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PubMed1996

The pH 6.7 Syrian hamster embryo cell transformation assay for assessing the carcinogenic potential of chemicals.

Cell transformation models have been established for studying the cellular and molecular basis of the neoplastic process. Transformation models have also been utilized extensively for studying mechanisms of chemical carcinogenesis and, to a lesser degree, screening chemicals for their carcinogenic potential. Complexities associated with the conduct of cell transformation assays have been a significant factor in discouraging broad use of this approach despite their reported good predictivity for carcinogenicity. We previously reported that many of the experimental difficulties with the Syrian hamster embryo (SHE) cell transformation assay could be reduced or eliminated by culturing these cells at pH 6.7 culture conditions compared to the historically used pH 7.1-7.3. We and others have shown that morphological transformation (MT), the earliest recognizable phenotype in the multi-step transformation process and the endpoint used in the standard assay to indicate a chemical's transforming activity, represents a pre-neoplastic stage in this model system. In the collaborative study reported here, in which approx. 50% of the chemicals were tested under code in one laboratory (Hazelton) and the other 50% evaluated by several investigators in the second laboratory (P & G), we have evaluated 56 chemicals (30 carcinogens, 18 non-carcinogens, 8 of inconclusive carcinogenic activity) in the SHE cell transformation assay conducted at pH 6.7 culture conditions with a standardized, Good Laboratory Practices-quality protocol. An overall concordance of 85% (41/48) between SHE cell transformation and rodent bioassay results was observed with assay sensitivity of 87% (26/30) and specificity of 83% (15/18), respectively. The assay exhibited a sensitivity of 78% (14/18) for Salmonella assay negative carcinogens, supporting its value for detecting non-mutagenic carcinogens. For maximum assay sensitivity, two exposure durations were required, namely a 24-h exposure and a 7-day exposure assay. Depending on the duration of chemical treatment required to induce transformation, insight into the mechanism of transformation induction may also be gained. Based on the data reported here, as well as the larger historical dataset reviewed by Isfort et al. (1996), we conclude that the SHE cell transformation assay provides an improved method for screening chemicals for carcinogenicity relative to current standard genotoxicity assays.

3T3 Cells↗
PubMed1999

Neonatal cranial ultrasound.

Neonatal cranial ultrasound continues to be a popular initial imaging modality because of the safety, low-cost, and portability of the examination. The higher frequency transducers and enhanced ability for signal processing that is possible with current ultrasound machines improves visualization of complex congenital anomalies, complications of pregnancy, and birth and neoplastic processes. This article reviews these conditions so that the reader will have a baseline knowledge of the ultrasound findings. With the use of neonatal cranial ultrasound, recognition of the maximum diagnostic information available on the sonogram and appropriate use of other cross-sectional imaging modalities are improved.

Brain↗
PubMed1987

The fine structure of gliomatosis cerebri.

The ultrastructural features of five biopsies of gliomatosis cerebri (GC) are described. Four main types of tumour cells are seen: anaplastic astrocytes poor in organelles with a variable amount of glial microfilaments; atypical oligodendrocytes with scanty cytoplasm in which microtubules are present; intermediate forms with aboundant cytoplasm rich in organelles, with microtubules and microfilaments; and small cells with round nuclei and a very scanty rim of cytoplasm. In two cases several concentrically folded cytoplasmic lamellae of glial processes were arranged either around themselves or around the perikaryon of other cells. This ultrastructural study indicates that GC is a neoplastic process of small undifferentiated elements, transitional forms of astroglia (to oligodendroglia) and anaplastic cells of astrocytic origin in all stages of development.

Adult↗
PubMed1983

Thymic nurse cells account for the thymus dependency of preleukemic cells in mice after inoculation of radiation leukemia virus.

Inoculation of Radiation Leukemia Virus (RadLV) into C57BL/Ka mice induces thymic lymphomas after a 3-6 month latent period. The leukemogenic process requires a sequence of events from the productive infection of susceptible target cells and induction of preleukemic cells to irreversible neoplastic transformation. Preleukemic cells were detected in the thymus during the first week following virus injection. The thymus dependency of these cells was shown to depend transiently upon peculiar lymphoepithelial complexes called "Thymic Nurse Cells" (TNCs). Indeed, the first preleukemic cells appearing in the RadLV-inoculated thymuses were observed selectively within TNCs. They remained closely associated with these complexes during the first 2 or 4 weeks. Later on, TNCs disappeared almost completely whereas non-TNCs associated preleukemic cells were found. Lymphoepithelial interactions within TNCs were thus required for the initial events of RadLV-induced lymphomagenesis. The subsequent TNCs depletion expressed a disturbance of thymic lymphopoiesis in relation with the neoplastic process.

Animals↗
PubMed2000

Congenital Heart Surgery Nomenclature and Database Project: diseases of the pericardium.

The extant nomenclature for pericardial disease is reviewed for the purpose of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. All efforts were made to include all relevant nomenclature categories, using synonyms where appropriate. No classification system has been reported. The groups were based on disease processes, and include: effusive pericarditis (pericardial effusion), constrictive pericarditis, cardiac tamponade, postoperative pericardial effusion, postoperative cardiac tamponade, postpericardiotomy syndrome, congenital defect, neoplastic process, benign mass, pericardial cyst, pneumopericardium, and chylopericardium. A comprehensive database set is presented that is based on a hierarchical scheme. Data are entered at various levels of complexity and detail, which can be determined by the clinician. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented that will allow for data sharing and would lend itself to basic interpretation of trends.

Databases, Factual↗
PubMed1988

Adult segmental cystic disease of the kidney: a renal-sparing management approach.

Segmental cystic disease of the kidney is a rare entity with the gross and microscopic features of autosomal dominant polycystic kidney disease localized to only a portion of a kidney. We report a renal-sparing management approach to a patient in whom a multifocal cystic process localized to 1 pole of the kidney was recognized preoperatively. Since neither computerized tomography nor ultrasound can exclude an underlying neoplastic process, surgery remains indicated. However, an understanding of the spectrum of diagnostic possibilities can have an impact on planning the most appropriate surgical approach. We conclude that partial nephrectomy, with appropriate intraoperative pathological assessment, may represent a satisfactory renal-sparing therapeutic algorithm for the management of localized cystic disease.

Adult↗
PubMed1999

Regulation of fatty acid homeostasis in cells: novel role of leptin.

It is proposed that an important function of leptin is to confine the storage of triglycerides (TG) to the adipocytes, while limiting TG storage in nonadipocytes, thus protecting them from lipotoxicity. The fact that TG content in nonadipocytes normally remains within a narrow range, while that of adipocytes varies enormously with food intake, is consistent with a system of TG homeostasis in normal nonadipocytes. The facts that when leptin receptors are dysfunctional, TG content in nonadipocytes such as islets can increase 100-fold, and that constitutively expressed ectopic hyperleptinemia depletes TG, suggest that leptin controls the homeostatic system for intracellular TG. The fact that the function and viability of nonadipocytes is compromised when their TG content rises above or falls below the normal range suggests that normal homeostasis of their intracellular TG is critical for optimal function and to prevent lipoapoptosis. Thus far, lipotoxic diabetes of fa/fa Zucker diabetic fatty rats is the only proven lipodegenerative disease, but the possibility of lipotoxic disease of skeletal and/or cardiac muscle may require investigation, as does the possible influence of the intracellular TG content on autoimmune and neoplastic processes.

Adipocytes↗
PubMed1990

Primary testicular choriocarcinoma with pulmonary metastases presenting as ARDS.

We report a case in which ARDS was the presenting manifestation of testicular choriocarcinoma with numerous metastases to the lungs. We also review the literature on other cases in which ARDS developed as a result of neoplastic infiltration of the lungs and stress the fact that it may be indistinguishable from ARDS from other causes. Because potentially effective chemotherapy for the neoplastic processes most commonly involved (ie, germ cell tumors, acute leukemia and lymphoma) is available, we emphasize the importance of considering a neoplastic disorder in the differential diagnosis of cases of otherwise unexplained ARDS. Early accurate diagnosis could conceivably result in an improved outcome in these cases.

Adult↗
PubMedDate not supplied

[Local immune reactions of the cerebrospinal fluid in meningeal brain tumors].

The paper analyzes the time course of immune processes in the cerebrospinal fluid of patients with primary meningeal tumors of the brain. It shows the formation of an immunobiochemical neoplastic process of varying degrees in relation to the magnitude of tumor malignancy. The paper also considers if the local immune system can trigger sanogenetic mechanisms in the postoperative period.

Adolescent↗
PubMed1990

Sonography of abnormal lymph nodes in vitro: correlation of sonographic and histologic findings.

The sonographic evaluation of lymph nodes is based primarily on evaluation of their shape and size. Recently, however, the availability of high-frequency transducers has made consideration of internal structure possible. An important objective is to determine whether node enlargement is due to inflammatory or neoplastic processes. To determine the accuracy of sonography for this purpose, we obtained in vitro sonograms of 53 enlarged lymph nodes excised from 41 patients during surgery for neoplastic or nonneoplastic disease. The sonograms were obtained with 7.5- and 10-MHz transducers. They were interpreted by a radiologist who was unaware of the clinical diagnosis. The nodes were subsequently processed for anatomohistologic study; findings were compared side by side. In 26 of the 53 nodes, sonograms showed an identifiable central echogenic line, which on histologic specimen corresponded to the internal part of the medulla where the lymphatic sinuses converge. All these nodes were benign. Two other nodes had an echogenic internal structure not resembling the normal hilum; in one case this was caused by metastatic disease and in the other by fibrosis. Sonograms of the remaining 25 nodes showed no detectable hilar structure; 21 were involved by a tumor and four had diffuse fatty replacement. Our results suggest that the sonographic finding of a central echogenic line is a valid criterion of benignity. Absence of this finding may be due to factors other than neoplastic disease, such as fatty replacement.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Sinonasal undifferentiated carcinoma: report of two cases and review of the literature.

Sinonasal undifferentiated carcinoma is a rare, highly aggressive neoplasm of the paranasal sinuses. Approximately 40 cases of this neoplasm have been reported to date. Microscopically, this neoplasm is composed of medium-sized cohesive cells arranged in nests, ribbons, and trabeculae having hyperchromatic nuclei, often with prominent nucleoli. A high mitotic rate, tumor necrosis, and prominent vascular invasion are conspicuous features. Squamous or glandular differentiation is not observed at the light-microscopic level. It appears to be a unique, distinctive clinicopathologic process that must be distinguished microscopically from other, less aggressive "round cell" sinonasal neoplasms. In this article, two additional cases of this neoplastic process are reviewed. Aggressive, multimodal treatment may offer the best chance for local control, palliation, and, ultimately, survival of the patient. The optimal treatment of SNUC, however, has yet to be determined.

Adult↗
PubMed2002

Early cellular events in colorectal carcinogenesis.

Colorectal cancer develops through a multistage process recognizable at a histopathological level by progression from normal mucosa to invasive carcinoma (the adenoma-carcinoma sequence). For many years, it has been hypothesized that increased cell proliferation in the colonic crypt represents the earliest recognizable stage in this sequence. This perspective is now changing. While several human studies have reported increased crypt cell proliferation in samples from at-risk patients, there are many inconsistencies and paradoxes in their conclusions. In addition, it is appreciated that the process of apoptosis (programmed cell death) is vital for normal crypt homeostasis and its impairment may be an early event in the neoplastic process. It is now believed that aberrant crypt foci (ACFs) represent the earliest step in colorectal carcinogenesis. Two ACF types are identifiable: hypercellular and dysplastic. Increased proliferative activity may be seen in both, but the dysplastic entity is most relevant to carcinogenesis. Animal and human studies support the notion that ACFs grow by crypt fission leading to the formation of microadenomas. Adenomas are monoclonal expansions of an altered cell, but very early lesions may be polyclonal. There are outward and inward theories of polypoid growth, and evidence to support both mechanisms. The ACF assay has become a useful tool to detect carcinogens in animal studies but has been less frequently used in human studies. For future cancer chemopreventive and risk assessment studies in humans, the identification and quantification of ACFs should be considered a more effective intermediate marker of risk than the determination of crypt cell proliferation alone.

Journal Article↗
PubMed1988

[Pathogenesis of the tumor process].

The paper deals with fundamentals underlying current views on cancerogenesis, morphogenesis and tumor growth with special emphasis on the mechanisms of malignant sequential and spasmodic transformation of target cells, a morphologic pattern of malignant transformation (uni- and multicenter development, tumor field theories) and mechanisms of tumor dissemination. Recent conceptions and theories are delineated. Original ideas of the nature of neoplastic process are suggested.

Cell Transformation, Neoplastic↗
PubMed2000

Co-existence of cutaneous T-cell lymphoma and B hairy cell leukemia.

A primary cutaneous form of peripheral T-cell lymphoma (PTCL) and a low grade B-cell non-Hodgkin's lymphoma that was classified as a variant of hairy cell leukemia (HCL) were simultaneously diagnosed in a 79-year-old woman by both phenotypic and genotypic analyses. The coexistence of a T- and B-cell lymphoma in the same patient is rare, and, to our knowledge, this particular association has not been previously described. The patient was referred to our Department for evaluation of multiple cutaneous itchy, reddish plaques; laboratory analyses disclosed a lymphocytosis, that presented 6 years earlier. A bone marrow aspirate showed a 50% B-cell interstitial infiltrate, while a skin biopsy surprisingly revealed a PTCL. Clonality of both neoplastic processes was assessed by Southern blot analysis. The indolent clinical course of the cutaneous disease, and the low and stable number of circulating neoplastic T cells supported the diagnosis of a mycosis fungoides (MF)-like PTCL. Possible oncogenic events and/or putative underlying viral infections which could have played a role in the occurrence of B- and T-cell non-Hodgkin's lymphomas in the same patient are discussed.

Aged↗
PubMed2006

A novel tumor marker, Niban, is expressed in subsets of thyroid tumors and Hashimoto's thyroiditis.

Niban is a recently identified molecular marker of renal carcinogenesis in the Tsc2 gene-mutant Eker rat. Niban expression is most dramatically increased in the early stage of renal carcinogenesis and might decline during malignant progression. Niban is also expressed in various histologic types of human renal cell carcinoma. Therefore, Niban might be a good marker for renal carcinogenesis in both animal models and humans. In the present study, we examined Niban expression in various thyroid lesions by immunohistochemical staining using polyclonal rabbit antihuman Niban antibody. Normal thyroid tissue never stained for Niban. Niban was most frequently expressed in tumors with oxyphilic cytoplasm, including oxyphilic variants of papillary carcinoma (4/4 = 100%), oxyphilic variants of follicular adenoma (7/7 = 100%), and oxyphilic variants of follicular carcinoma (5/5 = 100%). Eighty-one percent (44/54) of papillary carcinoma cases, including microcarcinomas, and follicular variants were also positively stained for Niban at variable intensities. Follicular carcinomas were less frequently and less intensely stained. In nonneoplastic lesions, cells were rarely positively stained. In Hashimoto's thyroiditis, scattered cells with oxyphilic cell metaplasia were weakly Niban-positive. Reverse transcriptase-polymerase chain reaction and Western blot analysis of frozen tissue confirmed Niban expression at the molecular level in 4 cases of papillary carcinoma. Taken together, Niban expression is up-regulated in various types of thyroid tumors. We postulate that Niban expression may play an important role in the tumorigenic process of the thyroid in several scenarios. (1) Niban expression may be closely related to the carcinogenic process, especially from the early stage of papillary thyroid carcinoma. (2) Niban may be closely associated with altered mitochondrial functions in preneoplastic and neoplastic processes of the thyroid. (3) Niban may be a molecular marker of the oxyphilic phenotype under various conditions. Further functional studies of Niban will clarify the role of Niban in various thyroid lesions.

Biomarkers, Tumor↗
PubMed2002

Clonal analysis of cutaneous fibrous histiocytoma (dermatofibroma).

BACKGROUND: Dermatofibroma (DF) or cutaneous fibrous histiocytoma is a common benign fibrohistiocytic lesion involving the dermis and subcutis. Histologically, it is subclassified into fibroblastic and histiocytoid forms. Its histogenesis is controversial. While often referred to as a neoplastic process, definite evidence of neoplasia in DF has been lacking. Alternatively, some authorities have suggested that DF is a fibrosing inflammatory process. Diagnostically, the most important question faced is the distinction from dermatofibrosarcoma protuberans (DFSP). Misdiagnosis can occur, as the early phase of DFSP can simulate DF, particularly the deep and cellular forms of DF. METHODS: To address this issue, and to investigate whether DF is in fact a neoplasm, we evaluated 31 examples of DF of various histological types in female patients and assessed clonality by analyzing X-chromosome inactivation as indicated by the methylation status of the androgen receptor gene (HUMARA). Representative cases of DFSP were analyzed for comparison. RESULTS: Among the selected 31 cases of DF, 24 cases provided intact DNA and informative polymorphism at the AR alleles, including one case of recurrent deep fibrous histiocytoma. Among these 24 cases, randomly inactivated AR alleles were observed in 17 cases including a deep, recurrent fibroblastic DF. A non-random inactivation at AR alleles was observed in seven cases, of which six cases showed either typical histiocytoid form of DF (four cases) or mixed cell types with predominant histiocytoid cell type (two cases). One fibroblastic DF also showed a monoclonal pattern. HUMARA analysis of DFSP revealed non-random inactivation of polymorphic AR alleles. CONCLUSIONS: These findings suggest that DF is a heterogeneous process. Monoclonal genotype was found in DFs with histiocytoid or mixed type with predominant histiocytoid features, suggesting that histiocytoid cells probably represent the neoplastic component. The fibroblastic form of DF may represent a reactive fibroblastic proliferation. Alternatively, it may represent a true neoplasm whose neoplastic cell type has been obscured by prominent reactive fibroblastic component.

Chromosomes, Human, X↗
PubMed2006

Colonic metastasis of Klatskin tumor: case report and discussion of the current literature.

We report the case of a 65-year old male patient who initially presented with recurrent episodes of upper abdominal pain, lack of appetite and weight loss. Abdominal ultrasound indicated enlarged intrahepatic bile ducts, abdominal CT scan and ERC were performed and bile duct carcinoma (Klatskin Type III b) was diagnosed. The tumor was located in the segments 2, 3, 4 and 1 with possible invasion of the left intrahepatic portal vein. Both the segments 2 and 3 of the liver were atrophic and displayed a cholestatic bile duct system. Preoperatively an intraductal stent was placed in the left bile duct using ERC to drain the left hepatic lobe. A specimen of the ascites present preoperatively displayed no malignant cells. After evaluation of the preoperatively obtained data left hepatic resection was planned. Following laparotomy we found local peritoneal carcinosis in the ligamentum hepatoduodenale with lymphatic nodules that tested positive for cholangiocellular carcinoma in online pathological examination. In the course of further exploration of the abdomen a solid tumor was detected in the sigmoid colon. Regarding the advanced stage of the neoplasm it was decided to cancel hemihepatectomy and perform sigmoid resection only in order to guarantee uncomplicated intestinal passage. The sigmoid colon was removed by a typical resection technique with end-to-end anastomosis. Histological examination of the resected sigmoid revealed transmural manifestation of a malignant neoplastic process with both a tubular and a solid growth pattern in conformity with metastasis of a Klatskin tumor. The mucosal layer showed no neoplastic alteration. Peritoneal carcinosis is a common phenomenon in the dissemination pattern of advanced-stage Klatskin tumors, yet to our knowledge this is the first case of intramural colonic growth following peritoneal metastasis.

Aged↗
PubMed2002

Bone lesions in malignant diseases--I. Current concepts of major pathogenetic mechanisms and forms.

Bones are among the major parts of the body that are targeted in neoplastic diseases. Bone lesions increasing in number and size and diffuse osteoporosis are found in 30-80% of cancer patients. All literature data about the pathogenetic factors of osteolytic and osteosclerotic bone lesions are classified into four groups: 1. Directly connected with the neoplastic tumour mass. 2. Humoral interaction between the tumour cells and bone cells. 3. Systemic effects and complications of the neoplastic process. 4. Extracancerous factors. We discuss here the basic pathogenetic forms of bone lesions in neoplasias: 1. Local osteolysis in the area of neoplastic infiltration. 2. Humorally activated demineralisation with hypercalcemia. 3. Light chain osteomalacia. 4. Hypophosphatemic osteomalacia. We consider the major current biochemical markers of bone remodelling and their use in diagnosing and monitoring bone disease in neoplastic conditions.

Biomarkers↗