ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Spatial ecology of jaguars, pumas, and ocelots: a review of the state of knowledge

Knowledge of the spatial ecology of mammalian carnivores is critical for understanding species’ biology and designing effective conservation and management interventions. We reviewed the available information about the spatial ecology of jaguars Panthera onca, pumas Puma concolor, and ocelots Leopardus pardalis, and we examined how sex and extrinsic variables affect their spatial behaviour. Sixty-one articles addressing home range, home range overlap, daily net displacement (straight-line distance between two locations on consecutive days), and/or distance of dispersal of the three species were included. Meta-analysis, ANOVA, ANCOVA, and beta regression tests were run to analyse differences among species and sexes and to elucidate the influence of other variables, such as latitude and ecoregion, on spatial behaviour. Pumas had on average larger home ranges (mean ± SE: 281.87 ± 35.76 km) than jaguars (128.61 ± 49.5 km) and ocelots (12.46 ± 3.39 km). Intersexual range overlap was higher than intrasexual range overlap in jaguars and pumas. Sex affected the home range size of all three species, but only influenced daily net displacement in ocelots. Ecoregion affected the home range size of all three species but did not significantly affect either the daily net displacement or the dispersal distance of pumas. Latitude affected the home range size of jaguars and pumas. It did not affect daily net displacement or dispersal distance in jaguars and pumas, but did affect daily net displacement in ocelots. Although there was a lack of studies in most countries for the three species, information was particularly lacking in the Neotropics for jaguars and pumas and in North America for ocelots. Researchers usually presented low sample sizes and used different methods to examine the ecological issues considered here. Homogenisation of methods is needed to clarify the ecology of these species and to allow a better understanding of the threats to their populations.Peer Reviewe

Impact of Local Congruences in Attribute Reduction

Local congruences are equivalence relations whose equivalence classes are convex sublattices of the original lattice. In this paper, we present a study that relates local congruences to attribute reduction in FCA. Specifically, we will analyze the impact in the context of the use of local congruences, when they are used for complementing an attribute reduction

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial. Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro. Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors. Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group

Inherited variants in regulatory T cell genes and outcome of ovarian cancer.

Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored. We analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 54 genes associated with Tregs in 3,662 invasive ovarian cancer cases. With adjustment for known prognostic factors, suggestive results were observed among rarer histological subtypes; poorer survival was associated with minor alleles at SNPs in RGS1 (clear cell, rs10921202, p = 2.7×10(-5)), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10(-4), and rs3753348, p = 9.0×10(-4), respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10(-4)). Fo0r the latter, correlative data support a CD80 rs13071247 genotype association with CD80 tumor RNA expression (p = 0.006). An additional eQTL SNP in CD80 was associated with shorter survival (rs7804190, p = 8.1×10(-4)) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies

Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy

Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours

Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas

<p>Abstract</p> <p>Background</p> <p>Advanced biliary tract carcinomas (BTCs) have poor prognosis and limited therapeutic options. Therefore, it is crucial to combine standard therapies with molecular targeting. In this study EGFR, HER2, and their molecular transducers were analysed in terms of mutations, amplifications and over-expression in a BTC case series. Furthermore, we tested the efficacy of drugs targeting these molecules, as single agents or in combination with gemcitabine, the standard therapeutic agent against BTC.</p> <p>Methods</p> <p>Immunohistochemistry, FISH and mutational analysis were performed on 49 BTC samples of intrahepatic (ICCs), extrahepatic (ECCs), and gallbladder (GBCs) origin. The effect on cell proliferation of different EGFR/HER2 pathway inhibitors as single agents or in combination with gemcitabine was investigated on BTC cell lines. Western blot analyses were performed to investigate molecular mechanisms of targeted drugs.</p> <p>Results</p> <p>EGFR is expressed in 100% of ICCs, 52.6% of ECCs, and in 38.5% of GBCs. P-MAPK and p-Akt are highly expressed in ICCs (>58% of samples), and to a lower extent in ECCs and GBCs (<46%), indicating EGFR pathway activation. HER2 is overexpressed in 10% of GBCs (with genomic amplification), and 26.3% of ECCs (half of which has genomic amplification). EGFR or its signal transducers are mutated in 26.5% of cases: 4 samples bear mutations of PI3K (8.2%), 3 cases (6.1%) in K-RAS, 4 (8.2%) in B-RAF, and 2 cases (4.1%) in PTEN, but no loss of PTEN expression is detected. EGI-1 cell line is highly sensitive to gemcitabine, TFK1 and TGBC1-TKB cell lines are responsive and HuH28 cell line is resistant. In EGI-1 cells, combination with gefitinib further increases the antiproliferative effect of gemcitabine. In TFK1 and TGBC1-TKB cells, the efficacy of gemcitabine is increased with addiction of sorafenib and everolimus. In TGBC1-TKB cells, lapatinib also has a synergic effect with gemcitabine. HuH28 becomes responsive if treated in combination with erlotinib. Moreover, HuH28 cells are sensitive to lapatinib as a single agent. Molecular mechanisms were confirmed by western blot analysis.</p> <p>Conclusion</p> <p>These data demonstrate that EGFR and HER2 pathways are suitable therapeutic targets for BTCs. The combination of gemcitabine with drugs targeting these pathways gives encouraging results and further clinical studies could be warranted.</p