Estrogen receptor-beta is a potential target for triple negative breast cancer treatment.

Triple Negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2. TNBC accounts for 15-20% of all breast cancer cases but accounts for over 50% of mortality. We propose that Estrogen receptor-beta (ERβ) and IGF2 play a significant role in the pathogenesis of TNBCs, and could be important targets for future therapy. Tissue microarrays (TMAs) from over 250 TNBC patients' were analyzed for ERβ and IGF2 expression by immunohistochemistry. Expression was correlated with clinical outcomes. In addition, TNBC cell lines Caucasians (CA): MB-231/BT549 and African Americans (AAs): MB-468/HCC70/HCC1806 were used to investigate the effect of hormonal and growth factor regulation on cell proliferation. TMAs from AAs had higher expression of ERβ and IGF2 expression when compared to CA. ERβ and IGF2 were found to be upregulated in our TNBC cell lines when compared to other cell types. TNBC cells treated with ERβ agonist displayed significant increase in cell proliferation and migration when compared to controls. AA tissue samples from TNBC patients had higher expression of ERβ. African-American breast cancer TNBC tissue samples from TNBC patients have higher expression of ERβ. In addition, TNBC cell lines were also found to express high levels of ERβ. IGF2 increased transcription of ERβ in TNBC cells. Understanding the mechanisms of IGF2/ERβ axis in TNBC tumors could provide an opportunity to target this aggressive subtype of breast cancer

Lactate, a Neglected Factor for Diabetes and Cancer Interaction

Increasing body of evidence suggests that there exists a connection between diabetes and cancer. Nevertheless, to date, the potential reasons for this association are still poorly understood and currently there is no clinical evidence available to direct the proper management of patients presenting with these two diseases concomitantly. Both cancer and diabetes have been associated with abnormal lactate metabolism and high level of lactate production is the key biological property of these diseases. Conversely, high lactate contribute to a higher insulin resistant status and a more malignant phenotype of cancer cells, promoting diabetes and cancer development and progression. In view of associations between diabetes and cancers, the role of high lactate production in diabetes and cancer interaction should not be neglected. Here, we review the available evidence of lactate's role in different biological characteristics of diabetes and cancer and interactive relationship between them. Understanding the molecular mechanisms behind metabolic remodeling of diabetes- and cancer-related signaling would endow novel preventive and therapeutic approaches for diabetes and cancer treatment

Rationale and preclinical efficacy of a novel anti-EMP2 antibody for the treatment of invasive breast cancer

Despite significant advances in biology and medicine, the incidence and mortality due to breast cancer worldwide is still unacceptably high. Thus, there is an urgent need to discover new molecular targets. In this article, we show evidence for a novel target in human breast cancer, the tetraspan protein epithelial membrane protein-2 (EMP2). Using tissue tumor arrays, protein expression of EMP2 was measured and found to be minimal in normal mammary tissue, but it was upregulated in 63% of invasive breast cancer tumors and in 73% of triple-negative tumors tested. To test the hypothesis that EMP2 may be a suitable target for therapy, we constructed a fully human immunoglobulin G1 (IgG1) antibody specific for a conserved domain of human and murine EMP2. Treatment of breast cancer cells with the anti-EMP2 IgG1 significantly inhibited EMP2-mediated signaling, blocked FAK/Src signaling, inhibited invasion, and promoted apoptosis in vitro. In both human xenograft and syngeneic metastatic tumor monotherapy models, anti-EMP2 IgG1 retarded tumor growth without detectable systemic toxicity. This antitumor effect was, in part, attributable to a potent antibody-dependent cell-mediated cytotoxicity response as well as direct cytotoxicity induced by the monoclonal antibody. Together, these results identify EMP2 as a novel therapeutic target for invasive breast cancer.Fil: Fu, Maoyong. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Maresh , Erin L.. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires; ArgentinaFil: Kiyohara, Meagan. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Qin, yu. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Ashki, Negin. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Daniels Wells, Tracy R.. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Aziz, Najib. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Gordon, Lynn K.. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Braun, Jonathan. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Elshimali, Yahya. Charles Drew University. Department of Pathology; Estados UnidosFil: Soslow, Robert A.. Memorial Sloan-Kettering Cancer Center. Department of Pathology; Estados UnidosFil: Penichet, Manuel L.. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Goodglick, Lee. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados UnidosFil: Wadehra, Madhuri. University of California Los Angeles. David Geffen School of Medicine at UCLA; Estados Unido

Elevated MED28 expression predicts poor outcome in women with breast cancer

Abstract Background MED28 (also known as EG-1 and magicin) has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression. Methods Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed. Results MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non-malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death. Conclusions We have demonstrated that MED28 expression is increased in breast cancer. In addition, although the patient size was limited (88 individuals with survival information) MED28 is a novel and strong independent prognostic indicator of survival for breast cancer

The Clinical Utilization of Circulating Cell Free DNA (CCFDNA) in Blood of Cancer Patients

Qualitative and quantitative testing of circulating cell free DNA (CCFDNA) can be applied for the management of malignant and benign neoplasms. Detecting circulating DNA in cancer patients may help develop a DNA profile for early stage diagnosis in malignancies. The technical issues of obtaining, using, and analyzing CCFDNA from blood will be discussed

Triple negative breast tumors in African-American and Hispanic/Latina women are high in CD44+, low in CD24+, and have loss of PTEN.

BACKGROUND:African-American women have higher mortality from breast cancer than other ethnic groups. The association between poor survival and differences with tumor phenotypes is not well understood. The purpose of this study is to assess the clinical significance of (1) Stem cell-like markers CD44 and CD24; (2) PI3K/Akt pathway associated targets PTEN, activation of Akt, and FOXO1; and (3) the Insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP3) in different breast cancer subtypes, and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status. METHODS:A total of N=318 African-American and Hispanic/Latina women, with clinically-annotated information within the inclusion criteria were included. Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques. Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival (DFS). RESULTS:The triple-negative-breast-cancer (TNBC) receptor-subtype was more prevalent among premenopausal women, and the Hormonal Receptor (HR) positive subtype was most common overall. TNBC tumors were more likely to have loss of PTEN, express high Ki67, and have increased CD44+/CD24- expression. TNBC was also associated with higher plasma-IGF-I levels. HR-/HER2+ tumors showed high pAkt, decreased FOXO1, and high CD24+ expression. The loss of PTEN impacted DFS significantly in African Americans, but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors. The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS, but were not independent predictors for DFS. HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment. CONCLUSIONS:TNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles. Our study also shows for the first time that TNBC was significantly associated with PTEN loss, high Ki67 and the CD44+/CD24- phenotype. The loss of PTEN impacts DFS significantly in African Americans

Relationships Between Serum Expression of IGF-1 and Metabolic Syndrome Metrics in Syrian Women with Breast Cancer

Background and aims: Insulin-like Growth Factors (IGF-1) plays as mediator between metabolic syndrome (MetS), oxidative stress and breast cancer (BrCa) progression. The objective of this study was to examine the relationships between IGF-1 serum levels and metabolic profile biomarkers in a population group of BrCa patients

Angiolymphoid hyperplasia with eosinophilia: a case report

Abstract Background Angiolymphoid hyperplasia with eosinophilia is a benign neoplasm that includes blood vessel proliferation and a dense eosinophilic inflammatory infiltrate. Mostly, it affects middle-aged adults manifesting as flesh/plum-colored pruritic nodules and papules, most commonly affecting the ear and the periauricular area. Case presentation In this case, we report a 13-year-old Caucasian girl with bilateral, huge, protruding, and yellowish nostril masses which were peculiar in location and of gross appearance. At first, the disease proved to be a diagnostic dilemma. After making a diagnosis of angiolymphoid hyperplasia with eosinophilia, the disease also proved to be a therapeutic dilemma. It did not respond to oral prednisolone or to oral indomethacin, and it proved to be resistant to topical steroids. Although surgery is the standard therapeutic approach, it recurred despite multiple surgical attempts. However, the only regimen that seemed to partially control the lesion was intralesional steroids combined with topical tacrolimus ointment. Conclusions Angiolymphoid hyperplasia with eosinophilia proves a therapeutic dilemma, because there is a large variety of proposed treatments, yet there is not enough data on most of them. Although the disease is not deadly by itself, it usually presents with disfiguring lesions that grimly affect the patient’s quality of life. This warrants further research and efforts to find an effective cure and a unified therapeutic approach

Green tea and quercetin sensitize PC-3 xenograft prostate tumors to docetaxel chemotherapy.

BackgroundChemotherapy with docetaxel (Doc) remains the standard treatment for metastatic and castration-resistance prostate cancer (CRPC). However, the clinical success of Doc is limited by its chemoresistance and side effects. This study investigated whether natural products green tea (GT) and quercetin (Q) enhance the therapeutic efficacy of Doc in CRPC in mouse models.MethodsMale severe combined immunodeficiency (SCID) mice (n = 10 per group) were inoculated with androgen-independent prostate cancer PC-3 cells subcutaneously. When tumors were established the intervention started. Mice were administered with GT + Q, Doc 5 mg/kg (LD), GT + Q + LD Doc, Doc 10 mg/kg (HD) or control. The concentration of GT polyphenols in brewed tea administered as drinking water was 0.07% and Q was supplemented in diet at 0.4%. Doc was intravenously injected weekly for 4 weeks, GT and Q given throughout the study.ResultsGT + Q or LD Doc slightly inhibited tumor growth compared to control. However, the combination of GT and Q with LD Doc significantly enhanced the potency of Doc 2-fold and reduced tumor growth by 62% compared to LD Doc in 7-weeks intervention. A decrease of Ki67 and increase of cleaved caspase 7 were observed in tumors by the mixture, along with lowered blood concentrations of growth factors like VEGF and EGF. The mixture significantly elevated the levels of tumor suppressor mir15a and mir330 in tumor tissues. An increased risk of liver toxicity was only observed with HD Doc treatment.ConclusionsThese results provide a promising regimen to enhance the therapeutic effect of Doc in a less toxic manner