Efficacy and tolerability of AFPep, a cyclic peptide with anti-breast cancer properties.

PURPOSE: The purpose of this study is to assess the efficacy and safety profile of AFPep, a 9-amino acid cyclic peptide prior to its entry into pre-clinical toxicology analyses en route to clinical trials. METHODS: AFPep was assessed for anti-estrogenic activity in a mouse uterine growth assay and for breast cancer therapeutic efficacy in a human tumor xenograft model in mice. AFPep was assessed for tolerability in a variety of in vivo models, notably including assessment for effects on rat liver and human hepatocellular carcinoma cell lines and xenografts. RESULTS: AFPep arrests the growth of human MCF-7 breast cancer xenografts, inhibits the estrogen-induced growth of mouse uteri, and does not affect liver growth nor stimulate growth of human hepatocellular carcinoma cell lines when growing in vitro or as xenografts in vivo. AFPep is well tolerated in mice, rats, dogs, and primates. CONCLUSIONS: AFPep is effective for the treatment of ER-positive breast cancer and exhibits a therapeutic index that is substantially wider than that for drugs currently in clinical use. The data emphasize the importance of pursuing pre-clinical toxicology studies with the intent to enter clinical trials.

A Project to Promote Adherence to Blood Pressure Medication Among People Who Use Community Pharmacies in Rural Montana, 2014-2016.

INTRODUCTION: Pharmacists can assist patients in managing their blood pressure levels. We assessed whether adherence to blood pressure medication improved among people who used community pharmacies in rural Montana after pharmacists initiated consultations and distributed educational materials developed for the Million Hearts Initiative's "Team Up. Pressure Down." (TUPD) program. METHODS: From 2014 to 2016, the Cardiovascular Health Program at the Montana Department of Public Health and Human Services conducted a statewide project to evaluate an intervention for adherence to blood pressure medication administered through community pharmacies. After the year 1 pilot, we redesigned the program for year 2 and year 3 and measured the percentage of participating patients who adhered to blood pressure medication. We also conducted a statewide survey to assess pharmacy characteristics, computer-system capabilities, and types of consulting services provided by pharmacists. RESULTS: Twenty-five community pharmacies completed Montana's TUPD program: 8 pharmacies in the pilot year, 11 pharmacies in year 2, and 6 pharmacies in year 3. For year 2 and year 3 combined, the percentage of participating patients who achieved blood pressure medication adherence improved preintervention to postintervention from 73% to 89%, and adherence improved in 15 of the 17 pharmacies. The pilot pharmacies identified 3 major barriers to project success: patient buy-in, staff burden in implementing the project, and funding. In the statewide assessment, TUPD-funded pharmacies were significantly more likely than non-TUPD-funded pharmacies to provide prescription synchronization and medication management with feedback to the patient's physician. CONCLUSION: Community pharmacies in rural areas can effectively use brief consultations and standard educational materials to improve adherence to blood pressure medication.

Heterogeneous catalysis for sustainable biodiesel production via esterification and transesterification.

Concern over the economics of accessing fossil fuel reserves, and widespread acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change from combusting such carbon sources, is driving academic and commercial research into new routes to sustainable fuels to meet the demands of a rapidly rising global population. Here we discuss catalytic esterification and transesterification solutions to the clean synthesis of biodiesel, the most readily implemented and low cost, alternative source of transportation fuels to meet future societal demands.

Orai3 is an estrogen receptor α-regulated Ca²âº channel that promotes tumorigenesis.

Store-operated Ca(2+) entry (SOCE) encoded by Orai1 proteins is a ubiquitous Ca(2+)-selective conductance involved in cellular proliferation and migration. We recently described up-regulation of Orai3 channels that selectively mediate SOCE in estrogen receptor α-expressing (ERα(+)) breast cancer cells. However, the connection between ERα and Orai3 and the role of Orai3 in tumorigenesis remain unknown. Here, we show that ERα knockdown decreases Orai3 mRNA (by ∼63%) and protein (by ∼44%) with no effect on Orai1. ERα knockdown decreases Orai3-mediated SOCE (by ∼43%) and the corresponding Ca(2+) release-activated Ca(2+) (CRAC) current (by ∼42%) in ERα(+) MCF7 cells. The abrogation of SOCE in MCF7 cells on ERα knockdown can be rescued by ectopic expression of Orai3. ERα activation increased Orai3 expression and SOCE in MCF7 cells. Epidermal growth factor (EGF) and thrombin stimulate Ca(2+) influx into MCF7 cells through Orai3. Orai3 knockdown inhibited SOCE-dependent phosphorylation of extracellular signal-regulated kinase (ERK1/2; by ∼44%) and focal adhesion kinase (FAK; by ∼46%) as well as transcriptional activity of nuclear factor for activated T cells (NFAT; by ∼49%). Significantly, Orai3 knockdown selectively decreased anchorage-independent growth (by ∼58%) and Matrigel invasion (by ∼44%) of ERα(+) MCF7 cells with no effect on ERα(-) MDA-MB231 cells. Moreover, Orai3 knockdown inhibited ERα(+) cell tumorigenesis in immunodeficient mice (∼66% reduction in tumor volume). These data establish Orai3 as an ERα-regulated channel and a potential selective therapeutic target for ERα(+) breast cancers.

Expression of the aryl hydrocarbon receptor is not required for the proliferation, migration, invasion, or estrogen-dependent tumorigenesis of MCF-7 breast cancer cells.

The AhR was initially identified as a ligand-activated transcription factor mediating effects of chlorinated dioxins and polycyclic aromatic hydrocarbons on cytochrome P450 1 (CYP1) expression. Recently, evidence supporting involvement of the AhR in cell-cycle regulation and tumorigenesis has been presented. To further define the roles of the AhR in cancer, we investigated the effects of AhR expression on cell proliferation, migration, invasion, and tumorigenesis of MCF-7 human breast cancer cells. In these studies, the properties of MCF-7 cells were compared with those of two MCF-7-derived sublines: AH(R100) , which express minimal AhR, and AhR(exp) , which overexpress AhR. Quantitative PCR, Western immunoblots, 17ß-estradiol (E2 ) metabolism assays, and ethoxyresorufin O-deethylase assays showed the lack of AhR expression and AhR-regulated CYP1 expression in AH(R100) cells, and enhanced AhR and CYP1 expression in AhR(exp) cells. In the presence of 1 nM E2 , rates of cell proliferation of the three cell lines showed an inverse correlation with the levels of AhR mRNA. In comparison with MCF-7 and AhR(exp) cells, AH(R100) cells produced more colonies in soft agar and showed enhanced migration and invasion in chamber assays with E2 as the chemoattractant. Despite the lack of significant AhR expression, AH(R100) cells retained the ability to form tumors in severe combined immunodeficient mice when supplemented with E2 , producing mean tumor volumes comparable to those observed with MCF-7 cells. These studies indicate that, while CYP1 expression and inducibility are highly dependent on AhR expression, the proliferation, invasion, migration, anchorage-independent growth, and estrogen-stimulated tumor formation of MCF-7 cells do not require the AhR.

Proof-of-Concept Study of an Alpha-Fetoprotein-Derived Peptide for the Management of Canine Mammary Cancer.

Novel, well-tolerated drugs are needed for the management of canine mammary cancer. Many of these cancers are promoted in their growth by estrogen. Alpha-fetoprotein (AFP) is a ubiquitous mammalian protein that has anti-estrogenic properties. AFPep (the anti-estrogenic site of AFP) has been developed into a readily synthesizable drug. AFPep has been shown to have anti-mammary cancer activity in several models of this disease, both in cell culture and in rodents. The purpose of the study reported herein was to determine the tolerability of AFPep in normal and tumor-bearing dogs. AFPep was given to dogs via both parenteral and oral routes in a single application and in repeated daily doses. Full clinical chemistry and hematology values were determined before and after drug administration. Blood levels of the drug were achieved in dogs that had been previously found to be oncostatic in rodents. No changes in clinical chemistry, hematology, and clinical behaviors were found in dogs following drug administration. The data support the further development of AFPep for clinical use against canine mammary cancer.

Mainstreaming of genomics in oncology: a nationwide survey of the genomics training needs of UK oncologists.

OBJECTIVE: Genomics is rapidly changing treatment paradigms for cancers, obligating oncologists to have good genomics knowledge. Through this survey, we aimed to assess the current understanding of cancer genomics among UK oncologists. METHODS: We conducted a web-based nation-wide self-assessment survey of the cancer genomics knowledge of UK clinical and medical oncology trainees and consultants. RESULTS: In total, 150 oncologists (81 consultants and 69 trainees) responded, representing 10% of UK oncologists.Formal training in genomics had not been received by 38.7% of oncologists and 92.7% identified a need for additional genomics training.In total, 71.3% self-reported to have good knowledge of defining somatic and germline mutations, falling to 35.3% for understanding principles of gene expression and regulation. Knowledge of cancer-predisposing syndromes was highest for Lynch syndrome (40.7% good knowledge) and lowest for multiple endocrine neoplasia (14.0% good knowledge).Overall, 49.0% of respondents had consented patients for germline testing, but 80.7% reported a lack of training in genetic counselling. CONCLUSION: Large knowledge gaps have been identified through this survey, highlighting the need for incorporation of improved formal training in cancer genomics for consultants and trainees, with an aim to equip oncologists for advances in clinical practice and to take up genetic mainstreaming confidently.

Enhanced hydrogenation catalyst synthesized by Desulfovibrio desulfuricans exposed to a radio frequency magnetic field.

Desulfovibrio desulfuricans reduces Pd(II) to Pd(0)-nanoparticles (Pd-NPs) which are catalytically active in 2-pentyne hydrogenation. To make Pd-NPs, resting cells are challenged with Pd(II) ions (uptake), followed by addition of electron donor to promote bioreduction of cell-bound Pd(II) to Pd(0) (bio-Pd). Application of radiofrequency (RF) radiation to prepared 5 wt% bio-Pd catalyst (60 W power, 60 min) increased the hydrogenation rate by 70% with no adverse impact on selectivity to cis-2-pentene. Such treatment of a 5 wt% Pd/carbon commercial catalyst did not affect the conversion rate but reduced the selectivity. Lower-dose RF radiation (2-8 W power, 20 min) was applied to the bacteria at various stages before and during synthesis of the bio-scaffolded Pd-NPs. The reaction rate (µ mol 2-pentyne converted s-1 ) was increased by ~threefold by treatment during bacterial catalyst synthesis. Application of RF radiation (2 or 4 W power) to resting cells prior to Pd(II) exposure affected the catalyst made subsequently, increasing the reaction rate by 50% as compared to untreated cells, while nearly doubling selectivity for cis 2-pentene. The results are discussed with respect to published and related work which shows altered dispersion of the Pd-NPs made following or during RF exposure.

Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells.

The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor alpha (ERalpha) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERalpha and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERalpha- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17beta-estradiol (E(2)). With these LTEE cells and with parallel control cells cultured without E(2) supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E(2)-dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E(2).

AFPep, a novel drug for the prevention and treatment of breast cancer, does not disrupt the estrous cycle or fertility in rats.

Pregnancy lowers the risk of breast cancer, largely attributable to alpha-fetoprotein (AFP). A small AFP-derived peptide (AFPep) which mimics the active site of AFP has been developed and may be useful for decreasing the risk of breast cancer for women. AFPep has been shown previously to stop the growth of estrogen-dependent human breast cancer xenografts in mice and prevent carcinogen-induced breast cancer in a rat model. Since AFPep disrupts an estrogen-responsive pathway, it is essential to assess its effects on the female reproductive cycle and fertility. Ten cycling female Sprague-Dawley rats (age 81 days) were given 100 microg AFPep in saline s.c. daily for 20 days. A second group of ten rats was given 50 microg tamoxifen s.c. daily and a third group received saline only. Vaginal smears were obtained twice per day and stained to assess estrous cycle phase. After completion of estrous cycle assessment (five cycles, 21 days), rats were maintained on drug and allowed to mate. Effects on birth of offspring and maternal body weights were assessed. AFPep had no significant effect on the incidence or duration of any estrous cycle phase, and no effect on reproductive potential or maternal body mass. Tamoxifen significantly increased the length of diestrus, locking the cycle in this phase for most animals. Only half of the tamoxifen-treated rats mated, and none became pregnant. Tamoxifen significantly slowed the rate of body mass increase. In rats, AFPep has no toxicity and no effect on female reproduction. This molecule may be developed into an attractive modality for prevention of breast cancer in women.

Herbal Medicines Attenuate PD-L1 Expression to Induce Anti-Proliferation in Obesity-Related Cancers.

Abstract: Pro-inflammatory hormones and cytokines (leptin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6) rise in obesity. Elevated levels of hormones and cytokines are linked with several comorbidities such as diabetes, heart disease, and cancer. The checkpoint programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) plays an important role in obesity and cancer proliferation. L-thyroxine (T4) and steroid hormones up-regulate PD-L1 accumulation and promote inflammation in cancer cells and diabetics. On the other hand, resveratrol and other herbal medicines suppress PD-L1 accumulation and reduce diabetic effects. In addition, they induce anti-cancer proliferation in various types of cancer cells via different mechanisms. In the current review, we discuss new findings and visions into the antagonizing effects of hormones on herbal medicine-induced anti-cancer properties.

A peptide derived from alpha-fetoprotein inhibits the proliferation induced by estradiol in mammary tumor cells in culture.

This study was aimed to obtain additional information on the activity of a cyclized 9-amino acid peptide (cP) containing the active site of alpha fetoprotein, which inhibits the estrogen-stimulated proliferation of tumor cells in culture and of xenografts in immunodeficient mice. Breast cancer cells cultured in the presence of 2 nM estradiol were exposed to cP for different periods and their proliferation, estradiol binding parameters, clustering tendency and expression of E-cadherin and p21Cip1 were analyzed by biochemical and cell biology methods. The proliferation of MCF7 cells was significantly decreased by the addition of 2 microg/ml cP to the medium. cP did not increase cell death rate nor alter the number of binding sites for estradiol nor the endogenous aromatase activity of MCF7 cells. cP also decreased the proliferation of estrogen-dependent ZR75-1 cells but had no effect on estrogen-independent MDA-MB-231 cells. An increased nuclear p21Cip1 expression detected after cP treatment suggests that cP slows MCF7 cell proliferation via this regulator. We propose that cP could represent a novel breast cancer therapeutic agent whose mechanism of action is different from that of tamoxifen or of inhibitors of aromatase.

Hormones of pregnancy, alpha-feto protein, and reduction of breast cancer risk.

Parity profoundly reduces breast cancer (BC) risk later in life. It has been reasoned that hormones (either estradiol E2 or estriol E3), progesterone (P) or human chorionic gonadotropin (hCG) in the serum of pregnant women might lead to that reduction in risk. These agents have been shown to reduce BC incidence in nonpregnant rats. We investigated the hypothesis that exogenously added E2, E3, P, or hCG are not the proximal effectors of risk reduction, but that they elicit alpha-fetoprotein (alphaFP) from the nonpregnant liver, and that cFP is the proximal agent by which reduction of BC risk is obtained. Methylnitrosourea (MNU)-exposed animals were treated with saline, E3, E2 + P, E3 + P, hCG, or were allowed to experience pregnancy, and AFP levels were measured in the serum and subsequent tumor incidence was recorded. Human HepG2 liver cells in culture were treated with E3, E2 + P, P, or hCG and elicited AFP was measured in the media. The HepG2 culture media containing elicited AFP was assessed for its ability to inhibit proliferation of T47D cells when applied to these human BC cells in culture, and to inhibit the estrogen-induced phosphorylation of the estrogen receptor in T47D cells. For each condition in the prevention studies, hormone treatment reduced the incidence of BC to an extent similar to that reported by the original studies. In each condition, alphaFP levels in serum were elevated over that in control animals. In culture, treatment of human liver cells with E3, E2 + P, or hCG, but not P alone, led to increased levels of AFP in the media. Media containing hCG-elicited AFP inhibited the estrogen-stimulated proliferation of T47D cells in culture, and inhibited phosphorylation of the estrogen receptor, whereas, estrogens and hCG did not inhibit the growth of these tumor cells in culture. In conclusion, since the hormones of pregnancy elicit alphaFP from the liver, and alphaFP but not the hormones of pregnancy has direct antitumor properties, it is concluded that alphaFP is the proximal agent through which reduction in BC incidence is realized from the experience of pregnancy.

Tetrac downregulates ß-catenin and HMGA2 to promote the effect of resveratrol in colon cancer.

The molecular pathogenesis of colorectal cancer encompasses the activation of several oncogenic signaling pathways that include the Wnt/ß-catenin pathway and the overexpression of high mobility group protein A2 (HMGA2). Resveratrol - the polyphenolic phytoalexin - binds to integrin αvß3 to induce apoptosis in cancer cells via cyclooxygenase 2 (COX-2) nuclear accumulation and p53-dependent apoptosis. Tetraiodothyroacetic acid (tetrac) is a de-aminated derivative of l-thyroxine (T4), which - in contrast to the parental hormone - impairs cancer cell proliferation. In the current study, we found that tetrac promoted resveratrol-induced anti-proliferation in colon cancer cell lines, in primary cultures of colon cancer cells, and in vivo The mechanisms implicated in this action involved the downregulation of nuclear ß-catenin and HMGA2, which are capable of compromising resveratrol-induced COX-2 nuclear translocation. Silencing of either ß-catenin or HMGA2 promoted resveratrol-induced anti-proliferation and COX-2 nuclear accumulation which is essential for integrin αvß3-mediated-resveratrol-induced apoptosis in cancer cells. Concurrently, tetrac enhanced nuclear abundance of chibby family member 1, the nuclear ß-catenin antagonist, which may further compromise the nuclear ß-catenin-dependent gene expression and proliferation. Taken together, these results suggest that tetrac targets ß-catenin and HMGA2 to promote resveratrol-induced-anti-proliferation in colon cancers, highlighting its potential in anti-cancer combination therapy.

Acetic Acid Ketonization over Fe3O4/SiO2 for Pyrolysis Bio-Oil Upgrading.

A family of silica-supported, magnetite nanoparticle catalysts was synthesised and investigated for continuous-flow acetic acid ketonisation as a model pyrolysis bio-oil upgrading reaction. The physico-chemical properties of Fe3O4/SiO2 catalysts were characterised by using high-resolution transmission electron microscopy, X-ray absorption spectroscopy, X-ray photo-electron spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, thermogravimetric analysis and porosimetry. The acid site densities were inversely proportional to the Fe3O4 particle size, although the acid strength and Lewis character were size-invariant, and correlated with the specific activity for the vapour-phase acetic ketonisation to acetone. A constant activation energy (∼110 kJ mol-1), turnover frequency (∼13 h-1) and selectivity to acetone of 60 % were observed for ketonisation across the catalyst series, which implies that Fe3O4 is the principal active component of Red Mud waste.

Use of resveratrol to improve the effectiveness of cisplatin and doxorubicin: study in human gynecologic cancer cell lines and in rodent heart.

OBJECTIVE: The purpose of this study was to investigate whether resveratrol adds to the growth inhibitory effects of cisplatin and doxorubicin on ovarian and uterine cancer cells and to evaluate whether resveratrol diminishes the cardiac toxicity of doxorubicin in rodent heart. STUDY DESIGN: Human ovarian (OVCAR-3) and uterine (Ishikawa) cancer cells in culture were treated with cisplatin and doxorubicin, respectively, with and without resveratrol; and cell growth and viability were evaluated. Neonatal rat ventricular myocytes received doxorubicin in the presence and absence of resveratrol, and cell viability was evaluated. Mice received doxorubicin +/- resveratrol, and electrocardiograms were evaluated. Data were analyzed with analysis of variance and Scheffe's test. RESULTS: Resveratrol combined with cisplatin or with doxorubicin demonstrated an additive growth-inhibitory anticancer effect with a left shift of the cisplatin and doxorubicin dose/response curves. Resveratrol increased the viability of neonatal rat ventricular myocytes that were treated with doxorubicin and reduced doxorubicin-induced bradycardia and QTc interval prolongation in mice. CONCLUSION: Resveratrol adds to the growth inhibitory/anticancer activity of cisplatin and doxorubicin in vitro and protects against doxorubicin-induced cardiac toxicity both in vitro and in mice.

Prevention of N-methyl-N-nitrosourea-induced breast cancer by alpha-fetoprotein (AFP)-derived peptide, a peptide derived from the active site of AFP.

PURPOSE: alpha-Fetoprotein (AFP) is a protein of pregnancy associated with a decrease in lifetime risk of breast cancer in parous women. A synthetic, cyclic nonapeptide has been developed that mimics the antioncogenic active site of AFP. To test the hypothesis that the AFP-derived peptide (AFPep) can prevent breast cancer, the N-methyl-N-nitrosourea-induced breast cancer model was used in rats. EXPERIMENTAL DESIGN: AFPep was given daily by injection beginning 10 days after N-methyl-N-nitrosourea treatment and continued for 23 days (a time designed to mimic pregnancy) or for other times to assess efficacy as a function of drug duration. Tumor incidence, multiplicity, and latency were noted as end points. At necropsy, pathology analysis of tumors and major organs were obtained. RESULTS: AFPep prevented cancer in a dose-dependent fashion. Significantly longer mean tumor-free days (P < 0.02), lower tumor incidence (P = 0.004), and lower tumor multiplicity were observed for AFPep-treated groups. No evidence of host toxicity as measured by body weight, cage activity, fur texture, and organ weights (liver, uterus, heart, kidney, and spleen) were found in animals treated with AFPep. Mechanistic studies using transplantable human breast cancer xenografts showed that the peptide interfered with estrogen-dependent breast cancer growth inhibited the phosphorylation of the estrogen receptor and activated phosphorylation of p53. CONCLUSIONS: AFPep is a well-tolerated, mechanistically novel, chemopreventive agent in models of breast cancer and warrants further development for the prevention and treatment of this disease in humans.

Elevated sod2 activity augments matrix metalloproteinase expression: evidence for the involvement of endogenous hydrogen peroxide in regulating metastasis.

PURPOSE: Elevated manganese superoxide dismutase (Sod2) levels have been reported to be associated with an increased frequency of tumor invasion and metastasis in certain cancers, and the aim of this study is to examine the molecular mechanisms by which this occurs. EXPERIMENTAL DESIGN: Sod2 and catalase overexpressing HT-1080 fibrosarcoma cell lines were used to evaluate the H(2)O(2)-dependent regulation of matrix metalloproteinase (MMP)-1 promoter activity, mitogen-activated protein (MAP) kinase signaling, DNA-binding activity, and MMP mRNA levels. The invasive and metastatic potential of Sod2 overexpressing cells was characterized using subrenal capsular implantation or tail vein injection of tumor cells into nude mice, respectively. RESULTS: Our data reveal that Sod2 overexpression increases the DNA-binding activity of transcription factors critical for MMP expression but also enhances MMP-1 promoter activity via the Ras//MAP/extracellular signal-regulated kinase (MEK) signaling cascade. A single nucleotide polymorphism that creates an Ets site at position -1607 bp confers Sod2-dependent MMP-1 promoter activity. Sod2 overexpression also increases the mRNA levels of MMPs-2, -3, -7, -10, -9, -11 and enhances the metastatic potential of fibrosarcoma cells when implanted in immunodeficient mice. The Sod2-dependent increases in AP-1 and SP-1 DNA-binding activity, MMP-1 promoter activity, general MMP expression, and collagen degradation can be reversed by the hydrogen peroxide-detoxifying enzyme, catalase. CONCLUSION: MMPs play a critical role in the process of stromal invasion and metastasis, and these findings suggest that the association between increased Sod2 and poor prognosis in certain cancers may be attributed to elevated MMP production.

Assessing diabetes patients' healthcare needs.

Pharmacists who possess the proper skills and knowledge can intervene with patients in a proactive manner by initiating a dialogue at the point of dispensing medication. After patients complete the DPAQ and the pharmacist assesses the information, a plan of care is developed. Proper documentation (e.g., using the SOAP format) is the first and most important step in caring for patients with diabetes. Such encounters impact on the level of care provided and are professionally and financially rewarding for the pharmacist.