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[Effects of Runing Recipe medicated serum on expressions of genes in breast cancer cells].

OBJECTIVE: To explore the mechanisms of the effects of Runing Recipe in anti-invasion and anti-recurrence of breast cancer by experimental research in vitro. METHODS: SD female rats were randomly divided into Runing Recipe-treated group and its decomposed formulas Kidney-Warming Recipe and Liver-Soothing Recipe-treated groups, tamoxifen (TAM) -treated group, cyclophosphamide (CTX) -treated group, and normal control group to make medicated serums. Methods of matrigel basement membrane and real-time reverse transcription polymerase chain reaction were employed to investigate the gene expressions of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) after MDA-MB-435 cells were treated with the medicated serums. RESULTS: The gene expression of VEGF was dropped in CTX-treated, TAM-treated and Liver-Smoothing Recipe-treated groups. The gene expression of TIMP-1 was up-regulated in CTX-treated, Runing Recipe-treated and Kidney-Warming Recipe-treated groups; while MMP-9 was down-regulated in these groups. CONCLUSION: The mechanisms of Runing Recipe in inhibiting the cancer cell invasion may be related to down-regulating the gene expressions of VEGF and MMP-9, and up-regulating the gene expression of TIMP-1.

Animals↗

Expression of thymidine phosphorylase by macrophages in colorectal cancer tissues.

AIM: To detect the thymidine phosphorylase (dThdPase) expression in human colorectal cancer tissues and cells. METHODS: Forty specimens resected from patients with colorectal cancer were immunohistochemically stained by 654-1, anti-dThdPase monoclonal antibody, PG-M1, anti-macrophage marker CD68 monoclonal antibody. Morphometrical analysis and positive cell counting were performed. In 27 of 40 specimens, dThdPase activity was also assayed by HPLC. Otherwise, the dThdPase level was measured by ELISA in 6 colorectal cancer cell lines, LS174T, Clone A, Colo320, CX-1, Lovo, and MIP101, as well as in 2 macrophage-like cell lines, THP-1 and U937. RESULTS: dThdPase activity was significantly increased in cancer tissues compared with adjacent normal tissue (P<0.01). In immunohistochemical analysis, it was confirmed that most cells expressed dThdPase were the stromal cells surrounding cancer nests or along the invasive margin of cancer. Based on their morphometrical characteristics, we found that most of them were tumor-associated macrophages (TAMs). The number of dThdPase-positive stromal cells was significantly correlated with the number of CD68-positive macrophages (r=0.76, P<0.0001). By ELISA, 18.2 unit/mg and 19.3 unit/mg of dThdPase protein were detected in THP-1 and U937, but only little was detected in 6 colorectal cancer cell lines. CONCLUSION: The present data suggest that dThdPase expression is seldom detected in colorectal carcinoma cells. TAM is the most important source of dThdPase in colorectal cancer tissues.

Adenocarcinoma↗

[Comparative assessment of antacid agents with intragastric ph-metry].

Alkalizing effects of maalox, renni and tams were compared in 63 patients (27 males and 36 females) aged 19-56 with endoscopically confirmed superficial gastroduodenitis using intragastric pH-metry. Liquid antacids (maalox) began their action quicker (1.3-1.7 times) than tablets (renni and tams) but the tablets had longer alkalizing effects. Maximal and minimal alkalizing effects were achieved with maalox and renni, respectively. It is inferred that rapid intragastric pH-metry can be used for comparative assessment of different antacid drugs. Of the drugs studied the highest antiacid effect was exhibited by maalox.

Adult↗

The effects of tamoxifen therapy on the endometrium.

From January 1992 to December 1998, 219 women (aged between 30 and 81 yrs; average 55 years) affected by breast cancer were treated. These women in addition to the usual adjuvant therapy, were treated with TAM 20 mg/day, for a period between 24 and 72 months (average 40). In this group there were 84 postmenopausal and 31 premenopausal women. In 8 fertile patients ovarian activity was suppressed with GnRh analogue therapy and one patient underwent attinic castration. Before performing TAM therapy, a hysteroscopic exam was done and patients were followed-up with an annual check-up. None had any endometrial side-effects after the first check-up. After two years, 31 women (26.9%) complained of endometrial alterations (hyperplasia, polyps and endometrial cancer). One women only after 6 years of follow-up, had metrorrhagia; an endometrial adenocarcinoma was found. We would like to point out the necessity of monitoring these patients with an annual check-up (transvaginal sonography and/or hysteroscopy).

Adenocarcinoma↗

[Acute leukemia in children with Down syndrome: analysis of cases].

An analysis of clinical and laboratory parameters and the results of treatment of 14 children with Down Syndrome and acute leukaemia was performed. The children were treated between 1986-1997. Their age ranged from 1 day to 13 years (average 5.5). There were 9 girls and 5 boys. Four of them had congenital heart disease. ALL was observed in 10, AML in 3 and TAM (Transient Abnormal Myelopoesis) in 1. Half of the children with ALL was classified as L1 according to FAB with the majority of common phenotypes and M6 in ANLL group. Remission was achieved in all ALL patients, six of them are still free of symptoms, the remaining four died of brain haemorrhage as a consequence of myelosuppression. Only 1 of 3 children with ANLL achieved remission. The child died of cardiac arrest after induction phase of BFM 95 programme (ADE). The 2 remaining children with ANLL also died of circulation failure before initiation of chemotherapy. The children had complicated cyanotic heart disease. The neonate with TAM is in clinical and hematological remission. In conclusion all children with ALL achieved hematological remission but tolerance of treatment was a problem. The majority of patients had diminished bone marrow reserve. Mortality was frequently related to circulatory failure in children with associated heart defects. It seems necessary to discuss the modification of accepted programmes for leukemia for the treatment of children with Down Syndrome.

Adolescent↗

Relationship between Ki-67 labeling index and survival in high-grade glioma patients treated after surgery with tamoxifen.

BACKGROUND: The Ki-67 is a nuclear antigen expressed in the G1, S, G2, and M phases of the cell cycle recognizable by the monoclonal antibody MIB-1. The Ki-67 labeling index (LI) is considered as a marker of proliferation (growth fraction rate), even if its use as prognostic indicator of cerebral high-grade gliomas is still debated. The aim of this study is to correlate the Ki-67 LI with survival in patients operated on for a malignant glioma and treated postoperatively with tamoxifen. METHODS: Using the MIB-1 antibody, the Ki-67 antigen staining of surgical specimens was obtained in 26 patients operated on for a malignant cerebral glioma. After operation, 9 patients started to receive 40 mg/day, 8 patients 80 mg/day, and 9 patients 120 mg/day of tamoxifen. In 20 cases one or more cycles of i.v. carboplatin was administered. All patients received radiotherapy (4500-6000 cGy). RESULTS: The overall mean survival rate was 19.8 months and the median 12 months; the 12-month and 24-month survival rates were 47% and 23%, respectively. The Ki-67 LI ranged from 2.3% to 62% (mean 24.1%, median 20.5%). Excluding 2 patients who died during the postoperative period, we analyzed the survival rates of the remaining 24 patients in relation to the value of Ki-67 LI. In relation to the index, patients have been divided into 3 groups, with different survival rates: L) Ki-67 LI < or =10%, with mean survival rate of 30.7 months, M) from 10.1% to 30%, with mean survival rate of 15.8 months, and H) >30%, with mean survival rate of 20.2 months. CONCLUSIONS: Our preliminary observations seem to confirm the efficacy of TAM in modifying the survival of malignant gliomas and seem to indicate that tumors with a lower LI and those with a LI >30% could be associated, if treated with TAM, with a better survival than gliomas belonging to group M, who could have a higher tumor proliferation rate in comparison to group L and a lower response to protein-kinase-C antagonists than group H.

Adult↗

[Tamoxifen and giant endometrial polyps].

Tamoxifen is a synthetic non-steroid anti-estrogen that has been used effectively for several years in the adjuvant treatment of breast cancer. Although its therapeutic effect is due to its anti-estrogenic properties, the drug also shows modest type B estrogen-receptor agonist activity during the menopausal period in which estrogens are at a low level. Owing to the fall in estrogen levels in menopause, tamoxifen provokes an up-regulation of both estrogen and progesterone receptors at an endometrial tissue is a direct consequence of this. This proliferation, which is the result of an inappropriate response of the basal layer and the basis for the onset of hyperplasia and polyps in the tissue. At standard therapeutic dosages, tamoxifen in postmenopausal women is associated with the onset of alterations in the vaginal and endometrial epithelium. Cases of endometrial hyperplasia, endometrial polyps, adenomyosis, endometriosis and fibromyomas are described in the literature. Endometrial polyps represent the most common pathology associated with TAM in women with previous breast cancer in menopause. The estrogenic stimulus to polyps following TAM treatment may be considerable, resulting in their growth to sizeable proportions, causing metrorrhagia and suspected neoplastic pathology. Two cases of patients receiving adjuvant treatment with tamoxifen for previous breast cancer, who presented two giant endometrial polyps of uncommon dimension, are reported.

Aged↗

A therapeutic target for hormone-independent estrogen receptor-positive breast cancers.

BACKGROUND: The action of the steroid hormone estradiol (E2) is mediated via interaction with a specific receptor (ER) that initiates a series of events downstream, leading to the modulation of hormone-responsive genes and cell proliferation. Antihormones also bind, but do not confer the active configuration to ER, thereby, blocking the transmission of E2-ER-initiated signals for cell proliferation. Although these compounds qualify for successful therapy of ER-positive [ER (+)] breast cancer patients, only a fraction of patients responds to antihormone treatment. In this study, the functional status of ER is determined to identify alternative targets for therapy of antihormone-resistant ER (+) breast cancers. METHOD: The interaction of ER with a specific DNA sequence, designated as E2 response element (ERE), was targeted to assess the functional state of ER. ER-ERE complex formation was measured by electrophoretic mobility shift assay (EMSA) and by a newly developed technique, based on the preferential binding of DNA-protein complex to a nitrocellulose membrane (NMBA) that measures both total and functional fraction of ER. RESULTS: The NMBA assay identified functional variants of ER among ER (+) breast cancer cell lines and breast tumor biopsy specimens. ER of (21PT) cells did not bind E2 and these cells were tamoxifen (TAM) resistant. However 21PT cells were sensitive to a calmodulin (CaM) antagonist, W7, that blocked ERE-ER complex formation. CONCLUSIONS: ER variants of the 21PT type were detected among breast cancer biopsy specimens, emphasizing the significance of an alternative therapeutic target for TAM-resistant ER (+) human breast cancers with compounds such as W7.

Adult↗

Considerations of marrow cellularity in 3-dimensional dosimetric models of the trabecular skeleton.

UNLABELLED: Dose assessment to active bone marrow is a critical feature of radionuclide therapy treatment planning. Skeletal dosimetry models currently used to assign radionuclide S values for clinical marrow dose assessment are based on bone and marrow cavity chord-length distributions. Accordingly, these models cannot explicitly consider energy loss to inactive marrow (adipose tissue) during particle transport across the trabecular marrow space (TMS). One method to account for this energy loss is to uniformly scale the resulting TMS absorbed fractions by reference values of site-specific marrow cellularity. In doing so, however, the resulting absorbed fractions for self-irradiation of the trabecular active marrow (TAM) do not converge to unity at low electron source energies. This study attempts to address this issue by using nuclear magnetic resonance microscopy images of trabecular bone to define 3-dimensional (3D) dosimetric models in which explicit spatial distributions of adipose tissue are introduced. METHODS: Cadaveric sources of trabecular bone were taken from both the femoral heads and humeral epiphyses of a 51-y-old male subject. The bone sites were sectioned and subsequently imaged at a proton resonance frequency of 200 MHz (4.7 T) using a 3D spin-echo pulse sequence. After image segmentation, voxel clusters of adipocytes were inserted interior to the marrow cavities of the binary images, which were then coupled to the EGS4 radiation transport code for simulation of active marrow electron sources. RESULTS: Absorbed fractions for self-irradiation of the TAM were tabulated for both skeletal sites. Substantial variations in the absorbed fraction to active marrow are seen with changes in marrow cellularity, particularly in the energy range of 100-500 keV. These variations are seen to be more dramatic in the humeral epiphysis (larger marrow volume fraction) than in the femoral head. CONCLUSION: Results from electron transport in 3D models of the trabecular skeleton indicate that current methods to account for marrow cellularity in chord-based models are incomplete. At 10 keV, for example, the Eckerman and Stabin model underestimates the self-absorbed fraction to active marrow by 75%. At 1 MeV, the model of Bouchet et al. overestimates this same value by 40%. In the energy range of 20-200 keV, neither model accurately predicts energy loss to the active bone marrow. Thus, it is proposed that future extensions of skeletal dosimetry models use 3D transport techniques in which explicit delineation of active and inactive marrow is feasible.

Adipocytes↗

[Prospective randomized trial on the efficacy of adjuvant endocrine therapy for ER-positive breast cancer patients after radical mastectomy].

OBJECTIVE: To asses the efficacy of adjuvant endocrine therapy in ER-positive breast cancer patients after radical mastectomy. METHODS: 369 estrogen receptor (ER)-positive breast cancer patients were divided into two groups after radical mastectomy: 1. Endocrine group (N-194). The postmenopausal patients in this group received oral tamoxifen (TAM) for five years and the premenopausal patients were first treated with bilateral ovary ablation and, then, given TAM for five years. 2. The chemotherapy group patients (N-175) received CTX + MTX + 5-Fu + VCR + DXM) (CMFVP) or CTX + MTX + 5-Fu (CMF) multi-drug chemotherapy. RESULTS: Postmenopausal patients in the endocrine and chemotherapy groups gave disease-free survival rates (DFSR) of 78.4% and 45.4% (P < 0.01). Their overall survival rates were 83.3% and 52.9% (P < 0.05). The premenopausal patients gave DFSR of 72.8% and 35.7% (P < 0.01), and their overall survival rates were 80.7% and 60.6% (P < 0.05). But, no significant difference was observed in the stage I patients and those having > or = 8 axillary lymph node metastases (P > 0.05). CONCLUSION: For ER-positive breast cancer patients, the adjuvant endocrine therapy gives results superior or equal to multi-drug chemotherapy after radical mastectomy.

Adult↗

Efficacy of chemopreventive agents for growth inhibition of Apc [+/-] 1638NCOL colonic epithelial cells.

Germline mutations of the Apc tumor suppressor gene result in increased risk for gastrointestinal carcinogenesis. The Apc1638N [+/-] mouse exhibits accelerated gastrointestinal carcinogenesis that is modifiable by select pharmacological and dietary agents. Experiments in the present study were conducted on a subculturable epithelial 1638NCOL cell line established from histologically normal colon of Apc1638N [+/-] mouse to examine the effects of selected chemopreventive agents that differ in their mechanism of action. Extent of growth arrest, number of cell population doublings, cell cycle progression and aneuploid G0/G1: S + G2/M ratio represented the quantitative endpoints for the susceptibility and efficacy of chemopreventive agents. Treatment of exponentially growing 1638NCOL cells with maximum cytostatic dose of 9cisRA, DFMO or SUL (100 microM) produced a 60-70% growth arrest, that with TAM and AMF (10 microM) produced a 20-40% growth arrest, while that with OLT (100 microM) produced a 25% growth arrest. This response was associated with corresponding decrease in the number of cell population doubling. 9cisRA, SUL or AMF increased the aneuploid G0/G1: S + G2/M ratio by inducing G1 checkpoint arrest, while DFMO, TAM and OLT decreased the ratio by inducing G2 checkpoint arrest. Thus, cell cycle phase-dependent susceptibility of the Apc [+/-] 1638NCOL cell line to mechanistically distinct chemopreventive agents validates a novel colon epithelial cell culture model for mechanistic, preventive or therapeutic studies on Apc regulated colon carcinogenesis.

Adenomatous Polyposis Coli Protein↗

Long-term results after primary repairs of zone 2 flexor tendon lacerations in children younger than age 6 years.

In young children, methods of primary flexor tendon repair in the digital canal are controversial. The authors reviewed 12 children younger than age 6 years with zone 2 flexor tendon repairs. The mean follow-up period was 8 years. In all cases, the flexor digitorum profundus tendons were repaired according to the Kessler modified technique and the hands were immobilized by an above-elbow cast. As for postoperative complications, there were no fingers with tendon rupture and two fingers with tendon adhesion. One finger needed tenolysis. The total active motion (TAM) in the interphalangeal joints evaluated with the Strickland formula averaged 155 degrees, and the TAM percentage averaged 89% (range 74%-100%). Eleven patients had an excellent result and one had a good result. The percentage phalangeal length averaged 99% (range 96%-100%). Functional motion and nearly normal growth of the finger can be expected after primary zone 2 flexor tendon repairs in children younger than age 6 years.

Child, Preschool↗

Response in DNA ploidy of hepatocytes to tamoxifen and/or melatonin in vivo.

Tamoxifen is known to induce hepatocarcinogenesis in experimental animals and reversible chronic liver diseases in humans. Melatonin has been recently introduced as an oncostatic agent, especially for hormone-dependent tumors. This study was designed in order to investigate whether melatonin has an effect onthe tamoxifen-induced hepatotoxicity. Wistar albino rats were injected tamoxifen citrate intraperitoneally in three different doses (10 mg/kg and 20 mg/kg bw for 26 days; and 45 mg/kg bw for three days). Another group of animals were treated with melatonin once a week in addition to daily tamoxifen injections, whereas the third group received melatonin only. The control animals were injected an equal volume of diluent at corresponding intervals. At the end of the experimental period, the animals were sacrificed and the livers were prepared for the flow cytometric DNA analysis. DNA histograms were analyzed using the multicycle program. In experimental groups, all animals had aneuploid cell population. The difference in the diploid/ aneuploid ratio of each experimental group as compared to the control group according to Fischer's exact test was found to be highly significant (p < 0.002 MEL vs control; and p < 0.0001 for both TAM vs control and MEL+TAM vs control). Among the tamoxifen-injected animals, the proportion of multiploidy to aneuploid cell population was 17, similar to those treated solely with melatonin. Although the melatonin plus tamoxifen group had higher multiploidy percentage (38%), the difference was not statistically significant as compared to the tamoxifen (or melatonin) groups. No significant difference was noted between the animals which were treated with three different doses of tamoxifen. S-phase fraction percentage was significantly different in melatonin- and melatonin plus tamoxifen-injected animals with regard to controls, the degree of significancy being < 0.05 for both. According to our data, tamoxifen injections induced DNA aneuploidy, but did not stimulate proliferation in the liver as estimated by S-phase fraction. Melatonin, whether alone or in combination with tamoxifen, stimulated cell proliferation and produced aneuploidy.

Aneuploidy↗

[A case of jejunal vein thrombosis due to medroxyprogesterone acetate].

The patient was a 68-year-old woman with advanced breast cancer which had been treated by modified radical mastectomy two years and nine months earlier. After the surgery, tamoxifen citrate (TAM) was orally administered in addition to various types of chemotherapy. Because the patient complained of nausea and weight loss, medroxyprogesterone acetate (MPA) was orally administered instead of TAM. The patient complained of intense abdominal pain on the 35th day of administration. Laparotomy was then performed for her acute abdominal problem. Because necrosis from bleeding due to jejunal vein thrombosis was observed in the jejunum for about 15 cm, resection of the jejunum was carried out. Histological observation demonstrated thrombosis in the vein, and cellular infiltration around the thrombosis. The postoperative prognosis has been favorable and the postoperative course is now being monitored at our clinic (2 months after surgery). The patient has no complications such as diabetes mellitus or hypercholesterolemia. The thrombosis observed in the jejunal vein, which is a rare site for it on the 35th day of MPA administration was induced by MPA. Due attention must be paid to the formation of thrombosis when using MPA.

Administration, Oral↗

Macrophages: modulators of breast cancer progression.

In many solid tumour types the abundance of tumour associated macrophages (TAMs) is correlated with poor prognosis. Macrophages are recruited through the local expression of chemoattractants such as colony stimulating factor 1 (CSF-1) and macrophage chemoattractant protein 1. Over-expression of both of these factors is correlated with poor prognosis in a variety of tumours. Macrophages also play an important physiological role in the development and function of many tissues ranging from the brain to the mammary gland. Thus we hypothesized that TAMs are recruited to tumours through the expression of potent chemoattractants and in this site their normal trophic functions are subverted to promote tumour progression and metastasis. To test this hypothesis we crossed mice deficient in macrophages owing to being homozygous for a null mutation in the CSF-1 gene with mice pre-disposed to mammary cancer due to the epithelial restricted expression of the polyoma middle T oncoprotein. The absence of macrophages did not change the incidence or growth of the primary tumour but decreased its rate of progression and inhibited metastasis. These data are explicable through the known macrophage functions in matrix remodelling, angiogenesis and stimulation of tumour growth and motility through the synthesis of growth and chemotactic factors. Interestingly, these functions are also normally found in wound healing or pathologically during chronic inflammation. This supports the notion that tumours are 'wounds that never heal' and suggests that chronic inflammation through persistent infection or by other means might be an important cofactor in the genesis and promotion of tumours. Macrophages might therefore be important targets for cancer therapies.

Animals↗

Development and pilot evaluation of user acceptance of advanced mass-gathering emergency medical services PDA support systems.

The support systems for the Emergency Medical Services (EMS) in the mass gatherings, such as the local marathon or the large international baseball games, had been underdeveloped. The purposes for this study were to develop triage-based EMS Personal Digital Assistant (PDA) support systems for the mass-gatherings and to evaluate users' perceived ease of use and usefulness of the systems in terms of Davis' Technology Acceptance Model (TAM). The systems were developed based on an established intelligent triage PDA support system and two other forms-the general EMS form from the Taipei EMT and the customer-made Mass Gathering Medical form used by a medical center. 23 nurses and 6 physicians in the medical center, who had ever served in the mass gatherings, were invited to examine the new systems and answered the TAM questionnaire. The results showed that the PDA systems included as many 450 information items inside 42 screens under 6 categories and the great potential of using triage-based PDA systems in the mass gatherings. Overall, most of the subjects agreed with that the systems were easy to use and useful for the mass gatherings, and they were willing to accept the systems.

Adult↗

1-hexylcarbamoyl-5-fluorouracil + cyclophosphamide + tamoxifen versus CMF + tamoxifen in women with lymph node-positive breast cancer after primary surgery: a randomized controlled trial.

We studied the usefulness of the oral 5-FU anti-cancer drug 1-hexylcarbamoyl-5-fluorouracil (HCFU) + cyclophosphamide (CPM) + tamoxifen (TAM) (HCT group) in comparison with CMF + TAM (CMFT group) in adjuvant therapy for breast cancer by a non-inferiority study based on a multi-institutional joint study. Clinical stage I, II primary breast cancers with histologically positive axillary lymph node metastasis were randomly assigned to the HCT group or the CMFT group after primary surgery. We registered 136 cases (HCT group 68 cases, CMFT group 68 cases). No significant difference in the 5-year overall survival rate (OS) and the 5-year disease-free survival rate (DFS) was found between the two groups. In the stratified analysis, DFS in cases in which the number of metastatic lymph nodes was 1-3 was significantly better in the HCT group (HCT group 84.3%, CMFT group 69.4%, log-rank test p=0.0496). No significant difference in the total incidence of adverse effects was found between the two groups, but there were significantly less adverse effects of grade 2 or over in the HCT group (p=0.034). The QOL survey at 3 months after surgery showed a significant decline of the QOL regarding lassitude, degree of difficulty in daily life, satisfaction with treatment and present mood in the CMFT group. Study results suggest that 2-year HCT therapy including the oral 5-FU anti-cancer drug HCFU is a useful adjuvant therapy which can replace CMFT therapy in early breast cancer cases with 3 or lower metastatic lymph nodes.

Adult↗

Tamoxifen down-regulates CaMKII messenger RNA levels in normal human breast tissue.

Tamoxifen was proven to reduce the incidence of breast cancer by 49% in women at increased risk of the disease in the Breast Cancer Prevention Trial. In order to identify potential candidates to explain the preventive effect induced by tamoxifen on breast cancer, normal breast tissue obtained from 42 fibroadenoma patients, randomly assigned to receive placebo or tamoxifen, was analyzed by the reverse Northern blot and RT-PCR techniques. The cDNA fragments used on Northern blot membranes were generated by the Human Cancer Genome Project funded by the Ludwig Institute for Cancer Research and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil). Total RNA was obtained from normal breast tissue from patients with clinical, cytological and ultrasound diagnosis of fibroadenoma. After a 50-day treatment with tamoxifen (10 or 20 mg/day) or placebo, normal breast tissue adjacent to the tumor was collected during lumpectomy with local anesthesia. One differentially expressed gene, Calcium/calmodulin-dependent protein kinase II (CaMKII), was found to be down-regulated during TAM treatment. CaMKII is an ubiquitous serine/threonine protein kinase that has been implicated in the diverse effects of hormones utilizing Ca2+ as a second messenger as well as in c-fos activation. These results indicate that the down-regulation of CaMKII induced by TAM might represent alternative or additional mechanisms of the action of this drug on cell cycle control and response to hormones in normal human breast tissue.

Antineoplastic Agents, Hormonal↗