Mihály Bak

Human tumor xenografts as model for drug testing

This paper reviews the history of xenografts, the endpoints commonly used to evaluate response and chemotherapeutic results obtained with serially maintained human tumor xenografts from different laboratories, and discusses the potential clinical relevance of the heterotransplant model for cancer chemotherapy. Specifically, an attempt is made to correlate the published xenograft data with the clinical data. Drug testing with different types of xenotransplanted tumors has shown that the response of xenografts obtained in immune-deficient animals is comparable to that in clinical practice. In addition, xenografts of a particular tumor type are able to identify agents of known clinical activity against that disease.

Expression of bcl-2 in testicular carcinoma: correlation with tumor progression and MDR1/Pgp.

The expression of bcl‐2 has been studied extensively in a variety of human tumors. However, there is a lack of clinical data regarding its expression in germ cell testicular tumors (GCTTs).

Detection of the multidrug resistant phenotype in human tumours by monoclonal antibodies and the streptavidin-biotinylated phycoerythrin complex method

The aim of this study was to find out whether the membrane glycoprotein P-170 can be detected in human tumours with both acquired and intrinsic resistance to chemotherapeutic agents using monoclonal antibodies (265/F4 and C219) and the streptavidin-biotinylated phycoerythrin complex method. Pretreated leukaemia cells and untreated lung and ovarian carcinomas were analysed. Two plasmacytomas and one leukaemia expressed high levels of P-glycoprotein, whereas two leukaemias showed moderate, and three leukaemias no expression of this protein. The intrinsic resistance was analysed with a panel of four human epidermoid lung cancer xenografts grown in nude mice. The expression of P-glycoprotein could be correlated with the degree of resistance. In addition, one out of five ovarian carcinomas revealed a high level of P-glycoprotein.

Induced multidrug resistance in murine leukemia L1210 and associated changes in a surface-membrane glycoprotein

SummaryThe aim of this study was to find out whether only resistant cells of the “multidrug-resistant” phenotype show the described changes of plasma membrane glycoprotein (170 kDa) or whether resistant cells that do not express this phenotype reveal corresponding results. Doxorubicin-resistant (L1210dox) and daunorubicin-resistant L1210 ascites tumor cells (L1210dur) (multidrug-resistant tumor cells) were therefore compared with cytosine-arabinoside-resistant (L1210AraC) and cyclophosphamide-resistant L1210 ascites tumor cells (L1210ctx) (not multidrug-resistant tumor cells). The resistant cell lines were generated in vivo in tumor-bearing mice and the resistance to cytostatic agents was evaluated in vivo and in vitro. Using the accumulation assay with rhodamine-123, the multidrug resistance can be detected. In order to determine alterations in the plasma membranes we used the monoclonal antibodies 265/F4 and C219, which were prepared against the membrane glycoprotein P170 (170 kDa) in colchicin-resistant Chinese hamster ovary cells. The results demonstrate that L1210dox and L1210dnr tumor cells show an intense immunostaining by the streptavidin/biotinylated-peroxidase-complex method and by the streptavidin/biotin/phycoerythrin immunofluorescence method. In contrast no specific immunostaining was observed in parental (sensitive) and L1210AraC or L1210etx tumor lines. The results were confirmed by immunoblotting. To determine whether multidrug-resistant DNA sequences were expressed in the multidrug-resistant tumor cells, Northern blots with RNA od sensitive and resistant cells were performed using the clone pcDR1.5. Elevated RNA levels were detected only in resistant cells with the multidrug-resistant phenotype. Thus, the results of this study demonstrate that only resistant cells with the multidrug-resistant phenotype show an increased expression of the membrane 170-kDa glycoprotein.

Do metallothioneins affect the response to treatment in testis cancers

Purpose: Data on the involvement of elevated metallothionein (MT) expression in resistance to some of the commonly used anticancer treatments are scattered and conflicting. This encouraged us to examine further the contribution of metallothionein expression to the development of this resistance phenotype. Patients and methods: Formalin-fixed, paraffin-embedded blocks of primary untreated germ cell testicular tumor specimens, obtained from 77 patients following radical orchiectomy, were examined for their MT expression using monoclonal antibody and immunohistochemistry. Clinical staging, the chemotherapeutic schedule and evaluation of response to treatment (defining objective response) were performed according to UICC criteria. Results: All tumor types, including seminomas and nonseminomas, expressed MT, regardless of their histology and clinical stage. The immunoreactivity of MT showed a significant positive correlation with the clinical sensitivity of cancer to antitumor therapy (P = 0.0001). Conclusion: In patients with germ cell testicular tumors, high MT expression, as detected by immunohistochemistry, predicts a better response rate to chemotherapy whereas tumors lacking or demonstrating low MT expression show a worse prognosis. These data do not support the hypothesis that MT overexpression contributes to cisplatinum resistance, at least in this tumor type.

Detection of drug resistance in human ovarian carcinoma

SummaryDrug-resistant cancer cells with the multidrug-resistance phenotype show overexpression ofP-glycoprotein, and we therefore tested carcinoma tissue from five patients with stage III or IV ovarian cancer forP-glycoprotein using 265/F4 and C 219 monoclonal antibodies, prepared against membrane glycoproteins in colchicine-resistant CHO cells. Using immunofluorescence and immunoblotting techniques, one of the tumors showed a positive reaction. Using the pcDR 1.5 clone we found that the same cancer tissue had elevated expression of the genes responsible for multidrug resistance. The demonstration of elevatedP-glycoprotein in ovarian carcinomas indicates thatP-glycoprotein overexpression is not limited to experimental tumor models.

[Quality assurance of fine-needle aspiration cytology of the organized mammography screening].

UNLABELLED The National Public Health Program has established the organized mammography screening in Hungary. AIM The aim of our study was to determine the quality assurance of breast aspiration cytology. METHOD Cytology results were rated to 5 categories (C1, C2, C3, C4 and C5). All cytology reports were compared with the final histology diagnosis. RESULTS 1361 women had aspiration cytology diagnosis performed from a total of 47718 mammography non-negative lesions. There were 805 (59.1%) benign and 187 (13.7%) malignant alterations. Sensitivity was 91%, specificity 88%, positive predictive value 96.6% and negative predictive value turned to be 71% (p<0.001). CONCLUSION The auditing values of fine needle aspiration cytology in our laboratory meet, or in certain aspects exceed the proposed minimum threshold values.

[Quality assurance of rapid on-site evaluation of CT-guided fine-needle aspiration cytology of lung nodules].

INTRODUCTION The methods available for the diagnosis of lung cancer include radiologic, cytologic and pathologic procedures. AIMS The aim of this study was to determine the quality assurance of CT guided fine needle aspiration cytology of lung nodules. METHODS Cytology results were rated to 4 categories (positive; suspicious; negative; not representative). All cytology reports were compared with the final histology diagnosis. RESULTS A total of 128 patients underwent CT-guided percutaneous fine-needle aspiration biopsy cytology (63 males; 65 females; mean age 62.8 years). Smears were adequate in 99 cases and inadequate in 29 cases. The average diameter of the nodules was 3.28 cm. Thirty three (25.6%) of the cases were histologically verified and 2 falsely negative and 2 falsely positive cases were detected. The sensitivity and the positive predictive value were 88.8% and 88.8%, respectively. Pneumothorax developed in 7 (5.4%) cases. CONCLUSION These results suggest that CT-guided transthoracic fine needle aspiration cytology has a high diagnostic accuracy and an acceptable complication rate. The auditing valves of the results meet the proposed threshold values.

A European Society of Breast Cancer Specialists (EUSOMA) előírásainak megfelelő emlőrákellátás minőségbiztosítási elemzése az Országos Onkológiai Intézetben

Absztrakt Bevezetes: A European Society of Breast Cancer Specialists letrehozta az emlőrakellatast vegző onkologiai kozpontok es szakorvosok europai minősegbiztositasi feltetelrendszeret, hogy egyseges minimumstandardok bevezetesevel csokkentse az emlőrak mortalitasat a kontinensen. Celkitűzes: Jelen vizsgalat celja, hogy az Orszagos Onkologiai Intezet Emlő- es Lagyreszsebeszeti Osztalyan operalt, illetve az intezetben multidiszciplinarisan kezelt emlődaganatok komplex onkologiai ellatasat a European Society of Breast Cancer Specialists minősegbiztositasi kivanalmai szerint elemezze es a nagy esetszamu, reprezentativ minta reven a magyar emlőrakos populaciorol reszletes klinikopatologiai adatokat szolgaltasson az onkologiai ellatorendszer szamara. Modszer: 2011. junius 1. es 2012. majus 31. kozott multidiszciplinarisan kezelt emlődaganatok reszletes klinikopatologiai retrospektiv adatfeldolgozasat vegeztek a European Society of Breast Cancer Specialists egyseges nemzetkozi kriteriumrendszere szerint. Ered...

Pajzsmirigygöbök vékonytű-aspirációs citológiai vizsgálata. A Bethesda-rendszer (2008) minőségbiztosítása

Absztrakt Bevezetes: A pajzsmirigybetegsegek diagnosztikajanak modszertana rendkivul szeles, magaba foglalja a fizikalis, radiologiai, ultrahang-, izotop-, laboratoriumi es a vekonytű-technikas aspiracios citologiai vizsgalatokat. Celkitűzes: A szerzők celja a pajzsmirigygobok aspiracios citologiai gyors, azonnal adott diagnozisainak kovetese, citohisztologiai osszehasonlitasa, illetve minősegbiztositasa volt. Modszer: 1348 beteg pajzsmirigy-aspiracios vizsgalatat vegeztek el. A citologiai diagnozisokat a Bethesda System for Reporting Thyroid Cytopathology (2008) klasszifikacio alapjan hat kategoriaba (I.: nem reprezentativ, II.: benignus, III.: atipusos, IV.: follicularis neoplasia, V.: malignitasra suspect, VI.: malignus) soroltak. A citologiai modszer diagnosztikus erzekenyseget a szovettani eredmenyekhez viszonyitva elemeztek. Eredmenyek: Az 1348 pajzsmirigygob citologiai diagnozisa a fenti csoportok szerint a kovetkező volt: I.: 214, II.: 986, III.: 56, IV.: 41, V.: 18, VI.: 33 eset. A mintaveteleket...