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1.
Bone health in women with breast cancer.
Ramchand, SK, Cheung, YM, Grossmann, M
Climacteric : the journal of the International Menopause Society. 2019;(6):589-595
Abstract
Women with early, estrogen receptor-positive breast cancer are treated with adjuvant endocrine therapy, using aromatase inhibitors or selective estradiol receptor modulators such as tamoxifen, to deprive breast tissue from the deleterious effects of estradiol action, hence improving long-term prognosis. Aromatase inhibitors and, in premenopausal women, tamoxifen accelerate bone loss and increase fracture risk. Therefore, all women commencing endocrine therapy need a targeted work-up to assess the baseline fracture risk, and monitoring of bone health during endocrine therapy should be individualized based on this baseline risk. While high-level evidence specific to early breast cancer is lacking, non-pharmacologic measures to maintain optimal bone health such as weight-bearing exercise and calcium and vitamin D sufficiency should be implemented in all women. Antiresorptive treatment should be initiated in all women with preexisting fragility fractures (including vertebral morphometric fractures) and should be considered in women with areal bone mineral density (BMD) T-scores < -2.0 (or Z-scores in women aged <50 years) or those experiencing rapid bone loss (≥5% per year), taking into consideration the baseline BMD and other risk factors for fracture. Further clinical trial evidence is required to provide definitive guidance regarding criteria to initiate antiresorptive treatment, choice of agents, and duration of treatment, taking into account potential oncologic benefits of antiresorptive therapy on breast cancer-related outcomes.
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2.
Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients.
Cuyàs, E, Fernández-Arroyo, S, Buxó, M, Pernas, S, Dorca, J, Álvarez, I, Martínez, S, Pérez-Garcia, JM, Batista-López, N, Rodríguez-Sánchez, CA, et al
Aging. 2019;(9):2874-2888
Abstract
Certain dietary interventions might improve the therapeutic index of cancer treatments. An alternative to the "drug plus diet" approach is the pharmacological reproduction of the metabolic traits of such diets. Here we explored the impact of adding metformin to an established therapeutic regimen on the systemic host metabolism of cancer patients. A panel of 11 serum metabolites including markers of mitochondrial function and intermediates/products of folate-dependent one-carbon metabolism were measured in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin. Metabolite profiles revealed a significant increase of the ketone body β-hydroxybutyrate and of the TCA intermediate α-ketoglutarate in the metformin-containing arm. A significant relationship was found between the follow-up levels of homocysteine and the ability of treatment arms to achieve a pathological complete response (pCR). In the metformin-containing arm, patients with significant elevations of homocysteine tended to have a higher probability of pCR. The addition of metformin to an established anti-cancer therapeutic regimen causes a fasting-mimicking modification of systemic host metabolism. Circulating homocysteine could be explored as a clinical pharmacodynamic biomarker linking the antifolate-like activity of metformin and biological tumor response.
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3.
Angiomammography: A review of current evidences.
Dromain, C, Vietti-Violi, N, Meuwly, JY
Diagnostic and interventional imaging. 2019;(10):593-605
Abstract
Although mammography is currently the imaging technique of choice for screening and diagnosis, it has some limitations, especially in patients with high-density breasts. The evolution from film screen to full-field digital mammography has recently led to the development of new imaging techniques, which are less expensive and widely available. Contrast-enhanced spectral mammography (CESM) is one of them, coupling X-ray breast imaging to the intravenous administration of an iodinated contrast material. CESM provides both morphological information, similar to mammography, and functional information of tumor perfusion. In this review, the imaging technique, the specificity of interpretation of CESM compared to MRI and the currently available data are presented. The clinical performances of CESM versus those of mammography and MRI and its additional value in preoperative local assessment and screening is discussed. The potential advantages and disadvantages are mentioned and we also discuss how CESM contributes to the detection of lesions and how it can be used in daily clinical workflow.
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4.
Non-muscle myosin IIA is post-translationally modified by interferon-stimulated gene 15 in breast cancer cells.
Cruz-Ramos, E, Macías-Silva, M, Sandoval-Hernández, A, Tecalco-Cruz, AC
The international journal of biochemistry & cell biology. 2019;:14-26
Abstract
ISG15 (interferon-stimulated gene 15) exists as free ISG15 or conjugated ISG15 modifying its target proteins via ISGylation. Few proteins have been identified and studied as ISGylation targets, and their relevance is not completely clear. Here, we isolated ISG15 from MDA-MB-231 breast cancer cells using immunoprecipitation and identified non-muscle myosin IIA (NMIIA) using mass spectrometry as endogenously associated with ISG15. The identification of NMIIA as an ISG15-interacting protein was important, because levels of NMIIA mRNA were not deregulated in all breast cancers, and because our in silico analysis indicated that NMIIA was the target of different posttranslational modifications and had an interactome associated with cytoskeletal remodeling. Furthermore, our experimental assays of co-immunoprecipitation and immunofluorescence confirmed that ISG15 was covalently associated with NMIIA in the cytoplasm of breast cancer cells and that interferon γ (IFN-γ) increased this association without alterations in the NMIIA levels. Thus, NMIIA ISGylation is regulated by IFN-γ, and this modification may modulate its interactions with proteins that remodel the cytoskeleton, participating in the growth and progression of mammary tumors.
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5.
A Review on Targeting Nanoparticles for Breast Cancer.
Alqaraghuli, HGJ, Kashanian, S, Rafipour, R
Current pharmaceutical biotechnology. 2019;(13):1087-1107
Abstract
Chemotherapeutic agents have been used extensively in breast cancer remedy. However, most anticancer drugs cannot differentiate between cancer cells and normal cells, leading to toxic side effects. Also, the resulted drug resistance during chemotherapy reduces treatment efficacy. The development of targeted drug delivery offers great promise in breast cancer treatment both in clinical applications and in pharmaceutical research. Conjugation of nanocarriers with targeting ligands is an effective therapeutic strategy to treat cancer diseases. In this review, we focus on active targeting methods for breast cancer cells through the use of chemical ligands such as antibodies, peptides, aptamers, vitamins, hormones, and carbohydrates. Also, this review covers all information related to these targeting ligands, such as their subtypes, advantages, disadvantages, chemical modification methods with nanoparticles and recent published studies (from 2015 to present). We have discussed 28 different targeting methods utilized for targeted drug delivery to breast cancer cells with different nanocarriers delivering anticancer drugs to the tumors. These different targeting methods give researchers in the field of drug delivery all the information and techniques they need to develop modern drug delivery systems.
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6.
Calcium electroporation and electrochemotherapy for cancer treatment: Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy.
Hoejholt, KL, Mužić, T, Jensen, SD, Dalgaard, LT, Bilgin, M, Nylandsted, J, Heimburg, T, Frandsen, SK, Gehl, J
Scientific reports. 2019;(1):4758
Abstract
Calcium electroporation is a novel anti-cancer treatment investigated in clinical trials. We explored cell sensitivity to calcium electroporation and electroporation with bleomycin, using viability assays at different time and temperature points, as well as heat calorimetry, lipidomics, and flow cytometry. Three cell lines: HT29 (colon cancer), MDA-MB231 (breast cancer), and HDF-n (normal fibroblasts) were investigated for; (a) cell survival dependent on time of addition of drug relative to electroporation (1.2 kV/cm, 8 pulses, 99 µs, 1 Hz), at different temperatures (37 °C, 27 °C, 17 °C); (b) heat capacity profiles obtained by differential scanning calorimetry without added calcium; (c) lipid composition by mass spectrometry; (d) phosphatidylserine in the plasma membrane outer leaflet using flow cytometry. Temperature as well as time of drug administration affected treatment efficacy in HT29 and HDF-n cells, but not MDA-MB231 cells. Interestingly the HT29 cell line displayed a higher phase transition temperature (approximately 20 °C) versus 14 °C (HDF-n) and 15 °C (MDA-MB231). Furthermore the HT29 cell membranes had a higher ratio of ethers to esters, and a higher expression of phosphatidylserine in the outer leaflet. In conclusion, lipid composition and heat capacity of the membrane might influence permeabilisation of cells and thereby the effect of calcium electroporation and electrochemotherapy.
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7.
Tailoring the Chemical Modification of Chitosan Hydrogels to Fine-Tune the Release of a Synergistic Combination of Chemotherapeutics.
Schneible, JD, Singhal, A, Lilova, RL, Hall, CK, Grafmüller, A, Menegatti, S
Biomacromolecules. 2019;(8):3126-3141
Abstract
Combination chemotherapy with a defined ratio and sequence of drug release is a clinically established and effective route to treat advanced solid tumors. In this context, a growing body of literature demonstrates the potential of hydrogels constructed with chemically modified polysaccharides as depots for controlled release of chemotherapeutics. Identifying the appropriate modification in terms of physicochemical properties of the functional group and its degree of substitution (χ) to achieve the desired release profile for multiple drugs is, however, a complex multivariate problem. To address this issue, we have developed a computational toolbox that models the migration of a drug pair through a hydrated network of polysaccharide chains modified with hydrophobic moieties. In this study, we chose doxorubicin (DOX) and Gemcitabine (GEM) as model drugs, as their synergistic effect against breast cancer has been thoroughly investigated, and chitosan as the model polymer. Our model describes how the modification of chitosan chains with acetyl, butanoyl, and heptanoyl moieties at different values χ governs both the structure of the hydrogel network and drug migration through it. Our experimental data confirm the in silico predictions for both single- and dual-drug release and, most notably, the counterintuitive inversion of release vs χ that occurs when switching from a single- to a dual-drug system. Consensus between predicted and experimental data indicates that acetyl modifications (χ = 32-42%) and butanoyl modifications (χ = 19-24%) provide synergistic GEM/DOX release molar ratios (i.e., 5-10). Collectively, these results demonstrate the potential of this model in guiding the design of chemotherapeutic hydrogels to combat cancer.
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8.
Effect of cimicifuga racemosa on menopausal syndrome caused by LHRH-a in breast cancer.
Wang, C, Huang, Q, Liang, CL, Zhang, YW, Deng, DH, Yu, Y, Chen, DB, Yang, HJ, Yu, XF
Journal of ethnopharmacology. 2019;:111840
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cimicifuga racemose is previously proved effective on nature menopausal syndrome (MPS). However, its clinical value in treating with MPS induced by luteinizing-hormone releasing hormone analogue (LHRH-a) therapy of pre-/peri-menopausal breast cancer patients is still unknown. AIM OF STUDY This perspective randomised-design study is to investigate the effect and safety of cimicifuga racemosa on MPS induced by LHRH-a in breast cancer (clinical trial registered: NCT03339882). MATERIALS AND METHODS Breast cancer patients planning for LHRH-a treatment were randomly divided into 2 groups. The control group which was being treated with the standard treatment of LHRH-a. The other group was being treated with Remifemin, the commercialized product of cimicifuga racemose extract, combined with LHRH-a, called Remifemin group. Our main endpoint was Kupperman menopause index (KMI). Hormone levels in peripheral blood and gynecological complications were also evaluated. RESULTS Totally, 85 patients (42 in Remifemin group and 43 in control group) were enrolled in Zhejiang Cancer Hospital. At the 4th, 8th and 12th week after using LHRH-a, the KMI were all significantly lower in Remifemin group than in control group (P < 0.01), while the hormone levels, including estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were similar in the two groups. In addition, the incidence of cervical cyst in Remifemin group was higher than that in control group (P = 0.02), and there was no significant difference in the other gynecological complications, including endometrial thickening, ovarian cyst or uterine fibroid (P > 0.05). CONCLUSIONS Cimicifuga racemose is effective, oncological safe and reliable for treatment of MPS caused by LHRH-a in breast cancer.
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9.
Associations between Dietary Acid Load and Biomarkers of Inflammation and Hyperglycemia in Breast Cancer Survivors.
Wu, T, Seaver, P, Lemus, H, Hollenbach, K, Wang, E, Pierce, JP
Nutrients. 2019;(8)
Abstract
Metabolic acidosis can lead to inflammation, tissue damage, and cancer metastasis. Dietary acid load contributes to metabolic acidosis if endogenous acid-base balance is not properly regulated. Breast cancer survivors have reduced capacities to adjust their acid-base balance; yet, the associations between dietary acid load and inflammation and hyperglycemia have not been examined among them. We analyzed data collected from 3042 breast cancer survivors enrolled in the Women's Healthy Eating and Living (WHEL) Study who had provided detailed dietary intakes and measurements of plasma C-reactive protein (CRP) and hemoglobin A1c (HbA1c). Using a cross-sectional design, we found positive associations between dietary acid load and plasma CRP and HbA1c. In the multivariable-adjusted models, compared to women with the lowest quartile, the intakes of dietary acid load among women with the highest quartile showed 30-33% increases of CRP and 6-9% increases of HbA1c. Our study is the first to demonstrate positive associations between dietary acid load and CRP and HbA1c in breast cancer survivors. Our study identifies a novel dietary factor that may lead to inflammation and hyperglycemia, both of which are strong risk factors for breast cancer recurrence and comorbidities.
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10.
Low-Fat Dietary Pattern among Postmenopausal Women Influences Long-Term Cancer, Cardiovascular Disease, and Diabetes Outcomes.
Prentice, RL, Aragaki, AK, Howard, BV, Chlebowski, RT, Thomson, CA, Van Horn, L, Tinker, LF, Manson, JE, Anderson, GL, Kuller, LE, et al
The Journal of nutrition. 2019;(9):1565-1574
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Abstract
BACKGROUND The preferred macronutrient dietary composition, and the health consequences of dietary fat reduction specifically, have been debated for decades. Here we provide a comprehensive overview of long-term health outcomes in the Women's Health Initiative Dietary Modification (DM) trial. OBJECTIVE The DM trial aimed to examine whether a low-fat dietary pattern would reduce the risk of invasive breast cancer, colorectal cancer, and, secondarily, coronary heart disease (CHD), with various other health outcomes also considered. METHODS The DM trial is a randomized controlled trial conducted at 40 centers in the US, among 48,835 postmenopausal women aged 50-79 y with baseline intake of ≥32% energy from fat. Participants were randomly assigned to a low-fat dietary pattern intervention group or to a usual-diet comparison group, during 1993-1998. Intervention goals were to reduce fat intake from ∼35% to 20% of total energy, in conjunction with increasing vegetables and fruit to 5 servings/d and grains to 6 servings/d. RESULTS Over an 8.5-y (median) intervention period, intervention and comparison group differences included lower fat by 8-10%, and higher carbohydrate by 8-10%, of total energy, in conjunction with higher consumption of vegetables, fruit, and grains. Time-to-outcome analyses did not show significant differences between intervention and comparison groups for invasive breast cancer, colorectal cancer, or CHD, either over the intervention period or over longer-term cumulative follow-up. Additional analyses showed significant intervention group benefits related to breast cancer, CHD, and diabetes, without adverse effects. Over a 19.6-y (median) follow-up period, HRs (95% CIs) were 0.84 (0.74, 0.96) for breast cancer followed by death, and 0.87 (0.77, 0.98) for diabetes requiring insulin. CONCLUSIONS Reduction in dietary fat with corresponding increase in vegetables, fruit, and grains led to benefits related to breast cancer, CHD, and diabetes, without adverse effects, among healthy postmenopausal US women. UNLABELLED This trial was registered at clinicaltrials.gov as NCT00000611.