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At least 613 records · Page 34Linked to original sources
PubMed1992

Is cancer cytogenetics reducible to the molecular genetics of cancer cells?

Whether cancer cytogenetics can be reduced to the molecular genetics of cancer cells is a question that must be addressed in three domains, focusing on its ontological, methodological, and epistemological dimensions. The possibility of ontological reduction hinges on whether chromosomes have other important constituents than molecules. Although this must obviously be answered in the negative, it should be emphasized that both cytogenetic and recombinant DNA investigations provide us with very selective pictures of genomic organization. This is of concern because the higher order packing of DNA and its joining with other molecules to form chromosomal structures give rise to emergent properties, functional features that become manifest only at higher levels of complexity and that may not be deducible from the base pair composition of the DNA. A position of extreme methodological reductionism would in our context be that the best research strategy is always to investigate the genetic changes of tumor cells at the highest possible resolution level, as alterations of genes and, ultimately, as changes in DNA primary structure. There are two fundamental differences between cytogenetic and molecular genetic techniques that make this stance untenable. First, whereas cytogenetic investigations are open-framed (all chromosome aberrations are revealed), molecular genetic analyses are highly specific (only those aberrations are revealed that one tests for). Second, whereas the molecular approach determines the genotypic constitution of an idealized, average tumor cell, cytogenetic analysis is of real, individual cells. These may not necessarily be representative of the main population of the tumor, but at least whatever karyotypic differences exist between them are detected. Heterogeneity and clonal evolution within the tumor can thereby be assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome Aberrations↗
PubMed2006

Expression of p53, Ki-67 and c-erb B2 in growth hormone-and/or prolactin-secreting pituitary adenomas.

The subcellular events implicated on the formation and behavior of pituitary adenomas are not fully understood. In this study we investigated the presence of p53, Ki-67 and c-erb B2 in 38 pituitary adenomas with immunohistochemical positivity for GH and prolactin (n=26; 68.4%), for prolactin (n=9; 23.7%) and for GH (n=3. 7.8%). The analyses revealed the following results: 24 (63.2%) tumors expressed variable positivity for c-erb B2, 11 (28.9%) expressed p53 positivity and 11 (28.9%) tumors were variably positive for Ki-67. Our results demonstrated a high percentage of GH/prolactin-, prolactin- and GH-secreting tumors with immunohistochemical positivity for c-erb B2. Once this membrane receptor is related to growth factors EGF and TGFalpha and both have a definite effect on tumor growth, our data suggest a possible role for c-erb B2 on the evolution of these tumors.

Adolescent↗
PubMed2006

[Development of research on tumor dormancy].

Tumor dormancy is not only a biologic character in malignant tumor cells but also the key cause of failure to the treatment, metastasis, and recurrence of tumors. In this article, the evidence of tumor dormancy in patients, the evolution of the definition of tumor dormancy, the establishment of the animal mode of tumor dormancy, and the molecular mechanism of tumor dormancy were reviewed. Recent progress on novel antitumor drugs through inducing tumor dormancy was summarized.

Animals↗
PubMed2002

Application of multicolor fluorescence in situ hybridization analysis for detection of cross-contamination and in vitro progression in commonly used murine tumor cell lines.

Murine tumor models are potent tools for cancer studies, most of which make use of a limited number of murine tumor cell lines that are exchanged by many research groups around the world. Although cross-contamination and in vitro karyotypic progression are well-known risks with respect to the identity of tumor cell lines, these parameters are rarely evaluated. Notably, routine karyotyping of murine cell lines is laborious and technically demanding because mouse chromosomes are morphologically similar. We therefore used a 21-color fluorescence in situ hybridization (FISH) approach (COBRA) for screening two groups of frequently used murine tumor cell lines, each of which shares known immunologic determinants. Multicolor analysis revealed that the sharing of immunologic determinants among three murine lymphoma cell lines (EL-4, MBL-2, and RBL-5) is directly related to their common origin. In several of the cell lines, the chromosomal derivatives had rearranged further, suggesting that the cross-contamination events were not recent. In contrast, karyotypic analysis of three murine colon cancer cell lines (C26, CC36, and C51) showed that these constituted independent tumor clones despite the sharing of immunologic determinants. Our data point out that cross-contamination and in vitro evolution of murine tumor cell lines are a common phenomenon, and that multicolor FISH analysis is an efficient tool for verifying the origin and tracking the evolution of murine cell lines.

Adenocarcinoma↗
PubMed1977

[Electronic microscopic study of a sacral chordoma. Characterization of various development stages of the tumor cells].

The electron microscopic study of a sacral chordoma, the cells of which contain variable amounts of glycogen, allowed to characterize different stages in the evolution of the tumoral cells. The young cells contain almost no glycogen ; progressively it becomes more abundant and fills up almost the whole cytoplasm. At the end of the evolution glycogen disappears while the cell becomes vacuolated. This suggests that enzymatic lysis of this polysaccharide could be the cause of the vacuolation which finally produces the physaliferous cell. Comparison between the cells of the chordoma and those of the normal notochord shows some morphological similarities in the development of these cells. These different data may be useful for a classification of the various types of chordomas.

Adult↗
PubMed2004

Evolution of p53 in hypoxia-stressed Spalax mimics human tumor mutation.

The tumor suppressor gene p53 controls cellular response to a variety of stress conditions, including DNA damage and hypoxia, leading to growth arrest and/or apoptosis. Inactivation of p53, found in 40-50% of human cancers, confers selective advantage under hypoxic microenvironment during tumor progression. The mole rat, Spalax, spends its entire life cycle underground at decidedly lower oxygen tensions than any other mammal studied. Because a wide range of respiratory adaptations to hypoxic stress evolved in Spalax, we speculated that it might also have developed hypoxia adaptation mechanisms analogous to the genetic/epigenetic alterations acquired during tumor progression. Comparing Spalax with human and mouse p53 revealed an arginine (R) to lysine (K) substitution in Spalax (Arg-174 in human) in the DNA-binding domain, identical to known tumor associated mutations. Multiple p53 sequence alignments with 41 additional species confirmed that Arg-174 is highly conserved. Reporter assays uncovered that Spalax p53 protein is unable to induce apoptosis-regulating target genes, resulting in no expression of apaf1 and partial expression of puma, pten, and noxa. However, cell cycle arrest and p53 stabilization/homeostasis genes were overactivated by Spalax p53. Lys-174 was found critical for apaf1 expression inactivation. A DNA-free p53 structure model predicts that Arg-174 is important for dimerization, whereas Spalax Lys-174 prevents such interactions. Similar neighboring mutations found in human tumors favor growth arrest rather than apoptosis. We hypothesize that, in an analogy with human tumor progression, Spalax underwent remarkable adaptive p53 evolution during 40 million years of underground hypoxic life.

Adaptation, Physiological↗
PubMed1983

[Localized pulmonary pseudo-tumoral form of Wegener's disease and fulminating evolution. Apropos of a case].

A case of Wegener's granulomatosis starting as a localized pseudo-tumoral lung lesion and following a fulminating course is reported. The histological diagnosis required thoracotomy. New pulmonary lesions developed post-operatively, together with severe renal failure which was responsible for the patient's death 5 weeks after the thoracotomy. The authors describe the lesions characteristic of the disease and their pathogenesis and discuss the relationship between Wegener's syndrome and other granulomatous angiitis.

Adult↗
PubMed1996

Expression and production of cytokines by heterohybrids and their parental B cells in CLL.

Three hybrids derived from CD5+ B cell chronic lymphocytic leukemia (B-CLL) and their parental B cells were studied for phenotypic evolution, immunoglobulin (Ig), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) secretion. When phenotypic evolution was examined, hybrids showed the loss of classical B cell markers, indicating that they follow the same pattern of phenotypic differentiation as normal B cells. Hybrids displayed spontaneous high Ig secretion, which did not appear to be modified through stimulation by phorbol 12-myristate 13-acetate (PMA), recombinant interferon-gamma (rIFN-gamma) and Staphylococcus aureus Cowan I (SAC). Parental cells secreted minimal amounts of Ig spontaneously or through IFN-gamma and SAC stimulation, whereas PMA succeeded in increasing this secretion. An opposite pattern was observed when TNF-alpha and IL-6 secretion an expression at the mRNA level were assessed in hybrids and parental cells. TNF-alpha and IL-6 were spontaneously secreted by parental cells and this secretion was increased after PMA and SAC stimulation, both cytokine secretion and expression at the mRNA level were negative in hybrid cells. The absence of expression of these cytokines could be explained either by chromosomal loss or by down regulation. These results indicate that when parental CLL cells are induced to differentiate in the heterohybrid model, they acquire high spontaneous secretion of Ig, lose the classical B cell phenotypic markers and down regulate the expression of the cytokines studied.

B-Lymphocytes↗
PubMed2001

Distinctive patterns of Her-2/neu, c-myc, and cyclin D1 gene amplification by fluorescence in situ hybridization in primary human breast cancers.

BACKGROUND: Human solid tumors undergo clonal evolution as they progress, but evidence for specific sequences of genetic changes that occur in individual tumors and are recapitulated in other tumors is difficult to obtain. METHODS: Patterns of amplification of Her-2/neu, c-myc, and cyclin D1 were determined by fluorescence in situ hybridization (FISH) in relation to the presence of p53 dysfunction and ploidy in 60 primary human breast cancers. RESULTS: We show that there are clusters of genophenotypic abnormalities that distinguish lobular breast cancers from nonlobular tumors; that cyclin D1 amplification occurs prior to the divergence of lobular breast cancers from nonlobular cancers; that p53 dysfunction, Her-2/neu amplification, and c-myc amplification are characteristic features of nonlobular breast cancers, but not of lobular breast cancers; and that the frequencies of amplification of all three oncogenes examined increase progressively with increasing aneuploidy, but that each gene exhibits a different profile of increasing amplification in relation to tumor progression. Early amplification of c-myc appears to be an especially prominent feature of hypertetraploid/hypertetrasomic tumors. CONCLUSIONS: The data suggest that in tumors containing multiple abnormalities, these abnormalities often accumulate in the same cells within each tumor. Furthermore, the same patterns of accumulation of multiple genophenotypic abnormalities are recapitulated in different tumors.

Alleles↗
PubMed1977

[Gingival metastasis of a malignant bronchial carcinoid tumor. Apropos of 1 case].

Secondary tumors of the mouth are rare and especially seated on the maxillaries. Metastasis to the soft tissues of the mouth, especially of cancers situated far from ORL and buccal areas are exceptional. The authors report an observation of a bronchial carcinoïd tumor with metastasis to the gums in a 24-year old man. The rapidity of the evolution of the tumor, the precocity and the very exceptional site of the metastasis as well as certain particularities of the histological pattern of the primitive bronchial tumor, once again states the problem of the confines with the Oat-Cell Carcinomas.

Adult↗
PubMedDate not supplied

Sequential measurement of intratumoral platinum concentration in cervix uterine tumors after cis-dichlorodiammineplatinum (CDDP) administration.

Intratumoral (cervix uterine tumors) distribution of platinum was studied in ten patients after IV administration of CDDP. Sequential tumoral measurement of platinum was carried out 4, 24, and 48 h after the IV infusion. Platinum concentration in the tumor samples ranged from 0 to 29,5 ng/mg tissue. For all patients, there was no definite evolution of the tumoral concentration with time and there was no good relation for the same patient between the platinum concentration in three successive biopsies. These results involve uncertainty in studies attempting to relate CDDP tumor levels (measured in one biopsy) and tumor response to chemotherapy.

Cisplatin↗
PubMed2006

[Tumoral and pilotropic mycosis fongoides without mucin: evolution towards a pustulous erythroderma].

INTRODUCTION: Pilotropic mycosis fongoides is a particular form of the disease, because of its clinical and histological aspects, its poor prognosis and its resistance to treatment. We report a case of pilotropic mycosis fongoides without mucinosis, immediately tumoral, the fatal progression of which was marked by the occurrence of pustular erythroderma. OBSERVATION: In 1998 a 69 year-old man presented with infiltrated erythro-squamatous plaques and nodules on the limbs associated with follicular lesions predominating on the cervical-cephalic area. Histological explorations revealed a pilotropic infiltrate with atypical CD4+ CD8 CD30 T-cells, without epidermotrophism or mucinosis. Study of genetic rearrangements found a clone lymphocyte T-cell in the skin. Diagnosis of pilotropic mycosis fongoides at the tumoral stage was made and, despite various treatments, the disease developed towards fatal pustular erythroderma. DISCUSSION: At the onset of its progression, pilotropic mycosis fongoides is sometimes difficult to distinguish from classical mycosis fongoides, during which follicular involvement is often seen. However it is important to differentiate these entities because of the poor prognosis of pilotropic mycosis fongoides. Development of tissue micro dissection techniques and lymphocyte T-cell clones from human skin would help to separate these cutaneous T-cell lymphoma sub-groups. Our case report is original because of the absence of dermal mucinosis combined with an immediately tumoral form and the progression towards generalized pustulosis. It also underlines the poor prognosis and resistance to treatment of pilotropic mycosis fongoides.

Aged↗
PubMed2005

Selective evolutionary pressure from the tissue microenvironment drives tumor progression.

Cells grow within defined environmental niches and are subject to microenvironmental control. Outside of their niche, the environment is hostile, the normal cells lack appropriate survival signals which leads to anoikis. During tumor development and progression, malignant cells must escape the local tissue control and resist anoikis. The inherent genetic instability of tumor cells makes their phenotype very plastic, which changes under continuous environmental selection pressure. In this way the microenvironment drives the somatic evolution of the tumor. In the current review, we assess how this environmental selection pressure fits into the classical scheme of tumor progression.

Animals↗
PubMed1999

Dynamic contrast-enhanced MRI and fractal characteristics of percolation clusters in two-dimensional tumor blood perfusion.

Dynamic contrast-enhanced magnetic resonance imaging (DE-MRI) of the tumor blood pool is used to study tumor tissue perfusion. The results are then analyzed using percolation models. Percolation cluster geometry is depicted using the wash-in component of MRI contrast signal intensity. Fractal characteristics are determined for each two-dimensional cluster. The invasion percolation model is used to describe the evolution of the tumor perfusion front. Although tumor perfusion can be depicted rigorously only in three dimensions, two-dimensional cases are used to validate the methodology. It is concluded that the blood perfusion in a two-dimensional tumor vessel network has a fractal structure and that the evolution of the perfusion front can be characterized using invasion percolation. For all the cases studied, the front starts to grow from the periphery of the tumor (where the feeding vessel was assumed to lie) and continues to grow toward the center of the tumor, accounting for the well-documented perfused periphery and necrotic core of the tumor tissue.

Animals↗
PubMed2004

Do collision tumors of the gastroesophageal junction exist? A molecular analysis.

Collision tumors are thought to arise from the accidental meeting of two independent tumors. Here we present five gastroesophageal junction tumors consisting of two collision tumors and three composite tumors (characterized by two divergent lineages originating from the same neoplastic clonal proliferation), as diagnosed on histology. In an attempt to prove this distinction at a genetic level, we performed TP53 sequence analysis and p53 immunohistochemistry. In addition, loss of heterozygosity (LOH) analysis using 10 microsatellite markers was carried out. An identical TP53 mutation and a similar pattern of retention and LOH were found in both neoplastic components of the presumed collision tumors, suggesting that both components are derived from a single precursor cell that undergoes divergent differentiation in the evolution of the tumor. In the composite group, 1 case had a genetic basis for the possible diagnosis of a collision tumor, with a TP53 mutation in the adenocarcinoma component only, and a different pattern of retention and loss of heterozygosity. These findings imply that it is not possible to recognize true collision tumors from immunohistologic appearance alone and suggest that the long-standing histologic criteria for the diagnosis of these neoplasms have no molecular basis.

Adenocarcinoma↗
PubMedDate not supplied

Interleukin-2 (IL-2) in the treatment of malignant brain tumors (glioblastomas).

The present study is aimed to provide a new possible approach to the treatment of glioblastomas, in an effort to control the extremely severe evolution of these tumors. Thus, from May 28, 1991, we started the administration of IL-2 (produced at the "Victor Babeş" Institute, Bucharest) in 9 glioblastoma patients (operated on at the Neurosurgery department VII of the "G. Marinescu" Hospital, Bucharest) by repeated intraoperative and postoperative local injections. The survival period from the first IL-2 administration was 7 months (1 case), 8 months (2 cases), 11 months (2 cases), 14 months (1 case) and 17 months (1 case). There are only 2 survivors: one 4 months and the other 23 months following the first injection of IL-2. The survivor whose condition 23 months following introduction of IL-2 therapy is very good, demonstrates that IL-2 offers some chance to these hopeless patients.

Brain Neoplasms↗
PubMedDate not supplied

Renal pathology in WAGR syndrome.

The Wilms' tumor-aniridia-genital anomalies-mental retardation (WAGR) syndrome is associated with an increased risk for developing Wilms' tumor. A right nephrectomy was performed following the diagnosis of Wilms' tumor in a 2-year-old girl with WAGR syndrome and chromosome 11, del 11p13. Pathologic examination revealed intralobar nephrogenic rests and a peripelvic multicystic mass, sharply delineated from the adjacent typical intralobar nephrogenic rests and renal parenchyma, which may represent a cystic Wilms' tumor (cystic partially differentiated nephroblastoma). We studied the expression of the H19 gene by in-situ hybridization performed on paraffin sections of the kidney. H19 is an imprinted maternally-expressed gene that is not translated to protein and functions as a regulatory RNA molecule. It is tightly linked with the paternally-imprinted gene of insulin-like growth factor 2. While IGF2 presumably plays a role in tumorigenesis of Wilms' tumor, H19 is not expressed in the majority of Wilms' tumors. The expression of H19 in the intralobar nephrogenic rests was found to be prominent in the component of the blastema and markedly reduced with differentiation to tubular structures similar to the fetal kidney. The differential diagnosis of hyperplastic intralobar nephrogenic rests from a small Wilms' tumor arising in intralobar nephrogenic rests is difficult. Complete understanding of the chain of molecular events occurring in the evolution of Wilms' tumors may lead to the development of tumor markers to be used on paraffin sections and so help in the differential diagnosis of hyperplasia versus malignant transformation.

Child, Preschool↗