883 research outputs found
C. Watanabe
No full textA portrait of a Japanese Peruvian man taken in Huacho, Peru. Autographed by: C. Watanabe. A photo from an album: Colonisation Japonaise au Perou (csudh_cjp_0001), page 5.Colonisation Japonaise au Pérou is a family photo album complied by a Japanese Peruvian family. The collected photographs depict the lives of the Japanese Peruvians in 1930-1950. Included are photographs of Japanese Peruvian workers and landscapes in a plantation, baseball players of Asahi, activities of a men’s club, aircrafts landed in the field in Peru, and family portraits
Mammographic density and molecular subtypes of breast cancer.
No full textBACKGROUND: Gene expression profiling has led to a subclassification of breast cancers independent of established clinical parameters, such as the Sorlie-Perou subtypes. Mammographic density (MD) is one of the strongest risk factors for breast cancer, but it is unknown if MD is associated with molecular subtypes of this carcinoma. METHODS: We investigated whether MD was associated with breast cancer subtypes in 110 women with breast cancer, operated in Stockholm, Sweden, during 1994 to 1996. Subtypes were defined using expression data from HGU133A+B chips. The MD of the unaffected breast was measured using the Cumulus software. We used multinomial logistic models to investigate the relationship between MD and Sorlie-Perou subtypes. RESULTS: Although the distribution of molecular subtypes differed in women with high vs low MD, this was statistically non-significant (P=0.249), and further analyses revealed no association between the MD and Sorlie-Perou subtypes as a whole, nor with individual subtypes. CONCLUSION: These findings suggest that although MD is one of the strongest risk factors for breast cancer, it does not seem to be differentially associated with breast cancer molecular subtypes. However, larger studies with more comprehensive covariate information are needed to confirm these results
Prognostic and predictive value of TP53 mutations in node-positive breast cancer patients treated with anthracycline- or anthracycline/taxane-based adjuvant therapy : results from the BIG 02-98 phase III trial
No full textIntroduction: Pre-clinical data suggest p53-dependent anthracycline-induced apoptosis and p53-independent taxane activity. However, dedicated clinical research has not defined a predictive role for TP53 gene mutations. The aim of the current study was to retrospectively explore the prognosis and predictive values of TP53 somatic mutations in the BIG 02-98 randomized phase III trial in which women with node-positive breast cancer were treated with adjuvant doxorubicin-based chemotherapy with or without docetaxel. Methods: The prognostic and predictive values of TP53 were analyzed in tumor samples by gene sequencing within exons 5 to 8. Patients were classified according to p53 protein status predicted from TP53 gene sequence, as wild-type (no TP53 variation or TP53 variations which are predicted not to modify p53 protein sequence) or mutant (p53 nonsynonymous mutations). Mutations were subcategorized according to missense or truncating mutations. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Cox-regression analysis was used to identify independent predictors of outcome. Results: TP53 gene status was determined for 18% (520 of 2887) of the women enrolled in BIG 02-98. TP53 gene variations were found in 17% (90 of 520). Nonsynonymous p53 mutations, found in 16.3% (85 of 520), were associated with older age, ductal morphology, higher grade and hormone-receptor negativity. Of the nonsynonymous mutations, 12.3% (64 of 520) were missense and 3.6% were truncating (19 of 520). Only truncating mutations showed significant independent prognostic value, with an increased recurrence risk compared to patients with non-modified p53 protein (hazard ratio = 3.21, 95% confidence interval = 1.740 to 5.935, P = 0.0002). p53 status had no significant predictive value for response to docetaxel. Conclusions: p53 truncating mutations were uncommon but associated with poor prognosis. No significant predictive role for p53 status was detected
Des Andes au Para : Équateur, Perou, Amazone
No full textSignaturizadoAntepAs il. son fotografías e gravado
Determining the Roles of MYB Family Transcription Factors in Breast Tumorigenesis
No full textA major advancement in the field of breast cancer research was the discovery of the
breast tumor intrinsic subtypes made through the utilization of gene expression microarrays.
Breast cancer can no longer be viewed as a single disease, but rather as at least five different
diseases each with unique biological activity and clinical outcomes. Targeted therapy
strategies are now employed to treat the different tumor types, such as estrogen receptor
modulators for ER-positive disease, and HER2-inhibitors for the treatment of HER2-positive
tumors. For tumors lacking therapeutic targets, patients are limited to cytotoxic
chemotherapy regimens. Consequently, additional research is crucial in further elucidating
the molecular pathways governing each breast tumor subtype.
Over one thousand genes are used to stratify the intrinsic molecular subtypes;
however, very few of these genes have been analyzed for their direct role in tumorigenesis.
This dissertation focuses on investigating two intrinsic genes, B-Myb and c-Myb, which are
both members of an evolutionarily conserved gene family first identified as transforming
genes in avian viruses. B-Myb is highly expressed in basal-like tumors, whereas c-Myb is
highly expressed in luminal tumors. We applied in vitro and in vivo analyses to ascertain the
roles of these genes within the molecular subtypes.
High B-Myb expression levels were predictive of poor outcomes across all breast
tumors and within subtypes. Mammary epithelial cells expressing high levels of B-Myb were
more sensitive to topoisomerase 2α inhibitors, but not other chemotherapeutics, via the
induction of G2/M cell cycle genes including TOP2A itself. We identified the first published
B-Myb germline variant causing an increased risk for basal-like disease.
We found that the c-Myb oncogene was behaving as a tumor suppressor in luminal
breast cancer through a novel p53 stabilization pathway. These results have significant
treatment implications in light of an ongoing hematologic malignancies clinical trial in which
c-Myb is targeted for knock-down through antisense oligonucleotides. These results point to
both B-Myb and c-Myb as important breast cancer biomarkers with potential clinical
importance for determining disease risk and guiding treatment, and provide important insight
into the roles of MYB family proteins in the etiology of breast cancer
Territórios nativos: a Carte de la terre ferme du Perou, du Brésil et du Pays des Amazones de Guillaume de L’Isle (1703) e a distribuição espacial das populações indígenas na Amazônia
No full textThis article aims to analyses the spatial distribution of indigenous populations during the colonial period, as well as to characterize them in terms of their use of space and habits. This study is based on the Carte de la terre ferme du Perou, du Brésil et du Pays des Amazones, produced by Guillaume de L’Isle in 1703, combined with documentary analysis of historical sources indicated by the author of the map himself. Aspects of the territorialization of indigenous peoples are identified amidst colonial expansion and political-spatial disputes between European empires. The geohistory of Brazil is thus reviewed, with an emphasis on the spatiality of indigenous peoples rather than colonial occupation, as historiography traditionally approaches this period.El objetivo final de este artículo es analizar la distribución espacial de las poblaciones indígenas durante el período colonial, así como caracterizarlas en términos de uso del espacio y hábitos. Este estudio se basa en la Carte de la terre ferme du Perou, du Brésil et du Pays des Amazones, elaborada por Guillaume de L’Isle en 1703, combinada con el análisis documental de fuentes históricas señalado por el propio autor del mapa. Se identifican aspectos de territorialización de los pueblos indígenas en medio de la expansión colonial y las disputas políticas espaciales entre los imperios europeos. Se revisa así la geohistoria de Brasil con énfasis en la espacialidad de los pueblos indígenas más que en la ocupación colonial, como tradicionalmente la historiografía aborda este período.Este artigo tem como objetivo final analisar a distribuição espacial das populações indígenas durante o período colonial, bem como caracterizá-las em termos de uso do espaço e hábitos. Este estudo tem por base a Carte de la terre ferme du Perou, du Brésil et du Pays des Amazones, produzido por Guillaume de L’Isle em 1703, combinada com a análise documental de fontes históricas apontadas pelo próprio autor do mapa. Identificam-se aspectos de territorialização dos povos indígenas em meio a expansão colonial e as disputas político espaciais entre impérios europeus. É revista assim a geohistória do Brasil tendo como ênfase a espacialidade dos povos indígenas ao invés da ocupação colonial, como tradicionalmente a historiografia aborda este período
Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer
No full textPurpose: The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). We strove to understand the biological, genomic, and clinical characteristics associated with SP142 PD-L1 positivity in TNBC patients.
Methods: Using 149 TNBC formalin-fixed paraffin-embedded tumor samples, tissue microarray (TMA) and gene expression microarrays were performed in parallel. The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides. We next generated a gene signature reflective of SP142 status and evaluated signature distribution according to TNBCtype and PAM50 subtypes. A SP142 gene expression signature was identified and was biologically and clinically evaluated on the TNBCs of TCGA, other cohorts, and on other malignancies treated with immune checkpoint inhibitors (ICI).
Results: Using SP142, 28.9% of samples were PD-L1 protein positive. The SP142 PD-L1-positive TNBC had higher CD8+ T cell percentage, stromal tumor-infiltrating lymphocyte levels, and higher rate of the immunomodulatory TNBCtype compared to PD-L1-negative samples. The recurrence-free survival was prolonged in PD-L1-positive TNBC. The SP142-guided gene expression signature consisted of 94 immune-related genes. The SP142 signature was associated with a higher pathologic complete response rate and better survival in multiple TNBC cohorts. In the TNBC of TCGA, this signature was correlated with lymphocyte-infiltrating signature scores, but not with tumor mutational burden or total neoantigen count. In other malignancies treated with ICIs, the SP142 genomic signature was associated with improved response and survival.
Conclusions: We provide multi-faceted evidence that SP142 PDL1-positive TNBC have immuno-genomic features characterized as highly lymphocyte-infiltrated and a relatively favorable survival.
629 The molecular portraits of breast cancer and their relationship to mammary stem cells
No full textAbstract SP116: B-cells and follicular T cells regulate responses to immune checkpoint inhibitors in breast tumors and melanomas
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