trans-retinoic acid acts synergistically with hydroxytamoxifen and transforming-growth factor beta to stimulate apoptosis in MCF-7 breast cancer cells.

The anti-estrogen 4-hydroxytamoxifen (TAM) and vitamin A-related compounds, the retinoids, in combination act synergistically to inhibit growth of breast cancer cells in vitro and in vivo. To clarify the mechanism of this synergism, the effect of TAM and all trans-retinoic acid (AT) on proliferation of MCF-7 breast cancer cells was studied in vitro. TAM and AT acted synergistically to cause a time-dependent and dose-dependent inhibition of MCF-7 cell growth. In a temporally related manner, TAM+AT acted synergistically to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis. TAM and AT each blocked cell cycle progression throughout 7 days of treatment but without any synergistic or additive effect on this process, indicating a selective synergism for apoptosis. The negative growth factor-transforming growth factor beta (TGFbeta) is secreted by these cells and was studied as a potential mediator of the synergistic effects of TAM+AT on apoptosis. TAM+AT acted synergistically to induce a fivefold increase in TGFbeta1 secretion over 72 h. TGFbeta1 alone had no apoptotic effects on these cells; however, TGFbeta1 in combination with AT acted synergistically to inhibit growth, to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis of these cells in a manner comparable with that noted for TAM+AT. The synergism of both TAM+AT and TGFbeta1+AT for apoptosis was suppressed by estradiol. Co-incubation of TAM+AT with anti-TGFbeta antibody did not block down-regulation of Bcl-2 protein expression or stimulation of apoptosis. The synergistic effects of TAM+AT on apoptosis therefore occur independently of TGFbeta, although TGFbeta may interact with AT in a novel manner to provide another important anti-proliferative mechanism for breast cancer cells.

Apoptosis↗
PubMed2001

Iatrogenic gallbladder perforation: conservative management by percutaneous drainage and cholecystostomy.

Gallbladder perforation is an uncommon complication of percutaneous liver biopsy. Diagnosis is usually made clinically and management has traditionally been by cholecystectomy. We report a case of gallbladder perforation secondary to percutaneous liver biopsy diagnosed by dimethyl iminodiacetic acid (HIDA) scan and managed successfully by percutaneous drainage and cholecystostomy. This case illustrates the role of conservative management in selected cases of gallbladder perforation.

Biopsy, Needle↗
PubMed2001

Noise reduction in oncology FDG PET images by iterative reconstruction: a quantitative assessment.

UNLABELLED: Tumor detection depends on the contrast between tumor activity and background activity and on the image noise in these 2 regions. The lower the image noise, the easier the tumor detection. Tumor activity contrast is determined by physiology. Noise, however, is affected by many factors, including the choice of reconstruction algorithm. Previous simulation and phantom measurements indicated that the ordered-subset expectation maximization (OSEM) algorithm may produce less noisy images than does the usual filtered backprojection (FBP) method, at equivalent resolution. To see if this prediction would hold in actual clinical situations, we quantified noise in clinical images reconstructed with both OSEM and FBP. METHODS: Three patients (2 with colon cancer, 1 with breast cancer) were imaged with FDG PET using a "gated replicate" technique that permitted accurate measurement of noise at each pixel. Each static image was acquired as a gated image sequence, using a pulse generator with a 1-s period, yielding 40 replicate images over the 10- to 15-min imaging time. The images were or were not precorrected for attenuation and were reconstructed with both FBP and OSEM at comparable resolution. From these data, images of pixel mean, SD, and signal-to-noise ratio (S/N) could be produced, reflecting only noise caused by the statistical fluctuations in the emission process. RESULTS: Noise did not vary greatly over each FBP image, even when image intensity varied greatly from one region to the next, causing S/N to be worse in low-activity regions than in high-activity regions. In contrast, OSEM had high noise in hot regions and low noise in cold regions. OSEM had a much better S/N than did FBP in cold regions of the image, such as the lungs (in the attenuation-corrected images), where improvements in S/N averaged 160%. Improvements with OSEM were less dramatic in hotter areas such as the liver (averaging 25% improvement in the attenuation-corrected images). In very hot tumors, FBP actually produced higher S/Ns than did OSEM. CONCLUSION: We conclude that OSEM reconstruction can significantly reduce image noise, especially in relatively low-count regions. OSEM reconstruction failed to improve S/N in very hot tumors, in which S/N may already be adequate for tumor detection.

Algorithms↗
PubMed1998

Selection of local therapy after neoadjuvant chemotherapy in patients with stage IIIA,B breast cancer.

BACKGROUND: Stage IIIA,B breast cancer is commonly treated with neoadjuvant chemotherapy because of high objective response rates and improved operability. Criteria for subsequent selection of local therapy--mastectomy, radiotherapy, or both--are not well defined. We adopted a policy of selective local therapy based on rebiopsy of the breast and clinical axillary lymph node status at the time of best response to chemotherapy. METHODS: Between 1980 and 1993, 126 patients with stage IIIA,B breast cancer were treated with neoadjuvant chemotherapy and definitive local therapy. The long-term incidence of locoregional failure (in-breast, chest wall, axilla, supraclavicular, neck), relapse-free survival, and overall survival was determined. RESULTS: The overall clinical objective response rate to chemotherapy was 95.2%. Eighty-three patients underwent mastectomy, with negative margins achieved in 91.6%. Forty-two patients had breast preservation; the overall in-breast recurrence rate was 19.0% (8 of 42 patients). The overall locoregional recurrence rate by site was: chest wall-8.7% (11 of 126 patients), axilla-8.7% (11 of 126 patients), supraclavicular-5.6% (7 of 126 patients), and neck-4.0% (5 of 126 patients). The axillary recurrence rate was 6.6% (5 of 76 patients) for clinically negative axilla treated with radiotherapy only, and 12.0% (6 of 50 patients) for clinically positive axilla treated with surgery only. The overall long-term survival probabilities (6 years) according to stage were: stage IIIA-58.0%, stage IIIB(noninflam)-58.0%, stage IIIB(inflam)-36.0%. CONCLUSIONS: These findings support a selective approach to local therapy in patients with stage IIIA,B breast cancer. This approach provides local control in most patients, and allows for breast preservation and elimination of axillary dissection in selected patients.

Adult↗
PubMed1998

Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity.

PURPOSE: This randomized, prospective study assesses the impact of postoperative external-beam radiation therapy on local recurrence (LR), overall survival (OS), and quality of life after limb-sparing resection of extremity sarcomas. PATIENTS AND METHODS: Patients with extremity tumors and a limb-sparing surgical option were randomized to receive or not receive postoperative adjuvant external-beam radiotherapy. Patients with high-grade sarcomas received postoperative adjuvant chemotherapy whereas patients with low-grade sarcomas or locally aggressive nonmalignant tumors were randomized after surgery alone. RESULTS: Ninety-one patients with high-grade lesions were randomized; 47 to receive radiotherapy (XRT) and 44 to not receive XRT. With a median follow-up of 9.6 years, a highly significant decrease (P2 = .0028) in the probability of LR was seen with radiation, but no difference in OS was shown. Of 50 patients with low-grade lesions (24 randomized to resection alone and 26 to resection and postoperative XRT), there was also a lower probability of LR (P2 = .016) in patients receiving XRT, again, without a difference in OS. A concurrent quality-of-life study showed that extremity radiotherapy resulted in significantly worse limb strength, edema, and range of motion, but these deficits were often transient and had few measurable effects on activities of daily life or global quality of life. CONCLUSION: This study indicates that although postoperative external-beam radiotherapy is highly effective in preventing LRs, selected patients with extremity soft tissue sarcoma who have a low risk of LR may not require adjuvant XRT after limb-sparing surgery (LSS).

Extremities↗
PubMed1998

Enterocutaneous fistula in cancer patients: etiology, management, outcome, and impact on further treatment.

Enterocutaneous fistulae that develop in patients with cancer represent a difficult management situation, which is often complicated by prior treatment including surgery, radiation therapy, and chemotherapy. A fistula may in turn delay potentially beneficial treatment of the underlying malignancy. To provide a better understanding of this problem, we reviewed the National Institutes of Health experience with enterocutaneous fistulae in adult patients with cancer. The medical records of patients with cancer who developed a fistula from the gastrointestinal tract during the period 1980 through 1994 were reviewed. Etiology, management, outcome, and impact on further treatment were assessed. Twenty-five patients with gastrointestinal fistulae were identified. The most common primary tumor site was the colon/rectum in males and the ovary in women. The majority of patients had metastatic disease at diagnosis and a history of prior therapy and presented with anorexia and weight loss. The fistula was usually single, most commonly developed from the jejunum/ileum (13 patients) or colon/rectum (6 patients), and occurred postoperatively after procedures on the small bowel (10 patients) or colon (8 patients). Malnutrition and sepsis developed in 60 per cent of patients. Thirty-day mortality was 16 per cent and correlated with prior radiation therapy, location and output from the fistula, and hypoalbuminemia. An enterocutaneous fistula negatively impacted on the provision of further therapy for the majority of patients (63%). Enterocutaneous fistula in the patient with cancer occurs most frequently in the setting of extensive prior therapy and is associated with prolonged morbidity. Identification of high-risk patients and early management of fistulas once they develop may prevent delays in subsequent cancer therapy and decrease morbidity.

Adult↗
PubMed1996

Upregulation of DF3, in association with ICAM-1 and MHC class II by IFN-gamma in short-term human mammary carcinoma cell cultures.

This study was designed to determine whether in vitro exposure of isolated short-term human primary and metastatic breast tumor cell cultures to interferon-gamma (IFN-gamma) could enhance expression of the breast tumor associated DF3 antigen in association with the intercellular adhesion molecule 1 (ICAM-1) and MHC class II molecules. Cell cultures were established from primary solid tumors and metastatic cells as previously described (Sgagias et al., 1995). Data show that recombinant human IFN-gamma treatment, in vitro, dramatically increased the breast tumor associated DF3 antigen, in association with ICAM-1, and MHC class II antigens in primary breast cancer cell cultures. All primary breast tumor cell cultures constitutively expressed high levels of HLA-class I antigen. Metastatic breast cancer cell cultures expressed high levels of DF3 and recombinant human IFN-gamma treatment, in vitro, upregulated ICAM-1 and MHC class II antigens before and after passage of the metastatic cells through the nude mouse. Metastatic breast cancer cells similar to primary breast cancer cells constitutively expressed high levels of MHC class I antigens. In addition, three LAK cell lines significantly lysed the primary and the metastatic breast tumor cell cultures to the same degree before and after passage of the metastatic cancer cells through the nude mouse. These data indicate the upregulation of the breast tumor associated DF3 antigen in vitro after IFN-gamma treatment and its persistence in vivo, after passage of the metastatic breast cancer cells through the nude mouse. The ability of IFN-gamma to upregulate the breast tumor associated DF3 antigen in association with the ICAM-1 and HLA class II antigens may play an important role in eliciting an immune response which may contribute to the immunodiagnosis, and immunotherapy of breast cancer.

Animals↗
PubMed1996

Tumor necrosis factor alpha enhances secretion of transforming growth factor beta2 in MCF-7 breast cancer cells.

We studied the effect of tumor necrosis factor alpha (TNF-alpha) on transforming growth factor beta (TGF-beta) secretion by human breast cell lines to further characterize the antitumor effects of TNF-alpha. We found that TNF-alpha increased the secretion of TGF-beta in two established breast cancer cell lines (MCF-7 and ZR-75-1) but not in two immortalized human mammary epithelial cell lines (184B5 and MCF-10A). In MCF-7 cells, TNF-alpha increased the secretion of total TGF-beta 6.1-fold within 72 h in a dose-dependent manner. The secretion of both latent and active forms of TGF-beta was increased, and their ratio altered from 25:1 to 12:1 in the medium. TNF-alpha converted the secretory pattern of TGF-beta by MCF-7 cells from the heterodimeric form TGF-beta1.2 to the homodimeric form TGF-beta2. Immunoblot analysis under nonreducing conditions identified four molecular mass species of TGF-beta secreted in the culture media of untreated MCF-7 cells (238, 210, 40-55, and 25 kDa). Under reducing conditions, three molecular mass species of TGF-beta were identified: 88, 44, and 12 kDa. Gel filtration analysis demonstrated that the secreted TGF-beta within the range of 12-88 kDa was biologically active. TNF-alpha treatment did not alter the size of molecular mass species secreted by MCF-7 cells and did not change steady-state levels of mRNA for TGF-beta1 or TGF-beta2. These findings indicate that TNF-alpha may regulate quantitatively and qualitatively TGF-beta secretion by human breast cancer cells in vitro. The diverse biological activities of TGF-beta may also allow TNF-alpha to regulate the growth and metabolism of human mammary epithelial cells and/or stromal cells in a paracrine manner.

Breast Neoplasms↗
PubMed1995

Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer.

BACKGROUND: Breast-conservation therapy for early-stage breast cancer is now an accepted treatment, but there is still controversy about its comparability with mastectomy. Between 1979 and 1987, the National Cancer Institute conducted a randomized, single-institution trial comparing lumpectomy, axillary dissection, and radiation with mastectomy and axillary dissection for stage I and II breast cancer. We update the results of that trial after a median potential follow-up of 10.1 years. METHODS: Two hundred forty-seven patients with clinical stage I and II breast cancer were randomly assigned to undergo either modified radical mastectomy or lumpectomy, axillary dissection, and radiation therapy. The 237 patients who actually underwent randomization have been followed for a median of 10.1 years. The primary end points were overall survival and disease-free survival. RESULTS: At 10 years overall survival was 75 percent for the patients assigned to mastectomy and 77 percent for those assigned to lumpectomy plus radiation (P = 0.89). Disease-free survival at 10 years was 69 percent for the patients assigned to mastectomy and 72 percent for those assigned to lumpectomy plus radiation (P = 0.93). The rate of local regional recurrence at 10 years was 10 percent after mastectomy and 5 percent after lumpectomy plus radiation (P = 0.17) after recurrences successfully treated by mastectomy were censored from the analysis. CONCLUSIONS: In the management of stage I and II breast cancer, breast conservation with lumpectomy and radiation offers results at 10 years that are equivalent to those with mastectomy.

Breast Neoplasms↗
PubMed1995

Cellular characterization and retroviral transduction of short-term breast cancer cells.

The effort to develop cell lines from surgical specimens has been a difficult goal for years. We derived short-term primary human mammary carcinoma cell lines from breast tumors in 20 of 23 patients. Morphologically, cultured cells showed small cells with high nuclear cytoplasmic ratio and larger cells with abundant dense cytoplasm. The nuclei were round to oval with one to four nucleoli. Immunocytochemically, the cells stained positive for keratin. Tumor cells showed phenotypic overexpression of the breast tumor-associated antigen DF3 compared with normal mammary epithelial cells. The doubling time of tumor cells in vitro ranged from 2.6 to 3.6 days. The cultured cells were characterized as mammary carcinoma cells by their tumorigenicity in nude mice. Of 14 of the 23 short-term cell lines tested, 5 grew in nude mice and eventually regressed, 3 grew progressively in nude mice, and the remaining 6 did not grow within 3 months. To examine the feasibility of cytokine gene transfer into human mammary carcinoma cells, we introduced the cDNA for human tumor necrosis factor-alpha (TNF-alpha) into short-term cell lines with a retroviral vector. In our short-term primary breast cancer cell lines derived from breast tumors, TNF-alpha secretion ranged between 89 ng/10(6) cells/48 h and 479 ng/10(6) cells/24 h. These findings indicate that short-term primary human mammary carcinoma cell lines can be grown consistently from breast tumors, and that retroviral mediated-cytokine gene transfer into short-term human mammary carcinoma cells is feasible and may be of potential use in immunotherapy trials.

Animals↗
PubMed1994

Postoperative complications in patients receiving suramin therapy.

BACKGROUND: Suramin is an antiparasitic agent that is currently being evaluated for antineoplastic activity. Documented toxicities of suramin include adrenal and renal insufficiency, coagulation factor abnormalities, immunosuppression, and polyneuropathy. These adverse effects have potential for contributing to postoperative morbidity in surgical patients. Because no experience with suramin has been reported in the surgical literature, this 5-year retrospective review of postoperative complications in patients receiving suramin was performed. METHODS: From a review of 171 charts, 14 patients were identified who had undergone a major surgical procedure either while receiving intravenous suramin or within 1 year after its administration. Primary diagnoses included prostate cancer (six), lymphoma (four), ovarian cancer (two), colon cancer (one), and glioblastoma (one). All patients received replacement dose hydrocortisone at the initiation of suramin therapy and thereafter. RESULTS: Eighteen major surgical procedures were performed with 18 complications occurring in five patients. The predominant complications encountered were hemorrhage (five), impaired wound healing (three), and bowel dysmotility (two). A highly significant relationship existed between the incidence of complications and interval from completion of suramin therapy to the time of operation (p < 0.0005), with 17 of the 18 morbidities occurring within the first month. The length of operation (p < 0.05) and amount of blood transfused during the procedure were related to postoperative morbidity (p < 0.05). No other factors evaluated were correlated to complications. CONCLUSIONS: This experience suggests the avoidance of elective procedures during the first month after suramin therapy and a heightened awareness of the potential for bleeding and wound healing problems in patients receiving suramin who do require an emergent procedure.

Adult↗
PubMed1993

Interleukin-1 alpha and interleukin-6 act additively to inhibit growth of MCF-7 breast cancer cells in vitro.

We studied the effects of interleukin-1 alpha (IL-1) and interleukin-6 (IL-6) on MCF-7 breast cancer cells to determine whether these cytokines act additively/synergistically to alter cell growth and metabolism. We found that IL-1 alone (1000 units/ml) inhibited cell growth to a greater degree (83.8%) than IL-6 alone (29.2%, P < 0.001). The combination of IL-1 + IL-6 caused greater inhibition of growth (92.9%, P < 0.02) than either cytokine alone. The additive effect was dose dependent for both IL-1 and IL-6. IL-1 and IL-6 also antagonized estradiol (10(-9) M) stimulated growth. Antagonism by the combination was greater than for either cytokine alone (P < 0.001). IL-1 or IL-6 alone each down-regulated the estrogen receptor (36.7%, P < 0.01, and 23.2%, P < 0.05, respectively), but the combination IL-1 + IL-6 did not cause a significantly greater effect than IL-1 alone. Neither IL-1 or IL-6 blocked estradiol stimulation of progesterone receptor (PR) synthesis; however, the combination IL-1 + IL-6 increased PR content by 28.4% (P < 0.01). IL-1, but not IL-6, increased secretion of transforming growth factor-beta (TGF-beta) by 2.45-fold over 72 h (P < 0.01). The increase was time dependent (detectable at 24 h) and dose dependent (maximum increase of 5.3-fold, 10,000 units/ml, P < 0.02). IL-1-induced TGF-beta secretion was blocked by estradiol (10(-9) M). Neither cytokine altered secretion of insulin-like growth factor-1. These findings indicate that IL-1 and IL-6 act additively to inhibit growth in the absence or presence of estradiol and modulate the estrogen receptor and progesterone receptor content of these cells. TGF-beta may mediate the effects of IL-1; however, other pathways appear to be required for the additive effects of these cytokines.

Breast Neoplasms↗
PubMed1993

Hepatic abscess in cancer patients. Characterization and management.

OBJECTIVE: To identify factors that may aid in the diagnosis and treatment of patients with malignant neoplasms in whom hepatic abscesses develop. DESIGN: Retrospective review of medical records. PATIENTS: Thirty-seven oncology patients in whom hepatic abscesses developed at the National Cancer Institute, Bethesda, Md, between June 1954 and October 1989. RESULTS: Among 37 cancer patients, bacterial abscesses developed in 17 and fungal abscesses developed in 20. Among the patients with bacterial abscesses, 12 (71%) had a solid-tissue malignant neoplasm, 10 (59%) had a prior invasive procedure, and six (35%) had prior chemotherapy. In comparison, among the patients with fungal abscesses, 15 (75%) had a hematologic malignant neoplasm and five (25%) had a solid-tissue malignant neoplasm (P2 = .014). Two patients with fungal abscesses (10%) had a prior invasive procedure (P2 = .004) and 19 (95%) had prior chemotherapy (P2 < .0001). As compared with fungal abscesses, bacterial abscesses were larger (P2 < .00001) and fewer (P2 = .004). Antibiotics and percutaneous or surgical drainage effectively treated bacterial abscesses. Amphotericin B usually eradicated hepatic fungal infections. CONCLUSIONS: The results of this study reveal the importance of the clinical setting in the diagnosis of hepatic abscesses in cancer patients. Aggressive treatment of these abscesses is indicated and is frequently effective.

Adult↗
PubMed1993

Tumour necrosis factor-alpha modulates oestradiol responsiveness of MCF-7 breast cancer cells in vitro.

We studied the effect of tumour necrosis factor-alpha (TNF) on oestradiol regulation of growth and metabolism of MCF-7 breast cancer cells to determine whether TNF altered the oestradiol responsiveness of these cells. We found that TNF antagonized oestradiol stimulation of cell growth in a dose-dependent manner, with partial inhibition at 1.0 U/ml and complete inhibition at 1000 U/ml. TNF inhibited cell cycle progression, increasing cells in the G0G1 phase and blocking oestradiol-stimulated progression into the S phase. We examined the effect of TNF on three oestrogen-regulated proteins, the oestrogen receptor (ER), the progesterone receptor (PR) and insulin-like growth factor-I (IGF-I). TNF down-regulated the ER and up-regulated the PR. Both of these processes were enhanced by the addition of oestradiol. The effects of TNF on the ER and PR were dose-dependent and occurred without a change in the Kd of the receptor. TNF did not change the respective steady-state mRNA levels. In addition, TNF did not alter secretion of IGF-I either in the absence or presence of oestradiol, indicating that the effects of TNF on oestrogen-regulated proteins in selective. These findings indicate an important interaction between the immune and endocrine systems. The cytokine TNF has a prominent effect on oestradiol stimulation of MCF-7 cells, blocking its proliferative response and enhancing certain metabolic effects. These actions may be mediated in part through modulation of the ER, although other pathways appear to be involved.

Blotting, Northern↗
PubMed1992

Low-grade angiosarcoma of the skin of the breast: a complication of lumpectomy and radiation therapy for breast carcinoma.

A case of low-grade angiosarcoma arising in the skin of a breast previously irradiated for breast carcinoma is reported. Initially, an asymptomatic breast mass was detected. Excisional biopsy and axillary lymph node dissection revealed a 1.5-cm infiltrating ductal carcinoma with 21 negative lymph nodes. The neoplasm was staged as T1, N0, M0. The patient was entered in a research protocol and was treated with high-dose external beam (4,860 rad) and iridium implant (1,860 rad) irradiation. Seven years later the patient developed low-grade angiosarcoma of the breast skin. The lesion recurred following excision and eventually was treated by simple mastectomy. The patient never had evidence of lymphedema. Cutaneous angiosarcomas occurring as a complication of lumpectomy and radiation therapy for breast carcinoma are rare. In some reported cases the patients have had lymphedema, a known factor predisposing to angiosarcoma. Furthermore, almost all cases previously reported have been high grade. This case suggests that radiation therapy for breast carcinoma may also be complicated by low-grade angiosarcoma.

Breast↗
PubMed1992

Mastectomy versus breast-conserving therapy in the treatment of stage I and II carcinoma of the breast: a randomized trial at the National Cancer Institute.

PURPOSE: Mastectomy versus excisional biopsy (lumpectomy) plus radiation for the treatment of stage I and II breast cancer was compared in a prospective randomized study. PATIENTS AND METHODS: From 1979 to 1987, 247 women were randomized and 237 were treated on this study. All patients received a full axillary dissection and all node-positive patients received adjuvant chemotherapy with cyclophosphamide and doxorubicin. Radiation consisted of external-beam therapy to the whole breast with or without supraclavicular nodal irradiation followed by a boost to the tumor bed. RESULTS: The minimum time on the study was 18 months and the median time on the study was 68 months. No differences in overall survival or disease-free survival were observed. Actuarial estimates at 5 years showed that 85% of mastectomy-treated patients were alive compared with 89% of the lumpectomy/radiation patients (P2 = .49; 95% two-sided confidence interval [CI] about this difference, 0% to 9% favoring lumpectomy plus radiation). The probability of failure in the irradiated breast was 12% by 5 years and 20% by 8 years according to actuarial estimates. Of 15 local breast failures, 14 were treated with and 12 were controlled by mastectomy; the ultimate local-regional control was similar in both arms of the trial. CONCLUSION: These data add further weight to the conclusion that breast conservation using lumpectomy and breast irradiation is equivalent to mastectomy in terms of survival and ultimate local control for stage I and II breast cancer patients.

Adult↗
PubMed1991

Interleukin 1 alpha blocks estradiol-stimulated growth and down-regulates the estrogen receptor in MCF-7 breast cancer cells in vitro.

We studied the effect of interleukin 1 alpha (IL-1 alpha) on estradiol stimulation of cell growth and estrogen receptor (ER) content in MCF-7 human breast cancer cells in vitro to determine if IL-1 alpha altered cellular estradiol responsiveness. We found that IL-1 alpha blocked estradiol-stimulated growth of these cells in a dose-dependent manner (complete antagonism at 1000 units/ml: day 7 mean growth = vehicle, 47.7 micrograms DNA; estradiol 10(-10) M, 95.1; IL-1 alpha/estradiol, 44.6) and at all concentrations of estradiol from 10(-8) to 10(-11) M. IL-1 alpha in combination with trans-hydroxytamoxifen further inhibited estradiol-stimulated growth (vehicle = 44.8 micrograms DNA, estradiol = 108.3, estradiol/trans-hydroxytamoxifen = 47.8, IL-1 alpha/estradiol/trans-hydroxytamoxifen = 3.0, P less than 0.01). Inhibition with trans-hydroxytamoxifen was IL-1 alpha dose dependent (maximum = 97% at 1000 units/ml, P less than 0.01) and estradiol dose dependent (reversible with 10(-8) M estradiol, maximum inhibition at 10(-10) M estradiol). Concomitantly, IL-1 alpha down-regulated ER concentration by 38.0-43.7% (P less than 0.01) as measured by immunoreactivity or Scatchard analysis, respectively. This occurred as early as 3 h without a change in the Kd (vehicle = 0.23 nM, IL-1 alpha = 0.24 nM), persisted for at least 48 h, was dose dependent (maximum, 43.7% at 1000 units/ml, P less than 0.01), and was blocked by cycloheximide. IL-1 alpha, however, did not block estradiol stimulation of progesterone receptor content (vehicle = 221.9, IL-1 alpha = 238.9 fmol/mg protein) and did not block estradiol down-regulation of ER content. Furthermore, IL-1 alpha alone did not alter levels of ER mRNA and did not alter estradiol down-regulation of ER mRNA. These findings indicate that while IL-1 alpha antagonizes estradiol stimulation of growth and reduces ER content, its mechanism may involve other non-estrogen-regulated pathways.

Breast Neoplasms↗