Splenic Elemental Composition of Breast Cancer-Suffering Rats Supplemented with Pomegranate Seed Oil and Bitter Melon Extract.

The aim of this study was to investigate how dietary modifications with pomegranate seed oil (PSO) and bitter melon aqueous extract (BME) affect mineral content in the spleen of rats both under normal physiological conditions and with coexisting mammary tumorigenesis. The diet of Sprague-Dawley female rats was supplemented either with PSO or with BME, or with a combination for 21 weeks. A chemical carcinogen (7,12-dimethylbenz[a]anthracene) was applied intragastrically to induce mammary tumors. In the spleen of rats, the selected elements were determined with a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). ANOVA was used to evaluate differences in elemental composition among experimental groups. Multivariate statistical methods were used to discover whether some subtle dependencies exist between experimental factors and thus influence the element content. Experimental factors affected the splenic levels of macroelements, except for potassium. Both diet modification and the cancerogenic process resulted in significant changes in the content of Fe, Se, Co, Cr, Ni, Al, Sr, Pb, Cd, B, and Tl in rat spleen. Chemometric analysis revealed the greatest impact of the ongoing carcinogenic process on the mineral composition of the spleen. The obtained results may contribute to a better understanding of peripheral immune organ functioning, especially during the neoplastic process, and thus may help develop anticancer prevention and treatment strategies.

Label-free Raman spectroscopy reveals tumor microenvironmental changes induced by intermittent fasting for the prevention of breast cancer in animal model.

The development of tools that can provide a holistic picture of the evolution of the tumor microenvironment in response to intermittent fasting on the prevention of breast cancer is highly desirable. Here, we show, for the first time, the use of label-free Raman spectroscopy to reveal biomolecular alterations induced by intermittent fasting in the tumor microenvironment of breast cancer using a dimethyl-benzanthracene induced rat model. To quantify biomolecular alterations in the tumor microenvironment, chemometric analysis of Raman spectra obtained from untreated and treated tumors was performed using multivariate curve resolution-alternative least squares and support vector machines. Raman measurements revealed remarkable and robust differences in lipid, protein, and glycogen content prior to morphological manifestations in a dynamically changing tumor microenvironment, consistent with the proteomic changes observed by quantitative mass spectrometry. Taken together with its non-invasive nature, this research provides prospective evidence for the clinical translation of Raman spectroscopy to identify biomolecular variations in the microenvironment induced by intermittent fasting for the prevention of breast cancer, providing new perspectives on the specific molecular effects in the tumorigenesis of breast cancer.

Body weight gain and control: beneficial effect of extra virgin olive oil versus corn oil in an experimental model of mammary cancer.

Obesity is a known risk factor for breast cancer, the most common malignancy among women worldwide. We have previously described different effects of high-fat diets on mammary experimental carcinogenesis. In this work, we analyzed the animal growth data obtained in six experimental assays, in healthy and carcinogen-induced rats undergoing different dietary interventions. The animals were fed with three experimental diets administered at different periods of development: a control low-fat diet, and two isocaloric high-fat diets (rich in corn oil or in extravirgin olive oil -EVOO-). Weekly weight throughout the development of 818 animals have been compiled and reanalyzed using adjusted mathematical models. Molecular mechanisms have been investigated: ethanolamides in small intestine, neuropeptides controlling satiety in hypothalamus, and proteins controlling lipid metabolism in adipose and mammary tissues. The results indicated that the effect of diets depended on type of lipid, timing of intervention and health status. The high corn oil diet, but not the high EVOO diet, increased body weight and mass, especially if administered from weaning, in healthy animals and in those that received a moderate dose of carcinogen. The potential protective effect of EVOO on weight maintenance may be related to anorexigenic neuropeptides such as oxytocin and lipolysis/deposition balance in adipose tissue (increasing phospho-PKA, HSL, MGL and decreasing FAS). In animals with cancer, body weight gain was related to the severity of the disease. Taken together, our results suggest that EVOO has a beneficial effect on body weight maintenance in both health and cancer.

The Role of Cancer and Somatic Stem Cells in the Anti-Inflammatory and Antitumor Effects of Aconitum baicalense Extract on Experimental Breast Cancer.

We studied the effects of the extract of the terrestrial part of Aconitum baicalense in BALB/c female mice at the early stages after the injection of N-methyl-N-nitrosourea (MNU). The extract reduced inflammatory activity and tumor growth in the mammary gland. The antitumor and anti-inflammatory effects of the extract are based on the inhibition of cancer stem cells, hematopoietic stem cells, and hematopoietic progenitor cells that promote inflammation. The extract of A. baicalense disrupted the recruitment of epithelial progenitor cells and angiogenesis precursors to the mammary gland preventing neovascularization and transformation of epithelial cells into tumor cells.

Environmental cadmium exposure facilitates mammary tumorigenesis via reprogramming gut microbiota-mediated glutamine metabolism in MMTV-Erbb2 mice.

Cadmium (Cd) is a heavy metal that has been widely reported to be linked to the onset and progression of breast cancer (BC). However, the mechanism of Cd-induced mammary tumorigenesis remains elusive. In our study, a transgenic mouse model that spontaneously develops tumors through overexpression of wild-type Erbb2 (MMTV-Erbb2) was constructed to investigate the effects of Cd exposure on BC tumorigenesis. The results showed that oral exposure to 3.6 mg/L Cd for 23 weeks dramatically accelerated tumor appearance and growth, increased Ki67 density and enhanced focal necrosis and neovascularization in the tumor tissue of MMTV-Erbb2 mice. Notably, Cd exposure enhanced glutamine (Gln) metabolism in tumor tissue, and 6-diazo-5-oxo-l-norleucine (DON), a Gln metabolism antagonist, inhibited Cd-induced breast carcinogenesis. Then our metagenomic sequencing and mass spectrometry-based metabolomics confirmed that Cd exposure disturbed gut microbiota homeostasis, especially Helicobacter and Campylobacter abundance remodeling, which altered the gut metabolic homeostasis of Gln. Moreover, intratumoral Gln metabolism profoundly increased under Cd-elevated gut permeability. Importantly, depletion of microbiota with an antibiotic cocktail (AbX) treatment led to a significant delay in the appearance of palpable tumors, inhibition of tumor growth, decrease in tumor weight, reduction in Ki67 expression and low-grade pathology in Cd-exposed MMTV-Erbb2 mice. Also, transplantation of Cd-modulated microbiota decreased tumor latency, accelerated tumor growth, increased tumor weight, upregulated Ki67 expression and exacerbated neovascularization as well as focal necrosis in MMTV-Erbb2 mice. In summary, Cd exposure induced gut microbiota dysbiosis, elevated gut permeability and increased intratumoral Gln metabolism, leading to the promotion of mammary tumorigenesis. This study provides novel insights into environmental Cd exposure-mediated carcinogenesis.

Protective Effects of Pelargonidin against DMBA-Induced Mammary Tumorigenesis in BALB/c Mice through Reduced Oxidative Stress and Lipid Anomalies.

Among luminal types of breast cancers, ER + breast cancer is the most frequently diagnosed cancer globally. ER + breast cancer is commonly treated with SERM drugs that block ER to prevent ER-mediated cancerous growth. Our previous computational screening found pelargonidin (PG) can inhibit ER-signaling with potent bioactivity and satisfactory toxicological features. The present study explored the anti-tumoral prospect of PG against DMBA-induced ER + murine mammary carcinogenesis. The female BALB/c mice were divided into control (A) and DMBA-exposed groups. Following tumor appearance, the DMBA-exposed group was divided into five groups: tumor control, PG-treated (Groups P25, P50, and P100), and tamoxifen-treated (TAM). The results indicated that PG-treatment dose-dependently reduced the mean tumor volume, reinstated body weight loss, and enhanced the percentage survival of tumor-bearing mice. In addition, we recorded a significant reduction in LPO, total cholesterol, and triglycerides and a surge in the activity of antioxidases and phase II detoxifying enzymes in PG-treated animals. PG also dose-dependently increased the serum level of unbound estradiol, an indicator of competitive ER binding by an ER agonist/antagonist. These data suggest that pelargonidin has potent anticancer potential against the animal model of ER + breast cancer that matches the efficiency of tamoxifen with conceivably fewer side effects.

Anticancer role of mango (Mangifera indica L.) peel and seed kernel extracts against 7,12- dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rats.

Breast cancer is the second leading cause of cancer death among women. The present study is an effort to reveal the antiproliferative and antioxidant actions of mango seed kernel extract (KE), peel extract (PE), and their combination (KEPE) on mammary tumors induced by 7,12 dimethylbenz[a]anthracene (DMBA). Seven groups of adult female Sprague-Dawley rats were prepared, including C: (control), DMBA: (rats were administered with DMBA), (DMBA-KE), (DMBA-PE), and (DMBA-KEPE): rats were administered with DMBA and then treated with KE, PE, and (both KE and PE), respectively, (KE) and (PE): rats were administered with KE and PE, separately. The study focused on the assessment of markers of endocrine derangement [serum 17-ß estradiol (E2)], apoptosis [caspase-3 and deoxyribonucleic acid fragmentation (DNAF)], and oxidative stress [lipid peroxidation and antioxidants (glutathione, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase)]. Histopathological examination and immunohistochemical expression of caspase-3 and estrogen receptor-α (ER-α) in mammary gland tissues (MGTs) were determined, as well as the characterization of mango extracts. The results showed that DMBA administration induced mammary tumors by increasing cell proliferation and evading apoptosis. In addition, DMBA administration caused oxidative stress by the production of reactive oxygen species, which increased lipid peroxidation and decreased cellular antioxidants, allowing cancer to progress. In contrast, treatment with DMBA-KE, DMBA-PE, or DMBA-KEPE diminished mammary tumors induced by DMBA, where they reduced oxidative stress via increased antioxidant parameters including reduced glutathione, superoxide dismutase, total glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Also, different treatments decreased proliferation through the reduction of E2, and ER-α expression levels. However, these treatments increased the apoptosis of unwanted cells as they increased caspase-3 activity and DNAF. All these changes led to the prevention of breast injuries and the reduction of mammary tumors. This demonstrates that the contents of mango extracts, especially phenolics and flavonoids, have an important role in mammary tumor treatment through their potential antioxidant, antiproliferative, proapoptotic, and anti-estrogenic effects. KE and PE administration for 4 weeks had no adverse effects. Conclusion: Each of KE, PE, and KEPE has a therapeutic effect against DMBA-induced mammary tumors via induction of apoptosis and reduction of each of the OS, proliferation, and estrogenic effects. So, they can play an important role in the pharmacological tole.

Herbal Honey Preparations of Curcuma Xanthorriza and Black Cumin Protect against Carcinogenesis through Antioxidant and Immunomodulatory Activities in Sprague Dawley (SD) Rats Induced with Dimethylbenz(a)anthracene.

BACKGROUND: Traditionally, Curcuma xanthorriza (CX), black cumin seed (BC), and honey have been used by the Indonesian people as medicinal ingredients to treat various health symptoms. CX extracts and BC have been proven in the laboratory as chemopreventive agents, antioxidants, and immunomodulators. In this study, we developed CX extract, BC oil, and honey into herbal honey preparations (CXBCH) and hypothesized that the preparations show chemopreventive activity. The purpose of the study was to determine the CXBCH potential as chemopreventive, antioxidant, and immunomodulatory. METHOD: In this experimental laboratory research, antioxidant, immunomodulatory, and cytotoxic activities were tested on human mammary cancer cell lines (T47D cells) while the chemopreventive activity of the CXBCH preparations on Sprague Dawley (SD) rats induced with dimethylbenzene(a)anthracene (DMBA). RESULTS: CXBCH preparations demonstrated immunomodulatory, antioxidant, and cytotoxic activities in T47D, Hela, and HTB-183 cells and in DMBA-induced SD rats, as the preparations inhibited tumor nodule formation, increased the number of CD4, CD8 and CD4CD25 cells, and glutathione-S-transferase (GST) activity, and decreased serum NO levels. CONCLUSIONS: CXBCH preparations display chemopreventive, antioxidant, and immunomodulatory properties.

Adolescent- and adult-initiated alcohol exposure in mice differentially promotes tumorigenesis and metastasis of breast cancer.

BACKGROUND: Alcohol exposure increases the risk of breast cancer. Alcohol consumption by adolescents is a serious social and public health issue. This study investigated the impact of adolescent alcohol consumption on mammary tumorigenesis and progression and compared it to that of adult alcohol exposure in animal models. METHODS: Female adolescent (5 weeks) and adult (8 weeks) MMTV-Wnt1 mice were exposed to alcohol either chronically or acutely. For chronic alcohol exposure, animals were fed a liquid diet containing 6.7% ethanol for 23 weeks. For acute exposure, animals were treated with ethanol (2.5 g/kg, 25% w/v) via intraperitoneal (IP) injection for 15 days. RESULTS: In control animals, the tumor latency was 18.5 to 22 weeks. Both chronic and acute alcohol exposure in adolescent mice significantly shortened the tumor latency to 9.5 and 8.4 weeks, respectively. However, adult-initiated alcohol exposure had little effect on the tumor latency. Both adolescent- and adult-initiated alcohol exposure significantly increased lung metastasis. Adolescent-initiated alcohol exposure but not adult-initiated alcohol exposure increased the breast cancer stem cell population. Adolescent-initiated alcohol exposure significantly altered the proliferation of mammary epithelial cells, ductal growth, and the formation of terminal end buds in the mammary glands. Adolescent-initiated alcohol exposure but not adult-initiated alcohol exposure increased estradiol levels in the blood. Acute adolescent alcohol exposure also significantly increased blood progesterone levels. Furthermore, adolescent-initiated alcohol exposure activated PAK1 and p38γ MAPK, critical regulators of mammary tumorigenesis and aggressiveness, respectively, while adult-initiated alcohol exposure activated only p38γ MAPK. In addition, both adolescent and adult alcohol exposure significantly decreased the levels of a prognostic marker miR200b. CONCLUSIONS: Adolescent-initiated alcohol exposure enhanced both tumorigenesis and aggressiveness of mammary tumors, while adult-initiated alcohol exposure mainly promoted tumor metastasis. Thus, adolescent mice were more sensitive than adult mice in response to alcohol-induced tumor promotion.

CEG-AgNPs Ameliorates DMBA-Induced Mammary Carcinogenicity by Alleviating Cytokines Expression.

<b>Background and Objective:</b> For more than a decade, breast cancer has been one of the most common forms of cancer among women around the world. The present article aimed to evaluate the protective activity of CEG-AgNPs against DMBA-induced mammary carcinoma. <b>Materials and Methods:</b> In this experimental study, green synthesis and characterization of CEG-AgNPs were carried as well as IC₅₀ against Mcf7 cell line and LD₅₀ on mice were evaluated. A total of 24 adult albino mice were divided into four groups six rats in each. Group I was given an equal amount of distilled water, group II was received 80 mg kg¹ b.wt., DMBA for 4 weeks, groups III and IV were treated with CEG-AgNPs (28.1 and 70.25 mg kg¹) from the 5th week of DMBA administration for 4 weeks, respectively. <b>Results:</b> CEG-AgNPs were approximately 42.32±9.52 nm with a negative zeta potential of -17.44. It is IC₅₀ against the Mcf7 cell line and LD₅₀ is equal to 82.76 µg mL¹ and 1405 mg kg¹ b.wt., A significant normalization in plasma ALT, AST, AST and LDH as well as mammary MDA, TNF-α, IL-6, P53, SOD, GPx and GSH levels have been observed in CEG-AgNPs treated mice. Oral CEG-AgNPs administration has suppressed VEGF-C gene expression in DMBA-treated mice. <b>Conclusion:</b> The present results, biochemical, histological and MRI results showed that CEG-AgNPs have potent anticancer activity against DMBA-induced mammary carcinoma in mice by inducing the biosynthesizes of antioxidant biomarkers and suppression of cytokines gene expression.

Canagliflozin interrupts mTOR-mediated inflammatory signaling and attenuates DMBA-induced mammary cell carcinoma in rats.

BACKGROUND: Breast cancer prevalence has been globally increasing, therefore, introducing novel interventions in cancer treatment is of a significant importance. The present study was designed to investigate the anti-cancer effect of Canagliflozin (CNG) in an experimental model of DMBA-induced mammary carcinoma in female rats. METHODS: 18 female rats were divided into three experimental groups: Normal control, DMBA control, DMBA+ CNG treated group. DMBA (7.5 mg/kg) was injected subcutaneously in the mammary cells twice weekly for 4 weeks and CNG (10 mg/kg) was orally administered daily for an additional 3 weeks while DMBA control rats only received the vehicle for 3 weeks. Tumors' weight and volume were measured, BRCA-1 and TAC were quantified in serum samples, mTOR, caspase-1, NFκB, IL-1ß, NLRP3, GSDMD and MDA were quantified in tumors' homogenates. RESULTS: CNG treatment increased the BRCA-1 expression, suppressed mTOR inflammatory pathway, attenuated tumor inflammatory mediators; NLRP3, GSDMD, NFκB, IL-1ß, suppressed the oxidative stress and inhibited tumor expression of the proliferation biomarker; Ki67. CONCLUSION: CNG modulated mTOR-mediated signaling pathway and attenuated pyroptotic, inflammatory pathways, suppressed oxidative stress and eventually inhibited DMBA-induced mammary carcinoma proliferation.

Ovarian status modulates endocrine and neuroinflammatory responses to a murine mammary tumor.

Patients with breast cancer have increased circulating inflammatory markers and mammary tumors increase neuroinflammation in rodent models. Menopausal status is not only important in the context of breast cancer as circulating estrogen influences tumor progression, but also because estrogen is anti-inflammatory and an essential modulator of endocrine function in the brain and body. Here, we manipulated "menopause" status (ovary-intact and ovariectomized) in an estrogen receptor (ER)+ mouse mammary tumor model to determine the extent to which ovarian status modulates: 1) tumor effects on estrogen concentrations and signaling in the brain, 2) tumor effects on estrogen-associated neurobiology and inflammation, and 3) the ability for tumor resection to resolve the effects of a tumor. We hypothesized that reduced circulating estradiol (E2) after an ovariectomy exacerbates tumor-induced peripheral and central inflammation. Notably, we observed ovarian-dependent modulation on tumor-induced peripheral outcomes, including E2-dependent processes and, to a lesser degree, circulating inflammatory markers. In the brain, ovariectomy exacerbated neuroinflammatory markers in select brain regions and modulated E2-related neurobiology due to a tumor and/or resection. Overall, our data suggest that ovarian status has moderate implications for tumor-induced alterations in neuroendocrinology and neuroinflammation and mild effects on peripheral inflammatory outcomes in this murine mammary tumor model.

Induced mammary cancer in rat models: pathogenesis, genetics, and relevance to female breast cancer.

Mammary cancer, or breast cancer in women, is a polygenic disease with a complex etiopathogenesis. While much remains elusive regarding its origin, it is well established that chemical carcinogens and endogenous estrogens contribute significantly to the initiation and progression of this disease. Rats have been useful models to study induced mammary cancer. They develop mammary tumors with comparable histopathology to humans and exhibit differences in resistance or susceptibility to mammary cancer depending on strain. While some rat strains (e.g., Sprague-Dawley) readily form mammary tumors following treatment with the chemical carcinogen, 7,12-dimethylbenz[a]-anthracene (DMBA), other strains (e.g., Copenhagen) are resistant to DMBA-induced mammary carcinogenesis. Genetic linkage in inbred strains has identified strain-specific quantitative trait loci (QTLs) affecting mammary tumors, via mechanisms that act together to promote or attenuate, and include 24 QTLs controlling the outcome of chemical induction, 10 QTLs controlling the outcome of estrogen induction, and 4 QTLs controlling the outcome of irradiation induction. Moreover, and based on shared factors affecting mammary cancer etiopathogenesis between rats and humans, including orthologous risk regions between both species, rats have served as useful models for identifying methods for breast cancer prediction and treatment. These studies in rats, combined with alternative animal models that more closely mimic advanced stages of breast cancer and/or human lifestyles, will further improve our understanding of this complex disease.

Zingiberene exerts chemopreventive activity against 7,12-dimethylbenz(a)anthracene-induced breast cancer in Sprague-Dawley rats.

Breast cancer is the primary cause of cancer-related death in females, wherein increased mortality of breast cancer patients is recorded worldwide. Zingiberene is a monocyclic sesquiterpene from the ginger plant and has many pharmacological benefits. In this exploration, we assessed the anticancer actions of Zingiberene against the 7,12-dimethylbenz(a)anthracene (DMBA)-stimulated mammary carcinogenesis in rats and MDA-MB-231 cells. Breast cancer was induced in the Female Sprague-Dawley rats through the 25 mg/kg of DMBA in 0.5 ml of corn oil and then treated with 20 and 40 mg/kg of Zingiberene, respectively. The body weight of animals and tumor volume was measured. Hematological parameters, transaminases, lipid profile, lipid peroxidation, and antioxidants status were scrutinized using standard techniques. The estrogen receptor-α and inflammatory markers were inspected by using respective assay kits. Histological damage scores were determined. In vitro experiments were conducted to scrutinize Zingiberene's effect on cell viability and apoptotic cell death in MDA-MB-231 cells. Zingiberene substantially modulated the DMBA-stimulated physiological and hematological changes and decreased the transaminases, and lipid peroxidation in the DMBA-stimulated animals. Zingiberene also elevated the antioxidant level and suppressed the inflammatory markers. Histological study revealed the protective effects of Zingiberene. The viability of MDA-MB-231 cells was noticeably diminished by the Zingiberene, thus inducing apoptotic cell death. Overall, our findings reliably proved the anticancer potential of Zingiberene against the DMBA-stimulated mammary tumorigenesis, and it could be a promising chemotherapeutic agent.

Copenhagen Rats Display Dominantly Inherited Yet Non-uniform Resistance to Spontaneous, Radiation-induced, and Chemically-induced Mammary Carcinogenesis.

BACKGROUND/AIM: Genetic and environmental factors interact to dictate the risk of cancer, and animal models are expected to provide avenues for identifying such interactions. The aim of the study was to clarify the genetic susceptibility of Copenhagen rats to spontaneous, radiation-induced, and chemically-induced mammary carcinogenesis. MATERIALS AND METHODS: Female Copenhagen and Sprague- Dawley rats and their F1 hybrids were subjected at age 7 weeks to γ-irradiation or intraperitoneal injection with 1-methyl-1-nitrosourea or were not treated, and palpable mammary tumours were diagnosed histologically. Data were pooled with previous data acquired for both nontreated and irradiated Sprague-Dawley rats. RESULTS: Radiation and 1-methyl-1-nitrosourea both significantly increased the incidence of mammary cancer in all strains. Copenhagen and F1 rats displayed a significantly lower incidence than Sprague-Dawley rats in all groups, with relatively higher incidence after irradiation. F1 rats exhibited significantly higher mammary cancer incidence than Copenhagen rats in the nontreated, but not the treated, groups. The interaction of the strain and exposure effects was suggested to be quasi-multiplicative. CONCLUSION: Copenhagen rats display non-uniform resistance to spontaneous, radiation-induced, and chemically-induced mammary carcinogenesis with dominant inheritance over Sprague-Dawley rats.

Chemopreventive Effect of Dietary Maranta arundinacea L. Against DMBA-Induced Mammary Cancer in Sprague Dawley Rats Through the Regulation of Autophagy Expression.

BACKGROUND: Breast cancer prevention still needs to be improved. Calorie restriction is thought to prevent breast cancer through the induction of autophagy. Maranta arundinacea L. (MA) has the potential for calorie restriction because it contains high fiber. This research aimed to observe the effect of dietary MA against dimethylbenz(a)anthracene (DMBA)-induced mammary cancer in Sprague Dawley rats related to autophagy. METHODS: Twenty-five Sprague Dawley rats were randomly divided into five groups: 1) control group without DMBA-induced with a standard diet, 2) 20 mg/kg BW of DMBA two times a week for five weeks with a standard diet, 3) DMBA and diet modification with 30% of MA, 4) DMBA and diet modification with 45% of MA, and 5) DMBA and diet modification with 60% of MA. Examination of the nodule was conducted once every week for 22 weeks. Breast tissue/tumor examination underwent histology examination with hematoxylin-eosin. Examinations of immunohistochemical staining against Beclin1, LC3B, and SQSTM1 were conducted to reveal autophagy. The difference of autophagy protein expression was analyzed using One way ANOVA with 95% confidence level and significance set as p<0.05. RESULTS: Cancer was detected in four rats of DMBA standard diet, two rats of 30% MA, one rat of 45% MA. No cancer was detected in the rats of control and rats with 60% of MA group. The Beclin1 expressions showed that the 60% of MA group had the highest score (2.5±0.52) followed by the 45% of MA group (1.87±0.49), control group (1.77±0.11), 30% of MA group (1.28±0.75), and DMBA with standard diet had the lowest score (1.28±0.91). The difference of Beclin1 expressions was statistically significant (p-value=0.03). However, the difference of the LC3B expressions (p-value=0.11) and SQSTM1 expressions (p-value=0.225) were not statistically significant. CONCLUSION: Dietary modifications with MA potentially prevent breast cancer and induce initiation of autophagy.

Effects of Pubertal Exposure to Butyl Benzyl Phthalate, Perfluorooctanoic Acid, and Zeranol on Mammary Gland Development and Tumorigenesis in Rats.

Endocrine-disrupting chemicals (EDCs)-including butyl benzyl phthalate (BBP), perfluorooctanoic acid (PFOA), and zeranol (α-ZAL, referred to as ZAL hereafter)-can interfere with the endocrine system and produce adverse effects. It remains unclear whether pubertal exposure to low doses of BBP, PFOA, and ZAL has an impact on breast development and tumorigenesis. We exposed female Sprague Dawley rats to BBP, PFOA, or ZAL through gavage for 21 days, starting on day 21, and analyzed their endocrine organs, serum hormones, mammary glands, and transcriptomic profiles of the mammary glands at days 50 and 100. We also conducted a tumorigenesis study for rats treated with PFOA and ZAL using a 7,12-dimethylbenz[a]anthracene (DMBA) model. Our results demonstrated that pubertal exposure to BBP, PFOA, and ZAL affected endocrine organs and serum hormones, and induced phenotypic and transcriptomic changes. The exposure to PFOA + ZAL induced the most phenotypic and transcriptomic changes in the mammary gland. PFOA + ZAL downregulated the expression of genes related to development at day 50, whereas it upregulated genes associated with tumorigenesis at day 100. PFOA + ZAL exposure also decreased rat mammary tumor latency, reduced the overall survival of rats after DMBA challenge, and affected the histopathology of mammary tumors. Therefore, our study suggests that exposure to low doses of EDCs during the pubertal period could induce changes in the endocrine system and mammary gland development in rats. The inhibition of mammary gland development by PFOA + ZAL might increase the risk of developing mammary tumors through activation of signaling pathways associated with tumorigenesis.

Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect.

Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, α-aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, DMBA, DMBA & α-aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. New α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one were synthesized and elucidated by different spectroscopic and elemental analysis. Histopathological examination showed marked proliferation of cancer cells in the DMBA group. Treatment with α-aminophosphonates mainly decreased tumor mass. Bcl2 expression increased in DMBA-administered rats and then declined in the treated groups, mostly with α-aminophosphonates. The level of CA15-3 markedly declined in DMBA groups treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. Gene expression of GST-P, PCNA, PDK, and PIK3CA decreased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.

Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma.

Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

Classification of rat mammary carcinoma with large scale in vivo microwave measurements.

Mammary carcinoma, breast cancer, is the most commonly diagnosed cancer type among women. Therefore, potential new technologies for the diagnosis and treatment of the disease are being investigated. One promising technique is microwave applications designed to exploit the inherent dielectric property discrepancy between the malignant and normal tissues. In theory, the anomalies can be characterized by simply measuring the dielectric properties. However, the current measurement technique is error-prone and a single measurement is not accurate enough to detect anomalies with high confidence. This work proposes to classify the rat mammary carcinoma, based on collected large-scale in vivo S[Formula: see text] measurements and corresponding tissue dielectric properties with a circular diffraction antenna. The tissues were classified with high accuracy in a reproducible way by leveraging a learning-based linear classifier. Moreover, the most discriminative S[Formula: see text] measurement was identified, and to our surprise, using the discriminative measurement along with a linear classifier an 86.92% accuracy was achieved. These findings suggest that a narrow band microwave circuitry can support the antenna enabling a low-cost automated microwave diagnostic system.