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Vimentin and glial fibrillary acidic protein expression in relation to neoplastic cell differentiation in glial tumors.

In the present work the expression of vimentin and glial fibrillary acidic protein (GFAP) was determined in homotypic, transitional and heterotypic astroglial neoplastic areas and gemistocytes. The expression of these intermediate filament (IF) proteins within oligodendroglial neoplastic cells was determined as well. The intensity of vimentin and GFAP immunoreactivity as well as the number of immunoreactive cells within astroglial areas of different grades of differentiation were different. While there was no immunoreactivity within heterotypic areas, transitional areas and gemistocytes mainly show the same intensity of immunoreactivity and number of immunoreactive cells for both analyzed IF proteins. Within homotypic astroglial areas the number of GFAP positive cells and intensity of GFAP immunoreactivity were higher than the same vimentin parameters. It is well known that vimentin and GFAP may form heteropolymers both in vitro and in vivo. Transitions in vimentin/GFAP expression reflect not only normal development of astroglial cells but occur also with the induction of neoplastic process. Our results suggest that immunoreaction intensity and number of vimentin or GFAP immunoreactive cells correlates with the degree of differentiation of specific neoplastic cell populations. It is suggested that transitions in vimentin and GFAP expression occur in the course of neoplastic progression presumably by the modulation of their incorporation into the same IF system according to the degree of neoplastic cell differentiation.

Brain Neoplasms↗

[Significance of chromosomal abnormalities in solid tumors of humans].

Solid tumours in man are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the tumour and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. Some primary abnormalities are so characteristic as to be virtually pathognomonic for particular types of solid tumours, eg, t (11;22)(q24;q12) in Ewing's sarcoma, t (9,22)(q22;q12) in extraskeletal myxoid chondrosarcoma, t (X;18)(p11;q11) in synovial sarcoma, and t (12;16)(q13;p11) in myxoid liposarcoma. To these purely cytogenetic data implicating specific genetic changes in carcinogenesis may now be added a growing evidence of molecular specificity emerging from recombinant DNA-studies. It appears that both currently known classes of directly cancer-relevant genes, the dominant oncogenes and the recessive tumour suppressor genes, are located at precisely those genomic sites that are visibly involved in neoplasia-associated chromosomal rearrangements. The importance of cytogenetic characterization of solid tumors is thus twofold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality identifies the presence of a neoplastic disease, and the specific type of aberration may reveal the true nature of the tumor and thus improve the diagnostic precision.

Chromosome Aberrations↗

[Fibrous pseudotumor of the epididymis].

Presentation of one case of fibrous pseudotumor of epididymis in a 33 year-old patient. Final diagnosis was achieved after surgical exeresis and its pathoanatomical examination. Etiopathogeny, clinic presentation and therapeutical approach are reviewed. Considering, in general, the clinical inespecificity of intrascrotal processes, we believe it is important to know this entity in order to be in a position to address differential diagnosis with truly neoplastic processes.

Adult↗

Chronic retroviruses and oncogenesis.

Chronic retroviruses are associated with both malignant and nonmalignant diseases in vertebrates. This review addresses the pathogenetic basis of neoplastic processes that have been directly or indirectly associated with chronic retroviruses.

Animals↗

Synovial chondromatosis of the temporomandibular joint.

Synovial Chondromatosis (SC) is a disease whose etiology is unknown, can be defined as a benign synovial process characterized by the formation of metaplastic cartilaginous nodes inside connective tissue of articular surfaces, is considered an active metaplastic phenomenon better than a neoplastic process; it presents a greater preference to affect women who constitute almost 70% of reported cases, the age range is wide and oscillates between 18-75 years (average 44.6 years). Between the main clinical findings are: pain, crackle, volume augmentation and a limited buccal opening. SC is an unusual state and the reports in the English literature are no more than 75 cases, only 66 of those where histologically verified, most of those were affecting great joints like hip, knee and shoulder, but if SC is not frequent in this sites, is even more infrequent on temporomandibular joint. The aim of this paper is to report a clinical case and at the same time to realize a brief review of the literature.

Chondromatosis, Synovial↗

Freeze-fracture study of intercellular junctions in benign and malignant mesothelial cells in effusions and a comparison with those seen in pleural mesotheliomas (solid tumour).

This study involves an analysis by thin section and freeze-fracture techniques of the intercellular junctions of exfoliated benign and malignant mesothelial cells obtained from 4 cases, two benign and two malignant effusions. Pleural biopsies (solid tumours) of two further cases of confirmed epithelial malignant mesotheliomas were also studied to compare the organization, distribution and characteristics of the tight junctions, gap junctions and desmosomes observed between the three groups of cases. The results showed that both tight and gap junctions varied greatly in their organization in the exfoliated benign and malignant mesothelial cells. However they were often large and very well developed. In contrast, the tight and gap junctions in the solid tumours were considerably reduced both in their size and frequency, a feature which is well recognized in the literature as consistent with the neoplastic process. Our observation of florid tight and gap junctions in the exfoliated benign and malignant mesothelial cells, raises some important aspects of behaviour of neoplastic cells in effusion fluid. It is our opinion that cells in the fluid are exposed to microenvironmental influences which are quite distinct from those in a 'solid' tumour. We suggest that alteration in the binding sites of the extracellular matrix molecules, their influence on the cytoskeleton and the consequent effect on the development of tight and gap junctions are important factors which need further elucidation. The most significant feature of this study is however the demonstration of essential differences in the cell junctional characteristics between neoplastic mesothelial cells in body cavity fluids and those in tissues thus emphasizing the importance of environmental influences in the development of a neoplasm and its spread.

Adult↗

Contrast-enhanced magnetic resonance imaging of the temporal bone.

The recent advances in MR imaging of the temporal bone brought about by the availability of intravenous contrast agents sensitive to the disruption of the blood-brain barrier have further expanded the role of MR imaging in the evaluation of this region. The main applications of contrast-enhanced MR imaging in the temporal bone are the evaluation of inflammatory and neoplastic processes of the labyrinth (in the general context of patients with sensorineural hearing loss or vertigo) peripheral seventh nerve palsies, and miscellaneous inflammatory and neoplastic conditions of the temporal bone itself.

Contrast Media↗

Promoter-region hypermethylation and gene silencing in human cancer.

In summary, it is apparent that alterations in DNA methylation are a fundamental molecular change associated with the neoplastic process and have important biologic implications for tumor initiation and progression. The promoter-region hypermethylation events covered in the present chapter are especially critical and can frequently serve as alternative mechanisms for coding-region mutations for loss of key gene function in neoplastic cells. The mechanisms underlying the precise role of this hypermethylation in gene silencing must be further defined, as must the determinants of the hypermethylation changes themselves. The therapeutic implications of promoter-region hypermethylation must be explored, and a potential use for establishing this change as a sensitive biomarker for use in multiple types of cancer-risk assessment and detection assays has already emerged. The next few years should see exciting advances in our understanding of an epigenetic process which, in conjunction with genetic alterations, appears to drive the process of neoplasia.

Cell Transformation, Neoplastic↗

Can melatonin regulate the expression of prohormone convertase 1 and 2 genes via monomeric and dimeric forms of RZR/ROR nuclear receptor, and can melatonin influence the processes of embryogenesis or carcinogenesis by disturbing the proportion of cAMP and cGMP concentrations? Theoretic model of controlled apoptosis.

The presented model of controlled apoptosis has been based on the assumption that correct information exchange between an organism as a whole, and each of its cells is conditioned by mutual proportions of cAMP and cGMP concentrations (CcAMP, CcGMP), according to the formula CcAMP x CcGMP = 'a' (constant). The regulation of balance of these 'second messengers' in a cell and an extracellular space would depend on the mutual proportions of concentrations of Melatonin and monomers of Melanin. These indoloderived compounds could be the activators of the transcription factors i.e. RZR and NFkappa-B, regulating the expression of Prohormone Convertase (PC) gen and Nitric Oxide Synthase (NOS) gen, respectively. Additionally, maternal Melatonin and Nitric Oxide (NO), being able to pass through trophoblast or placenta freely, would play decisive role in the synchronization of embryogenesis and intrauterine development of the fetus. In case of an embryo or a fetus, the result of CcAMP and CcGMP multiplication, different from the proper constant 'a'-value, would mean occurrence of disorders in the structure and functioning of the cellular tensegrity system and, in consequence, disturbances in the intercellular information exchange. It would lead to deviation in cellular metabolism, oriented cell movement, uncontrolled apoptosis, and as a consequence, would lead to the development of fetal defects. In case of a child or an adult, a sudden occurrence and prolongation of such disturbances in CcAMP-CcGMP proportions would induce a process of apoptosis of normal cells and an initiation of a cancerogenesis. On the other hand, the recovery of equilibrium in the information exchange system would initiate apoptosis of neoplastic cells, and simultaneously, proliferation of connective tissue cells. According to the presented hypothesis, a decrease in CcAMP and destabilization of the CcAMP-CcGMP balance in an embryo or a fetus would result from relatively excessive amounts of maternal Melatonin (monomers) in fetal circulation, while a decrease of CcAMP and destabilization of the CcAMP-CcGMP balance in a child or an adult would be a consequence of relatively insufficient amounts of Melatonin (dimers) in an organism. It seems possible, that determination of both CcAMP and CcGMP would enable an early detection of high risk of developmental defects occurrence in an embryo or a fetus and neoplastic processes in a child or an adult. This method might also be considerably useful in monitoring a safe substitutional hormonotherapy.

Apoptosis↗

Granulomatous diseases and chronic rhinosinusitis.

Chronic rhinosinusitis often fails to respond to standard medical or surgical treatment. In some of these cases, the underlying disease may be a chronic granulomatous process that requires aggressive topical, local, and in some instances, systemic therapy. Diseases that can present in this manner include autoimmune vasculitis, sarcoidosis, indolent infections, neoplastic processes, and various other miscellaneous conditions. This article reviews the typical presentations for some of these unusual conditions and discusses the appropriate evaluations that will lead to clinical identification and effective medical management.

Chronic Disease↗

[Multifocal ischaemic stroke and myocardial infarction in a woman with occult lung cancer complicated with chronic DIC and thrombotic endocarditis].

Ischaemic stroke in thromboembolic mechanism may be a first sign of neoplastic disease, as in the presented case of a 56-year-old woman. Progressive trombocytopenia, anaemia with reticulocytosis and schistocytes in peripheral blood smear, elevated serum LDH activity as well as coexisting myocardial infarction initially suggested Moschcowitz syndrome. However, plasma exchange did not improve her neurological status and D-dimer values increase in subsequent evaluations indicated chronic DIC. At the same time, on transesophageal echocardiography, thrombotic endocarditis was diagnosed. Screening for cancer showed high CA 125 marker and chest computed tomography revealed lung tumor, not visible on earlier chest X-ray. In further treatment she underwent palliative radiotherapy and continued low molecular weight heparin. The neoplastic process had an unfavorable course and she died after four months. The authors point out that in case of multifocal ischaemic stroke and coexistent thrombocytopenia, neoplastic hypercoagulable state and thrombotic endocarditis should be considered.

Chronic Disease↗

Stereotactic biopsy of 100 intracerebral lesions at Sir Charles Gairdner Hospital.

The pathological findings in a retrospective review of 100 consecutive intracranial stereotactic biopsies are presented. Definite diagnosis could be established in the majority (89) of cases and included 85 neoplasms (69 primary cerebral tumors, 10 non-Hodgkin's lymphomas and 6 metastases) and 4 non-neoplastic processes. In the remaining 11 samples the findings were non-diagnostic; 2 consisted of normal glial tissue, while the remainder variously showed changes of necrosis, hematoma, histiocytic reaction or astrocytic proliferations of uncertain nature. Verification of the stereotactic diagnosis by examination of lesional tissue obtained at subsequent craniotomy or postmortem was possible in 7 of 10 cases. Two broad categories of diagnostic difficulty were identified in interpreting stereotactic biopsies: (1) accurate tumor typing and grading, and (2) the distinction between reactive and neoplastic astrocytic proliferations. Two essential components in the diagnostic process are: (1) careful correlation with the clinical and radiological findings; and (2) use of intraoperative smear and/or frozen section preparations to confirm specimen adequacy. By adhering to these principles accurate intraoperative diagnosis can usually be established, particularly for high grade astrocytoma, lymphoma and metastasis. Tumor typing is aided by the use of immunohistochemistry and ultrastructural examination and the examination of serial sections is of value in grading.

Adolescent↗

[Pancreatic cancer. I. The age distribution and location of the tumor process in the gland (a statistical analysis based on autopsy data from the Department of Pathological Anatomy of the Biomedical Research Institute over the 25 years from 1963-1987].

The age distribution and localization of the neoplastic process in the pancreas was analyzed. Cancer of the pancreas was most common in the age from 41 to 80 years of age, with a peak in the sixth decade. A study of the anatomical localization of the tumor in the gland, purposely carried out, demonstrated that the head of the pancreas was the most common site of the tumor, with the body and tail ranking next.

Age Factors↗

New developments: a look to the future.

Inflammatory cytokines plus the human immunodeficiency virus Tat protein apparently trigger the development of early Kaposi's sarcoma. Activated spindle cells provide a self-perpetuating, autocrine-supported mechanism for further development of hyperplastic lesions. In more advanced stages, a true neoplastic process may develop.

Acquired Immunodeficiency Syndrome↗

Cytogenetic analysis in the diagnosis of acute leukemia.

Acute leukemias are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the leukemia and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. The pattern differs between acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) and from subtype to subtype. Some abnormalities are so characteristic as to be virtually pathognomonic for particular types of leukemia. The importance of cytogenetic characterization of leukemias is thus two-fold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality in hematopoietic cells identifies the presence of a neoplastic disease. The aberration profile may reveal whether the patient has ALL or ANLL and which subtype it is. Remission and relapse can be monitored by cytogenetic analyses. Finally, the karyotypic pattern is an independent prognostic parameter that should be considered when the choice of therapy is made.

Chromosome Aberrations↗

Deregulated expression of the PCPH proto-oncogene in rat mammary tumors induced with 7,12-dimethylbenz[a]anthracene.

The PCPH proto-oncogene was identified by its frequent activation in Syrian hamster fetal cells exposed to 3-methylcholanthrene. We previously isolated human PCPH cDNA and studied its expression in normal human tissues. We report herein the pattern of PCPH expression in normal rat tissues. Each tissue expressed one major PCPH polypeptide that varied in molecular mass in different tissues. Normal mammary gland expressed a single PCPH polypeptide of 27 kDa. This PCPH form also was expressed in lactating mammary glands but at significantly greater levels. These results suggest the existence of tissue-specific regulatory mechanisms for PCPH expression that may be influenced by the differentiation stage. Our previous studies on the involvement of PCPH in human cancer showed that human breast tumor cell lines have frequent alterations in PCPH, including multiple PCPH polypeptide forms that are not expressed in normal cells. These cell lines also have frequent loss of a 27-kDa form identified as the only PCPH polypeptide expressed by normal human breast epithelial cells. In this study, we found that these same alterations occurred in vivo during mammary carcinogenesis in Sprague-Dawley rats treated with 7,12-dimethylbenz[a]anthracene, in both benign and malignant tumors, indicating that stable changes in PCPH expression took place early in the neoplastic process. Results showed that this experimental system is relevant to human breast carcinogenesis and provides an excellent model to study the molecular basis of the regulation of PCPH expression during normal differentiation and pathologic stages of neoplasia of the mammary gland and to analyze the role of PCPH in the carcinogenic process. Furthermore, the detection of atypical PCPH polypeptides in tumors suggests that PCPH immunodetection may be applied as a diagnostic tool for the early identification of neoplastic breast epithelial cells.

9,10-Dimethyl-1,2-benzanthracene↗

Follicular centre cell lymphoma with alpha heavy chain disease. A histopathological and immunohistological study.

The first recorded case of a small intestinal lymphoma with alpha heavy chain disease occurring in Hungary is reported. The clinical manifestation of the disease and the focal distribution of mucosal alterations do not fulfill the criteria to make a diagnosis of Mediterranean type lymphoma (MTL) but the lymphomatous segments of the jejunum show the same pathological and immunohistological characteristics as seen in MTL. One of the basic features of MTL, the so called lympho-histiocytic nodules, which have been suspected by previous authors to represent an incipient neoplastic process involving histiocytic cells, is identified as follicular centroblastic/centrocytic malignant lymphoma. The cytogenetical connection between the massive proliferation of abnormal alpha chain producing plasma cells and neoplastic germinal centres is substantiated by direct immunohistological evidence using a combined immunofluorescent and immunoperoxidase technique to detect heavy and light chains within the same cell. The sarcomatous-appearing pleomorphic cell proliferation is interpreted as an anaplastic change in the centroblastic/centrocytic lymphoma. Unequivocal evidence for an abnormal IgA production in this pleomorphic component has not been obtained. Our observations suggest that in alpha heavy chain disease the neoplastic cell population originates in the germinal centres.

Heavy Chain Disease↗

[Dynamics of the course of neoplastic disease and status of antioxidant system].

The decreased ability to remove free radicals from organism is one of the factors which furthers the development of neoplastic process. Enzymes and substrates which can remove free radicals from organism from antioxidant barrier. The appreciation of some elements of antioxidant organism barrier in children with neoplastic disease was the study's purpose. We examined 100 children in the age from 6 months to 16 years (60 patients with malignant solid tumors and 40 healthy children as a control group). We investigated glutathione peroxidase, catalase and superoxide dismutase activities in erythrocytes. In these children we studied also catalase activity, ceruloplasmin concentration and antioxidant barrier level in plasma. We estimated antioxidant elements in patients with cancer before, during and after treatment and during remission and progression of the disease. The decrease of total antioxidant barrier was typical in introductory period of neoplastic disease. We observed the increase of superoxide dismutase and glutathione peroxidase in erythrocytes and catalase activity in plasma in children with clinical remission but we found the gradual decrease of ceruloplasmin level in plasma.

Adolescent↗