BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Background
The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) checklist consists of 20 items to report for published tumor marker prognostic studies. It was developed to address widespread deficiencies in the reporting of such studies. In this paper we expand on the REMARK checklist to enhance its use and effectiveness through better understanding of the intent of each item and why the information is important to report.

/pdf/reporting-recommendations-for-tumor-marker-prognostic-4alpnil2o3.pdf

Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration

Gastric cancer is the second most common cause of cancer-related deaths in the world, the epidemiology of which has changed within last decades. A trend of steady decline in gastric cancer incidence rates is the effect of the increased standards of hygiene, conscious nutrition, and Helicobacter pylori eradication, which together constitute primary prevention. Avoidance of gastric cancer remains a priority. However, patients with higher risk should be screened for early detection and chemoprevention. Surgical resection enhanced by standardized lymphadenectomy remains the gold standard in gastric cancer therapy. This review briefly summarizes the most important aspects of gastric cancers, which include epidemiology, risk factors, classification, diagnosis, prevention, and treatment. The paper is mostly addressed to physicians who are interested in updating the state of art concerning gastric carcinoma from easily accessible and credible source.

/pdf/gastric-cancer-epidemiology-prevention-classification-and-3npetq4wwh.pdf

Gastric cancer: epidemiology, prevention, classification, and treatment.

Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20–23-nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the translation and stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and invasion. miRNA targeting is initiated through specific base-pairing interactions between the 5′ end (“seed” region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3′ UTR lead to more effective mRNA destabilization. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. To provide a critical overview of miRNA dysregulation in cancer, we first discuss the methods currently available for studying the role of miRNAs in cancer and then review miRNA genomic organization, biogenesis, and mechanism of target recognition, examining how these processes are altered in tumorigenesis. Given the critical role miRNAs play in tumorigenesis processes and their disease specific expression, they hold potential as therapeutic targets and novel biomarkers.

/pdf/micrornas-in-human-cancer-1i28sad8nq.pdf

microRNAs in Human Cancer

Metabolic response-guided treatment individualization in neoadjuvant therapy of locally advanced adenocarcinoma of the esophagogastric junction (AEG)

Nuklearmedizinische Verfahren erlauben es, am Patienten physiologische und biochemische Prozesse im Tumorgewebe zu messen und bildlich darzustellen. Entsprechend der jeweiligen Fragestellung werden dazu verschiedene Testsubstanzen („Marker“) eingesetzt, deren Verteilung im Organismus durch die Markierung mit einem radioaktiven Nuklid mit Hilfe eines externen Detektors bestimmt werden kann. Da Radioaktivitat sehr empfindlich nachgewiesen werden kann, mussen nur minimale Mengen eingesetzt werden, die den zu untersuchenden Prozess nicht beinflussen und keine toxischen Wirkungen aufweisen. So ermoglichen es nuklearmedizinische Verfahren, Tumorgewebe durch den Nachweis von Rezeptoren, Antigenen oder Stoffwechselprozessen naher zu charakterisieren („biologische“ oder „molekulare“ Bildgebung). Mit dieser Bezeichnung wird betont, dass bei dieser Art der Bildgebung dem gemessenen Signal eine spezifische biologische Eigenschaft des Tumors zugrunde liegt, wahrend mit morphologischen bildgebenden Verfahren eher unspezifische Eigenschaften, wie die Rontgendichte des Gewebes und seine Gefaspermeabilitat dargestellt werden.

Nuklearmedizin: biologische Bildgebung und Response Evaluation

Background: Response to chemotherapy is likely to be predicted by tumor dependent characteristics as well as by constitutional genetic factors. There is evidence that polymorphisms of the DNA repair genes may be associated with differential DNA repair activity. Because increased DNA repair plays an important role in chemoresistance to platinum based therapy, we assessed 6 polymorphisms in 4 DNA repair genes for their association with response and prognosis. Methods: DNA was isolated from blood or non malignant tissue of 258 patients (pts.) with esophageal cancer (EC) (n=114) or gastric (GC) (n=144) staged cT3/4 Nany cM0 treated with cisplatinum based neoadjuvant polychemotherapy (CTx). Polymorphisms in XPC codon 499, XPC codon 939, XPD codon 312, XPD codon 751, XRCC3 codon 241 and XRCC1 codon 399 were genotyped by allelic discrimination method (TaqMan). Standardized histopathological workup, assessment of clinical and histopathological response and follow up were performed as previously described. Results: XPC939 was correlated with withdrawal of CTx due to toxicity or nonresponse (p=0.014) in EC, XPD751 in GC (p=0.048). None of the analyzed polymorphisms was associated with histopathological response, only XRCC3 was associated with clinical response in GC (p=0.048), XPC939 in GC (p=0.047). In the R0 resected pts. XPC939 (p=0.030) and XRCC3 (p=0.042) predicted survival for EC, XPC939 (p=0.047) for GC. Cox regression including the completely resected pts. revealed ypT-category [ypT0/1/2/3/4] (p=0.007) and XPC939 (p=0.012) as independent prognostic factors for EC, ypN-category [ypN0/+] (p=0.033) and histopathological response [regression la/b: less than 10% residual tumor] (p=0.005) for GC. Conclusion: The influence of polymorphisms in the DNA repair genes on measurable tumor response is low. However prognosis is influenced by the genotypes of XPC939 and XRCC3. These and further polymorphisms could lead to tailored treatment concepts based on pharmacogenetics in the future.

XPC 939 and XRCC3 polymorphisms as prognostic markers in locally advanced esophageal and gastric adenocarcinoma treated with cisplatin and 5-FU based neoadjuvant chemotherapy

Adenokarzinome des gastroosophagealen Ubergangs sind eine der am starksten zunehmenden Tumorentitaten in der westlichen Hemisphare und stellen mittlerweile eine der haufigsten Todesursachen durch Krebs dar. Die Prognose in den lokal fortgeschrittenen Stadien II und III ist ungunstig mit einer hohen Rate lokaler Rezidive und Fernmetastasen sowie einem 5-Jahres-Uberleben von lediglich 20–30%. Durch multimodale Behandlungsstrategien lasst sich die Prognose im Vergleich zu alleiniger chirurgischer Therapie verbessern. Zwei in Europa durchgefuhrte randomisierte Studien zeigten, dass perioperative Chemotherapie zu einem signifikanten Uberlebensvorteil fur Patienten mit Magenkarzinomen und Adenokarzinomen des gastroosophagealen Ubergangs fuhrt. Aufgrund aktueller Metaanalysen werden Patienten mit lokal fortgeschrittenen Adenokarzinomen des Osophagus entweder mit praoperativer Chemotherapie oder mit Radiochemotherapie vorbehandelt. Zusatzlich zur alleinigen Chemotherapie wird der perioperative Einsatz zielgerichteter Substanzen wie Bevacizumab, Cetuximab und Panitumumab derzeit in klinischen Studien bei resektablen gastroosophagealen Tumoren gepruft. Trotz der vielversprechenden Ergebnisse aus multimodalen Therapiekonzepten erhalt ein Grosteil der neoadjuvant behandelten Patienten eine ineffektive, nebenwirkungsreiche Therapie. Die Positronenemissiontomographie mit dem Glucoseanalogon [18F]-Fluorodesoxyglucose (FDG-PET) bietet die Moglichkeit, durch Messung quantitativer Anderungen der Glucoseanreicherung im Tumor fruh im Verlauf der Therapie das histopathologische Tumoransprechen sowie die Prognose des Patienten vorherzusagen. Insbesondere bei Patienten, die nicht auf eine Therapie ansprechen, besteht somit die Moglichkeit, im Verlauf einer Therapie das therapeutische Procedere zu andern und dem Patienten alternative Therapiekonzepte anzubieten.

Katja Ott

Papers

Metabolic response-guided treatment individualization in neoadjuvant therapy of locally advanced adenocarcinoma of the esophagogastric junction (AEG)

Nuklearmedizin: biologische Bildgebung und Response Evaluation

XPC 939 and XRCC3 polymorphisms as prognostic markers in locally advanced esophageal and gastric adenocarcinoma treated with cisplatin and 5-FU based neoadjuvant chemotherapy

Multimodale Therapie bei Karzinomen des gastroösophagealen Übergangs (GÖÜ)