Allyl Isothiocyanate Inhibits Invasion and Angiogenesis in Breast Cancer via EGFR Mediated JAK1/STAT3 Signaling Pathway

Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK1/STAT3 is a key intracellular signaling transduction path, which controls the growth, differentiation, apoptosis, invasion, and angiogenesis in various cancer cells. The existing study explored the impact of AITC on the JAK-1/STAT-3 pathway in DMBAinjected rat mammary tumorigenesis. The mammary tumor was initiated through a single dose of 25 mg DMBA/rat through a subcutaneous injection administered near the mammary gland. We observed decreased body weight and augmented the total number of tumors, tumor incidence, tumor volume, well-developed tumor, and histopathological abnormalities in DMBA-injected rats and that were modulated after being treated with AITC. Staining of mammary tissues showed a high accumulation of collagen in DMBAtreated rats and it was normalized by the AITC treatment. Moreover, DMBA-induced mammary tissues showed up-regulated expressions of EGFR, pJAK-1, pSTAT-3, the nuclear fraction of STAT-3, and its associated products like VEGF, VEGFR2, HIF-1α, MMP-2, and MMP-9 and the down-regulated expressions of cytosolic STAT-3 and TIMP-2. Oral administration of AITC on DMBAtreated rats inhibits angiogenesis and invasion through modified these angiogenic and invasive markers. The finding of the current study is further confirmed by molecular docking analysis that shows a strong binding interaction between AITC with STAT-3 and cocrystal structure of STAT3 glide energy of -18.123 and − 72.246 (kcal/mole), respectively. Overall, the results suggested that AITC inhibits activation of the JAK-1/STAT-3 path, which subsequently prevents angiogenesis and invasion. It was recommended that AITC might develop a beneficial effect against breast cancer.

Exploration of the lactation function of protein phosphorylation sites in goat mammary tissues by phosphoproteome analysis

Background Protein phosphorylation plays an important role in lactation. Differentially modified phosphorylation sites and phosphorylated proteins between peak lactation (PL, 90 days postpartum) and late lactation (LL, 280 days postpartum) were investigated using an integrated approach, namely, liquid chromatography with tandem mass spectrometry (LC-MS/MS) and tandem mass tag (TMT) labeling, to determine the molecular changes in the mammary tissues during the different stages of goat lactation. Results A total of 1,938 (1,111 upregulated, 827 downregulated) differentially modified phosphorylation sites of 1,172 proteins were identified (P values < 0.05 and fold change of phosphorylation ratios > 1.5). Multiple phosphorylation sites of FASN, ACACA, mTOR, PRKAA, IRS1, RPS6KB, EIF4EBP1, JUN, and TSC2 were different in PL compared with LL. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the calcium signaling pathway, oxytocin signaling pathway and MAPK signaling pathway were enriched. The western blot results showed that the phosphorylation levels of ACACA (Ser80), EIF4EBP1 (Thr46) and IRS1 (Ser312) increased and JUN (Ser63) decreased in PL compared with LL. These results were consistent with the phosphoproteome results. Conclusions In this study, we identified for the first time the differentially modified phosphorylation sites in goat mammary tissues between PL and LL. These results indicate that the multiple differentially modified phosphorylation sites of FASN, ACACA, mTOR, PRKAA, IRS1, RPS6KB, EIF4EBP1, TSC2, and JUN and proteins involved in the calcium signaling pathway, oxytocin signaling pathway, and MAPK signaling pathway are worthy of further exploration.

Capsaicin Encapsulated Chitosan Nanoparticles Augments Anticarcinogenic and Antiproliferative Competency Against 7,12 Dimethylbenz(a)anthracene Induced Experimental Rat Mammary Carcinogenesis

Background: Capsaicin is a powerful phytochemical spotted in chilies, starkly tied up with a bunch of health benefits but its clinical applications in cancer therapy are limited due to its poor solubility, and low bioavailability. Nanotechnology offers a strategy to discover new formulations for hydrophobic agent. Aim: The main intent of the current research was to investigate the effect of Capsaicin encapsulated chitosan nanoparticles (CAP@CS-NP) on 7,12-Dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in rats. Methodology: Mammary tumor was induced in female rats by injecting DMBA (25mg/kg b.wt) at the first week of the experiment. After 7 weeks, CAP@CS-NP (4mg/kg b.wt) was administered orally to DMBA induced tumor bearing rats for 21 days (thrice per week). The experiment was terminated at the end of the 14th week and their plasma and tissue sections were analyzed. Results: We found that significantly elevated levels of lipid peroxidation and diminished levels of antioxidant status in plasma, liver and mammary tissues. Increased levels of detoxification phase I enzymes and dropped levels of phase II enzymes in liver and mammary tissues in DMBA induced tumor bearing rats. As a result, oral administration of CAP@CS-NP suppressed the tumor growth, significantly raised body weight and restored abnormal enzymatic levels to near normal ranges. Additionally, histopathological and immunohistochemical analysis were also confirmed that CAP@CS-NP protects DMBA mediated cellular disruption and also inhibits abnormal cell proliferation. Conclusion: These findings suggest that nano encapsulation of CAP@CS-NP could be useful in targeted drug delivery and act as a promising chemotherapeutic agent to treat mammary carcinogenesis.

Early Dietary Exposures Epigenetically Program Mammary Cancer Susceptibility through IGF1-mediated Expansion of Mammary Stem Cells

Dietary exposures at early developmental stages have been shown to program lifetime breast cancer susceptibility. We previously reported that manipulation of gestational and postweaning diets leads to different mammary tumor outcomes in carcinogen-treated mice. The high tumor incidence (HT) groups (average 61.5% tumor incidence) received a low-fat, low-sugar, mildly restricted (12%v/v) (DR) diet during gestation, followed by a high-fat, high-sugar (HF) diet postweaning. Conversely, the low tumor incidence (LT) groups (average 20% tumor incidence) received the HF diet during gestation, followed by the DR diet postweaning. Herein, we extended these findings by demonstrating that HT animals had an expanded mammary stem cell (MaSC) population compared to LT animals before puberty, and this expansion persisted into adulthood. IGF1 expression was increased in mammary stromal cells from HT animals, which promoted the self-renewal capacity of MaSCs in a paracrine fashion. This increased IGF1 expression was programmed prepubertally through DNA hypomethylation of the IGF1 promoter 1, mediated by decreased DNMT3b levels. IGFBP5 mRNA and protein levels were also reduced in mammary tissues from HT animals, indicating an increased bioavailability of tissue IGF1. In association with these changes, mammary tissues from carcinogen-treated HT animals developed an increased proportion of mammary adenosquamous carcinomas compared to carcinogen-treated LT animals. This study provides novel mechanistic insights into how early dietary exposures program mammary cancer risk and tumor phenotypes by increasing IGF1 expression through epigenetic alterations, thereby expanding the MaSC population, resulting in a higher number of carcinogen targets susceptible to transformation in adulthood.SignificanceEarly high-fat dietary exposure programs lifetime mammary cancer susceptibility before puberty through epigenetic alterations of IGF1 promoters and IGF1-mediated paracrine regulation of mammary stem cell homeostasis.

Study on the small breast epithelial mucin tumor tissue expression difference and its relationship with survival in triple-negative breast cancer patients in Han, Miao and Buyi ethnic

Objective: To investigate Small breast epithelial mucin(SBEM) expression difference in mammary tissues and relationship with survival in thetriple-negative breast cancer(TNBC) patients in Han, Buyi and Miao ethnic.Methods: In our study, SBEM protein expressions were detected by means of immunohistochemistry in 297 patients diagnosed from 2014 to 2015,including 99 normal breast tissue specimens, 99 cases of breast benign tumor tissue specimens and 99 tissues specimens from TNBC patients.Each set of tissue specimens contains 33 samples from Han,Miao and Buyi ethnics, respectively.We analyze the expression of SBEM in different mammary tissues in different ethnics and the association of different SBEM expression levels in tissue of TNBC patients with clinical- pathological features, DFS and OS in Han,Miao and Buyi ethnics,respectively. Results: SBEM expression in breast cancer tumor cells were related to the ki67 in the Han, Miao and Buyi ethnic (P=0.034、0.027、0.047), respectively. There was a marked associations between the SBEM expression level and lymphatic metastasis (P = 0.042、0.039) in the Han and Miao ethnic, while the same results were not found in the Buyi people (P=0.072).There was significant difference in DFS ( P =0.028、0.013)and OS ( P =0.09、0.037) between the high expression group and low expression group in the Han and Miao ethnic.But there was no significant difference in DFS (P = 0.053 ) and OS (P = 0.088 )in the Buyi people.Conclusion: The SBEM positive detection rate was no significant difference in the han, miao and buyi ethnic groups. SBEM was associated with DFS and OS in the Han and Miao ethnic, while no correlation in the Buyi ethnic.

Apolipoproteins, as the carrier proteins for lipids, are involved in the development of breast cancer

Apolipoproteins, the key components of lipoproteins, play vital roles in the combination and transportation of lipids. Numerous research articles have accumulated solid evidence that lipoproteins are closely related to various types of tumorigenesis. In this review, we focused on the associations between several apolipoproteins and breast carcinoma and distinguished the effects and significance of apolipoproteins in different locations to validate their roles in breast carcinoma development. For example, apoD and apoE in serum are viewed as risk factors for breast carcinoma. ApoD, apoE and apoA-I in mammary tissues inhibit tumor growth. Moreover, apoB, apoJ and apoA-I have the potential to function as diagnostic or prognostic markers in the clinic. ApoEdp and apoJ treatment on breast carcinoma could significantly restrict tumor growth. In general, the aim of this review was to further analyze the associations between some members of the apolipoprotein family and breast cancer.

In Vivo Dielectric Properties of Healthy and Benign Rat Mammary Tissues from 500 MHz to 18 GHz

This work investigates the in vivo dielectric properties of healthy and benign rat mammary tissues in an attempt to expand the dielectric property knowledge of animal models. The outcomes of this study can enable testing of microwave medical technologies on animal models and interpretation of tissue alteration-dependent in vivo dielectric properties of mammary tissues. Towards this end, in vivo dielectric properties of healthy rat mammary tissues and chemically induced benign rat mammary tumors including low-grade adenosis, sclerosing adenosis, and adenosis were collected with open-ended coaxial probes from 500 MHz to 18 GHz. The in vivo measurements revealed that the dielectric properties of benign rat mammary tumors are higher than the healthy rat mammary tissues by 9.3% to 35.5% and 19.6% to 48.7% for relative permittivity and conductivity, respectively. Furthermore, to our surprise, we found that the grade of the benign tissue affects the dielectric properties for this study. Finally, a comparison with ex vivo healthy human mammary tissue dielectric properties revealed that the healthy rat mammary tissues best replicate the dielectric properties of healthy medium density human samples.

Aging-associated alterations in the mammary gland revealed by single-cell RNA sequencing

Aging of the mammary gland is closely associated with increased susceptibility to diseases such as cancer, but there have been limited systematic studies of aging-induced alterations within this organ. We performed high-throughput single-cell RNA-sequencing (scRNA-seq) profiling of mammary tissues from young and old nulliparous mice, including both epithelial and stromal cell types. Our analysis identified altered proportions and distinct gene expression patterns in numerous cell populations as a consequence of the aging process, independent of parity and lactation. In addition, we detected a subset of luminal cells that express both hormone-sensing and alveolar markers and decrease in relative abundance with age. These data provide a high-resolution landscape of aging mammary tissues, with potential implications for normal tissue functions and cancer predisposition.