PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Skin and Connective Tissue Diseases - Top 30 Publications

The prognostic value and potential drug target of phosphatase and tensin homolog in breast cancer patients: A meta-analysis.

The prognostic significance of phosphatase and tensin homolog (PTEN) in patients with breast cancer (BC) remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic value in patients with breast cancer.

A Mal De Meleda patient with severe flexion contractures of hands and feet: A case report in West China.

Palmoplantar keratoderma (PPK) is a genetically heterogeneous group of skin diseases, which is characterized by erythema and hyperkeratosis. Mal de Meleda (MDM) is a rare type of PPK with an estimated prevalence in the general population of 1 in 100,000.

BRCA Genetic Testing and Receipt of Preventive Interventions Among Women Aged 18-64 Years with Employer-Sponsored Health Insurance in Nonmetropolitan and Metropolitan Areas - United States, 2009-2014.

Genetic testing for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations can identify women at increased risk for breast and ovarian cancer. These testing results can be used to select preventive interventions and guide treatment. Differences between nonmetropolitan and metropolitan populations in rates of BRCA testing and receipt of preventive interventions after testing have not previously been examined.

Resection of Gastrointestinal Metastases in Stage IV Melanoma: Correlation with Outcomes.

The prognosis of patients with gastrointestinal (GI) melanoma metastases is poor. Surgery renders select patients disease free and/or palliates symptoms. We reviewed our single-institution experience of resection with GI melanoma metastases. A retrospective review was performed on patients who underwent surgery for GI melanoma metastases from 2007 to 2013. Fifty-four patients were identified and separated based on completeness of resection into curative 13 (24%) and palliative 41 (75.9%) groups. Thiry-six (63.2%) were symptomatic preoperatively with bleeding and/or obstruction/pain with 91.7 per cent achieving objective symptom relief. Thirty-day operative mortality was 0 per cent. The most common complication was wound infection (n = 5); major complications like anastomotic leak (n = 1) were uncommon. With a median follow-up of 9.5 months (range 0.2-75.8), median overall survival was not reached (curative) versus 9.53 months (palliative group). Median recurrence-free and progression-free survival after resection were 18.89 and 1.97 months in the curative versus palliative groups, respectively. On multivariate analysis, resection to no clinical evidence of disease (P = 0.012) and presence of single metastases (P = 0.031) were associated with improved overall survival. Surgery for GI metastases from melanoma provides symptomatic relief without major morbidity. Fewer metastases and curative resection were associated with improved survival.

Safety for Repeat Lumpectomy Without Radiotherapy for Ipsilateral Breast Tumor Recurrence.

There is little information on the local recurrence risk of patients who undergo repeat lumpectomy without radiotherapy after salvage surgery for ipsilateral breast tumor recurrence (IBTR).

Value of Additional Digital Breast Tomosynthesis for Preoperative Staging of Breast Cancer in Dense Breasts.

This retrospective study was initiated to determine the diagnostic value of additional preoperative breast tomosynthesis (DBT) for breast cancer staging in dense breasts.

The Local Recurrence of Breast Cancer with Squamous Metaplasia and Obvious Histological Heterogeneity.

We herein report a case of local recurrence of breast cancer with squamous metaplasia and obvious intratumoral and intertumoral heterogeneity. A 39-year-old female patient was diagnosed with T3N2M0 stage IIIB right breast cancer and underwent right total mastectomy and axillar lymph node dissection. At four years after surgery, she became aware of chest wall pain and diagnostic imaging revealed recurrence in the lung, right thoracic wall and sternum. The recurrent lesions remained stable for 18 months with endocrine therapy. Thereafter, the lesion in the right thoracic wall suddenly became enlarged. Moreover, liver metastasis was confirmed on FDG-PET/CT. She underwent right thoracic wall tumor resection. A biopsy was simultaneously performed to obtain a specimen from the site of liver metastasis. Postoperatively, the right chest wall mass showed obvious intratumoral heterogeneity; squamous differentiation with aggressive features and a papillotubular component similar to the primary tumor. The metastatic liver tumor showed similar pathological features to the primary tumor.

Risk-reducing Salpingo-Oophorectomy in Women at Higher Risk of Ovarian and Breast Cancer: A Single Institution Prospective Series.

Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center.

Discordance and Conversion Rates of Progesterone-, Estrogen-, and HER2/neu-Receptor Status in Primary Breast Cancer and Brain Metastasis Mainly Triggered by Hormone Therapy.

Knowing the molecular footprint of tumors is a precondition for personalized medicine. For breast cancer, targeted therapies are frequently based on the molecular status of the tissue gained from the primary tumor operation. However, it is unclear whether metastases in different organs maintain the same status.

Increased CXCL8 Expression Is Negatively Correlated with the Overall Survival of Patients with ER-Negative Breast Cancer.

C-X-C motif chemokine ligand 8 (CXCL8) is a multi-functional chemokine and has important roles during tumor formation and development. It was previously reported that increased CXCL8 protein levels occurred in certain patients.

Role of ARHGAP24 in ADP Ribosylation Factor 6 (ARF6)-dependent Pseudopod Formation in Human Breast Carcinoma Cells.

The small GTPase ADP ribosylation factor 6 (ARF6) promotes carcinoma cell invasion and metastasis through remodeling of actin cytoskeleton and formation of pseudopod that is regulated by RAC. RHO GTPase activating protein 24 (ARHGAP24), a RAC-specific GTPase activating protein, binds to activated ARF6 and is recruited to the plasma membrane. The aim of the present study was to demonstrate if ARHGAP24 is involved in the ARF6-mediated formation of pseudopods in breast carcinoma cells.

Probing the Molecular Mechanisms Governing the Oncolytic Activity of Paeonia suffruticosa on Triple-negative Breast Cancer Cells In Vitro.

Extracts of Paeonia suffruticosa are traditionally used in Chinese medicine to increase blood flow. Recently, this extract has been shown to possess anti-tumor and anti-inflammatory properties, though this mechanism remains unknown. In the current work, we prepared extracts of P. suffruticosa and analyzed their effects on MDA-MB-231 triple-negative breast cancer cells.

Inhibitory Activity of Iron Chelators ATA and DFO on MCF-7 Breast Cancer Cells and Phosphatases PTP1B and SHP2.

Rapidly-dividing cancer cells have higher requirement for iron compared to non-transformed cells, making iron chelating a potential anticancer strategy. In the present study we compared the anticancer activity of uncommon iron chelator aurintricarboxylic acid (ATA) with the known deferoxamine (DFO).

Will Chinese external therapy with compound Tripterygium wilfordii hook F gel safely control disease activity in patients with rheumatoid arthritis: design of a double-blinded randomized controlled trial.

Chinese external therapy (CET) is a topical application with mainly Chinese herb medicine therapy with thousands of years of historical implications and is a clinical routine that is commonly used for relieving joint-related symptoms in patients with arthritis in Chinese hospitals. However, there is a paucity of modern medical evidence to support its effectiveness and safety. Thus, we propose to implement a randomized, double-blinded, placebo-controlled clinical trial in patients with rheumatoid arthritis (RA) using, as the experimental intervention, topical application of a hospital-compounded gel preparation of Tripterygium wilfordii Hook F (TwHF).

Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis.

Indigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways.

The mucopolysaccharidoses: advances in medical care lead to challenges in orthopaedic surgical care.

The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders with clinical manifestations relevant to the orthopaedic surgeon. Our aim was to review the recent advances in their management and the implications for surgical practice. The current literature about MPSs is summarised, emphasising orthopaedic complications and their management. Recent advances in the diagnosis and management of MPSs include the recognition of slowly progressive, late presenting subtypes, developments in life-prolonging systemic treatment and potentially new indications for surgical treatment. The outcomes of surgery in these patients are not yet validated and some procedures have a high rate of complications which differ from those in patients who do not have a MPS. The diagnosis of a MPS should be considered in adolescents or young adults with a previously unrecognised dysplasia of the hip. Surgeons treating patients with a MPS should report their experience and studies should include the assessment of function and quality of life to guide treatment. Cite this article: Bone Joint J 2017;99-B:1132-9.

Estimated reduction in expenditure on hospital-acquired pressure injuries after an intervention for early identification and treatment.

An intervention designed to reduce numbers of hospital-acquired pressure injuries was delivered in Counties Manukau Health hospitals. An audit of a sample of patients was carried out to estimate the cost savings that would have been acquired across the district health board (DHB) due to a reduction in pressure injuries.

Classification and possible bacterial infection in outpatients with eczema and dermatitis in China: A cross-sectional and multicenter study.

Little is known about the classification and bacterial infection in outpatients with eczema and dermatitis in China.To investigate the prevalence of eczema and dermatitis in outpatients of dermatology clinics in China, examine classification and proportion of common types of dermatitis and the possible bacterial infection, and analyze the possible related factors.Outpatients with eczema or dermatitis from 39 tertiary hospitals of 15 provinces in mainland China from July 1 to September 30, 2014, were enrolled in this cross-sectional and multicenter study. Among 9393 enrolled outpatients, 636 patients (6.7%) were excluded because of incomplete information.The leading subtypes of dermatitis were unclassified eczema (35.5%), atopic dermatitis (13.4%), irritant dermatitis (9.2%), and widespread eczema (8.7%). Total bacterial infection rate was 52.3%, with widespread eczema, stasis dermatitis, and atopic dermatitis being the leading three (65.7%, 61.8%, and 61.4%, respectively). Clinically very likely bacterial infection has a significant positive correlation with disease duration, history of allergic disease, history of flexion dermatitis, and severe itching.Atopic dermatitis has become a common subtype of dermatitis in China. Secondary bacterial infection is common in all patients with dermatitis, and more attentions should be paid on this issue in other type of dermatitis apart from atopic dermatitis.

Are programmed cell death 1 gene polymorphisms correlated with susceptibility to rheumatoid arthritis?: A meta-analysis.

Several studies investigated the relationship between programmed cell death 1 (PDCD1) gene polymorphisms and rheumatoid arthritis (RA) risk, but the results were controversial. To explore whether PDCD1 gene polymorphisms have an effect on RA risk, we conducted this meta-analysis to investigate the relationships between PDCD1 polymorphisms (rs36084323 [PD-1.1 G/A], rs11568821 [PD-1.3 G/A] and rs2227981 [PD-1.5 C/T]) and RA risk under 4 genetic models.

A combination of levobupivacaine and lidocaine for paravertebral block in breast cancer patients undergoing quadrantectomy causes greater hemodynamic oscillations than levobupivacaine alone.

To test for differences in hemodynamic and analgesic properties in patients with breast cancer undergoing quadrantectomy with paravertebral block (PVB) induced with a solution of either one or two local anesthetics.

Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis.

Breast cancer is considered as the most prevalent malignancy in women worldwide. Despite emergence of several prognosticators for better management of patients, there are still limitations for their clinical application due to the complexity of breast tumors, and therefore, new biomarkers for better prognosis of clinical outcomes would be of the great essence. MicroRNAs are highly conserved small non-coding regulatory RNAs involved in post-transcriptional regulating of gene expression during different cellular mechanisms. Accumulating studies suggest that miR-218 plays a multifunctional role in various cancer types and different stages. Here, to address prognostic significance of miR-218 in breast cancer, we investigate the expression profile of miR-218 and B-cell-specific Moloney murine leukemia virus integration site 1 ( BMI1) gene, as one of the putative targets of miR-218, in 33 paired breast tumors and their adjacent normal tissues with respect to the clinicopathological features of patients using quantitative real-time polymerase chain reaction. The correlation of both miR-218 and BMI1 gene expression with overall survival of breast cancer patients was also examined recruiting OncoLNC data portal. Finally, to better understand biological function of miR-218 in breast cancer, we performed in silico Gene Ontology and signaling pathway enrichment analysis on miR-218 targetome. According to our data, significant elevation of the expression of miR-218 and downregulation of BMI1 were observed in clinical breast cancer specimens compared with normal tissues ( p < 0.0001). The lower expression of miR-218 was associated with lymph node metastases, higher grades, and poorer prognosis (logrank p = 0.00988), whereas no significant difference in overall survival was observed between patients with higher and lower expression of BMI1 (logrank p = 0.254). These findings suggest that miR-218 expression profiling might be clinically applicable as a prognostic biomarker in breast cancer. In addition, our in silico enrichment analyses revealed that the association of miR-218 expression with breast cancer prognosis might be through its involvement in endocytosis and gap junction biological pathways.

Racial and Ethnic Disparities in Patient-Provider Communication With Breast Cancer Patients: Evidence From 2011 MEPS and Experiences With Cancer Supplement.

The current study explores racial/ethnic disparities in the quality of patient-provider communication during treatment, among breast cancer patients. A unique data set, Medical Expenditure Panel Survey and Experiences With Cancer Supplement 2011, is used to examine this topic. Using measures of the quality of patient-provider communication that patients are best qualified to evaluate, we explore the relationship between race/ethnicity and patients' perspectives on whether (1) patient-provider interactions are respectful, (2) providers are listening to patients, (3) providers provide adequate explanations of outcomes and treatment, and (4) providers spend adequate time in interacting with the patients. We also examine the relationship between race/ethnicity and patients' perspectives on whether their (1) doctor ever discussed need for regular follow-up care and monitoring after completing treatment, (2) doctor ever discussed long-term side effects of cancer treatment, (3) doctor ever discussed emotional or social needs related to cancer, and (4) doctor ever discussed lifestyle or health recommendations. Multivariate ordinary least squares and ordered logistic regression models indicate that after controlling for factors such as income and health insurance coverage, the quality of patient-provider communication with breast cancer patients varies by race/ethnicity. Non-Hispanic blacks experience the greatest communication deficit. Our findings can inform the content of future strategies to reduce disparities.

Exploring virulence and immunogenicity in the emerging pathogen Sporothrix brasiliensis.

Sporotrichosis is a polymorphic chronic infection of humans and animals classically acquired after traumatic inoculation with soil and plant material contaminated with Sporothrix spp. propagules. An alternative and successful route of transmission is bites and scratches from diseased cats, through which Sporothrix yeasts are inoculated into mammalian tissue. The development of a murine model of subcutaneous sporotrichosis mimicking the alternative route of transmission is essential to understanding disease pathogenesis and the development of novel therapeutic strategies. To explore the impact of horizontal transmission in animals (e.g., cat-cat) and zoonotic transmission on Sporothrix fitness, the left hind footpads of BALB/c mice were inoculated with 5×106 yeasts (n = 11 S. brasiliensis, n = 2 S. schenckii, or n = 1 S. globosa). Twenty days post-infection, our model reproduced both the pathophysiology and symptomology of sporotrichosis with suppurating subcutaneous nodules that progressed proximally along lymphatic channels. Across the main pathogenic members of the S. schenckii clade, S. brasiliensis was usually more virulent than S. schenckii and S. globosa. However, the virulence in S. brasiliensis was strain-dependent, and we demonstrated that highly virulent isolates disseminate from the left hind footpad to the liver, spleen, kidneys, lungs, heart, and brain of infected animals, inducing significant and chronic weight loss (losing up to 15% of their body weight). The weight loss correlated with host death between 2 and 16 weeks post-infection. Histopathological features included necrosis, suppurative inflammation, and polymorphonuclear and mononuclear inflammatory infiltrates. Immunoblot using specific antisera and homologous exoantigen investigated the humoral response. Antigenic profiles were isolate-specific, supporting the hypothesis that different Sporothrix species can elicit a heterogeneous humoral response over time, but cross reaction was observed between S. brasiliensis and S. schenckii proteomes. Despite great diversity in the immunoblot profiles, antibodies were mainly derived against 3-carboxymuconate cyclase, a glycoprotein oscillating between 60 and 70 kDa (gp60-gp70) and a 100-kDa molecule in nearly 100% of the assays. Thus, our data broaden the current view of virulence and immunogenicity in the Sporothrix-sporotrichosis system, substantially expanding the possibilities for comparative genomic with isolates bearing divergent virulence traits and helping uncover the molecular mechanisms and evolutionary pressures underpinning the emergence of Sporothrix virulence.

Porphyria.

Rotator cuff surgery in patients with rheumatoid arthritis: clinical outcome comparable to age, sex and tear size matched non-rheumatoid patients.

Aims This study aimed to compare the clinical outcomes of rotator cuff repair in patients with rheumatoid arthritis with those of patients who have no known history of the disease. We hypothesised that the functional outcomes are comparable between patients and without rheumatoid arthritis and may be affected by the level of disease activity, as assessed from C-reactive protein (CRP) level and history of systemic steroid intake. Patients and methods We conducted a retrospective review of the institutional surgical database from May 1995 to April 2012. Twenty-nine patients with rheumatoid arthritis who had rotator cuff repair were enrolled as the study group. Age, sex, and tear size matched patients with no disease who were selected as the control group. The mean duration of follow-up was 46 months (range 24-92 months). Clinical outcomes were assessed with the American Shoulder and Elbow Surgeons (ASES) questionnaire, Constant score and visual analogue scale (VAS). All data were recorded preoperatively and at regular postoperative follow-up visits. CRP was measured preoperatively as the disease activity marker for rheumatoid arthritis. Medication history was thoroughly reviewed in the study group. Results In patients with rheumatoid arthritis, all shoulder functional scores improved after surgery (ASES 56.1-78.1, Constant 50.8-70.5 and VAS 5.2-2.5; P < 0.001). The functional outcome of surgery in patients with rheumatoid arthritis was comparable to that of the control group (difference with control: ASES 78.1 vs. 85.5, P = 0.093; Constant 70.5 vs. 75.9, P = 0.366; VAS 2.5 vs. 1.8, P = 0.108). Patients with rheumatoid arthritis who had an elevated CRP level (> 1 mg/dl) showed inferior clinical outcomes than those with normal CRP levels. Patients with a history of systemic steroid intake showed inferior functional outcomes than those who had not taken steroids. Conclusions Surgical intervention for rotator cuff tear in patients with rheumatoid arthritis improved the shoulder functional outcome comparable to that in matched patients without rheumatoid arthritis. Elevated preoperative CRP level and history of systemic steroid intake portend inferior functional outcome in patients with rheumatoid arthritis.

KAEMPFEROL, A FLAVONOID COMPOUND FROM GYNURA MEDICA INDUCED APOPTOSIS AND GROWTH INHIBITION IN MCF-7 BREAST CANCER CELL.

Kaempferol, a natural flavonoid, has been shown to induce cancer cell apoptosis and cell growth inhibition in several tumors. Previously we have conducted a full investigation on the chemical constituents of Gynura medica, kaempferol and its glycosides are the major constituents of G. medica. Here we investigated the growth inhibition and apoptosis induction effect of kaempferol extracted from G. medica.

Spatial distribution, Leishmania species and clinical traits of Cutaneous Leishmaniasis cases in the Colombian army.

In Colombia, the cutaneous leishmaniasis (CL) is the most common manifestation across the army personnel. Hence, it is mandatory to determine the species associated with the disease as well as the association with the clinical traits. A total of 273 samples of male patients with CL were included in the study and clinical data of the patients was studied. PCR and sequencing analyses (Cytb and HSP70 genes) were performed to identify the species and the intra-specific genetic variability. A georeferenced database was constructed to identify the spatial distribution of Leishmania species isolated. The identification of five species of Leishmania that circulate in the areas where army personnel are deployed is described. Predominant infecting Leishmania species corresponds to L. braziliensis (61.1%), followed by Leishmania panamensis (33.5%), with a high distribution of both species at geographical and municipal level. The species L. guyanensis, L. mexicana and L. lainsoni were also detected at lower frequency. We also showed the identification of different genotypes within L. braziliensis and L. panamensis. In conclusion, we identified the Leishmania species circulating in the areas where Colombian army personnel are deployed, as well as the high intra-specific genetic variability of L. braziliensis and L. panamensis and how these genotypes are distributed at the geographic level.

Modeling zoonotic cutaneous leishmaniasis incidence in central Tunisia from 2009-2015: Forecasting models using climate variables as predictors.

Transmission of zoonotic cutaneous leishmaniasis (ZCL) depends on the presence, density and distribution of Leishmania major rodent reservoir and the development of these rodents is known to have a significant dependence on environmental and climate factors. ZCL in Tunisia is one of the most common forms of leishmaniasis. The aim of this paper was to build a regression model of ZCL cases to identify the relationship between ZCL occurrence and possible risk factors, and to develop a predicting model for ZCL's control and prevention purposes. Monthly reported ZCL cases, environmental and bioclimatic data were collected over 6 years (2009-2015). Three rural areas in the governorate of Sidi Bouzid were selected as the study area. Cross-correlation analysis was used to identify the relevant lagged effects of possible risk factors, associated with ZCL cases. Non-parametric modeling techniques known as generalized additive model (GAM) and generalized additive mixed models (GAMM) were applied in this work. These techniques have the ability to approximate the relationship between the predictors (inputs) and the response variable (output), and express the relationship mathematically. The goodness-of-fit of the constructed model was determined by Generalized cross-validation (GCV) score and residual test. There were a total of 1019 notified ZCL cases from July 2009 to June 2015. The results showed seasonal distribution of reported ZCL cases from August to January. The model highlighted that rodent density, average temperature, cumulative rainfall and average relative humidity, with different time lags, all play role in sustaining and increasing the ZCL incidence. The GAMM model could be applied to predict the occurrence of ZCL in central Tunisia and could help for the establishment of an early warning system to control and prevent ZCL in central Tunisia.

Benefit of Local Anesthesia in Reducing Pain during Collagenase Injection for Dupuytren's Contracture.

Collagenase injection for Dupuytren's contracture is commonly administered without anesthesia. The authors studied the benefit of injecting local anesthesia before collagenase in reducing treatment-related pain. This prospective cohort study included 187 patients (mean age, 69 years; 80 percent men) at two orthopedic departments in Sweden. At one center, 161 consecutive patients scheduled for collagenase injection were assigned to two groups by alternating outpatient clinics; 78 received collagenase without local anesthesia using a modified method (injecting 0.80 mg in multiple spots in the cord) and 83 received local anesthesia injected in the proximal palm before collagenase. At the other center, 26 consecutive patients received collagenase using the standard method (0.58 mg injected in one spot) without local anesthesia. Immediately after the first injection (collagenase or local anesthesia), the patients rated the severity of injection-related pain on a visual analogue scale from 0 (no pain) to 10 (worst pain). Before finger manipulation 1 or 2 days after injection, the patients rated the pain experienced since injection. Mean score ± SD for pain experienced during modified collagenase injection was 4.3 ± 2.5 without local anesthesia and 2.3 ± 1.7 during injection of local anesthesia (before collagenase) (age- and sex-adjusted mean difference, 2.1; 95 percent CI, 1.5 to 2.7; p < 0.001). Mean pain score ± SD during standard collagenase injection without local anesthesia was 4.8 ± 1.8. Mean pain score ± SD during the injection-manipulation interval was 2.9 ± 1.9 in the group without local anesthesia and 2.9 ± 2.3 in the local anesthesia group (p = 0.79). This study shows that local anesthesia significantly reduces the patient's overall pain experience during collagenase treatment for Dupuytren's contracture.

Autologous Fat Grafting as a Novel Antiestrogen Vehicle for the Treatment of Breast Cancer.

Adipose fat transfer is increasingly used for contour corrections of the tumor bed after lumpectomy and breast reconstructions after mastectomy. The lipophilic nature of the fat tissue may render adipocytes an ideal vehicle with which to deliver a high boost of an antiestrogen to the tumor bed to serve as an adjunct systemic hormonal therapy. The authors therefore tested whether adipocytes could safely be loaded with an antiestrogen and allow for release at therapeutic concentrations to treat breast cancer.