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Zeitschriftenartikel zum Thema "Cancer du sein basal-Like"
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Treilleux, Isabelle, und Blandine Morellon-Mialhe. „Le cancer du sein de phénotype basal“. Annales de Pathologie 29, Nr. 3 (Juni 2009): 180–86. http://dx.doi.org/10.1016/j.annpat.2009.04.001.
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Garcia de la Fuente, I., F. Jolicoeur, A. Robidoux, I. Gorska, D. Balicki und L. Gaboury. „Caractérisation du cancer du sein de phénotype basal“. Annales de Pathologie 26, Nr. 1 (Februar 2006): 69–70. http://dx.doi.org/10.1016/s0242-6498(06)70671-x.
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Vincent-Salomon, A., G. Macgrogan, E. Charaffe-Jauffret, J. Jacquemier und L. Arnould. „Identification en pratique clinique des carcinomes basal-like du sein : des carcinomes « triple zéro/BRCA1-like »“. Bulletin du Cancer 97, Nr. 3 (März 2010): 357–63. http://dx.doi.org/10.1684/bdc.2010.1062.
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Leidy, Jennifer, Ashraf Khan und Dina Kandil. „Basal-Like Breast Cancer: Update on Clinicopathologic, Immunohistochemical, and Molecular Features“. Archives of Pathology & Laboratory Medicine 138, Nr. 1 (01.01.2014): 37–43. http://dx.doi.org/10.5858/arpa.2012-0439-ra.
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Context.—Basal-like breast carcinoma (BLBC) is a distinct molecular subtype of breast carcinoma identified through gene expression profiling studies. Objective.—To provide the clinical background, the histologic profile, and the immunohistochemical profile of these tumors and discuss the current knowledge of their molecular signature and their implications on targeted molecular therapy. Data Sources.—Data were obtained from review of the pertinent peer-reviewed literature. Conclusions.—Basal-like breast carcinomas are aggressive tumors with poor prognosis. Lack of targeted therapy makes their treatment a challenging task. Traditional chemotherapy is still associated with a high risk of relapse and death in a high percentage of patients. Platinum-based chemotherapy has been considered as a candidate for the treatment of BLBCs owing to their BRCA1 phenotype. Approximately 22% of patients treated with single-agent cisplatin show pathologic complete response, which is a comparable rate to that seen with nonplatinum agents. Antiangiogenic agents have been promising, but their currently demonstrated limited response is considered disappointing. Additionally, epidermal growth factor receptor was not shown to be a helpful target for BLBC. A recent study has shown that BLBC appears to be especially sensitive to MEK inhibitors, making it a promising therapeutic possibility. The list of new targets is still evolving and the “magic” therapeutic target is yet to be discovered.
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Liu, Ming, Julia Y. S. Tsang, Michelle Lee, Yun-Bi Ni, Siu-Ki Chan, Sai-Yin Cheung, Jintao Hu, Hong Hu und Gary M. K. Tse. „CD147 expression is associated with poor overall survival in chemotherapy treated triple-negative breast cancer“. Journal of Clinical Pathology 71, Nr. 11 (11.08.2018): 1007–14. http://dx.doi.org/10.1136/jclinpath-2018-205342.
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AimsIn breast cancer models, the functional roles of CD147 in proliferation, invasion and treatment resistance have been widely reported. However, there are only a few studies examining the clinicopathological correlation and prognostic relevance of CD147 in breast cancer, especially in relation to breast cancer molecular subtypes.MethodsIn this study, we analysed CD147 expression in a large cohort of breast cancers, correlating with clinicopathological features and the expression of a comprehensive panel of biomarkers in triple-negative breast cancer (TNBC) and non-TNBC subsets. Its relationship with patients’ survival was also analysed.ResultsCD147 was expressed in 11.9%(140/1174) of all cases and in 23.8% (40/168) of TNBC. The expression was associated with tumour histological subtypes (p=0.01) and most commonly seen in carcinoma with medullary features (26.0%). CD147 expression correlated with high tumour grade, presence of necrosis and basal-like breast cancer (BLBC) subtype, high Ki67 and expression of some other basal markers and stem-like markers. CD147 expression was also associated with poor overall survival in chemotherapy treated patients with TNBC.ConclusionsCD147 is a putative marker in identifying TNBC or BLBC, and may be useful as a prognosis indicator for patients with TNBC or BLBC post chemotherapy.
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Kardos, Jordan, Jonathan J. Melquist, David D. Chism, Woonyoung Choi, Katherine Cockerill, Ravi Kumar Paluri, Kelvin A. Moses et al. „Evaluation of basal and luminal subtypes of urothelial carcinoma in African American and non-African American patients.“ Journal of Clinical Oncology 33, Nr. 7_suppl (01.03.2015): 305. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.305.
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305 Background: African American (AA) patients with urothelial carcinoma (UC) have been known to have a worse prognosis even when corrected for variables such as tumor stage and grade. Analysis of gene expression of several malignancies has resulted in the discovery of molecular subtypes with well-defined intrinsic biology. Recent studies in high grade (HG), muscle-invasive UC have led to the identification of two intrinsic, molecular subsets termed “luminal” and “basal” with characteristics of stages of urothelial differentiation, and that remarkably reflect the luminal and basal-like molecular subtypes of breast cancer. Patients with basal-like UC have a significantly worse overall survival. Methods: A total of 215 HG muscle-invasive UC tumors from the MDACC (n=75) and TCGA (n=140) were used to make intrinsic subtype calls using gene expression profiling (MDACC: DASL [cDNA-mediated Annealing, Selection, extension, and Ligation] and TCGA: RNA seq). Basal and luminal subtype calls were derived using previously published subtype classifiers (Damrauer et. al. PNAS, 2014 and Choi et. al. Cancer Cell, 2014). Patients were classified into AA and non-AA (white, Hispanic, or Asian) based upon self-reported race. Results: In total there were 16 and 199 tumors from AA and non-AA patients respectively. In non-AA patients, the proportion of tumors that were classified as basal and luminal were approximately equal (93 and 106 respectively), while in AA patients, there was enrichment of basal tumors (12 basal and 4 luminal) (p=0.03735, Fisher’s exact test). Conclusions: AA patients are enriched in the basal molecular subtype of UC. Similar findings have been previously documented in AA women with breast cancer. The enrichment of basal UC in AAs suggests that a biological explanation may in part underlie the poor outcomes seen in AA patients. Future studies will explore the prognostic and predictive implications of basal subtype in AA patients with UC.
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Chukwuma, Uzoigwe J., Nzegwu M. Arinze, Onyishi N. Thaddeus, Ekwedigwe C. Kenneth, Edegbe O. Felix, Okani O. Chudi, Ajah O. Leonard und Ekwedigwe I. Paul. „The Histological Subtypes of Breast Cancer Seen in a Tertiary Hospital in South-East, Nigeria“. Global Journal of Health Science 12, Nr. 6 (20.04.2020): 93. http://dx.doi.org/10.5539/gjhs.v12n6p93.
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INTRODUCTION: Breast cancer is a disease with heterogeneous nature that may have different prognosis and respond to therapy differently despite similarities in histological type, grade and stage. It is common among women in both developed and developing countries of the world.
MATERIALS AND METHODS: This study was a 2-year retrospective study involving a systematic analysis of all the formalin-fixed paraffin-embedded tissue blocks previously diagnosed as breast cancers. The study occurred at the Department of Morbid Anatomy, University of Nigeria Teaching Hospital, Enugu. We retrieved all the archived tissue blocks and subjected them to further ancillary testing using the immunohistochemistry monoclonal antibodies: (Oestrogen receptors (ER), Progesterone receptors (PR) and Her-2 neu antibodies).
RESULTS: Out of 417 cases of breast cancer analysed, four hundred and Ten (410) were females representing 98.3%, seven (7) were males representing 1.7%. The mean age of all subjects in this study was 45.1±10.2 SD (years). The age of patients ranged from20 to 70 years. The age group 31 to 40 years showed the highest number of cases, 133 (32.4%). The cases positive for ER were 157 (37.6%), while 260 (62.4%) were negative. The cases positive for PR were 144 (34.5%) and 273 (65.5%) were negative. Fifty-four cases (12.9%) were HER2-neu positive, 15 (3.6%) were equivocal and could not be further analysed due to lack of the facility to do Fluorescence in-situ hybridisation, and 348 (83.5%) were HER-neu negative. Phenotypic classification based on ER, PR, and Her2 immunohistochemistry showed 113 cases (27.1%) were Luminal A, 45 cases (10.8%) were Luminal B, 23 cases (5.5%) were Her2 Enriched, 236 cases (56.6%) were Basal-like/Triple-negative, and none (0%) was Normal-like.
CONCLUSION: In conclusion, this study shows that Basal-like/Triple-negative breast cancers are most common and are seen more in premenopausal women in Enugu.
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Mayer, Ingrid A., Rebecca Dent, Tira Tan, Peter Savas und Sherene Loi. „Novel Targeted Agents and Immunotherapy in Breast Cancer“. American Society of Clinical Oncology Educational Book, Nr. 37 (Mai 2017): 65–75. http://dx.doi.org/10.1200/edbk_175631.
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The treatment of breast cancer is generally determined according to breast cancer subtype: hormone receptor–positive (luminal), triple-negative (basal-like), and HER2-overexpressing breast cancer. Recent years have seen the development of exciting novel and potent therapeutics based on molecular pathways, immune modulation, and antibody conjugates. In this article, we cover new and emerging therapeutic areas and ongoing clinical trials that may result in further improvements in breast cancer outcomes.
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Gao, Yang, Elena B. Kabotyanski, Jonathan H. Shepherd, Elizabeth Villegas, Deanna Acosta, Clark Hamor, Tingting Sun et al. „Tumor Suppressor PLK2 May Serve as a Biomarker in Triple-Negative Breast Cancer for Improved Response to PLK1 Therapeutics“. Cancer Research Communications 1, Nr. 3 (Dezember 2021): 178–93. http://dx.doi.org/10.1158/2767-9764.crc-21-0106.
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Polo-like kinase (PLK) family members play important roles in cell-cycle regulation. The founding member PLK1 is oncogenic and preclinically validated as a cancer therapeutic target. Paradoxically, frequent loss of chromosome 5q11–35, which includes PLK2, is observed in basal-like breast cancer. In this study, we found that PLK2 was tumor suppressive in breast cancer, preferentially in basal-like and triple-negative breast cancer (TNBC) subtypes. Knockdown of PLK1 rescued phenotypes induced by PLK2 loss both in vitro and in vivo. We also demonstrated that PLK2 directly interacted with PLK1 at prometaphase through the kinase but not the polo-box domains of PLK2, suggesting PLK2 functioned at least partially through the interaction with PLK1. Furthermore, an improved treatment response was seen in both Plk2-deleted/low mouse preclinical and patient-derived xenograft (PDX) TNBC models using the PLK1 inhibitor volasertib alone or in combination with carboplatin. Reexpression of PLK2 in an inducible PLK2-null mouse model reduced the therapeutic efficacy of volasertib. In summary, this study delineates the effects of chromosome 5q loss in TNBC that includes PLK2, the relationship between PLK2 and PLK1, and how this may render PLK2-deleted/low tumors more sensitive to PLK1 inhibition in combination with chemotherapy. Significance: The tumor-suppressive role of PLK2, and its relationship with oncogene PLK1, provide a mechanistic rationalization to use PLK1 inhibitors in combination with chemotherapy to treat PLK2-low/deleted tumors. TNBC, and other cancers with low PLK2 expression, are such candidates to leverage precision medicine to identify patients who might benefit from treatment with these inhibitors.
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Ladewig, Erik, Abbas Nazir, Christina Leslie und Charles Sawyers. „Abstract 2048: Mutations in FOXA1 alter chromatin remodeling and cell fate in prostate organoids“. Cancer Research 83, Nr. 7_Supplement (04.04.2023): 2048. http://dx.doi.org/10.1158/1538-7445.am2023-2048.
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Abstract Genomic analysis of targeted patient tumor sequencing identified frequent mutations, 41% in prostate cancer (Li, et al., 2020) in the gene FOXA1, a developmentally important pioneer transcription factor (TF) in mammary and prostate tissues. Previous work by our group and others has shown that these FOXA1 mutations alter global chromatin accessibility and promote growth in prostate cells (Adams, 2019), but the underlying molecular details, including the identity of partner TFs, remain unclear. To address this topic, we generated mouse prostate organoids expressing Foxa1 alleles harboring three distinct classes of mutations: (i) overexpression of WT Foxa1 (reflecting focal gene amplification seen in tumors), (ii) a series of mutants within the Wing2region of the forkhead binding domain (FHBD) and (iii) a mutant bearing a stop codon after the FHBD to represent a series of C-terminal truncation mutants. We performed single nucleus multiome sequencing to obtain gene expression (snRNA-seq) and chromatin accessibility (snATAC-seq) readouts from the same individual nuclei. Whereas each Foxa1 mutant has distinct, often mutant-specific features, several themes emerge. These include alterations in the relative proportion of stem-like (L2) luminal cells vs secretory (L1) luminal cells as well as changes in luminal or basal gene signatures, increased androgen receptor signaling output, and enrichment for motifs of distinct classes of partner TFs. For example, cells expressing the truncation mutant show gain in the accessibility of Gata3 and Pou2f1 TF binding motifs, as well as enhanced numbers of L1-like luminal cells. Functional studies demonstrate that Pou2f1 is specifically required for the pro-luminal phenotype in cells expressing the truncation mutant whereas Gata3 plays a more general pro-luminal role. Correlations in motif accessibility and transcription factor expression across single cells further revealed a composite androgen receptor (AR)-FOXA1 motif enriched in the pro-luminal truncation mutant, while the canonical AR motif was enriched in pro-basal cell mutants. Finally, Foxa1 mutants cooperative with Trp53 and Pten loss in orthotopic prostate tumorigenicity assays, most strikingly manifest by reversion of the basal-like features characteristic of Trp53/Pten loss tumors to Ck8+ luminal adenocarcinoma histology, mirroring that seen in Foxa1-mutant human prostate cancer tumors in mice. Thus, mutant Foxa1 alleles cooperate with canonical prostate cancer tumor suppressors and alter the histologic phenotype of prostate cancers in mice through the activation of basal or luminal lineage differentiation programs. Citation Format: Erik Ladewig, Abbas Nazir, Christina Leslie, Charles Sawyers. Mutations in FOXA1 alter chromatin remodeling and cell fate in prostate organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2048.
Dissertationen zum Thema "Cancer du sein basal-Like"
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Aho, Simon. „Rôle de la voie BMP dans l'émergence des cellules souches cancéreuses mammaires et l'initiation du cancer du sein basal-like“. Electronic Thesis or Diss., Lyon 1, 2024. https://theses.hal.science/tel-04811400.
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Introduction : Le cancer du sein est la première cause de décès par cancer chez la femme dans le monde. Il s’agit d’une maladie hétérogène dont il existe plusieurs sous-types moléculaires corrélés au pronostic. Parmi ces différentes entités, le sous-type basal-like présente le pronostic le plus défavorable. Il est caractérisé par une expression accrue de marqueurs de différentiation basale et une instabilité génétique importante, fréquemment due à des altérations de la recombinaison homologue. Il est également enrichi en cellules souches cancéreuses. Ces cellules semblent être impliquées dans les étapes précoces de la carcinogenèse mais également dans la résistance aux traitements cytotoxiques et la rechute. Plusieurs voies de signalisation influencent leur biologie, notamment la voie des « Bone Morphogenetic Proteins » (BMP). Des dérégulations de cette voie ont été mises en évidence dans certaines tumeurs mammaire de sous-type luminal mais son implication dans l’émergence des tumeurs basal-like reste à explorer. Matériels et méthodes : A l’aide d’échantillons primaires et en interrogeant des bases de données publiques, nous avons recherché des anomalies de la voie BMP dans des tumeurs basal-like et des tissus prédisposés mutés pour BRCA1. Nous avons également utilisé la lignée de cellules souches épithéliales mammaires humaines MCF10A afin de modéliser in vitro les processus d’inititation tumorale des cellules souches dans la glande mammaire. Résultats : Nous montrons que l’expression du récepteur BMPR1A et du ligand BMP4 sont dérégulés dans les tumeurs basal-like et les tissus prédisposés. Ces dérégulations entrainent une répression transcriptionnelle de BRCA1 dans notre modèle de cellules souches. Les conséquences fonctionnelles incluent une différentiation préférentielle selon le phénotype basal, une augmentation de la stemness et des altérations de la voie de la recombinaison homologue.Conclusion : Nous suggérons un rôle de l’axe BMP4-BMPR1A dans les étapes précoces de la carcinogénèse de certaines tumeurs mammaires basal-like (i) en soutenant le maintien d’un contingent de cellules souches dans la glande mammaire, (ii) en orientant leur différentiation vers un phénotype basal, (iii) en favorisant l’instabilité génétique nécessaire à leur transformation en cellules souches cancéreusesIntroduction: Breast cancer is the leading cause of cancer death in women worldwide. It is a heterogeneous disease with several molecular subtypes correlated to prognosis. Of these, the basal-like subtype displays the poorest prognosis. It is characterized by increased expression of basal differentiation markers and significant genetic instability, frequently due to alterations in homologous recombination. It is also enriched in cancer stem cells. These cells are thought to be involved in the early stages of carcinogenesis, but also in resistance to cytotoxic treatment and relapse. Several signaling pathways influence their biology, notably the Bone Morphogenetic Protein (BMP) pathway. Dysregulation of this pathway has been demonstrated in certain luminal breast cancers, but its involvement in the emergence of basal-like breast cancers remains to be explored. Materials and methods: Using primary samples and public databases, we searched for BMP pathway abnormalities in basal-like tumors and BRCA1-mutated predisposed tissues. We also used the MCF10A human mammary epithelial stem cell model to explore in vitro the processes of stem cell tumor initiation in the mammary gland. Results: We show that BMPR1A and BMP4 expression is deregulated in basal-like tumors and predisposed tissues. These deregulations lead to transcriptional BRCA1 repression in our stem cell model. Functional consequences include preferential differentiation according to basal phenotype, increased stemness and alterations in the homologous recombination pathway. Conclusion: We suggest a role for the BMP4-BMPR1A axis in the early steps of basal-like carcinogenesis by (i) promoting the maintenance of a stem cell contingent in the mammary gland, (ii) directing their differentiation towards a basal phenotype, (iii) supporting the genetic instability necessary for their transformation into breast cancer stem cells
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Yakhni, Mohamad. „Inhibition de la synthèse des protéines, un traitement adapté aux cancers du sein triple négatifs des sous-types moléculaires autres que basal-like 1“. Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAS025.
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Les cancers du sein triple négatifs (CSTN), sans mutations dans les gènes BRCA1 ou BRCA2 ou sans BRCAness sont, aujourd’hui, les tumeurs malignes du sein les plus difficiles à traiter. L’amélioration de leur traitement, pour toutes les phases de la maladie, est un important besoin médical non satisfait. Nous avons analysé l’effet de l’homoharringtonine, un inhibiteur naturel de la synthèse des protéines, approuvé pour le traitement de la leucémie myéloïde chronique, sur quatre lignées cellulaires représentant des CSTN, appartenant aux catégories génomiques agressives, mais sans mutation de BRCA1/2 Nous avons montré que l'homoharringtonine inhibe, de plus de 80%, la croissance in vitro de toutes les lignées cellulaires, après une exposition de 48 à 72 heures à 20-100 ng/ml, des concentrations pouvant être atteintes dans le plasma humain après administration de médicament par voie sous-cutanée. L'homoharringtonine, à 100 ng/ml, a fortement réduit les taux d'un facteur de survie très important pour le CSTN, la protéine anti-apoptotique Mcl-1. Cet effet s’est produit après seulement 2 heures d'exposition à la drogue, dans toutes les lignées cellulaires, sauf dans MDA-MB-231. D'autres protéines anti-apoptotiques, Bcl-2, survivine et XIAP, ont également été fortement sous-régulées. De plus, la croissance in vivo de la lignée cellulaire la moins sensible à l'homoharringtonine, MDA-MB-231, a été inhibée de 36,5% chez la souris, avec 1 mg/kg de médicament, administré par voie sous-cutanée, deux fois par jour, pendant 7 jours. Ces résultats démontrent une activité antinéoplasique marquée de l'homoharringtonine dans le CSTN. Sur cette base, nous concluons que l’homoharringtonine mérite un développement clinique dans le CSTN en monothérapie des CSTN métastatiques, et, ensuite, comme traitement de maintenance, après un traitement adjuvantTriple negative breast cancers (TNBC) without BRCA1/2 gene mutation or BRCAness are nowadays the breast malignancies most difficult to treat. Improvement of their treatment, for all phases of the disease, is an important unmet medical need. We analyzed the effect of homoharringtonine, a natural protein synthesis inhibitor approved for treatment of chronic myeloid leukemia, on four cell lines representing aggressive, BRCA1/2 non-mutated, TNBC genomic categories. We show that homoharringtonine inhibits in vitro growth of all cell lines for more than 80%, after 48-72h exposure to 20-100 ng/mL, the concentrations achievable in human plasma after subcutaneous drug administration. Homoharringtonine, at 100 ng/mL, strongly reduced levels of a major TNBC survival factor, anti-apoptotic protein Mcl-1, after only 2h of exposure, in all cell lines except MDA-MB-231. Other anti-apoptotic proteins, Bcl-2, survivin and XIAP, were also strongly downregulated. Moreover, in vivo growth of the least sensitive cell line to homoharringtonine in vitro, MDA-MB-231 was inhibited for 36.5% in mice, by 1 mg/kg of the drug, given subcutaneously, bi-daily, over 7 days. These results demonstrate marked antineoplastic activity of homoharringtonine in TNBC. Therefore, this drug is worth clinical evaluation in TNBC patients, as a single-agent in the metastatic or post-adjuvant maintenance setting
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Dufour, Robin. „Différentes approches de l'optimisation du traitement du cancer du sein de phénotype "basal like" triple négatif par un anti-PARP : contournement des protéines "Multidrug Resistance" et traitement combiné radiothérapie / chimiothérapie. Spécialité“. Thesis, Clermont-Ferrand 1, 2016. http://www.theses.fr/2016CLF1MM05/document.
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Le cancer du sein de phénotype « Basal-like » triple négatif (BLTN) est particulièrement agressif et de mauvais pronostic. Il est insensible aux traitements hormonaux laissant pour seule stratégie de traitement la chimiothérapie conventionnelle. De ce fait, de nouvelles thérapeutiques ciblées sont en développement, tels que les inhibiteurs de la Poly-ADP-Ribose-Polymerase (PARP). Dans ce contexte, nos travaux de recherche ont été orientés sur l’optimisation du traitement des cancers du sein BLTN en modélisant l’action d’un anti-PARP modèle, l’Olaparib sur la lignée SUM1315 de phénotype BLTN. Dans un premier temps, l’étude de la coexpression de la BCRP et de la P-gp, deux protéines « Multidrug Resistance » (MDR) majeures en présence de 50 µM d’Olaparib® a montré une induction de leurs expressions chez les cellules SUM1315, avec une réponse de type relais. La BCRP établirait une première ligne de défense cellulaire et son action serait ensuite relayée par la P-gp durant 24h de traitement. Ce mécanisme est en corrélation avec la concentration intracellulaire d’Olaparib mesurée par HPLC. L’ensemble de nos résultats suggère qu’il serait possible de contourner le mécanisme de résistance induit par les protéines MDR si une concentration stable en Olaparib est maintenue dans les cellules à long terme. Nous avons ensuite étudié la potentialisation de l’action de l’Olaparib en le combinant avec un traitement par radiothérapie à basse et haute énergie, sur la viabilité des cellules de la lignée SUM1315. La comparaison des résultats avec un traitement Olaparib seul ou irradiation seule et ceux des traitements combinés Olaparib/radiothérapie a alors mis en évidence un effet synergique des deux traitements sur la viabilité cellulaire. L’effet synergique de cette combinaison fonctionne même avec de faibles doses d’Olaparib. De cette manière, il serait possible de réduire les doses d’anti-PARP utilisées tout en gardant les bénéfices du traitement. Enfin, nous avons développé deux techniques de cultures cellulaires en trois dimensions (i) « hanging drop » et (ii) « liquid overlay », permettant de mimer plus fidèlement les conditions des tumeurs in vivo. L’observation en microscopie électronique à transmission et à balayage des sphéroïdes obtenus par ces deux techniques a permis de démontrer l’intégrité des cellules au sein des sphéroïdes ainsi que la formation de jonctions cellulaires. Cependant, les sphéroïdes obtenus en « liquid overlay » ont montré une meilleure intégrité ultra-structurale« Triple Negative Basal-Like » (BLTN) breast cancer is particularly aggressive and of poor prognosis. It is insensitive to hormone-targeted therapies leaving conventional chemotherapy as the only treatment strategy. Therefore, new promising targeted therapies are being developed, such as Poly-ADP-Ribose-Polymerase inhibitors (anti-PARPs). In this context, our research has been directed towards optimizing the treatment of BLTN breast cancer by modelling the action of an anti-PARP model, Olaparib®, on BLTN cell line SUM1315. Firstly, the study of the co-expression of BCRP and P-gp, two major “Multidrug Resistance” proteins (MDR) in the presence of 50 µM Olaparib® showed an induction of their expression in SUM1315 cells, with a relay-type response. BCRP would establish a first line of cellular defense and its action would then be taken over by P-gp, for 24h of treatment. This mechanism is correlated with the intracellular concentration of Olaparib® measured by HPLC. All of our results suggest that it would be possible to circumvent the induced MDR resistance mechanism if a stable concentration of Olaparib® is maintained in cells in the long term. Secondly, we studied the potentiation of the action of Olaparib® combining it with low and high-energy radiations on the viability of SUM1315 cells. Comparison of the results with single Olaparib®, single irradiation, or the combination of Olaparib®/radiotherapy then demonstrated a synergistic effect of the two treatments when delivered concomitantly, on cell viability. The synergistic effect of this combination works even with low doses of Olaparib®. In this way it would be possible to reduce the anti-PARP doses while maintaining the benefits of this treatment. Finally, we have developed two techniques of cell culture in three dimensions: (i) "hanging drop" and (ii) "liquid overlay", in order to mimic more accurately the conditions of tumours in vivo. Observations of spheroids obtained by these two techniques by transmission and scanning electron microscopy demonstrated the integrity of cells within as well as the formation of cell junctions. However, the spheroids obtained by "liquid overlay" showed better ultra-structural integrity
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Hassanein, Mohamed. „Facteurs prédictifs de mutation germinale BRCA1 dans le cancer du sein héréditaire“. Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX20714.
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En France, le cancer de sein héréditaire représente environ 2500 nouveaux cas par an, dont prés de la moitié est attribuée à la mutation du gène BRCA1.La recherche de la mutation par biologie moléculaire est un travail fastidieux, coûteux et long (8 mois d’attente environ actuellement).Pour trouver une solution à ce délai, nous avons étudié en immunohistochimie une série initiale de 21 anticorps répartis en 5 groupes : anticorps antiBrca1 du commerce, liés à la perte de l’inactivation de l’X, liés à la signature basale ou myoépithéliale, anticorps dits classiques du cancer de sein et finalement dérivés de signatures établies par cDNAarray.Nous avons utilisé la technique de’ tissue microarrays’ en utilisant de manière comparative une population de 27 cas de cancer de sein présentant une mutation germinale de BRCA1, et 81 cas témoins de cancer de sein sporadiques appariés à l’âge, ainsi qu’à des lignées cellulaires d’origine mammaires. Dans une deuxième série indépendante de validation nous avons appliqué les résultats obtenus de la première série sur 28 cas de cancer mammaire muté, et 28 cas du cancer mammaire sporadique dans les mêmes conditions initiales.Nos résultats montrent pour la première fois sur des tissus tumoraux une probabilité forte d’une association entre la mutation Brca1 et la perte de l’inactivation de l’X ; confirment la valeur de MS110 comme un bon anticorps prédictif d’une mutation de Brca1 ; apportent un argument pour une participation myoépithéliale dans l’oncogenèse de cancer mammaire Brca1 muté; appuient la relation entre ce dernier et les récepteurs RE,RP ainsi que P53 , Bcl2,Ki67 et valident en protéomique la valeur discriminant de CDC47 correspondant à un des gènes de la signature génomique.Après confirmation des mêmes résultats dans la série de validation, nous soutenons en analyses multivariés un modèle qui comprend seulement Grade 3, MS110, Lys27H3 négative, Vimentine et KI67 positive. Cette équation correspond à une sensibilité de 82% et spécificité de 81% et propose une approche rapide économique de pré- ciblage de la mutation Brca1 ; ce qui améliorait la prise en charge préventive, thérapeutique et globale des patients et leurs famillesFamily structure, lack of reliable information, cost and delay are usual concerns faced with when deciding to perform BRCA analyses. Testing the breast cancer tissues with four antibodies (MS110, lys27H3, Vimentin, KI67) in addition to grade evaluation enabled to rapidly select patients to carry out genetic testing identification. We constituted an initial breast cancer tissue micro-array, considered as a learning set comprising 27 BRCA1 and 81 sporadic tumours. A second independent validation set of 28 BRCA1 tumours was matched to 28 sporadic tumours using the same original conditions.We have investigated morphological parameters and 21 markers by immunohistochemistry.A logistic regression model was used to select the minimal number of markers providing the best model to predict BRCA1 status. The model was applied to the validation set to estimate specificity and sensibility.In the initial set, the univariate analysis identified 11 markers significantly associated with BRCA1 status. Then the best multivariate model comprised only Grade 3, MS110, Lys27H3, Vimentin and KI67. When applied to the validation set, BRCA1 tumours were correctly classified with a sensitivity of 83% and a specificity of 81%. The performance of this model was superior when compared to other profiles.This work offers a new rapid and economic method for the pre-screening of patients at high risk of being BRCA1mutation carriers, then to guide genetic testing, and finally to provide appropriate preventive measure, advices and treatments including targeted therapy to patients and their families
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LEVY, RAFAEL. „Oncogenes, facteurs de croissance et cancers du sein : revue de la litterature, etude de la regulation du recepteur a l'igf 1 dans la lignee mcf-7 et des polymorphismes des proto-oncogenes c-ha-ras 1 et c-mos dans des cas familiaux“. Lille 2, 1989. http://www.theses.fr/1989LIL2M316.
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Jehanno, Charly. „Régulation de l'activité de récepteur alpha des oestrogènes (ERα) par l'hypoxie et le facteur MKL1 dans un modèle de cellules cancéreuses mammaires“. Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1B050/document.
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Les œstrogènes, et en particulier l’œstradiol E2, régulent un nombre considérable de fonctions physiologiques au sein de l’organisme et permettent notamment l’établissement et le maintien des fonctions reproductives chez tous les vertébrés. L’E2 agit localement dans de multiples organes cibles via l’intermédiaire de ses récepteurs : ERα et ERβ. Par son action proliférative contribuant au renouvellement de l’épithélium mammaire, l’E2 ainsi que son récepteur ERα ont été associés au développement pathologique de tumeurs mammaires. Celles-ci sont qualifiées d’hormono-dépendantes car elles répondent pour la majorité d’entre elles à l’utilisation de l’hormonothérapie visant à bloquer leur croissance. Malheureusement, on estime que 30 à 40% des tumeurs mammaires finissent par présenter une résistance aux traitements anti-oestrogéniques, par des mécanismes extrêmement complexes. Les travaux présentés dans ce manuscrit ont pour objectifs de mieux comprendre les mécanismes moléculaires et cellulaires impliqués dans le phénomène d’échappement des cellules tumorales mammaires au contrôle hormonal. Dans le cadre de cette thèse, nous nous sommes intéressés à deux facteurs capables de moduler l’activité d’ERα : l’hypoxie, qui désigne l’appauvrissement en oxygène du microenvironnement cellulaire, et la voie RhoA/MKL1 fréquemment mise en place au cours de la transition épithélio-mésenchymateuse. L’hypoxie est une caractéristique majeure des tumeurs solides, et des études lui suggèrent un rôle dans l’apparition de résistance endocrine. Nous montrons que le stress hypoxique inhibe fortement l’expression d’ERα, principalement au niveau protéique, et qu’il abolit la prolifération et la survie cellulaire induites par l’E2. L’analyse transcriptomique démontre qu’un certain nombre de gènes cibles d’ERα sont également régulés par l’hypoxie, qui peut soit réprimer (CXCL12…) ou bien augmenter leur expression (AREG…). Par ailleurs, l’analyse du cistrome d’ERα démontre une perte massive du nombre d’ERBSs (Estrogen Receptor Binding Site) par l’hypoxie, mais également une apparition d’ERBSs hypoxie-spécifiques. Nos résultats suggèrent que le fort recouvrement de régulation entre ERα et l’hypoxie puisse moduler l’efficacité des thérapies antihormonales. Enfin, l’équipe a démontré que l’activation de la voie RhoA/MKL1 provoque une forte inhibition de la fonction AF1 d’ERα. Afin de mieux appréhender les effets de cette voie de signalisation sur l’activité d’ERα, une lignée cellulaire MCF7 exprimant stablement un mutant constitutivement actif du facteur MKL1 a été générée. Nous montrons que son expression modifie profondément le contexte cellulaire en provoquant le basculement d’un phénotype luminal vers un phénotype basal-like. L’analyse transcriptomique de la réponse à l’E2 montre que le changement d’orientation cellulaire induit par MKL1 abolit toute régulation transcriptionnelle des gènes cibles d’ERα. Ce changement d’orientation cellulaire s’accompagne d’une reprogrammation massive du cistrome d’ERα avec une perte importante de ses sites de fixation à la chromatine, mais également de façon inattendue, un enrichissement en nouveaux ERBSs. Enfin, nous montrons une forte augmentation des interactions « non-génomiques » d’ERα avec des partenaires cytoplasmiques tels que PI3K, MSK1 et Src. Ces données suggèrent que dans des cellules agressives de type mésenchymal exprimant ERα, l’activité du récepteur repose majoritairement sur son action « non-génomique ». De façon intéressante, l’utilisation de l’anti-œstrogène pur ICI 182 780 n’a aucun effet inhibiteur sur ces interactions, pour lesquelles un rôle fonctionnel reste à établirEstrogens, and in particular estradiol E2, regulate a considerable number of physiological functions in the body and allow the establishment and maintenance of reproductive functions in all vertebrates. E2 acts locally in multiple target organs via its receptors: ERα and ERβ. By its proliferative action contributing to the renewal of the mammary epithelium, E2 as well as its ERα receptor have been associated with the pathological development of mammary tumors. These are qualified as hormone-dependent because they, for the majority of them, respond to the use of hormone therapy to block their growth. Unfortunately, it is estimated that 30-40% of mammary tumors end up with resistance to anti-estrogen treatments, through extremely complex mechanisms. The work presented in this manuscript aims to better understand the molecular and cellular mechanisms involved in the escape of mammary tumor cells to hormonal control. In this thesis, we looked at two factors that can modulate the ERα activity: hypoxia, which refers to oxygen depletion in the cellular microenvironment, and the RhoA/MKL1 pathway that is frequently activated during the epithelial-mesenchymal transition. Hypoxia is a major feature of solid tumors, and studies suggest a role in the development of endocrine resistance in breast cancer. We show that hypoxic stress strongly inhibits the expression of ERα, mainly at the protein level, and that it abolishes E2-induced cell proliferation and survival. Transcriptomic analysis shows that a certain number of ERα target genes are also regulated by hypoxia, which can either repress (CXCL12) or increase their expression (AREG ...). Moreover, the analysis of the ERα cistrome demonstrates a massive loss of the number of ERBSs (Estrogen Receptor Binding Site) by hypoxia, but also an appearance of hypoxia-specific ERBSs. Our results suggest that the strong regulatory overlap between ERα and hypoxia may modulate the efficacy of anti-hormonal therapies. Finally, the team demonstrated that the activation of the RhoA/MKL1 pathway causes a strong inhibition of the ERα AF1 function. In order to better understand the effects of this signaling pathway on ERα activity, an MCF7 cell line stably expressing a constitutively active mutant of the MKL1 factor was generated. We show that its expression profoundly modifies the cellular context by causing the switch from a luminal phenotype to a basal-like phenotype. The transcriptomic analysis of the E2 response shows that the MKL1 induced change in cell fate abolishes any transcriptional regulation of ERα target genes. This change in cellular orientation is accompanied by massive reprogramming of the ERα cistrome with a significant loss of its chromatin binding sites, but also unexpectedly, an enrichment of new ERBSs. Finally, we show a strong increase of "non-genomic" ERα interactions with cytoplasmic partners such as PI3K, MSK1 and Src. These data suggest that in aggressive mesenchymal cells expressing ERα, the receptor activity is mainly based on its "non-genomic" action. Interestingly, the use of pure anti-estrogen ICI 182 780 has no inhibitory effect on these interactions, for which a functional role remains to be established
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Confort, Carole. „Etude d'une forme soluble du récepteur IGFII/M6P dans les cancers du sein“. Montpellier 1, 1995. http://www.theses.fr/1995MON1T025.
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Coutant, Pierre. „Valeur pronostique du dosage plasmatique de l'igf 1 dans le cancer du sein metastatique : etude portant sur 81 dossiers de patientes suivies au centre oscar lambret de lille“. Lille 2, 1992. http://www.theses.fr/1992LIL2M238.
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Bouchard, Alexanne. „La protéine de stress du réticulum endoplasmique GRP94 dans le cancer du sein triple négatif, intérêt diagnostique et thérapeutique“. Electronic Thesis or Diss., Bourgogne Franche-Comté, 2023. https://nuxeo.u-bourgogne.fr/nuxeo/site/esupversions/8b1b931d-83a7-49fd-9779-012ad3949e79.
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Le cancer du sein triple négatif (CSTN) est caractérisé par l’absence sur les cellules tumorales de récepteurs aux œstrogènes, à la progestérone ainsi que de HER2. Il s’agit du sous-type de cancer du sein le plus agressif et il est associé à un risque plus élevé de métastases. Il représente 15 à 20% de tous les cancers du sein. En raison du manque de cibles spécifiques, l'hormonothérapie et les médicaments ciblant HER2 sont inefficaces. Les CSTN représentent en fait un sous-groupe de tumeurs hétérogènes pouvant être classées en fonction de leurs caractéristiques moléculaires. Une meilleure compréhension des mécanismes moléculaires, notamment ceux impliqués dans la modulation de la réponse immunitaire, est nécessaire dans le but d’optimiser la prise en charge de ce cancer. Dans ce contexte, l'imagerie moléculaire peut représenter un outil intéressant : elle permet en effet l’identification non invasive et la visualisation in vivo de cibles spécifiques de la tumeur ou du microenvironnement tumoral (MET) grâce à des sondes moléculaires sélectives pouvant être utilisées à des fins diagnostiques et/ou thérapeutiques. Dans ce travail de thèse, deux cibles spécifiques du MET ont été étudiées à l’aide de telles sondes : les macrophages M2-like et la protéine GARP, un récepteur d’ancrage du TGF-β. Les macrophages de type M2-like sont reconnus comme ayant un rôle pro-tumoral majeur. Les résultats obtenus nous ont permis de mettre en évidence la présence de macrophages M2-like CD206+ dans notre modèle de CSTN grâce à l’imagerie multimodale in vivo. Au cours de cette étude, nous avons validé l’efficacité du 99mTc-Tilmanocept en SPECT/CT en tant que sonde pour imager les macrophages M2-like du MET de notre modèle de CSTN. Nous avons également montré une co-expression de ces macrophages M2-like CD206+ avec la protéine GRP94, un chaperon important impliqué dans les réponses immunitaires. Enfin, l'inhibition de GRP94 à l'aide d’un inhibiteur spécifique, le PU-WS13, a significativement diminué le nombre de macrophages M2-like ainsi que la croissance tumorale dans notre modèle de CSTN. Ainsi, l'imagerie SPECT avec le 99mTc-Tilmanocept pourrait représenter une méthode innovante pour l'imagerie des macrophages M2-like CD206+ en tant que biomarqueur potentiel pour le pronostic, la prédiction thérapeutique et/ou la surveillance des tumeurs solides. La seconde cible étudiée, la protéine GARP, est exprimée à la membrane des Tregs et des cellules tumorales et joue un rôle clé dans l’activation du TGF-β, une cytokine immunosuppressive majeure dans le développement du cancer. Le développement d'une approche théranostique ciblant GARP combinant l'imagerie (111In-DOTAGA-GARP) et la radiothérapie interne vectorisée (RIV) (177Lu-DOTAGA-GARP) a été réalisé. Nous avons montré dans notre modèle préclinique de CSTN que l'expression de GARP était augmentée après radiothérapie externe, une stratégie thérapeutique classique, et pouvait être spécifiquement détectée et quantifiée dans le MET en utilisant l'imagerie SPECT/CT in vivo avec la sonde 111In-DOTAGA-GARP. De plus, son utilisation sous sa forme thérapeutique (177Lu-DOTAGA-GARP) limitait la croissance tumorale. Cette stratégie théranostique pourrait permettre la personnalisation des traitements anticancéreux par l'identification et le traitement des patients susceptibles de répondre à une thérapie ciblant les Tregs via la RIVTriple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, as well as HER2, on tumor cells. It is the most aggressive subtype of breast cancer and is associated with a higher risk of metastasis. It accounts for 15-20% of all breast cancers. Due to the lack of specific targets, hormone therapy and HER2-targeted drugs are ineffective. TNBC represents a subgroup of heterogeneous tumors that can be classified according to their molecular characteristics. A better understanding of molecular mechanisms, particularly those involved in modulating the immune response, is needed to optimize the management of this cancer. In this context, molecular imaging can represent an interesting tool: it enables the non-invasive identification and in vivo visualization of specific targets in the tumor or tumor microenvironment (TME), thanks to selective molecular probes that can be used for diagnostic and/or therapeutic purposes. In this thesis work, two specific TME targets were studied using such probes: M2-like macrophages and GARP protein, a TGF-β anchoring receptor. M2-like macrophages are recognized as having a major pro-tumoral role. The results obtained enabled us to demonstrate the presence of CD206+ M2-like macrophages in our CSTN model using in vivo multimodal imaging. In this study, we validated the efficacy of 99mTc-Tilmanocept in SPECT/CT as a probe for imaging M2-like macrophages in the TME of our TNBC model. We also demonstrated co-expression of these CD206+ M2-like macrophages with the GRP94 protein, an important chaperone involved in immune responses. Finally, inhibition of GRP94 with a specific inhibitor, PU-WS13, significantly decreased the number of M2-like macrophages as well as tumor growth in our TNBC model. Thus, SPECT imaging with 99mTc-Tilmanocept could represent an innovative method for imaging CD206+ M2-like macrophages as a potential biomarker for prognosis, therapeutic prediction and/or monitoring of solid tumors. The second target studied, the GARP protein, is expressed at the membrane of Tregs and tumor cells and plays a key role in the activation of TGF-β, a major immunosuppressive cytokine in cancer development. The development of a theranostic approach targeting GARP combining imaging (111In-DOTAGA-GARP) and targeted radionuclide therapy (TRT) (177Lu-DOTAGA-GARP) has been achieved. We showed in our preclinical TNBC model that GARP expression was increased after external radiotherapy, a classic therapeutic strategy, and could be specifically detected and quantified in the TME using in vivo SPECT/CT imaging with the 111In-DOTAGA-GARP probe. Moreover, its use in its therapeutic form (177Lu-DOTAGA-GARP) limited tumor growth. This theranostic strategy could enable the personalization of cancer treatments by identifying and treating patients likely to respond to therapy targeting Tregs via TRT
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Houhou, Mona. „Caractérisation de sous-populations enrichies en cellules souches cancéreuses et rôle des régulateurs de la transition épithélio-mésenchymateuse dans la plasticité tumorale dans le cancer du sein de type basal“. Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT043.
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Il est généralement admis que le cancer du sein représente un ensemble de plusieurs maladies, définies comme des sous-types ayant des caractéristiques moléculaires et cliniques qui leurs sont propres. Une meilleure compréhension des mécanismes qui sous-tendent l'hétérogénéité du cancer du sein est essentielle au développement de thérapies mieux ajustées. Le concept de cellules souches cancéreuses (CSC) pourrait être un des clés de cette compréhension. A ce jour, un certain nombre de marqueurs ont été proposés pour isoler et caractériser les cellules souches dans le cancer du sein, mais aucun ne semble totalement satisfaisant.Le but de mon travail était de déterminer un marqueur ou une combinaison de marqueurs avec lesquels les fractions enrichies en CSC pourraient être isolées de manière reproductible dans le cancer du sein de sous-types basal (BLBC). En effet, les tumeurs basales représentent 15% de toutes les tumeurs mammaires, mais constituent le sous-type le plus agressif. À cet effet, j'ai analysé un certain nombre de marqueurs par analyse FACS et tri cellulaire et utilisé la capacité de formation de mammosphères (MS) comme critère de validation pour la présence de CSC. Les lignées cellulaires utilisées comme modèles étaient les SUM 159, MDA-MB-231, MDA-MB-436, HCC1143, MDA-MB-468, Hs578T et BT-549 correspondant aux modèles basal-A et B. J'ai également testé trois lignées luminales les MCF7, T47D et BT474.De tous les marqueurs testés, seules, la combinaison des protéines de surface cellulaire CD44/CD24/EpCAM et l’activité enzymatique ALDH élevée ont permis d’obtenir un enrichissement significatif en CSC. Toutefois, le niveau de l'activité ALDH est apparu inconstant d’une lignée cellulaire à une autre et selon le type de tumeurs. D'autres marqueurs membranaires ont donné des résultats mitigés dans le cancer du sein ER-. En effet, la plupart des lignées basales ont montré des profils FACS assez homogènes avec des proportions élevées de cellules CD44+. Cependant, l'association de la positivité de CD44 avec l'EMT et la souchitude, ainsi que la bonne corrélation observée dans les modèles luminaux de la population de cellules CD44+/CD24- avec l’enrichissement en CSC, nous a incité à déterminer si le niveau d'expression en CD44 faisait une différence dans les tumeurs basales. Sur cette base, j’ai montré que les cellules CD44 high présentent une forte capacité à former des MS dans toutes les lignées cellulaires testées. Cette constatation nous a incités à utiliser CD44high vs. CD44low comme critère de tri cellulaire et à utiliser ces fractions pour effectuer une analyse du transcriptome afin d'identifier d'autres marqueurs non encore déterminés, pouvant isoler des fractions cellulaires plus faibles avec un enrichissement plus élevé en CSCIt is now accepted that breast cancer is a compendium of several diseases defined as subtypesthat are associated with different clinical outcomes and molecular characteristics. A betterunderstanding of the mechanisms underlying breast cancer heterogeneity is critical to the development of better adjusted therapies. One of the keys to breast cancer heterogeneity may be explained by cancer stem cells (CSC). A number of markers have been proposed to isolate and characterize breast cancer stem cells, but none appears totally satisfactory.The purpose of my work was determine a marker or combination of markers with which CSC enriched fractions could be reproducibly isolated in basal like breast cancer (BLBC). BLBC represent 15% of all breast tumors, but are the most aggressive subtype. To this aim, I have analyzed a number of markers by FACS analysis and cell sorting and used the capacity to form mammospheres (MS) as a validation criterion for the presence of CSCs. The cell lines used as models were SUM 159, MDA-MB-231, MDA-MB-436, HCC1143, MDA-MB-468, Hs578T and BT-549 comprising both Basal A and Basal B models. I also tested three luminal models MCF7, T47D and BT474.Of all the markers tested those that most consistently allowed enrichment of CSCs were the combination of cell surface proteins CD44/CD24/EpCAM and elevated ALDH enzyme activity. However, ALDH activity appeared irregular, ranging from good to inconsistent according to the cell line. Other cell surface markers gave mixed results in ER- breast cancer because the elevated fraction of CD44+ cells found in most of basal breast cancer cell lines and their propensity to show rather homogenous FACS labeling patterns. However, the association of CD44 positivity with EMT and stemness, as well as the good correlation, we observed in luminal models, of CD44+/CD24- cell population with CSC enrichment incited us to determine whether the level of expression of CD44 could make a difference in basal like models. I show that CD44high cells present higher capacity to form MS in all cell line models tested. This prompted us to use CD44high vs. CD44low as a cell sorting criterion and use these fractions to perform transcriptome analysis in order to identify other markers yet not determined, that may point to smaller cell fractions with a higher CSC enrichment
Bücher zum Thema "Cancer du sein basal-Like"
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Pires, Maira Moura. Basal-like breast cancer: Modeling its initiation and characterizing novel EGFR variants. [New York, N.Y.?]: [publisher not identified], 2012.
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Green, Adèle C., Catherine M. Olsen und David J. Hunter. Skin Cancer. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780190676827.003.0015.
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Skin cancer is one of the few types of cancer for which exposure to the major carcinogen, solar ultraviolet (UV) radiation, is strongly implicated on the basis of descriptive epidemiologic data alone. There are three major forms of skin cancer considered in this chapter—melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC)—and each appears to have different causal relations to the pattern and total amount of sun exposure. High-intensity UV exposure and long-term UV exposure appear to be involved differentially in the various skin cancers and their subtypes. Underlying molecular mechanisms are becoming better understood, though many aspects like the cells of origin and the exact roles of intermediate lesions like actinic keratoses and nevi remain unclear. Because exposure of skin to UV radiation is modifiable, skin cancers are substantially preventable.
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Grant, Warren, und Martin Scott-Brown. Principles of oncogenesis. Herausgegeben von Patrick Davey und David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0322.
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It is obvious that the process of developing cancer—oncogenesis—is a multistep process. We know that smoking, obesity, and a family history are strong independent predictors of developing malignancy; yet, in clinics, we often see that some heavy smokers live into their nineties and that some people with close relatives affected by cancer spend many years worrying about a disease that, in the end, they never contract. For many centuries scientists have struggled to understand the process that make cancer cells different from normal cells. There were those in ancient times who believed that tumours were attributable to acts of the gods. Hippocrates suggested that cancer resulted from an imbalance between the black humour that came from the spleen, and the other three humours: blood, phlegm, and bile. It is only in the last 100 years that biologists have been able to characterize some of the pathways that lead to the uncontrolled replication seen in cancer, and subsequently examine exactly how these pathways evolve. The rampant nature by which cancer invades local and distant tissues, as well its apparent ability to spread between related individuals led some, such as Peyton Rous in 1910, to suggest that cancer was an infectious condition. He was awarded a Nobel Prize in 1966 for the 50 years of work into investigating a link between sarcoma in chickens and a retrovirus that became known as Rous sarcoma virus. He had shown how retroviruses are able to integrate sequences of DNA coding for errors in cellular replication control (oncogenes) by introducing into the human cell viral RNA together with a reverse transcriptase. Viruses are now implicated in many cancers, and in countries where viruses such as HIV and EBV are endemic, the high incidence of malignancies such as Kaposi’s sarcoma and Burkitt’s lymphoma is likely to be directly related. There are several families of viruses associated with cancer, broadly classed into DNA viruses, which mutate human genes using their own DNA, and retroviruses, like Rous sarcoma virus, which insert viral RNA into the cell, where it is then transcribed into genes. This link with viruses has not only led to an understanding that cancer originates from genetic mutations, but has also become a key focus in the design of new anticancer therapies. Traditional chemotherapies either alter DNA structure (as with cisplatin) or inhibit production of its component parts (as with 5-fluorouracil.) These broad-spectrum agents have many and varied side effects, largely due to their non-specific activity on replicating DNA throughout the body, not just in tumour cells. New vaccine therapies utilizing gene-coding viruses aim to restore deficient biological pathways or inhibit mutated ones specific to tumour cells. The hope is that these gene therapies will be effective and easily tolerated by patients, but development is currently progressing with caution. In a trial in France of ten children suffering from X-linked severe combined immunodeficiency and who were injected with a vector that coded for the gene product they lacked, two of the children subsequently died from leukaemia. Further analysis confirmed that the DNA from the viral vector had become integrated into an existing, but normally inactive, proto-oncogene, LM02, triggering its conversion into an active oncogene, and the development of life-threatening malignancy. To understand how a tiny change in genetic structure could lead to such tragic consequences, we need to understand the molecular biology of the cell and, in particular, to pay attention to the pathways of growth regulation that are necessary in all mammalian cell populations. Errors in six key regulatory pathways are known as the ‘hallmarks of cancer’ and will be discussed in the rest of this chapter.
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Ehrlich, Benjamin. Cajal’s Legacy. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190619619.003.0001.
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This chapter looks into the legacy of Santiago Ramón y Cajal. Historians rank Cajal alongside more recognizable names such as Darwin and Pasteur among the greatest biologists of the nineteenth century and Copernicus, Galileo, and Isaac Newton among the greatest scientists of all time. In his final testament to the neuron theory, Neuron Theory or Reticular Theory? Cajal reported to have seen more than a million neurons. Cajal’s drawings of these neurons are much like portraits. “Only true artists are attracted to science,” he once said. Although the majority of his work concerns the nervous system, Cajal was a physician who contributed to many other fields. To pathology, he contributed studies on tuberculosis, leprosy, syphilis, rabies, Alzheimer’s disease, and cancer. He also published science fiction and wrote one of the earlier manuals on color photography. Cajal was a true polymath and a national hero in his home country of Spain.
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Kaplan, Seth D. Fixing Fragile States. Greenwood Publishing Group, Inc., 2008. http://dx.doi.org/10.5040/9798400651755.
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Fragile states are a menace. Their lawless environments spread instability across borders, provide havens for terrorists, threaten access to natural resources, and consign millions of people to poverty. But Western attempts to reform these benighted places have rarely made things better. Kaplan argues that to avoid revisiting the carnage and catastrophes seen in places like Iraq, Bosnia, and the Congo, the West needs to rethink its ideas on fragile states and start helping their peoples build governments and states that actually fit the local landscape. Fixing Fragile States lays bare the fatal flaws in current policies and explains why the only way to give these places a chance at peace and prosperity is to rethink how development really works. Flawed governance systems, not corrupt bureaucrats or armed militias, are the cancers that devour weak states. The cure, therefore, is not to send more aid or more peacekeepers but to redesign political, economic, and legal structures-to refashion them so they can leverage local traditions, overcome political fragmentation, expand governance capacities, and catalyze corporate investment. After dissecting the reasons why some states prosper and others sink into poverty and violence, Fixing Fragile States visits seven deeply dysfunctional places—including Pakistan, Bolivia, West Africa, and Syria—and explains how even the most desperate of them can be transformed.
Buchteile zum Thema "Cancer du sein basal-Like"
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Cryns, Vincent L., Mervi Jumppanen und Jorma Isola. „Basal-like Breast Cancer“. In Encyclopedia of Cancer, 346–49. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-16483-5_531.
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Han, Bingchen, William Audeh, Yanli Jin, Sanjay P. Bagaria und Xiaojiang Cui. „Biology and Treatment of Basal-Like Breast Cancer“. In Cell and Molecular Biology of Breast Cancer, 91–109. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-634-4_5.
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Alver, Kadir Han. „Radiologic Imaging of Scalp Lesions“. In The Radiology of Cancer, 3–18. Istanbul: Nobel Tip Kitabevleri, 2024. http://dx.doi.org/10.69860/nobel.9786053359364.1.
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Scalp lesions present significant diagnostic challenges due to their similar appearances, making accurate radiological assessment crucial in lowering mortality and morbidity rates. Understanding the scalp's anatomy, which includes five distinct layers-skin, dense connective tissue, epicranial aponeurosis, loose connective tissue, and pericranium-enables precise lesion localization. The vast majority of scalp abnormalities (93–98%) are benign, with trichilemmal cysts being the most common, followed by epidermal and dermal cysts, lipomas, nevi, and sebaceous cysts. Although less frequent, malignant scalp tumors such as squamous cell carcinoma, basal cell carcinoma, lymphoma, metastases and malignant melanoma also occur and pose significant health risks. Radiological imaging, particularly CT and MRI, plays a vital role in differentiating between benign and malignant lesions. Some characteristic imaging features of specific benign lesions, such as calcifications in trichilemmal cysts, fat density in lipomas, diffusion restriction in epidermoid cysts, and the typical locations of dermoid cysts with well-defined, non-invasive imaging features, aid radiologists in accurate diagnosis. On the contrary, although an accurate diagnosis of malignant tumors cannot be reached by radiological imaging alone, aggressive characteristics like bone erosion, destruction, and infiltration into surrounding tissues should predominantly raise suspicion of malignancy. Proper radiological evaluation and familiarity with the imaging features of these lesions are essential for accurate diagnosis and effective treatment planning, whether surgical or nonsurgical.
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Tranvåg, Eirik Joakim, und Roger Strand. „Rationing of Personalised Cancer Drugs: Rethinking the Co-production of Evidence and Priority Setting Practices“. In Human Perspectives in Health Sciences and Technology, 235–50. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-92612-0_14.
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AbstractRising health care costs is a challenge for all health care systems, and new and expensive cancer drugs is an important contributor to this. Many countries – like Norway – have therefore established priority setting institutions and systems for drug appraisals where equal treatment, neutrality and transparency are key values. Despite this, controversy surrounding drug reimbursement decisions are persistent.The development of personalised cancer medicine is seen by many as a potential solution to difficult priority setting decisions, by tailoring the right drug to the right patient at the right time. We, however, see personalised oncology and medicine in general not only as a solution, but also as a potential contributor high costs and to persisting controversy. We will argue that attempts to improve and strengthen the priority setting system – without accepting that a wider perspective on science and society is required – is likely to fuel even more controversy.In contrast, our suggestion takes a different approach building on post-normal science. From a co-production perspective, scientific, technological and societal developments are causally entangled into each other. Alongside refining priority setting principles, one can and ought to raise normative questions about the trajectory of personalised cancer medicine and of how to create a well-functioning public sphere. How can we imagine a well-functioning system of technological development and health care priority setting? Which changes in research policy and funding could support such a system? And which properties could biomarkers have in order to help society manage the health gap?
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Attia, Adel, Ismail Siala und Fathi Azribi. „General Oncology Care in Libya“. In Cancer in the Arab World, 133–48. Singapore: Springer Singapore, 2022. http://dx.doi.org/10.1007/978-981-16-7945-2_9.
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AbstractLibya is a large country, ranking at fourth in terms of area both in the Arab world and the African continent (https://www.worldatlas.com/articles/which-are-the-10-largest-countries-of-africa-by-size.html). It is part of the World Health Organization–Eastern Mediterranean Regional Office (WHO–EMRO) region. Oil production is the main source of income which has transformed the country massively over the past 50 years and the healthcare system is one of the sectors that have improved significantly. The Health Act No (106), issued in 1973, guarantees free health services to all Libyans, with inevitable challenges regarding the delivery of adequate and sustainable services. The health system in Libya is a mix between the public sector and the private sector. The private sector is basically depending on funding through insurance companies and self-pay. It is not yet adequately developed but is striving and rapidly growing in the last two decades.The oncology services are accessible and available for all Libyans, most of the diagnostic and therapeutic facilities are of good standards and the modern treatments like immunotherapy and targeted therapies are also available. However, there were periods when the health care system—in general—was struggling to meet the increasing demand on health services and has seen considerable challenges, especially over the past few years due to the conflict, political, and economic instability of the country. This chapter covers the oncology care in Libya, describing the current state, challenges, and future directions.
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Agolti, Mariela, und Lucrecia Solari. „Review of F-18 FDG PET/CT in Evaluating Response to Immunotherapy Treatment“. In Beyond Becquerel and Biology to Precision Radiomolecular Oncology: Festschrift in Honor of Richard P. Baum, 11–29. Cham: Springer International Publishing, 2024. http://dx.doi.org/10.1007/978-3-031-33533-4_2.
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AbstractIntroduction: Immunotherapy is a wide-spreading therapeutic resource in oncology. The therapy is guided to improve the patient’s immune response to cancer cells, on the basis of the concept of immune surveillance by activating both cell-mediated and humoral immunity to fight cancer. Immunomodulatory monoclonal antibody therapy utilizes preformed monoclonal antibodies directed against molecular targets to regulate T-cell activation. There are three mechanisms involved in this kind of therapy: antibodies directed against the programmed death protein 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), such as nivolumab and CTLA-4 inhibitors that prevent inhibition of the activated T-cells.Material and Method: Different reveiw articles were reviewed to understand the differences in response assessment of immunotherapy as compared to conventional chemotherapy or radiotherapy when using F-18 FDG PET/CT.Results: When using FDG PET/CT for response assessment, following important items should be considered: (1) Pseudoprogression: meaning that we can see transient enlargement of tumors or the appearance of new tumors followed by tumor shrinkage or long-term stability of tumor size. (2) Hyperprogression which is characterized by rapid increase in tumor burden (more than 50% increase compared to basal) and also time to treatment failure less than 2 months and more than 2 times increase in tumor growth rate, with deteriorating clinical condition. (3) Response to treatment is generally slower than with conventional cytotoxic chemotherapy. (4) Adverse effects (irAE) that are more easily diagnosed through FDG PET CT, than through conventional CT, and the importance of being able to recognize and report them sometimes life-threatening like pneumonitis or colitis. Also nuclear medicine physician should report inflammatory changes like drug induced sarcoid-like lymph nodes and differentiate from progression disease or splenic/liver SUV, moreover keeping in mind that there is evidence of good association between the presence of irAE and good answer to treatment. (5) Evolution of irAE comparing the actual PET with previous reporting the change in 18FDG uptake.Conclusion: Reporting of F-18 FDG PET/CT after immunotherapy, should consider these different items: Pseudoprogression, hyperprogression, irAE, evolution of irAE, and other inflammatory signs related to immunotherapy to improve our methodology efficiency.
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Meslé, France, und Jacques Vallin. „Causes of Death at Very Old Ages, Including for Supercentenarians“. In Demographic Research Monographs, 69–84. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-49970-9_7.
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AbstractThe causes of death reported on the death certificates of the oldest old are generally seen as unreliable, and as thus providing little useful information on the process leading to death. However, in advanced countries, a majority of the people who die each year are relatively old, and the level of detail provided on medical certificates about the causes of death among this older population is improving. At the same time, scholars are becoming increasingly interested in studying not just the initial cause of death, but multiple causes of death, thereby taking all of the information reported on the certificate into account. This study demonstrates that in a country like France, the cause-of-death pattern evolves regularly until around age 105. The share of people dying of circulatory diseases tends to be quite stable over the age range, while the share of individuals dying of cancer is declining, and the share of people dying of respiratory/infectious diseases is rising. Furthermore, among people who die at very old ages, a typology of multiple causes of death highlights the growing importance of ill-defined causes, while opening the door to an interesting discussion about the concept of cause of death in the supercentenarian population. Instead of representing an ill-defined cause, senility could be considered an actual cause of death. This suggests that daily care is more crucial to the survival of the oldest old than any conventional medical care or treatment. Supercentenarians tend to be so frail that any minor health event or brief lapse of attention on the part of their caregivers can be lethal.
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Jones, Roger D., und Alan M. Jones. „A Proposed Mechanism for in vivo Programming Transmembrane Receptors“. In Communications in Computer and Information Science, 123–37. Cham: Springer Nature Switzerland, 2024. http://dx.doi.org/10.1007/978-3-031-57430-6_11.
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AbstractTransmembrane G-protein coupled receptors (GPCRs) are ideal drug targets because they resemble, in function, molecular microprocessors for which outcomes (e.g. disease pathways) can be controlled by inputs (extracellular ligands). The inputs here are ligands in the extracellular fluid and possibly chemical signals from other sources in the cellular environment that modify the states of molecular switches, such as phosphorylation sites, on the intracellular domains of the receptor. Like in an engineered microprocessor, these inputs control the configuration of output switch states that control the generation of downstream responses to the inputs.Many diseases with heterogeneous prognoses including, for example, cancer and diabetic kidney disease, require precise individualized treatment. The success of precision medicine to treat and cure disease is through its ability to alter the microprocessor outputs in a manner to improve disease outcomes. We previously established ab initio a model based on maximal information transmission and rate of entropy production that agrees with experimental data on GPCR performance and provides insight into the GPCR process. We use this model to suggest new and possibly more precise ways to target GPCRs with potential new drugs.We find, within the context of the model, that responses downstream of the GPCRs can be controlled, in part, by drug ligand concentration, not just whether the ligand is bound to the receptor. Specifically, the GPCRs encode the maximum ligand concentration the GPCR experiences in the number of active phosphorylation or other switch sites on the intracellular domains of the GPCR. This process generates a memory in the GPCR of the maximum ligand concentration seen by the GPCR. Each configuration of switch sites can generate a distinct downstream response bias. This implies that cellular response to a ligand may be programmable by controlling drug concentration. The model addresses the observation paradox that the amount of information appearing in the intracellular region is greater than amount of information stored in whether the ligand binds to the receptor. This study suggests that at least some of the missing information can be generated by the ligand concentration. We show the model is consistent with assay and information-flow experiments.In contrast to the current view of switch behavior in GPCR signaling, we find that switches exist in three distinct states: inactive (neither off nor on), actively on, or actively off. Unlike the inactive state, the active state supports a chemical flux of receptor configurations through the switch, even when the switch state is actively off. Switches are activated one at a time as ligand concentration reaches threshold values and does not reset because the ligand concentration drops below the thresholds. These results have clinical relevance. Treatment with drugs that target GPCR-mediated pathways can have increased precision for outputs by controlling switch configurations. The model suggests that, to see the full response spectrum, fully native receptors should be used in assay experiments rather than chimera receptors.Inactive states allow the possibility for novel adaptations. This expands the search space for natural selection beyond the space determined by pre-specified active switches.
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Jain, Ankit, Vijayakumar Chellappa und Kadambari Dharanipragada. „Inter-Relationship of Ki-67 and Triple-Negative Breast Cancer“. In Breast Cancer Updates [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.109586.
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Triple-negative breast cancer (TNBC) is a heterogeneous group characterized by an early onset, aggressive course of the disease, a higher tendency of visceral metastases, and a poorer prognosis. It is also associated with basal-like phenotype and germline mutations for BRCA genes in 10–20% and somatic mutations in 3–5% of cases. Based on gene expression profiling, TNBC is divided into four tumor-specific subtypes (Basal-like 1, Basal-like 2, Mesenchymal, and Luminal androgen receptor) with different clinical, prognostic, and therapeutic implications. The Ki-67 antigen, a non-histone nuclear protein, is a surrogate marker to assess tumor proliferation. As TNBCs are expected to be highly proliferating tumors, a higher baseline Ki-67 level has been seen. Although a higher Ki-67 level is associated with a higher pathological complete response rate, the best cutoff point of this marker as a prognostic and predictive factor in TNBC remains unclear.
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Salman Khalid, Muhammad, Muhammad Ammad Jamil, Adeeb Shehzad, Somia Mazhar und Farhan Hameed. „Basal cell carcinoma“. In Skin Cancer - Past, Present and Future [Working Title]. IntechOpen, 2024. http://dx.doi.org/10.5772/intechopen.1004884.
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Globally, Basal cell carcinoma is the most prevalent form of skin cancer, which originates from basal cells of the epidermis. Sun-exposed parts of the body (head, face, and neck) are mostly affected by BCC. Characteristics of BCC include local invasiveness, low potential of metastasis, and slow growth. Despite its relatively low rate of mortality, it presents a significant public health concern, as its incidence rate is continuously rising. Different factors like aging population, sun-exposure, and behavior changes in lifestyle plays an important role in increasing BCC incident rate. UV exposure remains the dominant factor, immunosuppression, environmental influences, and genetic susceptibility also play important roles in amplifying the impact of UV on the skin. Different signaling pathways are involved in BCC pathogenesis which leads to tumor formation and cell proliferation. Targeting these pathways could lead to new diagnostic tools and treatment therapies. Clinically, there are different subtypes of BCC with unique features, morphologies, and characteristics. After early detection through visual inspection, Dermascopy, biopsy, and confocal microscopy techniques are used to diagnose BCC. Available treatment options include surgical excision. Cryosurgery, Mohs micrographic surgery, photodynamic therapy (PDT), radiotherapy, curettage and electrodessication therapy, and targeted molecular therapies.
Konferenzberichte zum Thema "Cancer du sein basal-Like"
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Yoshimura, Adriana Akemi, André Mattar, Bruna S. Mota, Carlos Elias Fristachi, Eduardo Carvalho Pessoa, Felipe Eduardo Andrade, Giuliano Tosello et al. „A MULTICENTRIC STUDY ON BREAST CANCER IN ULTRA YOUNG WOMEN: II – HISTOPATHOLOGIC AND MOLECULAR DATA“. In Scientifc papers of XXIII Brazilian Breast Congress - 2021. Mastology, 2021. http://dx.doi.org/10.29289/259453942021v31s1062.
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Introduction: Ultra young women (UYW) is defined as women aged up to 30 years. UYW with BC share some unfavorable biological tumor characteristics as larger size at diagnosis, higher loca-regional recurrence rate and lower survival, and have been merited specialized care. Objectives: We aimed to determine histopathological and molecular characteristics of BC in UYW. Methods: We carried out a multicentric, observational, retrospective study of consecutive UYW patients with BC. Only patients with infiltrating BC were included. Nine Mastology Centers located in the State of São Paulo took part in the research. The follow data were recorded: pathological tumor histology, number of positive lymph nodes multicentricity/multifocality, presence or absence of peritumoral vascular invasion (PVI), histologic grade (HG), pT category, estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki67. We classified the neoplasias into five molecular subtypes by immunohistochemistry, based on modified recommendations of St. Gallen Consensus (2013): Luminal A-like, Luminal B-like HER2-, Luminal B-like HER2+, HER2 overexpressed (HER2+) non luminal and Triple-Negative. The frequency of the analysed parameters were calculated. The research protocol was approved by the Ethics Committee of all Collaborative Centers. Individual informed consent was waived. Results: Invasive carcinoma of no special type (NST) was observed in 243 patients (88%), and infiltrative lobular tumor was extremely rare, being found in 1.1%. The tumor size in surgical specimens was above 20 mm in 54% (in 10% there was no more evidence of tumor after neoadjuvant treatment). We found 52.6% of patients without invasion in lymph nodes (LN) whereas in 22.2% there was more than four LNs involved. Multifocality was seen in 12.4%. HG was 2 or 3 in 98.3%. In 67.5% the tumors expressed ER, 59.4% gR, and 25.1% were HER2+. In 61.5% Ki67 was higher than 20%. Tumor molecular subtypes were classified in 16.6% Luminal A-like, 35.9% Luminal B-like HER2-, 15.1% Luminal B-like HER2+, 9.3% HER2+ non-luminal and in 22.9% Basal-like. Conclusions: Our data from UYW with BC revealed unfavorable characteristics, with frequent adverse pathological and molecular prognostic factors.
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Aly, A., Q. Yang, E. Bilal, M. Yao, G. Bhanot, D. Toppmeyer, B. Haffty und S. Ganesan. „Abnormalities of 53BP1 in Basal-Like Breast Cancer.“ In Abstracts: Thirty-Second Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 10‐13, 2009; San Antonio, TX. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/0008-5472.sabcs-09-1122.
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Jonkers, J. „ES2-2: Mouse Models of Basal-Like Breast Cancer.“ In Abstracts: Thirty-Fourth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 6‐10, 2011; San Antonio, TX. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/0008-5472.sabcs11-es2-2.
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Quinn, Hazel M., Regina Vogel und Walter Birchmeier. „Abstract A12: YAP and cancer stem cells in basal-like breast cancer“. In Abstracts: AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; May 8-11, 2019; San Diego, CA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1557-3125.hippo19-a12.
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Mori, H., M. Kubo, M. Yamada, M. Kai, T. Osako, R. Nishimura, N. Arima et al. „Abstract P4-09-15: BRCAness and PD-L1 expression of basal-like and not basal-like triple negative breast cancer“. In Abstracts: Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.sabcs15-p4-09-15.
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Liu, Jin, und Philip Bernard. „Abstract 2960:TRIM29is a novel biomarker for basal-like breast cancer“. In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-2960.
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Sundaram, Sneha, David B. Darr, Kirk K. McNaughton, Joseph A. Galanko, Melissa A. Troester und Liza Makowski. „Abstract IA45: Obesity and the microenvironment in basal-like breast cancer“. In Abstracts: Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; November 9-12, 2014; San Antonio, TX. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7755.disp14-ia45.
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Manié, E., A. Vincent-Salomon, J. Lehmann-Che, G. Pierron, E. Turpin, M. Warcoin, N. Gruel et al. „ConsistentTP53mutations inBRCA1and sporadic basal-like breast tumors, while infrequent in luminalBRCA1tumors.“ In CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/0008-5472.sabcs-4070.
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Pei, X.-H., HL Chan, S. Liu, A. Scott, E. Pimentel, J. Slingerland, D. Robbins, A. Capobianco und F. Bai. „Abstract P6-08-08: GATA3 inhibits breast basal-like tumorigenesis“. In Abstracts: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, Texas. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.sabcs16-p6-08-08.
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Laine, A., S. Nagelli, E. Peuhu, CS Hau, O. Kauko, P. Kronqvist, H. Sihto, H. Joensuu, J. Westermarck und KE De Visser. „PO-300 CIP2A-mediated regulation of senescence in basal-like breast cancer“. In Abstracts of the 25th Biennial Congress of the European Association for Cancer Research, Amsterdam, The Netherlands, 30 June – 3 July 2018. BMJ Publishing Group Ltd, 2018. http://dx.doi.org/10.1136/esmoopen-2018-eacr25.813.
Der volle Inhalt der QuelleBerichte der Organisationen zum Thema "Cancer du sein basal-Like"
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Lawson, Campbell. The Oncogenic Role of RhoGAPs in Basal-Like Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, Februar 2015. http://dx.doi.org/10.21236/ada618217.
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Fagan-Solis, Katerina. Regulation and Action of SKP2 in Cell and Tumor Models: Mechanisms Underlying Aggressive Growth in Basal-Like Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, Juni 2011. http://dx.doi.org/10.21236/ada549245.
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Fagan-Solis, Katerina. Regulation and Action of SKP2 in Cell and Tumor Models: Mechanisms Underlying Aggressive Growth in Basal-Like Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, Dezember 2011. http://dx.doi.org/10.21236/ada561142.
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MacFarlane, Andrew. 2021 medical student essay prize winner - A case of grief. Society for Academic Primary Care, Juli 2021. http://dx.doi.org/10.37361/medstudessay.2021.1.1.
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As a student undertaking a Longitudinal Integrated Clerkship (LIC)1 based in a GP practice in a rural community in the North of Scotland, I have been lucky to be given responsibility and my own clinic lists. Every day I conduct consultations that change my practice: the challenge of clinically applying the theory I have studied, controlling a consultation and efficiently exploring a patient's problems, empathising with and empowering them to play a part in their own care2 – and most difficult I feel – dealing with the vast amount of uncertainty that medicine, and particularly primary care, presents to both clinician and patient. I initially consulted with a lady in her 60s who attended with her husband, complaining of severe lower back pain who was very difficult to assess due to her pain level. Her husband was understandably concerned about the degree of pain she was in. After assessment and discussion with one of the GPs, we agreed some pain relief and a physio assessment in the next few days would be a practical plan. The patient had one red flag, some leg weakness and numbness, which was her ‘normal’ on account of her multiple sclerosis. At the physio assessment a few days later, the physio felt things were worse and some urgent bloods were ordered, unfortunately finding raised cancer and inflammatory markers. A CT scan of the lung found widespread cancer, a later CT of the head after some developing some acute confusion found brain metastases, and a week and a half after presenting to me, the patient sadly died in hospital. While that was all impactful enough on me, it was the follow-up appointment with the husband who attended on the last triage slot of the evening two weeks later that I found completely altered my understanding of grief and the mourning of a loved one. The husband had asked to speak to a Andrew MacFarlane Year 3 ScotGEM Medical Student 2 doctor just to talk about what had happened to his wife. The GP decided that it would be better if he came into the practice - strictly he probably should have been consulted with over the phone due to coronavirus restrictions - but he was asked what he would prefer and he opted to come in. I sat in on the consultation, I had been helping with any examinations the triage doctor needed and I recognised that this was the husband of the lady I had seen a few weeks earlier. He came in and sat down, head lowered, hands fiddling with the zip on his jacket, trying to find what to say. The GP sat, turned so that they were opposite each other with no desk between them - I was seated off to the side, an onlooker, but acknowledged by the patient with a kind nod when he entered the room. The GP asked gently, “How are you doing?” and roughly 30 seconds passed (a long time in a conversation) before the patient spoke. “I just really miss her…” he whispered with great effort, “I don’t understand how this all happened.” Over the next 45 minutes, he spoke about his wife, how much pain she had been in, the rapid deterioration he witnessed, the cancer being found, and cruelly how she had passed away after he had gone home to get some rest after being by her bedside all day in the hospital. He talked about how they had met, how much he missed her, how empty the house felt without her, and asking himself and us how he was meant to move forward with his life. He had a lot of questions for us, and for himself. Had we missed anything – had he missed anything? The GP really just listened for almost the whole consultation, speaking to him gently, reassuring him that this wasn’t his or anyone’s fault. She stated that this was an awful time for him and that what he was feeling was entirely normal and something we will all universally go through. She emphasised that while it wasn’t helpful at the moment, that things would get better over time.3 He was really glad I was there – having shared a consultation with his wife and I – he thanked me emphatically even though I felt like I hadn’t really helped at all. After some tears, frequent moments of silence and a lot of questions, he left having gotten a lot off his chest. “You just have to listen to people, be there for them as they go through things, and answer their questions as best you can” urged my GP as we discussed the case when the patient left. Almost all family caregivers contact their GP with regards to grief and this consultation really made me realise how important an aspect of my practice it will be in the future.4 It has also made me reflect on the emphasis on undergraduate teaching around ‘breaking bad news’ to patients, but nothing taught about when patients are in the process of grieving further down the line.5 The skill Andrew MacFarlane Year 3 ScotGEM Medical Student 3 required to manage a grieving patient is not one limited to general practice. Patients may grieve the loss of function from acute trauma through to chronic illness in all specialties of medicine - in addition to ‘traditional’ grief from loss of family or friends.6 There wasn’t anything ‘medical’ in the consultation, but I came away from it with a real sense of purpose as to why this career is such a privilege. We look after patients so they can spend as much quality time as they are given with their loved ones, and their loved ones are the ones we care for after they are gone. We as doctors are the constant, and we have to meet patients with compassion at their most difficult times – because it is as much a part of the job as the knowledge and the science – and it is the part of us that patients will remember long after they leave our clinic room. Word Count: 993 words References 1. ScotGEM MBChB - Subjects - University of St Andrews [Internet]. [cited 2021 Mar 27]. Available from: https://www.st-andrews.ac.uk/subjects/medicine/scotgem-mbchb/ 2. Shared decision making in realistic medicine: what works - gov.scot [Internet]. [cited 2021 Mar 27]. Available from: https://www.gov.scot/publications/works-support-promote-shared-decisionmaking-synthesis-recent-evidence/pages/1/ 3. Ghesquiere AR, Patel SR, Kaplan DB, Bruce ML. Primary care providers’ bereavement care practices: Recommendations for research directions. Int J Geriatr Psychiatry. 2014 Dec;29(12):1221–9. 4. Nielsen MK, Christensen K, Neergaard MA, Bidstrup PE, Guldin M-B. Grief symptoms and primary care use: a prospective study of family caregivers. BJGP Open [Internet]. 2020 Aug 1 [cited 2021 Mar 27];4(3). Available from: https://bjgpopen.org/content/4/3/bjgpopen20X101063 5. O’Connor M, Breen LJ. General Practitioners’ experiences of bereavement care and their educational support needs: a qualitative study. BMC Medical Education. 2014 Mar 27;14(1):59. 6. Sikstrom L, Saikaly R, Ferguson G, Mosher PJ, Bonato S, Soklaridis S. Being there: A scoping review of grief support training in medical education. PLOS ONE. 2019 Nov 27;14(11):e0224325.