Environmental Pollution and Breast Cancer: The Microplastic Component BPA Regulates the Intratumoral Immune Microenvironment and Increases Lung Metastasis

Background: Metastasis is a complex process that involves the spread of the tumor to distant parts of the body from its original site. Metastatic dissemination represents the main physiopathology of cancer. Soluble factors such as cytokines have been closely related to breast cancer (BC) metastasis. Bisphenol A (BPA) is an endocrine disrupting chemical compound with estrogenic properties, which exposure in the early stages of neonatal life leads to an increase in the size and weight of breast tumors and cellular changes in the tumoral immune microenvironment. Methods: Thus, we used female BALB/c mice that were exposed neonatally to a single dose of BPA. Once sexual maturity was reached, a mammary tumor was induced injecting 4T1 cells in situ. After 25 days of injection, we evaluated endocrine alterations, cytokine expression, tissue alterations denoted by macro and micro metastases in the lung, and metastasis-induced cell infiltration. Results: BPA neonatal treatment did not show significant endocrine alterations. Nevertheless, BPA induced a great rate of metastasis to the lung associated with higher intratumoral expression of IL-1b, IL-6, IFN-g, TNF-a and VEGF. Conclusions Our data suggest that cytokines are key players in BC metastasis induction, and that BPA is a risk factor to be considered. This knowledge must be considered with the aim of recognizing environmental pollution in the clinical history of patients to possibly counter BC metastases.

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Clinical verification of body mass index and tumor immune response in patients with breast cancer receiving preoperative chemotherapy

10.21203/rs.3.rs-131688/v2 ◽

2021 ◽

Author(s):

Koji Takada ◽

Shinichiro Kashiwagi ◽

Yuka Asano ◽

Wataru Goto ◽

Rika Kouhashi ◽

...

Keyword(s):

Breast Cancer ◽

Body Mass Index ◽

Body Mass ◽

Preoperative Chemotherapy ◽

Early Stage ◽

The Body ◽

World Health ◽

Cancer Type ◽

Immune Microenvironment ◽

Tumor Immune Microenvironment

Abstract Purpose: The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors’ immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses.Methods: The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient’s height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥18.5 kg/m2 and >25 kg/m2 were considered normal weight (NW), those ≥25 kg/m2 and <30 kg/m2 were overweight (OW), and those ≥30 kg/m2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014.Results: The median BMI was 21.9 kg/m2 (range, 14.3–38.5 kg/m2); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p=0.001; vs. OW: p=0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p=0.031).Conclusions: Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.

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Laser-triggered combined chemotherapy and photodynamic therapy enabled by iron sulfide-doxorubicin@bovine lactoferrin nanozymes for breast cancer therapy

10.21203/rs.3.rs-332523/v1 ◽

2021 ◽

Author(s):

Qian Bai

Keyword(s):

Breast Cancer ◽

Iron Sulfide ◽

Drug Distribution ◽

The Body ◽

Bovine Lactoferrin ◽

Intravenous Injections ◽

Wet Chemical Synthesis ◽

Acidic Conditions ◽

4T1 Cells ◽

Cancerous Cells

Abstract BackgroundThe use of magnetic nanozymes with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. ResultsHence, in this study, we designed a bovine lactoferrin-coated iron sulfide nanozymes containing doxorubicin (FeS-Dox@bLf NZs) by wet chemical synthesis that can respond to tumor acidity. Then, the physicochemical properties of synthesized NZs were investigated by TEM, SEM, DLS and spectroscopic methods. Likewise, the level of Fe2+ release, H2S and Dox from FeS-Dox@Lf NZs under acidic conditions was evaluated. It was observed that Fe2+ and S2- caused significant OH and H2S release through the Fenton reaction. Also, the toxic effects of FeS-Dox@Lf NZs on 4T1 cancerous cells were investigated by MTT and flow cytometry assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. ConclusionOverall, FeS-Dox@Lf nanozymes with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer.

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Clinical Verification of Body Mass Index and Tumor Immune Response in Patients With Breast Cancer Receiving Preoperative Chemotherapy

10.21203/rs.3.rs-131688/v1 ◽

2020 ◽

Author(s):

Koji Takada ◽

Shinichiro Kashiwagi ◽

Yuka Asano ◽

Wataru Goto ◽

Rika Kouhashi ◽

...

Keyword(s):

Breast Cancer ◽

Body Mass Index ◽

Body Mass ◽

Preoperative Chemotherapy ◽

Early Stage ◽

The Body ◽

World Health ◽

Cancer Type ◽

Immune Microenvironment ◽

Tumor Immune Microenvironment

Abstract Background: The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors’ immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses.Methods: The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient’s height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥18.5 kg/m2 and >25 kg/m2 were considered normal weight (NW), those ≥25 kg/m2 and <30 kg/m2 were overweight (OW), and those ≥30 kg/m2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014.Results: The median BMI was 21.9 kg/m2 (range, 14.3–38.5 kg/m2); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p=0.001; vs. OW: p=0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p=0.031).Conclusion: Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.

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Laser-triggered combined chemotherapy and photodynamic therapy enabled by iron sulfide-doxorubicin@bovine lactoferrin nanozymes for breast cancer therapy

10.21203/rs.3.rs-332523/v2 ◽

2021 ◽

Author(s):

Shipeng Ning ◽

Yang Zheng ◽

Kun Qiao ◽

Guozheng Li ◽

Shouping Xu ◽

...

Keyword(s):

Breast Cancer ◽

Iron Sulfide ◽

Drug Distribution ◽

The Body ◽

Bovine Lactoferrin ◽

Intravenous Injections ◽

Wet Chemical Synthesis ◽

Acidic Conditions ◽

4T1 Cells ◽

Cancerous Cells

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Clinical verification of body mass index and tumor immune response in patients with breast cancer receiving preoperative chemotherapy

10.21203/rs.3.rs-131688/v4 ◽

2021 ◽

Author(s):

Koji Takada ◽

Shinichiro Kashiwagi ◽

Yuka Asano ◽

Wataru Goto ◽

Sae Ishihara ◽

...

Keyword(s):

Breast Cancer ◽

Body Mass Index ◽

Body Mass ◽

Preoperative Chemotherapy ◽

Early Stage ◽

The Body ◽

World Health ◽

Cancer Type ◽

Immune Microenvironment ◽

Tumor Immune Microenvironment

Abstract Purpose The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors’ immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses. Methods The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient’s height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥ 18.5 kg/m2 and > 25 kg/m2 were considered normal weight (NW), those ≥ 25 kg/m2 and < 30 kg/m2 were overweight (OW), and those ≥ 30 kg/m2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014. Results The median BMI was 21.9 kg/m2 (range, 14.3–38.5 kg/m2); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p = 0.001; vs. OW: p = 0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p = 0.031). Conclusions Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.

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Biological Role of CDK 11 and 12 in Cell Cycle and its Function in Tumorigenesis

Pakistan Journal of Medicine and Dentistry ◽

10.36283/pjmd9-3/020 ◽

2020 ◽

Author(s):

Shamim Mushtaq

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Web Of Science ◽

The Body ◽

Main Role ◽

Hallmarks Of Cancer ◽

Cyclin Dependent Kinases ◽

Tumor Studies ◽

Cycle Regulation

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.

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Bioinformatic Profiling of Prognosis-Related Genes in Breast Cancer Immune Microenvironment

SSRN Electronic Journal ◽

10.2139/ssrn.3377512 ◽

2019 ◽

Author(s):

Fang Bai ◽

Hongliang Chen ◽

Yipeng Fu ◽

Peng Zhang ◽

Mingdi Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Immune Microenvironment

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Breast Cancer Resistance Protein: A Potential Therapeutic Target for Cancer

Current Drug Targets ◽

10.2174/1389450121999201125200132 ◽

2020 ◽

Vol 21 ◽

Author(s):

Sonali Mehendale-Munj

Keyword(s):

Breast Cancer ◽

Breast Cancer Resistance Protein ◽

Protein A ◽

The Body ◽

Cancer Therapies ◽

Cancer Resistance ◽

Lung Cancers ◽

Resistance Protein ◽

Atp Regulation ◽

Treatment Procedures

: Breast Cancer Resistance Protein (BCRP) is an efflux transporter responsible for causing multidrug re-sistance(MDR). It is known to expel many potent antineoplastic drugs, owing to its efflux function. Efflux of chemothera-peutics because of BCRP develops resistance to manydrugs, leading to failure in cancer treatment. BCRP plays an important role in physiology by protecting the organism from xenobiotics and other toxins. It is a half-transporter affiliated to theATP-binding cassette (ABC) superfamily of transporters, encoded by the gene ABCG2 and functions in response to adenosine triphosphate (ATP). Regulation of BCRP expression is critically controlled at molecular levels which help in maintaining the balance of xenobiotics and nutrients inside the body. Expression of BCRP can be found in brain, liver, lung cancers and acute myeloid leukemia (AML). Moreover, it is also expressed at high levels in stem cells and many cell lines. This frequent expression of BCRP has an impact on the treatment procedures and if not scrutinized may lead to failure of many cancer therapies.

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Towards Breast Cancer Vaccines, Progress and Challenges

Current Drug Discovery Technologies ◽

10.2174/1570163815666180502164652 ◽

2019 ◽

Vol 16 (3) ◽

pp. 251-258 ◽

Cited By ~ 3

Author(s):

Javad Behravan ◽

Atefeh Razazan ◽

Ghazal Behravan

Keyword(s):

Breast Cancer ◽

Adverse Effects ◽

Cancer Vaccine ◽

Cancer Vaccines ◽

Weight Control ◽

The Body ◽

Phase Iii ◽

Current Therapy ◽

Surgical Ablation ◽

Breast Cancer Vaccine

Breast cancer is the second leading cause of cancer death among women. National cancer institute of the US estimates that one in eight women will be diagnosed with breast cancer during their lifetime. Considering the devastating effects of the disease and the alarming numbers many scientists and research groups have devoted their research to fight breast cancer. Several recommendations are to be considered as preventing measures which include living a healthy lifestyle, regular physical activity, weight control and smoking cessation. Early detection of the disease by annual and regular mammography after the age of 40 is recommended by many healthcare institutions. This would help the diagnosis of the disease at an earlier stage and the start of the treatment before it is spread to other parts of the body. Current therapy for breast cancer includes surgical ablation, radiotherapy and chemotherapy which is often associated with adverse effects and even may lead to a relapse of the disease at a later stage. In order to achieve a long-lasting anticancer response with minimal adverse effects, development of breast cancer vaccines is under investigation by many laboratories. The immune system can be stimulated by a vaccine against breast cancer. This approach has attracted a great enthusiasm in recent years. No breast cancer vaccines have been approved for clinical use today. One breast cancer vaccine (NeuVax) has now completed clinical trial phase III and a few preventive and therapeutic breast cancer vaccines are at different steps of development. We think that with the recent advancements in immunotherapy, a breast cancer vaccine is not far from reach.

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Design, Synthesis and Antitumor Assessment of Phenylureas Bearing 5-Fluoroindolin-2-one Moiety

Medicinal Chemistry ◽

10.2174/1573406416666200206123319 ◽

2020 ◽

Vol 16 (7) ◽

pp. 958-968

Author(s):

Yunrui Cai ◽

Tong Chen ◽

Huajian Zhu ◽

Hongbin Zou

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Human Cancer ◽

The Body ◽

Human Breast ◽

Design Synthesis ◽

Human Carcinoma ◽

Xenograft Models ◽

New Compounds ◽

Mcf 7

Background: The development of novel antineoplastic agents remains highly desirable. Objective: This study focuses on the design, synthesis, and antitumor evaluation of phenyl ureas bearing 5-fluoroindolin-2-one moiety. Methods: Three sets of phenylureas were designed and synthesized and their antiproliferative ability was measured against four human carcinoma cell lines (Hela, Eca-109, A549, and MCF-7) via MTT assay. In vivo anticancer activity was further evaluated in xenograft models of human breast cancer (MCF-7). Results: A total of twenty-one new compounds were synthesized and characterized by means of 1H and 13C NMR as well as HR-MS. Three sets of compounds (1a‒1c, 2a‒2c, and 3a‒3c) were initially constructed, and preliminary antiproliferative activities of these molecules were evaluated against Hela, Eca-109, A549 and MCF-7, highlighting the meta-substituted phenylureas (1a‒1c) as the most cytotoxic set. A series of meta-substituted phenylureas derivatives (1d‒1o) were then designed and synthesized for structure-activity relationship study. Most of the new compounds showed desirable cytotoxicity, among which compound 1g exhibited the most remarkable cytotoxic effects against the tested human cancer cells with IC50 values ranging from 1.47 to 6.79 μM. Further studies showed that compound 1g suppressed tumor growth in human breast cancer (MCF- 7) xenograft models without affecting the body weight of its recipients. Conclusion: In this study, twenty-one new compounds, containing the privileged structures of phenylurea and 5-fluoroindolin-2-one, were designed and synthesized. Subsequent structureactivity studies showed that 1g was the most bioactive antitumor agent among all tested compounds, hence a potentially promising lead compound once given further optimization.

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