• EGFR inhibitors
• EGFR kinase selectivity
• apoptosis induction
• breast cancer (BC)
• marine-derived compounds

• Biomarker
• Pan-cancer
• Prognosis
• Proteome
• Survival analysis
• Transcriptome

Previous experiments have shown that growth factor receptors play important role in tumor proliferation, metastasis, and therapeutic effect of chemotherapeutic drugs. At the same time, forkhead box D1 (FOXD1) plays an important role in a variety of signal transmission, but its expression profile was known little about head and neck cancer. The purpose of this experiment was to explore the regulation of FOXD1 on the tumor progression of head and neck cancer and to explore the correlation of FOXD1 on the expression of growth factor receptors (EGFR).

The bioinformatics online database analyzed the expression of FOXD1 and EGFR in tumor tissues and nontumor tissues. Real-time quantitative PCR was used to detect the FOXD1 and EGFR expression in 45 tumor tissues and 15 nontumor tissues. The plasmid was used to construct FOXD1 overexpressing head and neck squamous cell cancer lines and observe the clonal formation and invasion of tumor cells under the intervention of EGFR-specific antibody—cetuximab.

The expression of FOXD1 and EGFR in tumor tissues was higher than that in nontumor tissues. The higher expression of FOXD1 and EGFR was not conducive to the prognosis of patients. The expression of FOXD1 and EGFR was positively correlated, and immunohistochemical analysis showed the high expression of FOXD1 and EGFR has close relation to the advanced stage of the tumor. In vitro cell experiments proved that overexpression of FOXD1 can partially offset the cloning ability of cetuximab on head and neck tumor cells.

FOXD1 has an important regulatory role in the progression of head and neck cancer, and its abnormally high expression was not conducive to the prognosis of cancer patients. FOXD1 can regulate the expression of growth factor receptors in head and neck cancer, which provides a new idea for the better use of tumor growth factor receptor-specific antibodies for collaborative therapy.

The incidence of breast cancer among women of reproductive age is increasing, as well as the desire for children at late childbearing age. Identifying factors that may be associated with fetal malformation and maternal and fetal prognosis has gained importance. We describe a 32-year-old woman with breast cancer who gave birth to a son with congenital bilateral cryptorchidism after treatment, with a literature review performed.

A 32-year-old woman with breast cancer who had been treated by surgery and radiotherapy experienced recurrence and underwent a second surgery, adjuvant chemotherapy, and targeted therapy. Her tumor cells were negative for estrogen receptor (ER) α, progesterone receptor (PR), and p53; positive for ERβ, human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR), and Ki67. She had pathogenic BRCA gene mutations. She became pregnant within 2 years and delivered a boy with congenital bilateral cryptorchidism. The boy underwent bilateral orchidopexy. As of this writing, the woman and her son are both healthy.

HER2 overexpression, positivity for EGFR, Ki67, and ER, and PR negativity are associated with a poor prognosis in breast cancer. While no link has been established statistically between treatment for breast cancer and cryptorchidism in a subsequent pregnancy, this case suggests the possibility that ERβ and gene mutations may be contributing factors.

• Pregnancy
• Breast cancer
• Chemotherapy
• Cryptorchidism
• Case report

Enhanced serum secreted clusterin (sCLU) protein was associated with progression, poor prognosis and chemotherapy sensitivity evaluation in malignant patients. However, the clinical significance of serum sCLU protein levels in patients with invasive breast cancer (IBC) is unknown. In this study, the serum sCLU protein in 2648 patients with IBC was detected. The diagnostic value and treatment responses of serum sCLU protein in patients with IBC were also performed. The results showed that the serum sCLU protein level was significantly higher in IBC patients compared to the healthy controls (P < 0.0001), and strongly correlated with higher clinical tumor stage (P < 0.001), lymph node metastasis (P < 0.001), shorter overall survival (OS) (P = 0.032) and disease-free survival (DFS) (P = 0.029), respectively. Using the cutoff value of 18.46 μg/mL, the sensitivity and specificity were 86.26% and 73.46% to separate IBC patients from noncancerous and healthy controls. The postoperative patients showed lower serum sCLU levels compared to the preoperative patients (P = 0.003). The chemoresistant patients showed higher serum sCLU levels compared to the chemosensitive patients (P < 0.001). These data indicated that serum sCLU levels are effective indicators for diagnosis and chemotherapy sensitivity evaluation in patients with IBC.

• Invasive breast cancer
• chemotherapy
• clusterin
• diagnosis
• prognosis

Epidermal growth factor receptor (EGFR) and its ligands are involved in cancer pathogenesis. The emerging role of treatments co-targeting the EGFR system in breast cancer has increased the need to identify companion biomarkers. The aim of this study is to investigate whether pretreatment serum levels of EGFR and EGFR ligands in early-stage breast cancer patients might provide prognostic information as a stepping stone for further investigation. The study, which included 311 early-stage breast cancer patients, investigated associations between preoperative serum levels of EGFR and EGFR ligands (epidermal growth factor, heparin-binding epidermal growth factor (HBEGF), amphiregulin, transforming growth factor-α and betacellulin) and survival. Cutoffs were determined using Youden’s method, and overall survival (OS) and invasive disease-free survival (IDFS) were evaluated using Cox regression. Preoperative S-EGFR < 60.3 ng/mL was associated with shorter OS and IDFS in both univariate analyses and when adjusting for standard prognostic factors (p < 0.05). Preoperative S-HBEGF < 21.4 pg/mL was associated with shorter OS in both univariate and multivariate analyses, whereas association with shorter IDFS could only be demonstrated in the univariate analysis. In conclusion, our study demonstrated shorter survival in early-stage breast cancer patients who had low pretreatment levels of either S-EGFR or S-HBEGF.

• cancer biomarkers
• epidermal growth factor receptor
• epidermal growth factor receptor ligands
• reference interval
• serum

• Adult
• Aged
• Amphiregulin/analysis
• Amphiregulin/blood
• Betacellulin/analysis
• Betacellulin/blood
• Biomarkers/blood
• EGF Family of Proteins/analysis
• EGF Family of Proteins/blood
• Epidermal Growth Factor/analysis
• Epidermal Growth Factor/blood
• ErbB Receptors/analysis
• ErbB Receptors/blood
• Female
• Heparin-binding EGF-like Growth Factor/analysis
• Heparin-binding EGF-like Growth Factor/blood
• Humans
• Ligands
• Middle Aged
• Reference Standards
• Reference Values
• Transforming Growth Factor alpha/analysis
• Transforming Growth Factor alpha/blood

Healthy diet and physical activity are able to induce beneficial molecular modifications that have been associated with a lower risk of breast cancer (BC) incidence and a better prognosis for BC patients. Although the beneficial effects of healthy lifestyle have been described, the beneficial epigenetic modifications induced by dietary and exercise intervention in BC patients have not been elucidated yet. On these bases, the aim of the present study was to computationally identify microRNAs (miRNAs) strictly associated with BC progression and with dietary and exercise interventions. Through several computational approaches, a set of miRNAs modulated by diet and exercise and useful as diagnostic and prognostic biomarkers for BC was identified. The results obtained represent the starting point for further validation analyses performed on BC patients undergoing lifestyle interventions to propose the miRNAs here identified as novel biomarkers for BC management.

Background: Several studies have shown that healthy lifestyles prevent the risk of breast cancer (BC) and are associated with better prognosis. It was hypothesized that lifestyle strategies induce microRNA (miRNA) modulation that, in turn, may lead to important epigenetic modifications. The identification of miRNAs associated with BC, diet, and physical activity may give further insights into the role played by lifestyle interventions and their efficacy for BC patients. To predict which miRNAs may be modulated by diet and physical activity in BC patients, the analyses of different miRNA expression datasets were performed. Methods: The GEO DataSets database was used to select miRNA expression datasets related to BC patients, dietary interventions, and physical exercise. Further bioinformatic approaches were used to establish the value of selected miRNAs in BC development and prognosis. Results: The analysis of datasets allowed the selection of modulated miRNAs associated with BC development, diet, and physical exercise. Seven miRNAs were also associated with the overall survival of BC patients. Conclusions: The identified miRNAs may play a role in the development of BC and may have a prognostic value in patients treated with integrative interventions including diet and physical activity. Validation of such modulated miRNAs on BC patients undergoing lifestyle strategies will be mandatory.

• bioinformatics
• biomarkers
• breast cancer
• diet
• epigenetic
• microRNA
• physical activity
• prognosis

• Bioinformatics
• Breast cancer
• Guizhi Fuling Decoction
• HTS2 assay
• Systems pharmacology

The epidermal growth factor receptor (EGFR) family members EGFR and HER2 play pivotal roles in oncogenesis and tumor progression. Anticancer drugs targeting EGFR and HER2 have been developed. Long noncoding RNAs (lncRNAs) have been reported to regulate cancer development and progression through signaling pathways. However, lncRNAs that regulate EGFR and HER2 expression remain unknown. Here, we show that lncRNA myosin light chain kinase-antisense RNA 1 (MYLK-AS1) promotes EGFR and HER2 expression and activates their downstream signaling pathway. MYLK-AS1 increases hepatocellular carcinoma (HCC) cell proliferation, migration, and invasion in vitro. Consistently, MYLK-AS1 knockdown hinders tumor growth in vivo. Mechanistically, MYLK-AS1 enhances HCC cell proliferation, migration, and invasion through stimulating the EGFR/HER2-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In addition, MYLK-AS1 is overexpressed in HCC patients and negatively correlated with HCC prognosis. Thus, MYLK-AS1 is an upstream regulator of EGFR/HER2, and acts as an oncogene, suggesting an additional target for cancer therapeutics.

• EGFR
• HER2
• LncRNA
• MYLK-AS1
• hepatocellular carcinoma

The epidermal growth factor receptor (EGFR) and its ligands are involved in cancer pathogenesis and they might serve as circulating biomarkers. The current study aims to investigate if abnormal pre-treatment serum levels of EGFR and EGFR ligands are present in women with early-stage breast cancer and if up- or downregulation of EGFR and EGFR ligands occur in defined patient subgroups. Pre-treatment serum samples were obtained from 311 women with newly diagnosed early-stage breast cancer and from 419 healthy women and analysed for EGFR and the ligands: Epidermal growth factor (EGF), heparin-binding epidermal growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), and transforming growth factor α (TGF-α). Previously, age-dependent 95% reference intervals for EGFR and the EGFR ligands have been established based on the healthy women population. S-EGFR, S-EGF, S-HBEGF, S-AREG, and S-TGFα were all significantly different in women with breast cancer compared to healthy women (p < 0.05). Elevated S-EGFR, according to the reference intervals, was present in 11.3% of breast cancer patients, whereas decreased S-EGF was found in 11.6%. Elevated S-EGFR was associated with estrogen receptor positivity of tumor (ER+) and a subgroup of ER + breast cancer patients showed markedly elevated S-EGFR (>120 ng/mL).

• Kinesin-4 family genes
• biomarker
• pancreatic ductal adenocarcinoma
• prognosis

• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/surgery
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kinesins/genetics
• Male
• Nomograms
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/surgery
• Pancreaticoduodenectomy
• Prognosis
• Survival Analysis
• Treatment Outcome
• Up-Regulation
• Pancreatic Neoplasms

• JGY2018037 2018 Innovation Project of Guangxi Graduate Education
• YCBZ2018036 2018 Innovation Project of Guangxi Graduate Education
• GXCDCKL201902 Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis
• 81802874 National Natural Science Foundation of China
• 2018GXNSFBA138013 Natural Science Foundation of the Guangxi Province of China
• GKE2018-01 Key laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education
• GKEAB18221019 Guangxi Key R & D Program
• National Natural Science Foundation of China

• clearance
• diagnosis and therapy
• fluorescent nanoparticles
• tumor targeting strategies

• Animals
• Fluorescent Dyes/adverse effects
• Fluorescent Dyes/chemistry
• Fluorescent Dyes/pharmacokinetics
• Fluorescent Dyes/therapeutic use
• Humans
• Molecular Targeted Therapy/methods
• Nanoparticles
• Neoplasms/diagnosis
• Neoplasms/drug therapy
• Neoplasms/pathology
• Safety
• Theranostic Nanomedicine/methods

• CA153
• CEA
• CIN
• Cell-free DNA
• Recurrent breast cancer

• Aryl hydrocarbon receptor
• Breast cancer
• Endocrine disruptor
• Hexachlorobenzene
• Mammary gland

• Animals
• Breast Neoplasms
• Child
• Endocrine Disruptors
• Female
• Fungicides, Industrial
• Hexachlorobenzene
• Humans
• Mammary Glands, Animal
• Signal Transduction

• Breast Cancer (BC)
• Diagnosis
• affinity biosensors (AS)
• enzyme-linked immunosorbent assay (ELISA)

• Autoantibodies/metabolism
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/metabolism
• Breast Neoplasms/diagnosis
• Breast Neoplasms/mortality
• Breast Neoplasms/pathology
• Female
• Humans
• Mammography
• Metabolomics
• MicroRNAs/metabolism
• Mucins/metabolism
• Saliva/chemistry
• Saliva/metabolism

• Primispot UK-Lebanon Tech Hub
• 768686 Horizon 2020 Framework Programme

• bladder cancer
• immunotherapy
• targeted therapy

• EGFR
• cell proliferation
• epigenetic drugs
• glioblastoma
• therapeutic targeting

• Brain Neoplasms/drug therapy
• Brain Neoplasms/genetics
• Brain Neoplasms/metabolism
• Cell Proliferation/drug effects
• Cell Transformation, Neoplastic
• DNA Methylation/drug effects
• Drug Resistance, Neoplasm/drug effects
• Epigenesis, Genetic
• ErbB Receptors/genetics
• ErbB Receptors/metabolism
• Glioblastoma/drug therapy
• Glioblastoma/genetics
• Glioblastoma/metabolism
• Histone Deacetylase Inhibitors/pharmacology
• Humans
• Protein Kinase Inhibitors/pharmacology
• Signal Transduction/drug effects

• Angiogenin
• Cancer
• Epidermal growth factor receptor
• Ligand
• Receptor tyrosine kinase
• Ribonuclease
• Serum biomarker
• Targeted therapy
• Tyrosine kinase inhibitor

• Humans
• Ligands
• Multigene Family/genetics
• Multigene Family/physiology
• Protein Binding
• Receptor Protein-Tyrosine Kinases/genetics
• Receptor Protein-Tyrosine Kinases/metabolism
• Ribonucleases/genetics
• Ribonucleases/metabolism

• CA211615 NIH HHS
• P30 CA016672 NCI NIH HHS
• CA201777 NIH HHS
• CA016672 NIH HHS
• U01 CA201777 NCI NIH HHS
• CA186892 NIH HHS
• R01 CA211615 NCI NIH HHS
• T32 CA186892 NCI NIH HHS
• National Institutes of Health
• Breast Cancer Research Foundation
• Ministry of Health and Welfare

• epidermal growth factor receptor
• invasive breast cancer
• paratumor breast tissues
• positive expression

• EGF-family
• EGFR-family
• Membrane dynamics
• Signaling
• Targeting
• Tyrosine kinase

• Digital ELISA
• EGFR ligands
• Multiplexed immunoassays
• Simoa
• Single molecule array

The hypothesis of this study was that MRI-based radiomics has the ability to predict recurrence-free survival “early on” in breast cancer neoadjuvant chemotherapy.

A subset, based on availability, of the ACRIN 6657 dynamic contrast-enhanced MR images was used in which we analyzed images of all women imaged at pre-treatment baseline (141 women: 40 with a recurrence, 101 without) and all those imaged after completion of the first cycle of chemotherapy, i.e., at early treatment (143 women: 37 with a recurrence vs. 105 without). Our method was completely automated apart from manual localization of the approximate tumor center. The most enhancing tumor volume (METV) was automatically calculated for the pre-treatment and early treatment exams. Performance of METV in the task of predicting a recurrence was evaluated using ROC analysis. The association of recurrence-free survival with METV was assessed using a Cox regression model controlling for patient age, race, and hormone receptor status and evaluated by C-statistics. Kaplan-Meier analysis was used to estimate survival functions.

The C-statistics for the association of METV with recurrence-free survival were 0.69 with 95% confidence interval of [0.58; 0.80] at pre-treatment and 0.72 [0.60; 0.84] at early treatment. The hazard ratios calculated from Kaplan-Meier curves were 2.28 [1.08; 4.61], 3.43 [1.83; 6.75], and 4.81 [2.16; 10.72] for the lowest quartile, median quartile, and upper quartile cut-points for METV at early treatment, respectively.

The performance of the automatically-calculated METV rivaled that of a semi-manual model described for the ACRIN 6657 study (published C-statistic 0.72 [0.60; 0.84]), which involved the same dataset but required semi-manual delineation of the functional tumor volume (FTV) and knowledge of the pre-surgical residual cancer burden.

• Breast cancer survival
• Dynamic contrast-enhanced breast MRI
• Most-enhancing tumor volume
• Radiomics