Two-dimensional electrophoretic comparison of metastatic and non-metastatic human breast tumors using in vitro cultured epithelial cells derived from the cancer tissues

<p>Abstract</p> <p>Background</p> <p>Breast carcinomas represent a heterogeneous group of tumors diverse in behavior, outcome, and response to therapy. Identification of proteins resembling the tumor biology can improve the diagnosis, prediction, treatment selection, and targeting of therapy. Since the beginning of the post-genomic era, the focus of molecular biology gradually moved from genomes to proteins and proteomes and to their functionality. Proteomics can potentially capture dynamic changes in protein expression integrating both genetic and epigenetic influences.</p> <p>Methods</p> <p>We prepared primary cultures of epithelial cells from 23 breast cancer tissue samples and performed comparative proteomic analysis. Seven patients developed distant metastases within three-year follow-up. These samples were included into a metastase-positive group, the others formed a metastase-negative group. Two-dimensional electrophoretical (2-DE) gels in pH range 4–7 were prepared. Spot densities in 2-DE protein maps were subjected to statistical analyses (R/maanova package) and data-mining analysis (GUHA). For identification of proteins in selected spots, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed.</p> <p>Results</p> <p>Three protein spots were significantly altered between the metastatic and non-metastatic groups. The correlations were proven at the 0.05 significance level. Nucleophosmin was increased in the group with metastases. The levels of 2,3-trans-enoyl-CoA isomerase and glutathione peroxidase 1 were decreased.</p> <p>Conclusion</p> <p>We have performed an extensive proteomic study of mammary epithelial cells from breast cancer patients. We have found differentially expressed proteins between the samples from metastase-positive and metastase-negative patient groups.</p

The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus

Pretherapeutic identification of oesophageal squamous cell carcinomas that will respond to neoadjuvant chemoradiotherapy is an important attempt for improvement of patient's prognosis. In the current study, pretherapeutic biopsies from 94 oesophageal squamous cell carcinomas (cT3, cN0/+, cM0) in patients who underwent neoadjuvant chemoradiotherapy (RCTx: 45 Gy plus cisplatin and 5-fluorouracil) and subsequent oesophagectomy in the setting of a single-centre prospective treatment trial were investigated by means of immunohistochemistry. Expression of proteins involved in DNA repair and/or cell-cycle regulation, that is p53, p53 (phosphorylated at Ser15), EGFR, ATM protein kinase (phosphorylated at Ser1981) and checkpoint kinase 2 (CHK2) (phosphorylated at Thr68) was correlated with the response to RCTx and with overall survival. Tumours that were positive for CHK2 expression more frequently showed clinically determined regression after RCTx (69.4%) than tumours that were negative for CHK2 expression (32.1%; P=0.0011), whereas other parameters did not correlate with tumour regression. Expression of ATM correlated with expression of CHK2 (P=0.0061) and p53-phospho (P=0.0064). Expression of p53 correlated with expression of p53-phospho (P<0.0001). In contrast to clinical and histopathological response evaluation, none of the molecular parameters under investigation correlated with overall survival. In conclusion, expression analysis of p53, EGFR CHK2 and ATM has no predictive value in multimodally treated oesophageal squamous cell carcinoma

A self-renewal assay for cancer stem cells

Cancers of epithelial origin are responsible for the majority of cancer-related deaths in the USA. Unfortunately, although chemotherapy and/or radiation therapy can sometimes shrink tumors, metastatic cancers of epithelial origin are essentially incurable. It is clear that new approaches are needed to treat these diseases. Although cancer cell lines provide invaluable information, their biological properties often differ in crucial ways from de novo cancer cells. Our laboratory has developed a novel mouse model that reliably permits individual cancer cells isolated directly from patients’ tumors to be assayed. This will allow the characterization of crucial signaling pathways involved in processes such as self-renewal that are critical for tumor formation by the cancer cells within de novo tumors. These tools should lead to new insights into the cellular and molecular mechanisms that drive human breast cancer growth and invasion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46932/1/280_2005_Article_97.pd

Irwin H. Krasna Papers, 1971, 2003

The collection documents the trip to the Soviet Union that Dr. Irwin H. Krasna, a pediatric surgeon and his twin brother, Dr. Alvin I. Krasna, a Professor of Biochemistry at Columbia University, took in September-October 1971, traveling under the auspices of Arye Kroll, a prominent Israeli Zionist and representative of Lishkat Hakesher (commonly known as Nativ), the Israeli liaison Bureau that carried out clandestine activities to establish contact with Jews in Eastern Europe during the Cold War to encourage them to immigrate to Israel.Finding Aid available in Reading Room and on Internet.Donated by Dr. Irwin H. Krasna inAJHS.2007.038far031

Postgraduate Employment Outcomes of Undergraduate and Graduate Public Health Students:A Scoping Review

ObjectivesA key goal of schools and programs of public health is to prepare graduates for careers in the public health workforce after graduation, but are they achieving this goal? We assessed how the employment outcomes of students earning public health degrees are collected and described in the literature.MethodsUsing the Kirkpatrick model of training evaluation as a framework, we conducted a 6-step scoping review: (1) formulating the research question, (2) identifying relevant studies, (3) selecting studies, (4) charting the data, (5) collating and summarizing the results, and (6) consulting stakeholders. We included articles published from January 1, 1993, through July 4, 2020, that provided data on employment status, employment sector/industry, job function, or salary of public health graduates. We excluded articles that were not written in English and were about dual-degree (ie, doctor of medicine-master of public health) students. We found and reviewed 630 articles.ResultsWe found 33 relevant articles. Most articles focused on a single school and combined multiple graduating classes, focused on subspecializations of public health, or focused on graduates' satisfaction with their curriculum but not employment outcomes. Data were inconsistently categorized, and studies were difficult to compare.ConclusionsResearch on public health graduates' employment outcomes is scarce and does not follow consistent protocols. New standards should be adopted to systematize the collection of data on employment outcomes of public health graduates

Labour market competition for public health graduates in the United States: A comparison of workforce taxonomies with job postings before and during the COVID-19 pandemic

A strong public health workforce (PHW) is needed to respond to COVID‐19 and public health (PH) issues worldwide. However, classifying, enumerating, and planning the PHW is challenging. Existing PHW taxonomies and enumerations focus on the existing workforce, and largely ignore workforce competition for public health graduates (PHGs). Such efforts also do not utilize real time data to assess rapid changes to the employment landscape, like those caused by COVID‐19. A job postings analysis can inform workforce planning and educational program design alike. To identify occupations and industries currently seeking PHGs and contrast them with existing taxonomies, authors matched existing PHW taxonomies to standardized occupational classification codes, then compared this with 38,533 coded, US job postings from employers seeking Master’s level PHGs from 1 July 2019 to 30 June 2020. Authors also analysed 24,516 postings from March 2019 to October 2019 and compared them with 24,845 postings from March 2020 to October 2020 to assess changing employer demands associated with COVID‐19. We also performed schema matching to align various occupational classification systems. Job postings pre‐COVID and during COVID show considerable but changing demand for PHGs in the US, with 16%–28% of postings outside existing PHW taxonomies, suggesting labour market competition which may compound PHW recruitment and retention challenges.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167771/1/hpm3128_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167771/2/hpm3128.pd