A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Breast cancer - Top 30 Publications

Bladder Metastases from Breast Cancer: Managing the Unexpected. A Systematic Review.

Breast cancer (BrC) has the highest incidence among females world over and it is one of the most common causes of death from cancer overall. Its high mortality is mostly due to its propensity to rapidly spread to other organs through lymphatic and blood vessels in spite of proper treatment. Bladder metastases from BrC are rare, with 50 cases having been reported in the last 60 years. This review aims to discuss some critical points regarding this uncommon condition. First, we performed a systematic review of the literature in order to draw a clinical and pathological profile of this entity. On this basis, its features in terms of diagnostic issues, imaging techniques, and survival are critically examined. Most bladder metastases from BrC are secondary lobular carcinoma, which mimic very closely the rare variant of urothelial cancer with lobular carcinoma-like features (uniform cells with an uncohesive single-cell, diffusely invasive growth pattern); thus, immunohistochemistry is mandatory to arrive at a correct diagnosis. This article summarizes the current knowledge regarding the incidence, clinical presentation, diagnosis, prognosis, and treatment of bladder metastases in patients with BrC.

A cost-sensitive Bayesian combiner for reducing false positives in mammographic mass detection.

Mammography is the most widely used modality for early breast cancer detection. This work proposes a new computer-aided mass detection approach, in which a denoising method called BM3D is first applied to mammograms. Afterwards, using an adaptive segmentation algorithm, images are segmented to suspicious regions of interest (ROIs) and then a classifier is used to understand the features of true positive (TP) and false positive (FP) patterns. In this way, from selected suspicious ROIs, fractal dimension, texture and intensity features are extracted. Subsequently, a discretization approach followed by correlation-based feature selection (CFS) is combined with a genetic algorithm to obtain the most representative features. To neutralize the classifier's bias in favor of the major class in imbalanced datasets, an oversampling algorithm is used. In the next step, a cost-sensitive ensemble classifier based on a trainable combiner is proposed in order to reduce the number of FP samples. Finally, the presented method is validated on miniMIAS and INBreast datasets. The free-response receiver operating characteristic (FROC) analysis results prove the efficiency of the proposed approach. A sensitivity of 88% and false positive per image (FPpI) of 0.78 for miniMIAS and also a sensitivity of 86% and FPpI of 0.75 for INBreast dataset were obtained.

Response rate as a potential surrogate for survival and efficacy in patients treated with novel immune checkpoint inhibitors: A meta-regression of randomised prospective studies.

To assess the role of the tumour response rate (RR) after immune checkpoint inhibitors-based therapy as a potential surrogate end-point of progression-free survival (PFS) and overall survival (OS) in patients with solid tumours, we performed a trial-based meta-regression of randomised studies comparing different immune checkpoint inhibitors-based treatments.

Small size mesoporous organosilica nanorods with different aspect ratios: Synthesis and cellular uptake.

In the work, small size thioether-bridged mesoporous organosilica nanorod (MONRs) are successfully synthesized using cetyltrimethylammonium bromide (CTAB) as structure-directing agent and bis[3-(triethoxysilyl)propyl]tetrasulfide (TETS) and tetraethoxysilane (TEOS) as co-precursors. The MONRs have tunable aspect ratios of 2, 3, and 4 (denoted as MONRs-2, MONRs-3, and MONRs-4), small and controllable lengths (75-310nm), high surface area (570-870cm(2)g(-1)), uniform mesopores (2.4-2.6nm), large pore volume (0.34cm(3)g(-1)), and excellent biocompatibility. The uptake of the MONRs by multidrug resistant human breast cancer MDR-MCF-7 cells is related to their aspect ratios. The MONRs-3 shows a faster and higher cellular internalization compared to the MONRs-4 and MONRs-2, respectively. Thanks to the high cellular uptake, doxorubicin (DOX) loaded MONRs-3 show obviously improved chemotherapeutic effect on MDR-MCF-7 cancer cells. It is expected that the MONRs provide a useful platform for drug delivery and therapeutics.

α-Actinin-4 confers radioresistance coupled invasiveness in breast cancer cells through AKT pathway.

Acquired radioresistance accompanied with increased metastatic potential is a major hurdle in effective radiotherapy of breast cancers. However, the nature of their inter-dependence and the underlying mechanism remains largely intangible. By employing radioresistant (RR) cell lines, we herein demonstrate that MCF-7 RR cells display phenotypic and molecular alterations evocative of epithelial to mesenchymal transition (EMT) with increased traction forces and membrane ruffling culminating in boosted invasiveness. We then show that these changes can be attributed to overexpression of alpha-actinin-4 (ACTN4), with ACTN4 knockdown near-completely abrogating both radioresistance and EMT-associated changes. We further found that in MCF-7 RR cells, ACTN4 mediates the observed effects by activating AKT, and downstream AKT/GSK3β signalling. Though ACTN4 plays a similar role in mediating radioresistance and invasiveness in MDA-MB-231 RR cells, co-immunoprecipitation studies reveal that these changes are effected through increased association with AKT and not by overexpression of AKT. Taken together, our study identifies ACTN4/AKT/GSK3β as a novel pathway regulating radioresistance coupled invasion which can be further explored to improve the radiotherapeutic gain.

Decrypting the PAK4 transcriptome profile in mammary tumor forming cells using Next Generation Sequencing.

The p-21 Activated Kinase 4 (PAK4) protein kinase is implicated in many cancers, including breast cancer. Overexpression of PAK4 is sufficient to cause mouse mammary epithelial cells (iMMECs) to become tumorigenic. To gain insight into the long-term gene expression changes that occur downstream to PAK4, we performed Next Generation Sequencing of RNA collected from PAK4 overexpressing iMMECs and wild-type iMMECs. We identified a list of genes whose expression levels were altered in response to PAK4 overexpression in iMMECs. Some of these genes, including FoxC2 and ParvB, are consistent with a role for PAK4 in cancer. In addition, PAK4 regulates many genes that are frequently associated with the inflammatory response, raising the possibility that there is a connection between PAK4, inflammation, and the tumor microenvironment. This study delineates the PAK4 transcriptome profile in transformed mammary cells and can provide translational utility in other types of cancers as well.

Trop2 antibody-conjugated bioreducible nanoparticles for targeted triple negative breast cancer therapy.

Trop2, a transmembrane glycoprotein, has emerged as a biomarker for targeted cancer therapy since it is overexpressed in 80% of triple negative breast cancer (TNBC) patients. For the site-specific delivery of the anticancer drug into TNBC, Trop2 antibody-conjugated nanoparticles (ST-NPs) were prepared as the potential nanocarrier, composed of carboxymethyl dextran (CMD) derivatives with bioreducible disulfide bond. Owing to its amphiphilicity, the CMD derivatives were self-assembled into nano-sized particles in an aqueous condition. Doxorubicin (DOX), chosen as a model anticancer drug, was effectively encapsulated into the nanoparticles. DOX-loaded ST-NPs (DOX-ST-NPs) rapidly released DOX in the presence of 10mM glutathione (GSH), whereas the DOX release is significantly retarded in the physiological condition (PBS, pH 7.4). Confocal microscopic images and flow cytometry analysis demonstrated that DOX-ST-NPs were selectively taken up by MDA-MB-231 as the representative Trop2-expressing TNBC cells. Consequently, DOX-ST-NPs exhibited higher toxicity to Trop2-positive MDA-MB-231 cancer cells, compared to DOX-loaded control nanoparticles without the disulfide bond or Trop2 antibody. Overall, ST-NPs might be a promising carrier of DOX for targeted TNBC therapy.

Sphingosine kinase 1 in breast cancer.

Breast cancer affects 1 out of 8 women in the US and is the second highest cause of death from cancer for women, leading to considerable research examining the causes, progression, and treatment of breast cancer. Over the last two decades, sphingosine-1-phosphate (S1P), a potent sphingolipid metabolite, has been implicated in many processes important for breast cancer including growth, progression, transformation and metastasis, and is the focus of this review. In particular, one of the kinases that produces S1P, sphingosine kinase 1 (SphK1), has come under increasing scrutiny as it is commonly upregulated in breast cancer cells and has been linked with poorer prognosis and progression, possibly leading to resistance to certain anti-cancer therapies. In this review, we will also discuss preclinical studies of both estrogen receptor (ER) positive as well as triple-negative breast cancer mouse models with inhibitors of SphK1 and other compounds that target the S1P axis and have shown good promise in reducing tumor growth and metastasis. It is hoped that in the future this will lead to development of novel combination approaches for effective treatment of both conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer.

Geriatric assessment and biomarkers in patients with metastatic breast cancer receiving first-line mono-chemotherapy: Results from the randomized phase III PELICAN trial.

To determine predictive/prognostic factors for patients with metastatic breast cancer (MBC) receiving first-line monochemotherapy using biomarker analysis and geriatric assessment (GA).

Mobile Versus Fixed Facility: Latinas' Attitudes and Preferences for Obtaining a Mammogram.

Mobile mammographic services have been proposed as a way to reduce Latinas' disproportionate late-stage presentation compared with white women by increasing their access to mammography. The aims of this study were to assess why Latinas may not use mobile mammographic services and to explore their preferences after using these services.

Spiral shape microfluidic channel for selective isolating of heterogenic circulating tumor cells.

Detecting heterogenic tumor cells that are traveling in our body through blood stream for the tumor metastasis is one way for cancer prognosis. Due to the heterogeneity of circulating tumor cells (CTCs), further identification of tumor cell types should be accompanied with CTCs isolation from blood cells in peripheral blood sample. Both negative enrichment and recollection of isolated CTCs are required in the downstream analysis, which are time-consuming, labor-intensive, and massive equipment required. To solve these limitations, we have developed a simple and disposable spiral shape microfluidic channel that can separate all CTCs from blood cells, and at the same time, can identify the types of CTCs based on epithelial cell adhesion molecule (EpCAM) expression level. Two different types of tumor cells, MCF-7 and MDA-MB-231, both from the same origin of breast carcinoma cells, were used to demonstrate the functionality of the developed system. The spiral channel system could capture the EpCAM positive and negative CTCs with 96.3% and 81.2% purity, respectively, while both EpCAM positive and negative CTCs were differently positioned along the microfluidic channel. The average selectivity of EpCAM positive and negative CTCs is 6.1:4.8. In addition, the throughput of the system was optimized at a sample flow rate of 150µl/min. The developed system successfully demonstrated its potential to identify biomarkers, including EpCAM, for detecting the heterogenic CTCs.

The childhood maltreatment influences on breast cancer patients: A second wave hit model hypothesis for distinct biological and behavioral response.

Stress and cancer are two complex situations involving different biological and psychological mechanisms. Their relationship have long been studied, and there is evidence of the impact stress has on both, development and disease progression. Furthermore, early stress has been studied as an important factor associated to this relationship, since its impacts on the immune, endocrine and cognitive development throughout life is already known. Therefore, understanding early stress as a first wave of stress in life is necessary in order to explore a possible second wave hit model. From this perspective, we believe that breast cancer can be understood as a second wave of stress during development and that, in addition to the first wave, can cause important impacts on the response to cancer treatment, such as increased chances of disease progression and distinct behavioral responses. In this article we propose a second wave hit hypothesis applied to breast cancer and its implications on the immune, endocrine and cognitive systems, through mechanisms that involve the HPA axis and subsequent activations of stress responses.

Trends in incidence and associated risk factors of suicide mortality among breast cancer patients.

Breast cancer patients are associated with an increased risk for committing suicide. The purpose of this study is to study the trends in the incidence of suicide mortality and identify pertinent risk factors among patients with breast cancer.

In Defense of Progesterone: A Review of the Literature.

Context • The medical literature on the use of progesterone in postmenopausal women is often confusing and contradictory. Some physicians implicate natural progesterone in an increase in the risk of breast cancer. The chemical structure of natural progesterone (P4) is quite different from chemically altered, synthetic chemicals called progestins, which results in different actions at the cell level. Objective • The research team intended to review the literature to examine the benefits and safety of natural progesterone and determine whether it can cause an increase or decrease in breast cancer risk. Design • A review of the medical literature to examine the benefits and safety of natural progesterone as compared with synthetic progestins. Intervention • Studies examined compared controls not receiving hormone therapy with women receiving estrogen alone and in combination with natural progesterone and with various synthetic progestins, such as medroxyprogesterone acetate-the most commonly used synthetic progestin. Outcome Measures • Outcome measures included factors such as progression and survival of breast and other cancers and other epidemiological and laboratory data. Results • A meta-analysis of 3 studies involving 86 881 postmenopausal women reported that the use of natural progesterone was associated with a significantly lower risk of breast cancer compared with synthetic progestins. Anovulation and low levels of serum progesterone have been associated with a significantly higher risk of breast cancer in premenopausal women. Use of progesterone has been linked to lower rates of uterine and colon cancers and may also be useful in treating other cancers such as ovarian, melanoma, mesothelioma, and prostate. Progesterone may also be helpful in preventing cardiovascular disease and preventing and treating neurodegenerative conditions such a stroke and traumatic brain injury. Conclusions • Physicians should have no hesitation prescribing natural progesterone. The evidence is clear that progesterone does not cause breast cancer. Indeed, progesterone is protective and preventative of breast cancer.

Three-dimensional versus two-dimensional shear-wave elastography: Associations of mean elasticity values with prognostic factors and tumor subtypes of breast cancer.

To explore associations between prognostic factors and subtypes of invasive breast cancer (IBC) and elasticity values using three-dimensional (3D) and two-dimensional (2D) shear-wave elastography (SWE).

Evaluation of the antioxidant impact of ginger-based kombucha on the murine breast cancer model.

Background Abnormal metabolism is a common event in cancerous cells. For example, the increase of reactive oxygen species (ROS) production, particularly due to aerobic respiration during invasive stage, results in cancer progression. Herein, the impact of kombucha tea prepared from ginger on the alteration of antioxidant agents was assessed in the breast cancer animal model. Methods Two types of kombucha tea with or without ginger were administered to BALB/c mice before and after tumor challenge. Superoxide dismutase (SOD), catalase, glutathione (GSH) and malondialdehyde (MDA) were evaluated in tumor, liver and kidney. Results Administration of kombucha ginger tea significantly decreased catalase activity as well as GSH and MDA level in tumor homogenate (p<0.001). A significant decrease in SOD activity and increase in MDA quantity was determined in the kidney which had received kombucha ginger tea (p<0.01). Conclusions The consumption of kombucha prepared from ginger could exert minor antioxidant impacts by balancing multi antioxidant factors in different tissues in the breast cancer models.

Cognition, quality-of-life and symptom clusters in breast cancer: using Bayesian networks to elucidate complex relationships.

Breast cancer patients frequently complain of cognitive dysfunction during chemotherapy. Patients also report experiencing a cluster of sleep problems, fatigue and depressive symptoms during chemotherapy. We aimed to understand the complex dynamic interrelationships of depression, fatigue, and sleep to ultimately elucidate their role in cognitive performance and quality of life among breast cancer survivors undergoing chemotherapy treatment.

Gonadotropin-releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta-analysis.

To evaluate the effectiveness of GnRH agonist (GnRHa) administration before and/or during cancer chemotherapy for the protection of ovarian reserve in premenopausal women.

Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men.

Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and tallness are risk factors for MBC, but the role of adolescent fatness is largely unknown. We aimed to assess the association between body mass index (BMI) in adolescence and the incidence of MBC in a large cohort of 16-19 year-old Israeli males. 1,382,093 Jewish Israeli males aged 16-19 who underwent anthropometric measurements, a General Intelligence Test (GIT) and other examinations during 1967-2011, were followed up to 31.12.2012 for MBC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as WHO BMI categories and as age-specific CDC percentiles) and time to MBC diagnosis, adjusting for sociodemographic covariates. Of 100 MBC cases diagnosed during 29,386,233 person-years of follow-up, 97 were included in multivariable analyses. Compared to 'healthy' BMI (18.5-24.9kg/m(2) ) and adjusted for year of birth, country of origin and GIT score, higher adolescent BMI was associated with higher MBC risk: hazard ratio (HR)=2.01 (95% confidence interval [CI]1.14-3.55, p=0.015) in overweight (25.0≤BMI<30.0kg/m(2) ) adolescents; and HR=4.97 (95%CI 2.14-11.53, p=0.0002) in obese (BMI≥30.0kg/m(2) ) adolescents. When CDC age-specific BMI percentiles were assessed results were similar and statistically significant for obesity. Additionally, low (vs. high) GIT score (HR=4.76, 95%CI 1.96-12.50, p=0.001) and European (vs. west-Asian) origin (HR=1.99, 95%CI 1.19-3.34, p=0.009) were independent predictors of MBC. Measured adolescent overweight and obesity are associated with increased risk of MBC, suggesting a modifiable risk factor potentially allowing for early intervention. The novel association with cognitive function should be further explored. This article is protected by copyright. All rights reserved.

Protein acyltransferase DHHC3 regulates breast tumor growth, oxidative stress and senescence.

DHHC-type protein acyltransferases may regulate the localization, stability and/or activity of their substrates. In this study, we show that the protein palmitoyltransferase DHHC3 is upregulated in malignant and metastatic human breast cancer. Elevated expression of DHHC3 correlated with diminished patient survival in breast cancer and six other human cancer types. ZDHHC3 ablation in human MDA-MB-231 mammary tumor cell xenografts reduced the sizes of both the primary tumor and metastatic lung colonies. Gene array data and fluorescence dye assays documented increased oxidative stress and senescence in ZDHHC3-ablated cells. ZDHHC3-ablated tumors also showed enhanced recruitment of innate immune cells (anti-tumor macrophages, natural killer cells) associated with clearance of senescent tumors. These anti-tumor effects were reversed upon reconstitution with wildtype, but not enzyme-active site-deficient DHHC3. Concomitant ablation of the upregulated oxidative stress protein TXNIP substantially negated the effects of ZDHHC3 depletion on oxidative stress and senescence. Diminished DHHC3-dependent palmitoylation of ERGIC3 protein likely played a key role in TXNIP upregulation. In conclusion, DHHC3-mediated protein palmitoylation supports breast tumor growth by modulating cellular oxidative stress and senescence.

Breast Cancer Cells Recycle Ammonia to Generate Amino Acids.

Ammonia generated from glutamate metabolism enhances the proliferation of breast cancer cells.

Caveolae-mediated endocytosis as a novel mechanism of resistance to trastuzumab emtansine (T-DM1).

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that has demonstrated clinical benefit for patients with HER2+ metastatic breast cancer, however its clinical activity is limited by inherent or acquired drug resistance. The molecular mechanisms that drive clinical resistance to T-DM1, especially in HER2+ tumors, are not well understood. We used HER2+ cell lines to develop models of T-DM1 resistance utilizing a cyclical dosing schema in which cells received T-DM1 in an "on-off" routine until a T-DM1 resistant population was generated. T-DM1 resistant N87 cells (N87-TM) were cross-resistant to a panel of trastuzumab-ADCs (T-ADCs) with non-cleavable-linked auristatins. N87-TM cells do not have a decrease in HER2 protein levels or an increase in drug transporter protein (e.g. MDR1) expression compared to parental N87 cells. Intriguingly, T-ADCs utilizing auristatin payloads attached via an enzymatically cleavable linker overcome T-DM1 resistance in N87-TM cells. Importantly, N87-TM cells implanted into athymic mice formed T-DM1 refractory tumors which remain sensitive to T-ADCs with cleavable-linked auristatin payloads. Comparative proteomic profiling suggested enrichment in proteins that mediate caveolae formation and endocytosis in the N87-TM cells. Indeed, N87-TM cells internalize T-ADCs into intracellular caveolin-1 (CAV1) positive puncta and alter their trafficking to the lysosome compared to N87 cells. T-DM1 colocalization into intracellular CAV1 positive puncta correlated with reduced response to T-DM1 in a panel of HER2+ cell lines. Together, these data suggest caveolae-mediated endocytosis of T-DM1 may serve as a novel predictive biomarker for patient response to T-DM1.

Breast cancer in Latinas: a focus on intrinsic subtypes distribution.

Breast cancer is the most frequent cancer in women worldwide. It is classified into intrinsic subtypes characterized by different molecular profiles and prognosis. The prevalence of the different intrinsic subtypes varies between population groups. Immunohistochemistry surrogates based on the expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) have been widely used to study the distribution of intrinsic subtypes in Non-Hispanic Whites and African Americans, but data is limited for Hispanic/Latina women. Similarly, most studies analyzing gene expression profiles only include women of European descent. The present review focuses on studies that describe the distribution of breast cancer subtypes in Hispanic/Latina women and highlights the need for more research in this population.

Natural killer T-cell immunotherapy in combination with chemotherapy-induced immunogenic cell death targets metastatic breast cancer.

Natural killer T (NKT) cells are glycolipid-reactive lymphocytes that promote cancer control. In previous studies, NKT-cell activation improved survival and antitumor immunity in a post-surgical mouse model of metastatic breast cancer. Herein, we investigated whether NKT-cell activation could be combined with chemotherapeutic agents to augment therapeutic outcomes. Gemcitabine and cyclophosphamide analogs enhanced the potential immunogenicity of 4T1 mammary carcinoma cells by increasing the expression of antigen-presenting molecules (MHC-I, MHC-II, and CD1d) and promoting exposure or release of immunogenic cell death markers (calreticulin, HMGB1 and ATP). In 4T1 primary tumor and post-surgical metastasis models, BALB/c mice were treated with cyclophosphamide or gemcitabine. NKT cells were then activated by transfer of dendritic cells loaded with the glycolipid antigen α-galactosylceramide (α-GalCer). Chemotherapeutic treatments did not impact NKT-cell activation but enhanced recruitment into primary tumors. Cyclophosphamide, gemcitabine, or α-GalCer-loaded dendritic cell monotherapies decreased tumor growth in the primary tumor model, and reduced metastatic burden and prolonged survival in the metastasis model. Combining chemotherapeutics with NKT cell activation therapy significantly enhanced survival, with surviving mice exhibiting attenuated tumor growth following a second tumor challenge. The frequency of myeloid derived suppressor cells was reduced by gemcitabine, cyclophosphamide, or α-GalCer-loaded dendritic cell treatments; cyclophosphamide also reduced the frequency of regulatory T cells. Individual treatments increased immune cell activation, cytokine polarization, and cytotoxic responses, although these readouts were not enhanced further by combining therapies. These findings demonstrate that NKT-cell activation therapy can be combined with gemcitabine or cyclophosphamide to target tumor burden and enhance protection against tumor recurrence.

The role of patient and physician advocacy in reducing wait times for cancer care: a qualitative analysis.

There is growing interest in the role of physician as health advocate; however, few studies have documented advocacy from the patient's perspective. To address this gap, we examined the experiences of patients with cancer from the onset of symptoms to the start of treatment in Newfoundland and Labrador and aimed to describe wait times and efforts to improve timeliness of care from the patients' perspective.

Systematic evaluation of cell-SELEX enriched aptamers binding to breast cancer cells.

The sensitive and specific detection of pathogenic cells is essential in clinical diagnostics. To achieve this, molecular tools are required that unequivocally recognise appropriate cell surface molecules, such as biomarkers that come along with disease onset and progression. Aptamers are short single-stranded oligonucleotides that interact with cognate target molecules with high affinity and specificity. Within the last years they have gained an increased attention as cell-recognition tools. Here, we report a systematic analysis of a cell-SELEX procedure, for the identification of aptamers that recognise breast cancer cells. Besides a comparison of conventional (Sanger) with high-throughput sequencing techniques (next-generation sequencing), three different screening techniques have been applied to characterise the binding properties of selected aptamer candidates. This method has been found to be beneficial in finding DNA aptamers, rarely enriched in the libraries. Finally, four DNA aptamers were identified that exhibit broad-spectrum interaction patterns to different cancer cell lines derived from solid tumours.

Developing a Xenograft Human Tumor Model in Immunocompetent Mice.

Animal models are essential to cancer research, but current xenograft models are limited in their utility especially due to the lack of an immune system. Here we demonstrate that a xenograft tumor model can be developed in immunocompetent mice by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were injected into day E14 fetuses and after birth mice were challenged with A375 cells to determine their ability to develop tumors. Intravenous injections of cells resulted in metastatic-like lung tumors, which were verified to be human in origin by immunohistochemistry and PCR. These results were replicated with several other human tumor types: BxPC3 (human pancreatic adenocarcinoma), MDA-MB-231 (human breast adenocarcinoma), M21 (human melanoma), and HeLa (human cervical adenocarcinoma). Development of an immunocompetent xenograft tumor model would allow the further elucidation of the interaction of the immune system with therapy in both preclinical research and patient derived xenografts.

Novel p-carborane-containing multitarget anticancer agents inspired by the metabolism of 17β-estradiol.

The female hormone 17 β-estradiol (E2) is synthesized from estrone by steroid sulfatase (STS), and metabolized into 2-methoxyestradiol (2-ME), whereby the biological activity of the latter is substantially different from that of E2. Based on the metabolic pathways of E2, a carborane-containing 2-ME mimic (1c) and its derivatives (1 and 2) were designed and synthesized as novel multitarget anticancer agents. Bissulfamate 1f exhibited potent STS-inhibitory activity and tubulin-polymerization-inhibitory activity. Moreover, the cell-growth-inhibitory (CGI) activity of 1f was similar to that of 2-ME in a panel screening against 39 human cancer cell lines. Accordingly, 1f should be a promising perspective therapeutic agent for hormone-dependent breast tissue.

Breast Cancer Survivorship Care Variations Between Adjuvant Chemotherapy Regimens.

Treatment-related toxicity can vary substantially between chemotherapy regimens. In this study we evaluated the frequency of outpatient office visits among a cohort of early stage breast cancer survivors after completion of 4 different adjuvant chemotherapy regimens to better understand how differences in toxicities between regimens might affect health care use.

CD21(lo/med)CD27(+) proinflammatory B cells are enriched in breast cancer patients and promote antitumor T cell responses.

Breast cancer is a common malignancy and a major cause of death in women worldwide. The immunomodulatory role of B cells is being increasingly recognized in autoimmune diseases and cancers. In recent years, immunotherapeutic strategies that upregulate the patient's own antitumor T cell responses have shown promise in treating solid tumors and are being developed for breast cancer. In this study, we discovered that the B cells in breast cancer patients were enriched with interferon (IFN)-γ-expressing cells and presented high potency for IFN-γ production. These IFN-γ-expressing B cells were enriched in, but did not completely overlap with, the CD21(lo/med)CD27(+)IgM(-)IgD(-)IgG(+)IgA(-) B cell subset, which was consistent with IgG-expressing memory B cells. Compared to CD27(+)IgG(-) B cells, the CD27(+)IgG(+) B cells expressed significantly higher IFN-γ expression. Given that B cells demonstrate important antigen-presenting function to T cells, we incubated CD27(+)IgG(-) B cells and CD27(+)IgG(+) B cells with autologous CD4(+) T cells. Compared to the CD4(+) T cells that were incubated with CD27(+)IgG(-) B cells, the CD4(+) T cells that were incubated with CD27(+)IgG(+) B cells presented significantly higher TBX21 and lower FOXP3 expression, suggesting that the CD27(+)IgG(+) B cells, but not the CD27(+)IgG(-) B cells, promoted Th1 and suppressed regulatory T cell responses. IFN-γ-expressing B cells were further enriched in the intratumoral environment of breast cancer patients. Together, we discovered that breast cancer patients presented an upregulation of IFN-γ-expressing proinflammatory B cells with the potency to promote Th1 responses.