Decreased functional activity of multidrug resistance protein in primary colorectal cancer

BACKGROUND The ATP-Binding Cassette (ABC)-transporter MultiDrug Resistance Protein 1 (MDR1) and Multidrug Resistance Related Protein 1 (MRP1) are expressed on the surface of enterocytes, which has led to the belief that these high capacity transporters are responsible for modulating chemosensitvity of colorectal cancer. Several immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) studies have provided controversial results in regards to the expression levels of these two ABC-transporters in colorectal cancer. Our study was designed to determine the yet uninvestigated functional activity of MDR1 and MRP1 transporters in normal human enterocytes compared to colorectal cancer cells from surgical biopsies. METHODS 100 colorectal cancer and 28 adjacent healthy mucosa samples were obtained by intraoperative surgical sampling. Activity of MDR1 and MRP1 of viable epithelial and cancer cells were determined separately with the modified calcein-assay for multidrug resistance activity and sufficient data of 73 cancer and 11 healthy mucosa was analyzed statistically. RESULTS Significantly decreased mean MDR1 activity was found in primary colorectal cancer samples compared to normal mucosa, while mean MRP1 activity showed no significant change. Functional activity was not affected by gender, age, stage or grade and localization of the tumor. CONCLUSION We found lower MDR activity in cancer cells versus adjacent, apparently, healthy control tissue, thus, contrary to general belief, MDR activity seems not to play a major role in primary drug resistance, but might rather explain preferential/selective activity of Irinotecan and/or Oxaliplatin. Still, this picture might be more complex since chemotherapy by itself might alter MDR activity, and furthermore, today limited data is available about MDR activity of cancer stem cells in colorectal cancers. VIRTUAL SLIDES The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1675739129145824

Improved Accuracy of Lymph Node Staging and Long-Term Survival Benefit in Colorectal Cancer With Ex Vivo Arterial Methylene Blue Infiltration

Introduction:Ex vivo methylene blue (MB) injection into the main supplying arteries of the colorectal specimen after surgical removal is an uncomplicated technique to support lymph node harvest during pathological evaluation. The primary aim of this randomized, interventional, bicentric trial was to evaluate the impact of MB injection on lymph node yield, with secondary aims assessing the accuracy of lymph node staging and the effect on 5-year overall survival for patients undergoing resection of colorectal cancer.Methods: In the study period between December 2013 and August 2015, 200 colorectal resections were performed at two independent onco-surgery centers of Hungary. Following surgical resection, each specimen was randomly assigned either to the control (standard pathological work-up) or to the MB staining group before formaldehyde fixation. Patient-level surgical and clinical data were retrieved from routinely collected clinical datasets. Survival status data were obtained from the National Health Insurance Fund of Hungary.Results: A total of 162 specimens, 82 in the control and 80 in the MB groups, were included for analysis. Baseline characteristics were equally distributed among study groups, except for specimen length. Both the median of total number of lymph nodes retrieved (control 11 ± 8 [0–33] nodes vs. MB 14 ± 6 [0–42] nodes; p < 0.01), and the ratio of cases with at least 12 removed lymph nodes (36/82, 43.9% vs. 53/80, 66.3%; p < 0.01) were higher in the MB group. The rate of accurate lymph node staging was non-significantly improved. As for rectal cancer, nodal staging accuracy (16/31, 51.6% vs. 23/30, 76.7%; p = 0.04) and the proportion with minimum 12 lymph node retrieval (7/31, 22.6%, vs. 18/30, 60%; p < 0.01) was improved by MB injection. In Mantel–Cox regression, a statistically significant survival benefit with methylene blue injection at 5 years post-surgery was proven (51.2% vs. 68.8%; p = 0.04).Conclusion: In our experience, postoperative ex vivo arterial methylene blue injection appears to be an uncomplicated technique, improving lymph node yield and decreasing the chance of insufficient nodal staging. The technique might also associate with a 5-year overall survival benefit

Projektalapú mintagyűjtéstől a biobankig = From project based sample collection to a biobank

A kutatócsoport sebészeti műtétek során eltávolított daganatos szövetekből vesz ischaemiás időn belül molekuláris genetikai vizsgálatokra mintákat, amelyeket folyékony nitrogénben tárol. A betegek klinikai adatait egy saját fejlesztésű informatikai rendszerben tárolja. A vizsgálatokba bevont betegeket egy erre a célra létrehozott, nem OEP-támogatott ambuláns rendelésen követi. A szövettani mintákkal és a követési adatokkal molekuláris genetikai laboratóriumokkal alakít ki kutatások céljából együttműködéseket. Orv. Hetil., 2011, 152, 606–609. | The research group takes samples for molecular genetical examinations from tumors removed during operations within ischemic time interval. Samples are stored in liquid nitrogen. Clinical data of these patients are recorded in an informatics system developed by the group. Patients are followed in an out-patient clinic set up for this purpose not financed by the National Health Insurance Fund. Tissue samples and follow up data are used to cooperate with molecular genetical laboratories. Orv. Hetil., 2011, 152, 606–609

Az emlődaganatok diagnózisa és kezelése | Diagnosing and Treating Breast Tumours

A női mell, az anyaság egyik szimbóluma sok művészt ihletett meg, a szoptatás halhatatlan műalkotások sorának tárgya, a mell anya és gyermeke csodálatos, szívet melengető kapcsolatának a jelképe. Szerepe másfelől jelentős a nő és a férfi érzelmi együttlétében is. Azaz aligha vitatható, hogy kiegyensúlyozott, tartalmas életvitelünk szerves tartozéka. A mell azonban sajnos nemritkán komoly problémák, bajok forrása is lehet. A betegségek főként a női szervezetben jelentkeznek, s az emberiség történelme folyamán gyakorlatilag az utolsó száz évig alig voltak befolyásolhatók, és sokszor vezettek tragédiához. Közülük elsősorban a daganatos jellegű elváltozások voltak azok, amelyekkel szemben elődeink és sokszor a ma embere is tehetetlennek érzi magát. A 20. század, s elsősorban annak második fele azonban igen jelentős fejlődést tudott felmutatni az emlődaganat kezelésében. Az előadás bemutatja, hogy milyen utat járt be az emlőbetegségek – elsősorban a rosszindulatú daganatok – kezelése, hol tartunk jelenleg, mit tudunk tenni embertársaink egészségének visszaadásáért, életének biztosításáért. Megismertet az emlődaganatok keletkezésének és kórismézésének néhány kérdésével, különösen tekintettel a remélhetőleg mindinkább elterjedő szűrővizsgálatokra. | The lecture presents how the treatment of breast diseases, primarily malignant tumours, developed, where we stand now and what physicians can do to ensure the survival of sufferers. The introduction clarifies the notion of tumour and the difference between malignant and non-malignant tumours, then goes on to describe the diagnostic and treatment possibilities of breast tumours. Perhaps the most important message of the lecture is that self-examination, regular medical checks and mammograms play a vital role in early diagnosis. In essence there are three treatment options for breast tumours: surgery, radiation therapy, chemotherapy and hormone therapy. Nowadays, less radical surgical interventions than surgery are preferred, considerably decreasing the burden breast cancer puts on patients, without lessening therapeutic effectiveness. This of course, requires a better understanding of the biological behaviour of tumours and the development of radio- and pharmacotherapy

Egy örökzöld klasszikus újra olvasva - Daniel Gile alapfogalmai és modelljei három évtized távlatából

Vajon mitől válik „klasszikus” olvasmánnyá egy tudományos mű egy adott szak- területen? Mi az a titkos összetevő, amitől az utókor szemében mérföldkőnek számít egy könyv