Solicitantes de asilo en Bulgaria

Los solicitantes de asilo soportan un trato terrible en el centro de detención de inmigrantes de Bulgaria. Considerados como inmigrantes indocumentados, son sancionados y deportados, en un claro quebrantamiento de la legislación búlgara y de las obligaciones de la Convención sobre los Refugiados

ACROBAT -- a multi-stain breast cancer histological whole-slide-image data set from routine diagnostics for computational pathology

The analysis of FFPE tissue sections stained with haematoxylin and eosin (H&E) or immunohistochemistry (IHC) is an essential part of the pathologic assessment of surgically resected breast cancer specimens. IHC staining has been broadly adopted into diagnostic guidelines and routine workflows to manually assess status and scoring of several established biomarkers, including ER, PGR, HER2 and KI67. However, this is a task that can also be facilitated by computational pathology image analysis methods. The research in computational pathology has recently made numerous substantial advances, often based on publicly available whole slide image (WSI) data sets. However, the field is still considerably limited by the sparsity of public data sets. In particular, there are no large, high quality publicly available data sets with WSIs of matching IHC and H&E-stained tissue sections. Here, we publish the currently largest publicly available data set of WSIs of tissue sections from surgical resection specimens from female primary breast cancer patients with matched WSIs of corresponding H&E and IHC-stained tissue, consisting of 4,212 WSIs from 1,153 patients. The primary purpose of the data set was to facilitate the ACROBAT WSI registration challenge, aiming at accurately aligning H&E and IHC images. For research in the area of image registration, automatic quantitative feedback on registration algorithm performance remains available through the ACROBAT challenge website, based on more than 37,000 manually annotated landmark pairs from 13 annotators. Beyond registration, this data set has the potential to enable many different avenues of computational pathology research, including stain-guided learning, virtual staining, unsupervised pre-training, artefact detection and stain-independent models

MicroRNA-519a is a novel oncomir conferring tamoxifen resistance by targeting a network of tumour-suppressor genes in ER+ breast cancer

Cataloged from PDF version of article.Tamoxifen is an endocrine therapy which is administered to up to 70% of all breast cancer patients with oestrogen receptor alpha (ERα) expression. Despite the initial response, most patients eventually acquire resistance to the drug. MicroRNAs (miRNAs) are a class of small non-coding RNAs which have the ability to post-transcriptionally regulate genes. Although the role of a few miRNAs has been described in tamoxifen resistance at the single gene/target level, little is known about how concerted actions of miRNAs targeting biological networks contribute to resistance. Here we identified the miRNA cluster, C19MC, which harbours around 50 mature miRNAs, to be up-regulated in resistant cells, with miRNA-519a being the most highly up-regulated. We could demonstrate that miRNA-519a regulates tamoxifen resistance using gain- and loss-of-function testing. By combining functional enrichment analysis and prediction algorithms, we identified three central tumour-suppressor genes (TSGs) in PI3K signalling and the cell cycle network as direct target genes of miR-519a. Combined expression of these target genes correlated with disease-specific survival in a cohort of tamoxifen-treated patients. We identified miRNA-519a as a novel oncomir in ER+ breast cancer cells as it increased cell viability and cell cycle progression as well as resistance to tamoxifen-induced apoptosis. Finally, we could show that elevated miRNA-519a levels were inversely correlated with the target genes' expression and that higher expression of this miRNA correlated with poorer survival in ER+ breast cancer patients. Hence we have identified miRNA-519a as a novel oncomir, co-regulating a network of TSGs in breast cancer and conferring resistance to tamoxifen. Using inhibitors of such miRNAs may serve as a novel therapeutic approach to combat resistance to therapy as well as proliferation and evasion of apoptosis in breast cancer. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

The Prognostic Significance of Phosphatase and Tensin Homolog Loss in Breast Cancer

AIM: This study aims to determine the prognostic significance of phosphatase and tensin homolog (PTEN) loss in breast cancer. METHODS: We conducted a meta-analysis study. Sample of this study were research articles that evaluated PTEN loss and prognosis in breast cancer patients. We searched for relevant studies published in PubMed and Proquest from January 2010 to July 2018. We reviewed studies that examined the association between immunohistochemical expression of PTEN and breast cancer prognosis using meta-analysis methods. Pooled risk ratios (RR) were calculated using fixed and random-effect models. Data were processed using Review Manager 5.3 (RevMan 5.3). RESULTS: There were 7 studies conducted a systematic review then continued to evaluate the association of PTEN loss and breast cancer prognosis by meta-analysis. There was a significant association of PTEN loss with poor prognosis of breast cancer (RR = 0.76 [95% CI 0.59-0.98 p <0.07), and there was not any significant publication bias for studies included. CONCLUSION: This study confirmed PTEN loss is an important independent factor for breast cancer prognosis

Risk stratification in early breast cancer in premenopausal and postmenopausal women: integrating genomic assays with clinicopathological features.

PURPOSE OF REVIEW: There is growing consensus that genomic assays provide useful complementary information to clinicopathological features in oestrogen receptor-positive breast cancers. Here, ongoing research with multigene tests used for postmenopausal breast cancer and new emerging prognostic and predictive markers for pre and postmenopausal women are summarised. RECENT FINDINGS: Results of the TAILORx trial have shown that women with an intermediate risk score do not benefit from adjuvant chemotherapy. Prosgina has been further investigated in a contemporary patient population in postmenopausal women and its use has been extended for premenopausal women. The EndoPredict was extensively used in decision-impact studies showing that its use can potentially reduce the need for adjuvant chemotherapy. Several new genomic assays have been developed, with some of them showing promising use for women with early oestrogen receptor-positive breast cancer. SUMMARY: New areas of research for prediction of recurrence and risk stratification involve the development of immune gene signatures that carry modest but significant prognostic value. The recent expansion of high-throughput technology platforms including circulating tumour DNA/RNA and microRNA offer new opportunities to improve prediction models, particularly in women with oestrogen receptor-negative disease and premenopausal women. Genomic assays have clearly improved prognostication of early oestrogen receptor-positive breast cancer but it is clear that standard clinicopathological parameters are still very important when identifying patient for adjuvant chemotherapy.is work has been supported by Cancer Research U

Clinical Utility of Multigene Profiling Assays in Early-Stage Invasive Breast Cancer: An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline

Objective: The purpose of this guideline is to determine the clinical utility of multigene profiling assays in individuals with early-stage invasive breast cancer. Methods: This guideline was developed by Ontario Health (Cancer Care Ontario)’s Program in Evidence-Based Care (PEBC) through a systematic review of relevant literature, patient- and caregiver-specific consultation and internal and external reviews. Recommendation 1: In patients with early-stage estrogen receptor (ER)-positive/human epidermal growth factor 2 (HER2)-negative breast cancer, clinicians should consider using multigene profiling assays (i.e., Oncotype DX, MammaPrint, Prosigna, EndoPredict, and the Breast Cancer Index) to help guide the use of systemic therapy. Recommendation 2: In patients with early-stage node-negative ER-positive/HER2-negative disease, clinicians may use a low-risk result from Oncotype DX, MammaPrint, Prosigna, EndoPredict/EPclin, or Breast Cancer Index assays to support a decision not to use adjuvant chemotherapy. Recommendation 3: In patients with node-negative ER-positive/HER2-negative disease, clinicians may use a high-risk result from Oncotype DX to support a decision to offer chemotherapy. A high Oncotype DX recurrence score is capable of predicting adjuvant chemotherapy benefit. Recommendation 4: In postmenopausal patients with ER-positive/HER2-negative tumours and one to three nodes involved (N1a disease), clinicians may withhold chemotherapy based on a low-risk Oncotype DX or MammaPrint score if the decision is supported by other clinical, pathological, or patient-related factors. Recommendation 5: The evidence to support the use of molecular profiling to select the duration of endocrine therapy is evolving. In patients with ER-positive disease, clinicians may consider using a Breast Cancer Index (H/I) high assay result to support a decision to extend adjuvant endocrine therapy if the decision is supported by other clinical, pathological, or patient-related factors

Late recurrence of breast cancer — case report

Rak piersi jest najczęściej występującym nowotworem u kobiet. Upowszechnienie przesiewowych badań mammograficznych oraz leczenia uzupełniającego zabieg operacyjny przyczyniły się do poprawy przeżycia chorych na wczesnego i miejscowo zaawansowanego raka piersi. Pomimo to u części chorych dochodzi do nawrotu miejscowego lub przerzutów odległych. Najczęściej następuje to w ciągu 2–3 lat po leczeniu pierwotnym, możliwy jest jednak nawrót choroby po wielu latach. Poniżej opisano przypadek wznowy odległej po 26 latach od zakończenia leczenia.Breast cancer is the most common malignancy of women. Progress in screening mammography and adjuvant therapy contributed to improve the survival of patients with early and locally advanced breast cancer. Despite that, in some patients develop local recurrence or distant metastases. It occurs most often during the 2–3 years after primary treatment, however, relapse is possible even after many years. Here in the case of distant recurrence 26 years after the end of primary treatment is described

Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines

Aim: The impact of combinations of anti-cancer drugs and growth factors on tumour cells may differ from the assumed sum of the effects of each factor separately. Therefore it is important to study the effects of different combinations of various drugs and treatments. Our aim was to study the effects on breast cancer cell proliferation of EGF, TGFβ and 17β-oestradiol, three important regulators of breast tumourigenesis, and their respective inhibitors in different combinations. Materials and Methods: We screened the effects on proliferation of MCF7 and MDA-MB-231 cells of ninety different combinations of EGF, TGFβ and 17β-oestradiol, Iressa, SB431542 and Tamoxifen. Meta-data analysis of available clinical data was performed to validate observed proliferation data. Results: In MDA-MB-231 cells, TGFβ1 was found inhibitory when cells were simultaneously treated with EGF and 17β-oestradiol, with the effect potentiated by addition of all inhibitors combined. In the same cells, Iressa when combined with EGF was paradoxically stimulatory. Tamoxifen inhibited MCF7 cells co-treated with EGF or oestrogen, and enhanced the inhibitory effect of TGFβ in MDA-MB-231 cells. Meta-analysis of clinical gene expression studies confirmed several of these points, showing enhanced TGFβ and EGF expression in Tamoxifen-treated patients to correlate with decreased tumour size and grade respectively, and combined TGFβ-EGF expression to decrease the risk of metastasis. Conclusion: Our study shows significant differences in proliferation response to drugs and growth factors between MCF7 cells which do not have propensity to form metastases in animal models and MDA-MB-231 cells which may form metastases upon inoculation into animals. Several of these differences are unexpected and confirmed by clinical observations. Key Words: breast cancer, combinatorial treatment, EGF, oestrogen, TGFβ