Search Results (56)

Although thymoquinone (TQ) has been reported as an anti-tumor small molecule well investigated in numerous tumors. In this study, we designed and synthesized a novel TQ derivative, TQFL28, with a molecular formula of C₂₀H₂₃NO₂. TQFL28 showed stronger cytotoxicity or anti-proliferative activities against triple-negative breast cancer (TNBC) cell lines (BT549, MDA-MB-231, or 4T1) than TQ but is lower in the normal mammary epithelial cells, MCF10A. TQFL28 exhibited lower IC₅₀ values toward BT549 (38.78 ± 1.589) and MDA-MB-231 (39.63 ± 1.598) cells compared to TQ, indicating its efficacy for TNBC cytotoxicity. TQFL28 inhibited the growth, migration, and invasiveness of TNBC cells of 4T1 and BT549 in vitro and tumor progression and metastasis in a 4T1 allograft animal model in vivo. Moreover, TQFL28 presents lower toxicity than TQ in mice, showing a 7-day half-lethal dose (LD₅₀) of 59.43 mg/kg (41.6–83.6, 95% confidence interval). Altogether, our study obtained. In addition, TQFL28 induced a significant reduction in tumor volumes in the mouse model in comparison to the vehicle group. TQFL28, a novel small molecule, has a superior inhibitory effect and lower toxicity on TNBC both in vitro and in vivo. Thus, TQFL28 might have potential as a therapeutic small molecule for breast cancer, especially in TNBC. Full article

Background/Objective: Breast cancer remains the most common malignancy among women worldwide, contributing to high morbidity and mortality rates. Many anti-cancer drugs have been derived from medicinal plants, and frankincense from Boswellia carterii is notable for its anti-inflammatory, anti-neoplastic, and anti-carcinogenic properties. Using gas chromatography/mass spectrometry (GC/MS), 48 components were identified in B. carterii essential oil, and the major constituent was α-pinene (35.81%). Method: In this study, we investigated the anti-tumor effects of frankincense essential oil (FEO) and its nano-formulation with chitosan (FEO-CSNPs) using in vitro breast cancer models (MCF-7, MDA-MB-231, and 4T1 cells) and in vivo mouse mammary carcinoma (4T1) models (Balb/c). Results: The results showed significant reductions in cell viability. At 10 μg/mL, the FEO showed the highest reduction in the C-166 cells, while at 100 μg/mL, the FEO exhibited a stronger cytotoxicity in the MDA-MB-231 and 4T1 cells compared to the FEO-CSNPs and CSNPs. The FEO-CSNPs exhibited cell growth arrest in the S, G2/M, and G1/S phases in the MCF-7, MDA-MB-231, and 4T1 cell lines (36.91%, 23.12%, and 33.58%), in addition to increased apoptosis rates in the MCF-7, MDA-MB-231, and 4T1 cell lines (33.04%, 36.39%, and 42.19%). The wound healing assays revealed a decreased migratory ability in the treated cells. The in vivo experiments in the balb/c mice demonstrated a reduction in the tumor volume, with a histopathological analysis confirming extensive tumor necrosis. Moreover, the FEO and FEO-CSNPs showed notable antioxidant and arginase activity. The gene expression analysis via qPCR indicated the upregulation of tumor suppressor genes and the downregulation of oncogenes. Conclusions: These findings suggest that FEO and its nano-formulation, particularly in the form of FEO-CSNPs as an oral formulation, display enhanced efficacy, warranting further preclinical and clinical research to develop innovative treatment strategies. Full article

This study investigates the effects of xylitol, a natural sugar alcohol, on tumor progression in syngeneic mouse cancer models. Xylitol is known for its dental health benefits, but emerging evidence suggests broader biological roles, including potential anti-cancer properties. We explored xylitol’s impact on two mouse cancer models: 4T1 mammary carcinoma and B16F10 melanoma. Xylitol’s efficacy in inhibiting cancer cell lines and modulating tumor progression was assessed using immunocompetent female mice. The experiments involved intratumoral and peritumoral administration of a 20% xylitol solution in two mouse strains: BALB/c (4T1 mammary carcinoma) and C57BL/6 (B16F10 melanoma). Tumor volume, histopathology, and metabolomic analyses were conducted to gauge xylitol’s influence. The study revealed that xylitol administration initially reduced tumor growth in the B16F10 melanoma model, accompanied by alterations in tumor metabolism. However, similar effects were not observed in the 4T1 mammary carcinoma model, and melanoma tumor growth re-commenced in the melanoma model after stroma deterioration caused xylitol solution leakage. These findings suggest that xylitol may have potential as an adjunct therapy in cancer treatment, specifically in melanoma. The differential response between the two cancer models underscores the complexity of cancer biology and the need for further investigation into xylitol’s mechanisms of action and its role in cancer therapy. Full article

(1) Background: The percentage of breast augmentations has increased in recent years alongside the frequency of implant removals. Musculoskeletal and postural disorders are often overlooked during this removal process. Research indicates that excess anterior load from breast implants can disrupt postural control and potentially lead to short- or long-term musculoskeletal dysfunction. This study aims to evaluate the immediate changes in postural control after artificial breast augmentation in healthy female volunteers. (2) Methods: Spinal angles, the center of pressure (CoP), and electromyographic activity of the spinal muscles were recorded in the static position and during the functional reach test (FRT) without and with implants of different volumes (220 mL, 315 mL, and 365 mL). Subjective perceptions of effort, comfort, weight, and performance in the FRT were also assessed. (3) Results: Statistical differences were significant in the scapular elevator during the one-minute standing position (lower activation with the 220 mL implant compared to the control and 315 mL) and in the trapezius muscles during the FRT (lower activation in the upper trapezius in the 315 mL vs. control in the reach phase and 220 mL vs. control in the return phase and higher activation in the lower trapezius in the 315 and 365 mL vs. control in the reach phase). Additionally, significant differences were identified in the performance of the FRT and the associated subjective perceptions. (4) Conclusions: Breast implants with sizes of 220, 315, and 365 mL can alter scapular neuromuscular control, but these differences do not seem substantial enough to result in negative biomechanical effects in the short-term analysis. Full article

This pre-clinical study was designed to demonstrate how vascular disrupting agents (VDAs) should be administered, either alone or when combined with radiation in clinically relevant fractionated radiation schedules, for the optimal anti-tumor effect. CDF1 mice, implanted in the right rear foot with a 200 mm³ murine C3H mammary carcinoma, were injected with various doses of the most potent VDA drug, combretastatin A-1 phosphate (CA1P), under different schedules. Tumors were also locally irradiated with single-dose, or stereotactic (3 × 5–20 Gy) or conventional (30 × 2 Gy) fractionation schedules. Tumor growth and control were the endpoints used. Untreated tumors had a tumor growth time (TGT5; time to grow to 5 times the original treatment volume) of around 6 days. This increased with increasing drug doses (5–100 mg/kg). However, with single-drug treatments, the maximum TGT5 was only 10 days, yet this increased to 19 days when injecting the drug on a weekly basis or as three treatments in one week. CA1P enhanced radiation response regardless of the schedule or interval between the VDA and radiation. There was a dose-dependent increase in radiation response when the combined with a single, stereotactic, or conventional fractionated irradiation, but these enhancements plateaued at around a drug dose of 25 mg/kg. This pre-clinical study demonstrated how VDAs should be combined with clinically applicable fractionated radiation schedules for the optimal anti-tumor effect, thus suggesting the necessary pre-clinical testing required to ultimately establish VDAs in clinical practice. Full article

Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3 to 5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMECs) at 2.5% w/v, and it was found that MH reduced the proliferation of MCF-7 cells but not that of HMECs. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, the effects of MH induced the activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose-dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro, which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions. Full article

Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are highly aggressive neoplastic diseases that share numerous characteristics. In IBC and IMC, chemotherapy produces a limited pathological response and anti-androgen therapies have been of interest for breast cancer treatment. Therefore, the aim was to evaluate the effect of a therapy based on bicalutamide, a non-steroidal anti-androgen, with doxorubicin and docetaxel chemotherapy on cell proliferation, migration, tumor growth, and steroid-hormone secretion. An IMC-TN cell line, IPC-366, and an IBC-TN cell line, SUM149, were used. In vitro assays revealed that SUM149 exhibited greater sensitivity, reducing cell viability and migration with all tested drugs. In contrast, IPC-366 exhibited only significant in vitro reductions with docetaxel as a single agent or in different combinations. Decreased estrogen levels reduced in vitro tumor growth in both IMC and IBC. Curiously, doxorubicin resulted in low efficacy, especially in IMC. In addition, all drugs reduced the tumor volume in IBC and IMC by increasing intratumoral testosterone (T) levels, which have been related with reduced tumor progression. In conclusion, the addition of bicalutamide to doxorubicin and docetaxel combinations may represent a potential treatment for IMC and IBC. Full article

Proton therapy presents a promising modality for treating left-sided breast cancer due to its unique dose distribution. Helium ions provide increased conformality thanks to a reduced lateral scattering. Consequently, the potential clinical benefit of both techniques was explored. An explorative treatment planning study involving ten patients, previously treated with VMAT (Volumetric Modulated Arc Therapy) for 50 Gy in 25 fractions for locally advanced, node-positive breast cancer, was carried out using proton pencil beam therapy with a fixed relative biological effectiveness (RBE) of 1.1 and helium therapy with a variable RBE described by the mMKM (modified microdosimetric kinetic model). Results indicated that target coverage was improved with particle therapy for both the clinical target volume and especially the internal mammary lymph nodes compared to VMAT. Median dose value analysis revealed that proton and helium plans provided lower dose on the left anterior descending artery (LAD), heart, lungs and right breast than VMAT. Notably, helium therapy exhibited improved ipsilateral lung sparing over protons. Employing NTCP models as available in the literature, helium therapy showed a lower probability of grade ≤ 2 radiation pneumonitis (22% for photons, 5% for protons and 2% for helium ions), while both proton and helium ions reduce the probability of major coronary events with respect to VMAT. Full article

Numerous factors not consistently identified in pregnancy are linked with decreased breastfeeding exclusivity and durations. These factors may be considered in three domains: the anatomical, metabolic, and psychosocial domains. As fundamental research into lactation has increased, it is now often possible to identify or speculate the mechanisms by which these factors potentially reduce milk production. The first domain describes the anatomical characteristics of the breast, including intrinsic factors such as hypoplasia (underdevelopment), which may have a genetic component and can be masked by breast augmentation surgery. Hypoplasia has long been associated with the inability to make a full milk production that satisfyies the infant’s needs, although it is not possible to predict a woman’s 24-h milk production so that appropriate complementary feeds can be advised. Extrinsic causes such as breast reduction surgery impact the volume of glandular tissue, thereby reducing the synthetic capacity of the breast. Whereas nipple piercings may damage milk ducts, obstructing milk flow from the breast and thereby reducing milk supply via the autocrine pathway. Various maternal metabolic disorders (intrinsic) comprise the second domain, which includes conditions such as gestational diabetes mellitus, type 1 and 2 diabetes, polycystic ovarian syndrome (often undiagnosed), and hypothyroidism. The aberrant levels of hormones associated with these disorders, such as insulin, are also implicated in breast development, raising the possibility of reduced mammary growth in pregnancy and, consequently, milk production. Much more research is needed in this area, not only to understand mechanisms by which lactation is impacted but also to identify the women at risk of reduced lactation capacity. The third and final domain includes psychosocial issues such as short intended breastfeeding durations, a lack of breastfeeding support, and maternal anxiety and depression. With respect to anxiety and depression, their association with reduced breastfeeding is likely multifaceted, encompassing mood and the potential biochemical changes associated with these states, such as lower levels of circulating oxytocin and higher cortisol levels. Possessing a knowledge of the negative impacts of the intrinsic and extrinsic factors within the maternal anatomical, metabolic, and psychosocial domains provides the impetus for antenatal lactation screening. The antenatal identification of risk factors enables anticipatory guidance and education during pregnancy, as well as early postpartum intervention should breastfeeding issues occur. Full article

Animal models show a more rapid mammary gland response and more milk with subsequent lactations, as well as impairment of lactation performance by obesity. Whilst maternal obesity is linked to reduced breastfeeding initiation, breastfeeding confidence, and duration as well as early introduction of formula, maternal adiposity, breast anatomy and milk production (MP) have not been assessed in this population. Thirty-four lactating mothers 1–6 months postpartum and with BMI range of 17–35 kg/m² participated in this study. We conducted ultrasound examination imaging to assess breast anatomy. The amount of glandular tissue (glandular tissue representation (GTR)) was classified as low, moderate, or high. Number and diameters of milk ducts as well as mammary blood flow (the resistive index) were measured. Maternal bra cup volume was calculated from current bra size. Maternal body composition was measured with bioimpedance spectroscopy. Mothers completed a questionnaire regarding their medical, obstetric and lactation history, and conducted a 24 h MP study to enable calculation of total volume, average and maximum feed volumes and breast storage capacity (24 h MP parameters). For statistical analysis, we used the correlation networks method (directions of multiple significant correlations are reported). Correlation networks show that pathways culminating in either high or low MP start as early as puberty. In this study, later menarche correlates with the absence of breast growth during both puberty and pregnancy, which further correlate with lower numbers of ducts and smaller diameters. Higher maternal adiposity correlates with larger bra cup volume (both correlate with absence of breast growth during pregnancy and low GTR) and lower 24 h MP parameters. Larger numbers of ducts and duct diameters correlate with higher parity and longer durations of previous lactations, and higher 24 h MP parameters. Mammary blood flow shows no correlations. Findings from this cross-sectional study corroborate animal studies showing that a number of modifiable and non-modifiable maternal factors may impact breast development and MP. Further research may inform interventions, such as maintaining healthy adiposity not only during pre-conception, pregnancy, and lactation, but as early as childhood and potentially infancy. Moreover, the results provide rationale for antenatal lactation assessment of women and intervention in high-risk mothers to ensure they reach their full lactation potential. Full article

Background: Magnetic resonance imaging (MRI) is a non-invasive imaging modality which, in conjunction with biopsies, provide a qualitative assessment of tumor response to treatment. Intravenous injection of contrast agents such as fluorine (¹⁹F) nanoemulsions labels systemic macrophages, which can, then, be tracked in real time with MRI. This method can provide quantifiable insights into the behavior of tumor-associated macrophages (TAMs) in the tumor microenvironment and macrophage recruitment during therapy. Methods: Female mice received mammary fat pad injections of murine breast or colon cancer cell lines. The mice then received an intravenous ¹⁹F nanoemulsion injection, followed by a baseline ¹⁹F MRI. For each cancer model, half of the mice then received 8 Gy of localized radiation therapy (RT), while others remained untreated. The mice were monitored for two weeks for tumor growth and ⁹F signal using MRI. Results: Across both cohorts, the RT-treated groups presented significant tumor growth reduction or arrest, contrary to the untreated groups. Similarly, the fluorine signal in treated groups increased significantly as early as four days post therapy. The fluorine signal change correlated to tumor volumes irrespective of time. Conclusion: These results demonstrate the potential of ¹⁹F MRI to non-invasively track macrophages during radiation therapy and its prognostic value with regard to tumor growth. Full article

Due to climate change, diverse territories of the planet will suffer from water restrictions. Goats are perceived as the most resilient ruminants in this scenario. So, various studies have focused on describing how a lower water intake influences milk production, especially in breeds adapted to desert environments. In water-stress situations, goats lose up to 32% of their body weight (BW), the rate of passage is reduced, and the digestibility of the feed increases. When goats consume water again, the rumen prevents hemolysis and osmotic shock from occurring. Regarding milk production, the response varies depending on the breed and the level of water restriction, maintaining the milk volume or reducing it by up to 41%. Systemically, it decreases the urinary volume and glomerular filtration rate, increasing blood osmolality and the vasopressin (ADH) concentration. Studies are scarce regarding changes in blood flow to the mammary gland, but there would be a reduction in blood flow velocity of up to 40% without changing blood pressure. New studies must be undertaken to determine which breeds or crosses are the best adapted to changing environmental conditions and to improve our understanding of the changes that occur at the morphophysiological level of the caprine mammary gland. Full article

Background: Multimodality is required for the treatment of breast cancer. Surgery, radiation (RT), and systemic therapy were traditionally used. Pharmacotherapy includes different drug mechanisms, such as chemotherapy, hormone therapy, and targeted therapies, alone or in combination with radiotherapy. While radiation offers numerous benefits, it also has certain harmful risks. such as cardiac and pulmonary toxicity, lymphedema, and secondary cancer. Modern radiation techniques have been developed to reduce organs at risk (OAR) doses. Materials and Methods: This study is a prospective feasibility trial conducted at the Fayium Oncology Center on patients with left breast cancer receiving adjuvant locoregional radiotherapy after either breast conservative surgery (BCS) or modified radical mastectomy (MRM). This study aimed to assess the proportion of patients who are fit both physically and intellectually to undergo breast radiotherapy using the deep inspiratory breath-holding (DIBH) technique, comparing different dosimetric outcomes between the 3D dimensional conformal with DIBH and 4D-CT IMRT plans of the same patient. Results: D95 of the clinical target volume (CTV) of the target is significantly higher in the 3D DIBH plan than in the IMRT plan, with an average of 90.812% vs. 86.944%. The dosimetry of the mean heart dose (MHD) in the 4D-CT IMRT plan was significantly lower than in the 3D conformal with the DIBH plan (2.6224 vs. 4.056 Gy, p < 0.0064), and no significant difference between the two plans regarding mean left anterior descending artery (LAD) (14.696 vs. 13.492 Gy, p < 0.58), maximum LAD (39.9 vs. 43.5 Gy, p < 0.35), and V20 of the ipsilateral lung (18.66% vs. 16.306%, p < 0.88) was observed. Internal mammary chain (IMC) irradiation was better in the 4D-CT IMRT plan. Conclusions: Radiotherapy of the breast and chest wall with the 4D-CT IMRT technique appears not to be inferior to the 3D conformal with the DIBH technique and can be used as an alternative to the 3D conformal with the DIBH technique in patients meeting the exclusion criteria for performing the DIBH maneuver concerning coverage to target volumes or unacceptably high doses to OAR. Full article

Objectives: Breast density is considered an independent risk factor for the development of breast cancer. This study aimed to quantitatively assess the percent breast density (PBD) and the mammary glands volume (MGV) according to the patient’s age and breast quadrant. We propose a regression model to estimate PBD and MGV as a function of the patient’s age. Methods: The breast composition in 1027 spiral breast CT (BCT) datasets without soft tissue masses, calcifications, or implants from 517 women (57 ± 8 years) were segmented. The breast tissue volume (BTV), MGV, and PBD of the breasts were measured in the entire breast and each of the four quadrants. The three breast composition features were analyzed in the seven age groups, from 40 to 74 years in 5-year intervals. A logarithmic model was fitted to the BTV, and a multiplicative inverse model to the MGV and PBD as a function of age was established using a least-squares method. Results: The BTV increased from 545 ± 345 to 676 ± 412 cm³, and the MGV and PBD decreased from 111 ± 164 to 57 ± 43 cm³ and from 21 ± 21 to 11 ± 9%, respectively, from the youngest to the oldest group (p < 0.05). The average PBD over all ages were 14 ± 13%. The regression models could predict the BTV, MGV, and PBD based on the patient’s age with residual standard errors of 386 cm³, 67 cm³, and 13%, respectively. The reduction in MGV and PBD in each quadrant followed the ones in the entire breast. Conclusions: The PBD and MGV computed from BCT examinations provide important information for breast cancer risk assessment in women. The study quantified the breast mammary gland reduction and density decrease over the entire breast. It established mathematical models to estimate the breast composition features—BTV, MGV, and PBD, as a function of the patient’s age. Full article

Breast cancer, due to its high incidence and mortality, is a public health problem worldwide. Current chemotherapy uses non-specific cytotoxic drugs, which inhibit tumor growth but cause significant adverse effects. (−)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids. It is widely distributed in the plant kingdom; it can be found in green tea, grapes, and cocoa. Several studies in animals and humans have shown that EC induces beneficial effects in the skeletal muscle and the cardiovascular system, reducing risk factors such as arterial hypertension, endothelial dysfunction, damage to skeletal muscle structure, and mitochondrial malfunction by promoting mitochondrial biogenesis, with no adverse effects reported. Recently, we reported that EC had an antitumor effect in a murine triple-negative mammary gland tumor model, decreasing tumoral size and volume and increasing survival by 44%. This work aimed to characterize the effects of flavanol EC on proliferation, migration, and metastasis markers of triple-negative murine breast (4T1) cancer cells in culture. We found proliferation diminished and Bax/Bcl2 ratio increased. When the migration of culture cells was evaluated, we observed a significant reduction in migration. Also, the relative expression of the genes associated with metastasis, Cdh1, Mtss1, Pten, Bmrs, Fat1, and Smad4, was increased. In conclusion, these results contribute to understanding molecular mechanisms activated by EC that can inhibit metastatic-associated proliferation, migration, and invasion of murine breast cancer cells. Full article