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PubMed2005

Differential phosphodiesterase expression and cytosolic Ca2+ in human CNS tumour cells and in non-malignant and malignant cells of rat origin.

A promising attempt in the field of tumour therapy is the modulation of intracellular, proliferation-associated signalling pathways. The role of cyclic nucleotide phosphodiesterases (PDEs), key enzymes in cAMP/cGMP signal transduction, was investigated in two human CNS tumour cell lines as well as in the rat glioblastoma cell line C6 in comparison with rat cerebellar astrocytes with the emphasis on target evaluation. We found differential PDE expression patterns in human CNS tumour cell lines as well as in CNS cells of rat origin. In human glioblastoma cells, intracellular cAMP and Ca(2+) levels correlated well with the PDE expression pattern. There were, however, marked differences in PDE expression and Ca(2+) kinetics between the human glioblastoma cell lines. In contrast to human epithelial tumour cells, shown earlier by us to express significantly enhanced cAMP-specific PDE activity, this was not the case in rat glioblastoma cells compared with non-malignant rat astrocytes. Despite different levels of PDE1 and PDE4 expression and activity, cyclic nucleotide and Ca(2+) levels in non-malignant and malignant rat CNS cells were similar. These in vitro data do not support the concept of PDE1C representing a target exploitable for drug treatment of malignant CNS tumours.

Animals↗

PubMed1985

Decreased risk of subsequent primary noncutaneous malignancies among patients with primary cutaneous malignant melanoma.

It is established in the clinical literature that patients who develop specific types of malignancies are at an increased statistical risk for the development of a second primary malignancy. Previous studies have supported the theory that patients who develop primary cutaneous malignant melanoma (PCMM) have a greater risk for the development of a secondary primary noncutaneous malignancy (SPNM). Taken from the tumor registry of a community hospital, data for 504 consecutive patients (254 men and 250 women) with a diagnosis of PCMM were evaluated for the incidence of subsequent SPNM by comparing this series of patients to the general population of Connecticut. It was demonstrated that patients with PCMM had a significantly reduced incidence of SPNM (p = 0.002). Consideration should be given to possible biological and behavioral mechanisms which could explain the observed deficit.

Adult↗

PubMed1992

A case-control study of malignant and non-malignant respiratory disease among employees of a fiberglass manufacturing facility.

A case-control study was conducted to determine the influence of non-workplace factors on risk of respiratory disease among workers at the Owens-Corning Fiberglas plant in Newark, Ohio. Cases and controls were drawn from a historical cohort mortality study conducted on behalf of the Thermal Insulation Manufacturers Association (TIMA) of workers employed at Newark for at least one year between 1 January 1940 and 31 December 1963 and followed up to the end of 1982. The TIMA study reported a statistically significant increase in respiratory cancer (compared with national death rates). Interviews were completed for 144 lung cancer cases and 299 matching controls and 102 non-malignant respiratory disease cases and 201 matching controls. Unadjusted odds ratios (ORs) were used to assess the association between lung cancer or non-malignant respiratory disease and birthplace, education, income, marital state, smoking with a duration of six months or more, age at which smoking first started, and duration of smoking. Only the smoking variables were statistically significant. For lung cancer, of the variables entered into a conditional logistic regression model, only the smoking OR of 23.4 (95% CI 3.2-172.9) was statistically significant. For non-malignant respiratory disease no variables entered into the final model were statistically significant. Results of the interview portion of our case-control study clearly indicate that smoking is the most important non-workplace factor for risk of lung cancer in this group of workers. Smoking does not seem to play as important a part, however, for non-malignant respiratory disease. Prevalence of cigarette smoking at the Newark plant was estimated for birth cohorts by calendar year. Corresponding data for the United States were compiled from national smoking surveys. Prevalence of cigarette smoking for Newark in 1955 appears to be sufficiently greater than the corresponding United States data in 1955 to suggest that some of the previously reported excess of lung cancer for Newark based on United States mortality may be accounted for by differences in the prevalence of cigarette smoking between white men in Newark and those in the United States as a whole.

Aged↗

PubMed1997

Expression of NM23 protein in acquired melanocytic nevi, malignant melanoma and metastases of malignant melanoma: an immunohistological assessment in human skin.

BACKGROUND: It has been suggested that nm23 may exert metastasis suppressor function in human tumors. OBJECTIVE: We have analyzed expression of nm23 polypeptide in acquired melanocytic nevi (n = 19), dysplastic nevi (n = 19), malignant melanomas (n = 22) and metastases of malignant melanomas (n = 47) in situ. METHODS: Nm23 protein was detected immunohistochemically on paraffin sections using the highly sensitive labeled avidin-biotin technique. RESULTS: We found that (1) nm23 polypeptide is predominantly expressed in the cytoplasmic but also in nuclear and membrane compartments of melanocytic human cells, (2) expression of nm23 protein does not correlate with benign or malignant phenotype in melanocytic tumors of human skin. CONCLUSION: Our study challenges the hypothesis that nm23 may function in malignant melanomas as a tumor suppressor gene.

Antigens, Neoplasm↗

PubMedDate not supplied

Cytohistologic correlation in malignant peritoneal washings. Analysis of 75 malignant fluids.

OBJECTIVE: To determine the value of peritoneal washing (PW) cytology alone in upstaging carcinomas of the female genital tract (FGT). STUDY DESIGN: The histologic reports and slides of surgically resected FGT carcinomas related to 75 malignant PWs were reviewed. For inclusion in the study, no ascites was present. The cases consisted of 28 primary and 4 metastatic ovarian tumors, 9 peritoneal "serous implants" from second-look laparotomy, 3 metastatic peritoneal carcinomas, 1 primary peritoneal serous carcinoma, and 19 endometrial, 6 cervical and 5 tubal carcinomas. RESULTS: Cytologic examination alone was responsible for the upstaging of 0-75% of carcinomas, depending on tumor origin. Malignant cells were seen in 97% (73/75) of the cytologic smears and in 51% (28/75) of the cell blocks prepared from the PWs. CONCLUSION: The clinical value of PW cytology lies in the upstaging of 63% of borderline ovarian tumors, 50% of primary ovarian malignancies of nonserous type and 11% of endometrial adenocarcinomas. PW cytology is not recommended for primary carcinomas of the cervix, fallopian tube or peritoneum or for ovarian carcinoma of serous and metastatic types. Furthermore, PW cell blocks were less sensitive than cytocentrifuged smears and contributed only a single additional malignant PW.

Carcinoma↗

PubMed1980

Studies on the surface properties of hybrid cells. I. Sialyl-transferase activity in homogenates of malignant and non-malignant cells.

We report here a method for the assay of the sialyl-transferase activity in crude homogenates of a wide range of cell lines growing in tissue culture. Our results indicate that particulate preparations from both malignant and non-malignant cells show a Km of 0.25 mM towards CMP-sialic acid in the presence of an excess of glycoprotein acceptor. There appear to be increased amounts of the enzyme associated with the preparations from malignant sources which are reflected in an increase in the apparent Vmax of these. The elevated level of sialyl-transferase activity seen in the malignant cell populations is, paradoxically, associated with a decrease in the amount of bound sialic acid associated with both the whole cell homogenate preparations and the surface of these cells.

Animals↗

PubMed1979

The screening test of various chemotherapeutic drugs in primary malignant melanoma cells and human malignant melanoma cell line (TM-1).

The sensitivities to various chemotherapeutic drugs of the primary malignant melanoma cell of the esophagus and the malignant melanoma cells established from human skin were studied by determining the incoporation of 3H-thymidine into tumor cells using the tissue culture method. The incorporation of 3H-thymidine was depressed by a low concentration of Actinomycin D in malignant melanoma cells of the esophagus and by a low concentration of Adriamycin or Actinomycin D in the established malignant melanoma cells. When Actinomycin D was clinically used according to the experimental results, the subcutaneously metastasized tumor was remarkably reduced.

Aged↗

PubMed2003

Differential expression of galectin-3 in papillary projections of malignant and non-malignant hyperplastic thyroid lesions.

Galectin-3 is a a beta-galactoside binding protein recently proposed to be a promising presurgical molecular marker for distinguishing benign from malignant thyroid neoplasms. We analyzed galectin-3 expression immunohistochemically in papillary areas of hyperplastic lesions of benign thyroid tissue in comparison with malignant papillary projections of papillary thyroid carcinoma (PTC). A monoclonal antibody to galectin-3 and ABC immunohistochemical technique were used to evaluate galectin-3 expression in 26 cases of benign papillary hyperplasia (8 cases of hyperplastic adenoma, 8 cases of hyperplastic colloid goiter, 10 cases of Graves disease) in comparison with 25 cases of PTC. Immunohistochemical results showed no reactivity for galectin-3 in papillary areas of benign hyperplastic lesions. Strong cytoplasmic galectin-3 immunoreactivity was found in all 25 cases of PTC. These results show that galectin-3 expression is a feature of malignant papillary projections but not of benign papillary hyperplasia. Thus, the immunohistochemical evaluation of galectin-3 might contribute to differential diagnosis between malignant and benign thyroid lesions with papillary projections.

Biomarkers, Tumor↗

PubMed1981

A study of estrogen and progesterone cytosol receptor concentration in benign and malignant ovarian tumors and a review of malignant ovarian tumors treated with medroxy-progesterone acetate.

ER and PR were assayed in 13 malignant and 20 benign ovarian tumors of different histologic types. ER was detectable in 67% and PR in 40% of the malignant tumors, compared with 35 and 45% in the benign tumors, respectively. The ER concentration was somewhat higher in the malignant lesions but there was no difference in the PR level. A retrospective review of 39 primary ovarian tumors of different pathologic stages and classes, treated postoperatively with medroxyprogesterone acetate (MPA, Depo-Provera, UpJohn) and in most cases Melphalan, showed a high Karnofsky performance index and good complete and partial response rates. The need for a prospective, controlled study of the role of MPA treatment of malignant ovarian tumors in evident.

Adult↗

PubMed1976

Trends in mortality rate from malignant skin melanoma and other malignant skin neoplasms in Czechoslovakia during the period 1921--1970.

Mortality from malignant skin melanoma (172 ICD) has an ascending trend in Czechoslovakia (CSSR) the rate being higher after the year 1960 in Bohemia (CSR) than the Slovakia (SSR). Mortality from other malignant neoplasms of the skin (173 ICD) declines; this decline for the whole of Czechoslovakia has been statistically influenced mainly by the lower death rate from this cause in Bohemia, for in Slovakia this mortality rate has risen, although significantly only in women. The proportion of deaths from malignant skin melanoma (172 ICD) out of the total number of deaths from malignant skin neoplasms (172 + + 173 ICD) is relatively low in Czechoslovakia--lower in Slovakia than in Bohemia.

Adolescent↗

PubMed2000

Detection of K-ras and p53 mutations in bronchoscopically obtained malignant and non-malignant tissue from patients with non-small cell lung cancer.

Molecular screening may increase the likelihood to identify early malignant lesions in non-small cell lung cancer. However the presence of gene mutations in non-malignant bronchial tissue has remained controversial. The present study was carried out to investigate systematically the presence of mutations of the K-ras and p53 gene in bronchial biopsies taken during routine bronchoscopy of normal as well as tumour tissues from a series of 40 patients with histologically verified non-small cell lung cancer (NSCLC). K-ras mutations were analysed with specific detection oligonucleotides, p53 mutations were examined by SSCP analysis. In all biopsies the wildtype of both K-ras and p53 could be detected. The overall frequency of mutations was 14 (35%) with 2 K-ras mutations (5%) and 12 mutations of the p53 gene (30%). In 3 cases (1 ras mutation, 2 p53 mutations) the same mutation could be shown in the tumour biopsy and in the distant normal control. In another case only the normal appearing tissue had a mutation of the p53 gene. All other mutations could be detected in the tumour tissue only. Our data confirm that K-ras mutations and p53 can be detected not only in malignant but also in non-malignant bioptic samples from patients with NSCLC. The use of molecular screening for the early detection of lung cancer may be a promising new approach.

Adenocarcinoma↗

PubMedDate not supplied

Anti-p53 and anti-heat shock proteins antibodies in patients with malignant or pre-malignant lesions of the oral cavity.

BACKGROUND: Evaluation of circulating anti-p53 antibodies is an easy-to-perform, widely employed, procedure to assess the p53 status in cancer patients. MATERIALS AND METHODS: Levels of circulating anti-p53 antibodies in patients affected either by oral SCC or by pre- malignant oral lesions were assayed using a commercial ELISA kit. Autoantibody titers to Hsp60 and Hsp72 were determined by conventional ELISA. RESULTS: Anti-p53 antibodies were detected in 3 out of 16 SCC-bearing patients (18.7%) and in 9 out of 13 patients suffering from pre-malignant oral lesions (69.2%). High titers of anti-Hsp60 autoantibodies were detected in 3 out of 29 patients (10.3%), while in all patients anti-Hsp72 titers were in the normal range. CONCLUSION: The presence of anti-p53 antibodies in both SCC-bearing patients and in patients with pre-malignant lesions support the notion that p53 gene mutation is an early event in oral tumorigenesis and suggest that this assay could be useful for diagnostic screening of pre-neoplastic lesions at high risk of recurrence and/or transition towards overt malignancy.

Adult↗

PubMed1991

Malignant mixed tumor (malignant ameloblastoma and fibrosarcoma) of the maxilla.

We present a rare case of carcinosarcoma (malignant ameloblastoma and fibrosarcoma) of the left maxilla that developed in a 63-year-old Japanese man. The tumor recurred repeatedly despite multiple surgical removals, radiotherapy, and chemotherapy and led to progressive cachexia; the patient died after 3.8 years of hospitalization. Histopathologic examination revealed that the recurrent tumor was carcinosarcoma, which had progressed from malignant ameloblastoma with fibroma. An autopsy confirmed the diagnosis of malignant mixed tumor with lung metastasis of malignant ameloblastoma and fibrosarcoma.

Ameloblastoma↗

PubMed1990

Malignant giant cell tumor of bone: malignant transformation of a benign giant cell tumor treated by surgery.

A case of a giant cell tumor of the right proximal femur that developed malignant change following surgical treatment ("secondary" malignant giant cell tumor) is presented. The patient had a cystic lesion that was initially interpreted as an aneurysmal bone cyst. A local recurrence six months later demonstrated the histological features of typical giant cell tumor. A further recurrence 22 months after the original treatment showed histological malignancy. Death was due to massive local recurrence and to extension of the malignancy to the pleura.

Adult↗

PubMed1990

ME1. A monoclonal antibody that distinguishes epithelial-type malignant mesothelioma from pulmonary adenocarcinoma and extrapulmonary malignancies.

ME1 is a monoclonal antibody reactive in frozen tissue sections with normal mesothelial cells and malignant mesotheliomas. In this immunoperoxidase study, ME1 reacted with all 40 epithelial type malignant mesotheliomas. Fifty percent or more of the mesothelioma cells were stained in all cases and the staining intensity was strong in 32 and moderate in eight. In contrast, all 19 well- and moderately differentiated pulmonary adenocarcinomas were completely negative, and of the total 88 non-mesotheliomatous malignancies studied, staining comparable to the mesotheliomas was seen in only 6 tumors (2 pulmonary adenocarcinomas, 2 adenocarcinomas of the breast, 1 adenocarcinoma of the pancreas, and 1 melanoma), although limited, weaker staining was seen in additional cases. Five of the six strongly to moderately positive nonmesotheliomatous tumors had immunoreactivity for complementary immunoreactants (CEA, Leu-M1, S-100 protein, HMB-45). Our results with ME1, the first monoclonal antibody that recognizes malignant mesothelial cells, provides a basis for using this reagent in the differential diagnosis of tumors of the pleura and peritoneum.

Adenocarcinoma↗

PubMed1979

[Mature benign teratomas with malignant tumors and malignant monodermal ovarian teratomas. Anatomo-clinical presentation of 10 cases].

The clinicopathologic features are presented of 8 malignant neoplasms occurring in adult teratomas, and of 2 malignant monodermal teratomas found in a continuous series of 1029 cases of ovarian adult teratomas. The age of the patients was 44--76 years. The first 8 observations included 6 epidermoid carcinomas, 1 undifferentiated carcinoma and 1 strumal carcinoid. In the epidermoid carcinomas malignancy was recognized peroperatively only in three instances. One tumor had infiltrated the broad ligament on one side and another the urinary bladder. The neoplasm appeared as a mass which thickened the wall of a typical dermoid cyst. Four patients died of the tumor from 3 months to 1 year after operation; one is alive more than 19 years later and one is lost to follow-up. The crucial factor in prognosis is the integrity of the ovarian capsule. The undifferentiated carcinoma, which had infiltrated the pelvic walls, could only be incompletely resected and caused death within 3 1/2 months. The strumal carcinoid was discovered by chance during laparotomy for a far-advanced adenocarcinoma of the pancreas which led to death within 2 months. The two cases of malignant monodermal teratoma comprised 1 thyroid papillary carcinoma and 1 carcinoid. Both patients are alive more than 8 and 5 years after operation. The carcinoid manifested itself by persistant diarrhea which ceased soon after operation and did not recur subsequently.

Adult↗

PubMed1981

[Mesoblastic nephroma--a malignant tumor with low grade of malignancy].

The mesodermally differentiated and only in newborns and young infants occurring mesoblastic nephroma is regarded as benign. Recidivations with malignant course, inclination to infiltration and richness in mitosis make arise doubts about the benignity despite good prognosis. The results of a proliferation-kinetic examination received by an autoradiographic in vitro method of a mesoblastic nephroma which was observed in a 20-day-old infant are characteristic for a malignant tumour of low degree of malignity: 3H-thymidine marking index 5.8%, DNA synthesis time 18.2 hours, mean generation time 141.1 hours (= 5.9 days). Growth fraction 0.28 and potential doubling time of the tumour 16.4 days. These data decisively deviate from those of the Wilms-tumours, which are cell-kinetically characterized as extraordinarily quickly growing, highly malignant tumours. The position of the mesoblastic nephroma in the system of the dysontogenetic renal tumours is briefly discussed. The ureteronephrectomy performed in time is the only necessary therapeutic measure, since also the mesoblastic nephroma follows the general rule of dysontogenetic tumours that the prognosis is the better the younger the infant is.

Humans↗

PubMed1984

[Unrecognized malignant lymphomas simulating a primary gynecologic malignancy].

The discovery of a so far unknown lymphoma in the female genital tract is rare. According to Chorlton et al., malignant lymphoma manifests itself primarily in the ovary and uterus in 0.3% and 0.12% of cases respectively. Four personally observed cases are reported with special emphasis on the clinical and histological difficulties encountered in the diagnosis of this rare clinical picture. After analysis of data in the literature, an attempt is made to define criteria, which should lead clinicians and pathologists to consider the possibility of such an event. Women of all age groups may be affected. Malignant lymphoma occurring primarily in the uterus usually mimics infiltrative carcinoma of the cervix causing vaginal discharge and post-coital bleeding. There are no specific symptoms. The presence of an undifferentiated round-cell tumor which is difficult to classify histologically and develops rapidly should suggest the possibility of malignant lymphoma. When the primary manifestation is an ovarian tumor, the lesion is bilateral in about 55% of cases. The presence of ascites is very rarely reported. In most cases these tumors are histologically misdiagnosed primarily as granulosa cell tumors, dysgerminomas or undifferentiated carcinomas. The diffuse and poorly differentiated lymphocytic type is most frequently encountered in adults. In children, granulocytic sarcoma or so-called chloroma may be found. In the presence of bilateral ovarian tumor without ascites and displaying unclear histological features in frozen sections, the possibility of malignant lymphoma should always be considered. In such cases it is advisable to process some of the tumor tissue for special subsequent morphologic and/or immunologic investigations.

Adolescent↗