PubMed Health⌕ Search

Biomedical subjects

A Zalatnai

Publications and source records attributed to A Zalatnai.

At least 19 recordsLinked to original sources

[Pathologic diagnosis of pancreatic cancer--facts, pitfalls, challenges].

Discrimination between the well differentiated pancreatic carcinoma and the chronic fibrotizing pancreatitis is one of the most difficult diagnostic problems in the field of pancreatology, and it is also a challenge for the pathologist. The author outlines those objective facts that might lead to diagnostic errors. The two diseases may coexist; on the one hand, malignant tumor can be developed as a complication of a long-standing chronic pancreatitis, while on the other hand, pancreatic carcinoma is frequently accompanied by chronic inflammation. The majority of adenocarcinomas induce a striking desmoplastic stromal reaction, but the chronic pancreatitis is also characterized by a vigorous fibroblast proliferation leading to the possibility of macroscopical misdiagnosis. Microscopically, the pancreatitis can be mistaken for carcinoma, because the actively growing connective tissue irregularly separates the ducts and in addition, the continuous regenerative activity may lead to regressive atypia. For that reason, cytopathologist must evaluate several criteria together, because the nuclear alterations by themselves can be misleading. Although there are some promising new differential diagnostic techniques (apomucins, CAM 17.1, telomerase activity, loss of chromosome Y), so far the most reliable method has been the meticulous evaluation of the cellular and histological findings by the well trained pathologist. To date, molecular pathological methods have shown no advantage in the differential diagnosis.

Adenocarcinoma↗

Wheat germ extract inhibits experimental colon carcinogenesis in F-344 rats.

It has been demonstrated for the first time that a wheat germ extract prevents colonic cancer in laboratory animals. Four-week-old inbred male F-344 rats were used in the study. Colon carcinogenesis has been induced by azoxymethane (AOM). Ten rats served as untreated controls (group 1). For the treatment of the animals in group 2, AOM was dissolved in physiologic saline and the animals were given three subcutaneous injections 1 week apart, 15 mg/kg body weight (b/w) each. In two additional groups Avemar (MSC), a fermented wheat germ extract standardized to 2,6-dimethoxy-p-benzoquinone was administered as a tentative chemo-preventive agent. MSC was dissolved in water and was given by gavage at a dose of 3 g/kg b/w once a day. In group 3, animals started to receive MSC 2 weeks prior to the first injection of AOM daily and continuously thereafter until they were killed 32 weeks later. In group 4 the basal diet and MSC were administered only. At the end of the experiment all the rats were killed by exsanguination, the abdominal large vessels were cut under a light ether anesthesia and a complete autopsy was performed. Percentage of animals developing colon tumors and number of tumors per animals: group 1 - 0 and 0; group 2- 83.0 and 2.3; group 3 - 44.8 (P < 0.001) and 1.3 (P < 0.004), group 4 - 0 and 0. All the tumors were of neoplastic nature also histologically. The numbers of the aberrant crypt foci (ACF) per area (cm(2)) in group 2 were 4.85 while in group 3 the ACF numbers were 2.03 only (P < 0.0001).

Animals↗

[Somatostatin analogs in the treatment of pancreatic cancer: utopia or feasible alternative?].

The authors give an overview on the clinical treatment results of pancreatic carcinoma with somatostatin analogs including octreotide, lanreotide and vapreotide. Numerous preclinical studies provided solid evidence that the growth of ductal pancreatic adenocarcinoma can successfully be inhibited using such synthetic analogs via direct (apoptosis-inducing) and various indirect mechanisms. In the clinical practice their role still remains contradictory. Monotherapy did not result in a prolongation of the survival, however, in 15-20% of patients the progression of the process has been halted for several months accompanied by a significant improvement of the clinical condition without notable side effects. Combination of octreotide with tamoxifen yielded a survival benefit in addition to the stabilization of the general condition, although reduction of the tumor mass has not been documented. Despite the modest results these finding reinforce the responsiveness of the pancreatic ductal cancer to the hormonal manipulations and further studies on optimization of the effects are of worth. While in the majority of cases the somatostatin receptors have been lost, hormonal control of the pancreatic cancer could be achieved by combination treatment modalities.

Antineoplastic Agents↗

[Secondary cutaneous infiltration in B-cell chronic lymphocytic leukemia (B-CLL)].

Authors report here on a case presenting as B-CLL and complicated with cutaneous infiltration involving the legs and the trunk a year later. Immunohistochemic analysis and the immunoglobulin heavy chain gene rearrangement confirmed cell invasion into the skin identical with the underlying disorder. After failure of conventional chemotherapy, interferon alpha 2b therapy has been started with satisfactory result. Few cases presenting cutaneous infiltration in the course of B-CLL has already been reported in the literature. Secondary cutaneous B-cell lymphoma represents an entity of the poorest prognosis in comparison with primary cutaneous form treated with conventional therapy as well as with lymphomas lacking skin manifestations. Interferon alpha 2b therapy cleans up the skin and yields a favourable survival so it's introduction recommended in this entity. Authors summarise the characteristics of secondary cutaneous B-cell lymphomas on the basis of literature survey. According to authors investigations histidine decarboxylase activity was found to be absent from the lymphocytes infiltrating the skin in contrast to those remaining in the circulation. This seems to be a newly recognised feature of these cells. The changing character of the disease raises the possibility of an altered gene expression pattern of the cells invading the skin. Authors summarise data from the literature concerning suspected molecular mechanism of tissue invasion.

Antineoplastic Agents↗

Papillary microcarcinoma of the thyroid gland in renal transplant patients.

Among organ transplant recipients there is a world wide increase in the number of de novo tumors as well as a decrease in the time of the first appearance after the transplantation. Between 1973 and the 31st of August 1999 1709 cadaver renal allograft transplantations were performed in our Department. Four thyroid cancers were detected among the renal transplanted patients. Two of them proved to be papillary microcarcinomas. Although the elevated risk of thyroid cancers is well established in the literature papillary microcarcinomas have never been reported before in an immunosuppressed patient. Authors highlight that the thyroid gland should always be carefully checked in organ transplant recipients, since better survival might be achieved even in the immunosuppressed population. Metastatic tumor is relatively benign which is in correlation with the literature, but there has been little experience in organ transplanted patients so far.

Brain Neoplasms↗

Elevated serum dipeptidyl peptidase IV (CD26, EC 3.4.14.5) activity in experimental liver cirrhosis.

BACKGROUND: Dipeptidyl peptidase IV (DPP IV) is a cell surface ectoenzyme widely distributed in the rat body, present on the epithelial cells of the brush border membranes (e.g. bile canaliculi) and on the surface of reactive lymphocytes and fibroblasts. DPP IV has been implicated in hepatocyte-extracellular matrix interactions, fibroblast activation and proliferation and in T-cell activation. Aberrant DPP IV expression was found in human liver cirrhosis, and elevated serum DPP IV activity was reported in patients with primary biliary cirrhosis and chronic hepatitis C virus infection. The aim of the study was to examine serum DPP IV activity in experimental liver cirrhosis. METHODS: Liver cirrhosis was induced by administering diethyl-nitrosamine, phenobarbital and CCl4 in Fischer-344 male rats (n = 22). Phenobarbital-treated (n = 9) and nontreated (n = 9) male rats were used as controls. Serum DPP IV activity was measured using a microplate-based continuous-monitoring assay. Recombinant rat DPP IV was used as standard and Gly-Pro-PNA was used as substrate. Enzyme activity was given in nmol mL-1 min-1 (U L-1). RESULTS: Significantly higher DPP IV activity was found in the sera of rats with experimental liver cirrhosis (39.2 +/- 3.7; mean +/- SD) compared to phenobarbital-treated (11 +/- 4, P < 0.000002) and nontreated (10.9 +/- 0.9, P < 0.000002) rats. There was a positive correlation between DPP IV activity and concentrations of aspartate aminotransferase (r = 0.73, P = 0.0001) and alanine aminotransferase (r = 0.69, P = 0.0004). CONCLUSIONS: The significantly higher serum DPP IV activity found in experimental liver cirrhosis is in concordance with human observations. The elevation was probably not due to the enzyme induction effect of phenobarbital. In this experimental model, serum DPP IV seems to be an indicator for chronic liver injury.

Animals↗

Secondary cutaneous infiltration in B cell chronic lymphocytic leukemia.

We describe a patient presenting with B cell chronic lymphocytic leukemia (B-CLL) who subsequently developed cutaneous infiltrates. Specimens of the blood, bone marrow and cutaneous infiltrations all showed the same heavy-chain gene rearrangement. Following failure of conventional chemotherapy, and in view of the similarity of the disease to cutaneous T cell lymphoma, interferon-alpha therapy was employed with satisfactory results. Introduction of this cytokine to the therapeutic modalities for secondary cutaneous B-CLL would hopefully change the poor outcome of this entity, or at least could produce a better quality of life. Loss of histidine decarboxylase activity in the infiltrating cells - in contrast to circulating lymphocytes - may be associated with the transformation of B-CLL to a more aggressive infiltrative form, offering a possible explanation for tissue invasiveness. The changing character of the disease raises the possibility of a second mutational event in the course of B-CLL.

Antineoplastic Combined Chemotherapy Protocols↗

Epithelial mesothelioma with deciduoid features.

A rare case of malignant mesothelioma in a 15-year-old girl is described. The patient presented with secondary amenorrhoea and clinical symptoms resembling those of an ovarian cyst. One large and multiple small peritoneal nodules were found at laparoscopy. Histologically the tumour was characterised by an unusual pattern with a superficial resemblance to decidual reaction, but because of significant mitotic activity the diagnosis of a malignant tumour, epithelial mesothelioma with deciduoid features, was made. The patient died 11 months after diagnosis. Post-mortem examination revealed extensive extraperitoneal spread.

Adolescent↗

Establishment and long-term xenografting of human pancreatic carcinomas in immunosuppressed mice: changes and stability in morphology, DNA ploidy and proliferation activity.

The prognosis of pancreatic carcinoma is grave, therefore the experimental model systems remain major tools for testing new treatment modalities. We have developed human pancreatic cancer lines growing in immunosuppressed mice and characterized them by morphological and flow-cytometric studies. Immunosuppression has been achieved in young (4-week-old) CBA/CA mice by thymectomy, whole-body irradiation and bone marrow reconstruction. Twelve surgically removed human pancreatic carcinomas were implanted subcutaneously and serially transplantable xenografts have been established. Altogether 129 samples derived from 59 generations have been analyzed. Out of 12 carcinomas, 6 developed continuously growing and transplantable xenografts (PZX-2, PZX-5, PZX-11, PZX-15, PZX-16, PZX-20; take rate: 50%). They were successfully maintained for 9-16 passages, for 18-25 months. New subpopulations developed during transplantations in 3 tumor lines and these morphological changes have been reflected by the appearance of an aneuploid peak in flow cytometry. In 1 tumor line, however, DNA aneuploidy was observable despite the unaltered histology. The PZX-20 line retained its original morphology and aneuploid pattern during 9 consecutive passages and over 18 months. The results indicate that the artificially immunosuppressed CBA/CA mice are suitable hosts for accepting and maintaining human pancreatic carcinomas. During successive xenograftings the regular morphological characterization must be supplemented by flow cytometry, because new tumorous clones may develop despite the unchanged histological picture.

Adenocarcinoma↗

Epidermal growth factor receptor, somatostatin and bcl-2 in human pancreatic tumor xenografts. An immunohistochemical study.

Xenografted human pancreatic tumors (5 ductal adenocarcinomas, 1 leiomyosarcoma, altogether 26 samples) were investigated about their immunohistochemical expression of epidermal growth factor receptor (EGFR), somatostatin (SS) and bcl-2 protein. The expression of the EGFR varied from tumor to tumor. One originally negative carcinoma became immunoreactive during passagings, one tumor has lost its early positive expression, and in 3 cancer lines a phenotypically constant pattern was seen. SS immunoreactivity was practically absent in all tumor samples. Concerning bcl-2 expression, different staining patterns were observed among the carcinomas, but the leiomyosarcoma has retained its strong positivity during xenograftings. In the PZX-5 carcinoma line that was originally negative, the one month Sandostatin treatment induced the strong expression of bcl-2 protein suggesting a development of an acquired resistance against programmed cell death in this tumor.

Animals↗

Human pancreatic leiomyosarcoma (PZX-7) growing as a serially transplantable xenograft in immunosuppressed mice.

BACKGROUND: Several human leiomyosarcoma xenografts have been established, but pancreatic smooth muscle sarcomas have never been serially transplanted and investigated. METHOD: Immunosuppression of CBA/CA mice was achieved by thymectomy, whole-body irradiation, and bone marrow reconstruction. Tumor fragments were subcutaneously implanted from a Grade III pancreatic leiomyosarcoma and serially passaged for more than 24 mo. The xenografted tumors were characterized by morphological, morphometrical, biochemical, and flow cytometric methods. RESULTS: The tumor has retained its characteristic morphology and no further differentiation occurred. The mitotic counts and the amount of the connective tissue all remained constant. The calculated volume doubling time was 11.3 d. Immunohistochemically, the tumor proved to be p53-negative, but the strong expression of the bcl-2 remained as a constant feature throughout successive transplantations. The DNA index and the proliferation indices did not change significantly with the time (mean DI: 1.65, range: 1.561-1.70; mean PI: 17.9%, range: 15.3-20.7%). Lactose dehydrogenase (LDH) isoenzyme electrophoresis evidenced a retained human pattern of the tumor even after 32 mo of transplantations. CONCLUSION: The first human pancreatic leiomyosarcoma xenograft (PZX-7) growing in immuno-suppressed mice is described and characterized.

Animals↗

Establishment and characterization of a new transplantable pancreatic cancer xenograft (PZX-5) in immunosuppressed mice.

CONCLUSION: A new, stable, transplantable human pancreatic cancer xenograft (PZX-5) model has been established in CBA immunosuppressed mice. BACKGROUND: Numerous human pancreatic carcinomas have been successfully transplanted into athymic nude mice. However, artificially immunosuppressed animals have rarely been used as recipients. Because this model system proved to be reliable for hosting many human malignancies at our institute, successive xenotransplantations of a ductal adenocarcinoma have been carried out. METHOD: Immunosuppression of CBA/CA mice was achieved by thymectomy, whole-body irradiation and bone-marrow reconstruction. Tumor fragments were subcutaneously implanted from a well/moderately differentiated ductal pancreatic adenocarcinoma and serially transplanted for more than 20 mo. The xenografted tumors were characterized using morphological, immunohistochemical, biochemical, and flow cytometric methods. RESULTS: During the serial transplantations, the neoplasm maintained its original morphological-pathobiological characteristics. It produced a large amount of mucin and expressed carcinoembryonic antigen (CEA). Neither the mitotic activity nor the degree of differentiation was altered, and CEA was permanently detected. Flow cytometric DNA analysis revealed an aneuploid pattern (DNA index 1.45+/-0.03), which has remained within the same range during xenograftings. The doubling time in an in vitro system proved to be 18 h. The human character has been well preserved even 9 mo posttransplantation, as was evidenced by LDH-isoenzyme electrophoresis. The results indicate that the thymectomized--whole-body irradiated--bone-marrow reconstructed immunosuppressed mice are also appropriate hosts for pancreatic cancer xenografts.

Adult↗

Coccidioidomycosis in Hungary. The first import case.

A case of an isolated subcutaneous coccidioidomycosis in a 61-year-old man is presented. The patient has lived and worked in Arizona for 3 years previously but developed no apparent clinical signs of the disease. The painless, cavitating, tumor-like mass was surgically excised and the diagnosis was established by histological demonstration of the fungi and confirmed by serum counterimmunoelectrophoresis. This represents the first imported case of coccidioidomycosis in Hungary.

Arizona↗

Pancreatic leiomyosarcoma. Case report with immunohistochemical and flow cytometric studies.

A leiomyosarcoma originating from the pancreas of a 57-year-old man is presented. A 6x5x4 cm tumour was located in the head region, and the patient underwent surgical palliation. Immunohistochemical studies excluded an epithelial origin; a myogenic origin was suggested by strong vimentin and smooth muscle actin positivity. Flow cytometric analysis revealed an aneuploid pattern (DNA index: 1,561). The patient died with widespread metastases 7 month after the operation.

Actins↗

Human and experimental hepatocarcinogenesis.

Human liver cancer is increasing worldwide, including in Hungary. The detection of liver tumors in premalignant or early malignant states is essential for successful treatment. MC-29 virus-induced chicken hepatoma and rodent, fish and monkey models for chemical hepatocarcinogenesis were studied and compared to humans. Changes in phenotypic enzyme alterations and in the expression of certain oncogens and growth factors characterize the experimentally induced hepatomas, and might also be characteristic of human premalignant and malignant focal liver lesions. Fish hepatocarcinogenesis is useful for studying compounds in environmental pollution. Increased expression of transforming growth factor á can be observed both in experimental and human liver tumors. Increased tumor incidence was detected in transgene mice containing both transforming growth factor alpha and c-myc genes. Animal models of hepatocarcinogenesis help to understand the development of liver tumors. Methods applied in studies using those models are useful in the study of premalignant and malignant human liver lesions.

Animals↗

The pathomorphology of a human xenotransplanted basaloid squamous cell carcinoma.

To elucidate some factors related to the malignant phenotype of an oral tumor with mixed cell population the question has been raised whether the biological behavior of the basaloid or the squamous cells show any difference in an immunosuppressed host organism. Basaloid squamous cell carcinoma (BSCC) surgically removed from sublingual location was xenotransplanted either subcutaneously or in the oral submucosa and the histology, ultrastructures, LDH isoenzyme pattern were investigated. The epithelial origin of the established tumor line (HTB-1) could be recognized according to the characteristic epithelial ultrastructures, while the type of the LDH isoenzymes proved its human origin. The squamous cell population dominating the parent surgical specimen of BSCC regressed during xenotransplantation in the subcutan location, on the contrary the basaloid cells grew and maintained the tumor. Interestingly the basaloid cells transplanted from the subcutis to the oral submucosa generated a squamous cell population with an infiltrative growth pattern. The xenografted BSCC offer a promising model to investigate the contribution of each cell populations in the malignant phenotype. The presented data indicate that the basaloid cells are responsible for maintaining the tumor cell population, but certain malignant features (i.e. infiltrative growth) is associated to the squamous cells which are generated from the basaloid cells only under specific circumstances. Thus this particular model system showed that different malignant features could be associated to the basaloid and to the squamous cell component.

Animals↗

[Androgen-producing adrenocortical adenoma in childhood. Pitfalls of differential diagnosis].

A two-year-old girl presented with clitoromegaly and an abdominal mass. Diagnostic procedures including sonography, computerized tomography, scintigraphy and measurement of catecholamines in urine excluded neuroblastoma, but suspected Wilms-tumor. Before completing the steroid measurements therapy was initiated according to Wilms-tumor (preoperative cytostatic therapy followed by surgical removal of the tumor). Morphology of the tumor, the serum and urinary steroid profile proved a benign adrenocortical adenoma producing mainly delta 5-steroids including the weak androgen, dehydroepiandrosterone.

Adenoma↗