Helminths, particularly some Schistosoma species, have been associated with cancer in humans. Neurocysticercosis, produced by cysticerci of the helminth Taenia solium, has been associated with the emergence of brain tumours and haematological malignancies. Local tumours, such as glioblastoma, could be explained by the induction of DNA damage in cells surrounding the cysticercus and chronically exposed to an inflammatory host response. However, systemic effects such as haematological malignancies are not easy to understand. The present work was conducted in Mexico to find out whether DNA damage arises in peripheral lymphocytes in patients with neurocysticercosis. We utilized a highly sensitive technique to analyse chromosomal aberrations, in-situ hybridization with probes against chromosomes 1, 2 and 4, and in addition the blocked-cytokinesis technique was used to determine the formation of micronuclei, a peculiar form of DNA damage. The study was made in lymphocytes from 8 patients before and after the administration of praziquantel, 1 of the 2 drugs used for neurocysticercosis treatment. The frequencies of chromosome aberrations and micronuclei in peripheral blood lymphocytes were higher in the infected patients as compared to those observed both in healthy donors and in the group of patients after praziquantel therapy. Our results suggest that chromosome aberrations induced in peripheral cells during neurocysticercosis could be associated with the development of haematological neoplasias.

Adult↗

PubMedDate not supplied

I-FISH control of CGH-detected gain of DNA sequence copy number in oral squamous cell carcinomas (OSCC).

Interphase fluorescence in situ hybridization (I-FISH) was used to control the gain of genomic material in 21 human oral squamous cell carcinomas (OSCC) which had been detected by comparative genomic hybridization (CGH). DNA probes for 3q27, for 5p15.2, and for the protooncogenes c-myc (8q24) and c-abl (9q34), were used for I-FISH examination of the interphase nuclei of paraffin sections of the tumors. The corresponding alphoid DNA probes for the centromeric regions of the respective chromosomes and a probe on 5q served as controls of aneusomy. Previous examinations with int2 (11q13) and erbB2 (17q11.2-13) were included for comparison. I-FISH analysis detected a gain of 3q27 in 17, of 5p15.2 in 7, of c-myc in 14, of c-abl in 10, and formerly, of int2 in 12 and of erbB2 in 10 of the examined tumors. There was an overall confirmation of the CGH findings by the I-FISH data in 63% (36-83% depending on the studied chromosomal site), and vice versa of 76% of the I-FISH results by the CGH data. Based on these results it is recommended to use a combination of both I-FISH and CGH for the detection of genomic changes in human solid tumors as the data obtained by both techniques ideally complete each other. For this reason both techniques have now enriched the spectrum of molecular histopathology.

Adult↗

PubMedDate not supplied

The cytogenetic view of standard comparative genomic hybridization (CGH): deletions of 20q in human leukemia as a measure of the sensitivity of the technique.

BACKGROUND: The limits of the resolving power of comparative genomic hybridization (CGH) have been given as 10-20 Mbp if at least 50% of the studied neoplastic cell population carried the corresponding aberration. MATERIAL AND METHODS: Genomic DNA of five cases of hematologic neoplasias, in all of which--among other anomalies--deletions of different size of chromosome 20q were found by GTG banding and confirmed by FISH analyses, was subjected to CGH. RESULTS: CGH revealed four types of del(20q), and, in addition, detected a tiny terminal del(3p) in one of the cases. The size of the smallest deleted segment, clearly visible by eye on the CGH metaphase image, was estimated to range between 5 and 7 Mbp. CONCLUSION: Visual determination was shown to have a stronger resolving power in CGH than software used for the analysis in one case, while in another one, the results obtained from the ratio profiles would have been considered insignificant without the knowledge of the hybridization pattern on the corresponding CGH metaphase images. The potential of the standard CGH technique not only to detect, but visualize small segmental aneusomies as well, suggests that its resolution actually mirrors the resolution of banding techniques.

Cell Nucleus↗

PubMedDate not supplied

Chromosome and oncogene studies in human rectal and colon carcinomas.

Cytogenetic examinations of 48 rectal and 17 colon carcinomas and analyses of proto-oncogene activation on 67 of the former and 8 of the latter tumors were performed. Besides a general considerable heterogeneity of chromosome counts, some chromosomes were found to contribute non-randomly to hypersomies (# 2, 3, 7, 9, 19, 20 and 6) and to hyposomies (# 14, 15, Y, 21, and 18) in this material. Chromosomal markers non-randomly involved breakpoint clusters on 17p11, 13q11, 7p, 1p11, and 1p36 and on the centromeric regions of chromosomes 1, 8, 14, 15 and 21. Cytogenetic equivalents of gene amplification ("double minutes") were present in only rather small cell fractions (less than 20%) of 50% of the studied tumors. Using a cDNA technique and a battery of respective probes, proto-oncogene overexpression was screened for in the tumor samples, but also in 24 samples of inconspicuous mucosae of tumor patients and in two mucosae of healthy individuals. Simultaneous overexpression of several proto-oncogenes was the most characteristic finding in the tumor cells. However several of the mucosa samples obtained from tumor patients also just exhibited clear signals of proto-oncogene overexpression, which were not found in epithelial cells from non-tumor patients.

Adult↗

PubMedDate not supplied

Expression of oncogenes in human breast cancer specimens.

More than 60 breast cancer specimens were screened for their expression status of 25 different proto-oncogenes. The screening method is based on in vitro synthesis of a radioactive cDNA copied from the total cellular RNA of tumor tissue. This cDNA is hybridized to cloned oncogene probes which are immobilized to a GeneScreen membrane. Frequently multiple oncogenes were found expressed although expression levels were rather moderate. 25-30% of the analyzed tumors showed significant expression of either erbB, src, raf1, lck or H-ras. Although neu expression--an oncogene believed to be particular relevant as prognostic parameter for mamma carcinoma--was screened for most of the tumors with a heterologous gene probe, expression signals could be detected in about 20% cases. The only notable correlation with classical clinical parameters such as tumor size and proliferation stage, hormone receptor status and different DNA indices was the observation that tumors lacking the progesterone receptor frequently express multiple oncogenes. Advantages and limitations of the cDNA/dot-blot screening for oncogene expression are discussed.

Animals↗

PubMedDate not supplied

Clastogenic action of chemotherapy in humans (review).

Examinations of the chromosome damaging (clastogenic) action of chemotherapy not only present valuable insights into the genetic hazards for man resulting from the respective drugs, but also can be used for control of success of certain treatments. In addition, those studies may be helpful in detecting "high-risk" individuals and, in consequence, in protecting them from the detrimental action of therapeutics they are highly sensitive to. Clastogenic activity should not be discussed without considering the close correlation between induction of mutations (e.g. chromosome changes) and malignant transformation, as documented by recent evidence on the meaning of point mutations as well as of chromosomal rearrangements in oncogene activation.

Chromosome Aberrations↗

PubMedDate not supplied

Proto-oncogene activation in surgical specimens of rectal carcinoma.

26 rectal carcinoma samples were screened for proto-oncogene activation. In addition, seven normal mucosae taken at a distance of 10 cm from the tumor were analyzed. Our results are based on hybridization assays of 32P labelled cDNA synthesized on cellular poly (A+)RNA with proto-oncogene dot-blots. This analytical concept offers the advantage of a comprehensive analysis of very limited amounts of biopsy material. Multiple proto-oncogenes could be detected as being over expressed for the analyzed rectal carcinomas. However, morphologically inconspicuous mucosae from tumor patients, classified as such by the pathologist, also already show clear signals of proto-oncogene over expression.

DNA Replication↗

PubMedDate not supplied

Cytogenetic and cell cycle studies in metastatic cells from ovarian carcinomas.

Metastatic cells in 34 malignant effusions from 24 women with carcinoma of the ovary were analysed for numerical and structural chromosome aberrations, presence of cytogenetic equivalents of gene amplification, and characteristics of their interphase cell cycles. Besides striking deviations in chromosome number and the presence of conspicuous clonal and non-clonal marker chromosomes, the prevalence of double minutes (DM) in 22 of the 34 effusions (in 19 of the 24 patients) was notable. The pattern of G1, S, and G2 phase distribution evaluated, following induction of premature chromosome condensation (PCC), varied significantly from patient to patient, depending apparently on factors such as: duration of cell culture, therapy, peculiarities and time elapsed from the diagnosis of the malignancy. The introduction of the PCC-technique has commendably extended the possibilities of cytogenetic studies in human tumor cells.

Adult↗

PubMedDate not supplied

Sister chromatid exchanges and proliferation kinetics of human metastatic breast tumor cells lines.

The rate of sister chromatid exchanges (SCEs) and the profiles of proliferation (= number of first, second, and third cycle metaphases distinguishable by their staining patterns after BrDU substitution for one, two, or three rounds of DNA replication) have been estimated in three (resp. five) metastatic human breast tumor cell lines. Line MDA MB 231 exhibited SCE rates equalling the level of normal cells, while line MDA MB 435 exhibited a slight increase, and line MDA MB 468 a more distinct increase of the SCE rate over the baseline frequency of normal cells. By the BRDU labelling technique the lines 231 and 435 were shown to be rather fast proliferating in culture, while the line 468, and even more the lines 330 and 361 showed a much slower proliferation pattern. From these results it was concluded that increased SCE rates are rather a facultative than an obligatory feature of malignant cells, and that the Br-DU-labelling technique might be suitable for gaining additional information on proliferation characteristics of tumor cells lines.

Breast Neoplasms↗