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PubMedDate not supplied

[Nucleolar organizer as a marker of malignancy grade and prognosis of non-Hodgkin's malignant lymphoma].

There were 51 cases of non-Hodgkin's malignant lymphoma (NHL) and 9 cases of reactive follicular hyperplasia among 60 cases of lymphoproliferative conditions. According to the Kiel classification, lymphomas of a low grade of malignancy (17 cases) and lymphomas of a high grade of malignancy (34 cases) were distinguished among NML. Significantly higher activity of the nucleolar organizers (NO) was observed in lymphomas of a high malignancy grade, particularly in lymphomas formed of cells of early differentiation stages, and enhancement of NO activity with development of lymphoma aggression. "Anomalies" of NO activity expression reflecting clinical lymphoma presentation were noted among NML of various malignancy grade. NML with a high NO activity are described as having less favourable prognosis compared to lymphomas with low NO activity. No significant difference in NO activity was found between reactive follicular hyperplasia and follicular centroblast-centrocytic lymphoma. Thus, NO activity can be considered as an additional diagnostic marker of NML grade of malignancy and prognosis.

Biomarkers, Tumor↗

PubMed1986

Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity.

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.

Animals↗

PubMed1994

Malignant mixed tumor of the skin (malignant chondroid syringoma).

Two cases of malignant mixed tumor of skin were studied, one of which demonstrated regional metastasis. The immunohistochemical features of these 2 neoplasms and of the 2 malignant mixed tumors previously described in Western Australia indicate that these neoplasms show eccrine differentiation and suggest their origin from both the secretory and ductal segments of the gland. The histological criteria of malignancy are discussed, with particular reference to those features which indicate malignant potential in neoplasms which otherwise lack overt morphological criteria of malignancy.

Adult↗

PubMed2004

[Complications of malignant tumors--malignant pleural effusions].

Malignant pleural effusion is a complication of malignant diseases that has an appreciable negative impact on the patient's quality of life. In view of the greatly reduced life expectancy of between 3 and 12 months (median), diagnostic and therapeutic management must be orientated to the principles of palliation. Diagnostic measures comprise cytological/histological confirmation of the malignant effusion and, where necessary, of the underlying malignant disease and the extent of the intrathoracic tumor growth. In view of the tendency of malignant pleural effusion to relapse, pleurodesis is indicated, which is most effectively accomplished by video-assisted thoracoscopic talcum poudrage.

Biopsy↗

PubMed1994

Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation, with emphasis on the malignant Triton tumor.

Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation can be divided into three groups. Group I consists of tumors with only sarcomatous differentiation. Included in this group are malignant mesenchymoma, dedifferentiated chondrosarcoma, and the dedifferentiated retroperitoneal liposarcoma. Epithelial or Sertoli-Leydig cell elements represent the second component of tumors in group II. The best known tumor in this group is the malignant mullerian mixed tumor, but other well described tumors with rhabdomyosarcomatous differentiation are the carcinosarcoma, mullerian adenosarcoma, Sertoli-Leydig cell tumor, mammary cystosarcoma, and blastomas. Most of the tumors in groups I and II are derived from mesenchymal tissue. A neuroectodermal origin is shared by all tumors in group III. This includes the medulloblastoma, retinoblastoma and, most frequently, the malignant Triton tumor. The tumors in all three groups are clinically malignant to a varying degree.

Humans↗

PubMed1999

P-glycoprotein is positively correlated with p53 in human oral pre-malignant and malignant lesions and is associated with poor prognosis.

P-glycoprotein (Pgp) encoded by the MDR1 gene, a predictor of chemoresistance, may also serve as a prognosticator of clinical outcome in cancer patients. The mutant tumour-suppressor p53 protein has been shown to activate the MDR1 promoter, whereas the wild-type p53 represses this activity in cultured cells. We have described the differential expression of Pgp and p53 proteins in betel- and tobacco-related oral tumorigenesis in the Indian population. Herein, Pgp expression was analysed in relation to p53 protein accumulation in pre-malignant and malignant oral lesions by immunohistochemical and flow-cytometric analyses. The relationship between Pgp and p53 protein accumulation and clinicopathological parameters as well as prognosis was determined. Expression of Pgp was observed in 81% of oral squamous cell carcinomas (SCCs) and 71% of pre-malignant lesions. Sixty-five of 75 p53-positive oral SCCs and 21/24 p53-positive pre-malignant lesions showed expression of Pgp. Significant correlation between Pgp and p53 expression was found not only in oral SCCs but also in pre-malignant lesions. Co-expression of Pgp and p53 proteins was indicative of poor prognosis. Follow-up studies of 35 patients showed that 7 of 10 oral SCCs with accumulation of Pgp and p53 proteins also exhibited shorter disease-free survival (recurrence/metastases). Our findings provide clinical evidence for a significant association between Pgp and p53 protein expression in oral tumorigenesis and may account for the aggressive nature of the tumour and poor prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1986

Sinusoidal hematolymphoid malignancy ("malignant histiocytosis") presenting as atypical sinusoidal proliferation. A study of nine cases.

A number of cases of sinusoidal hematolymphoid malignancy ("malignant histiocytosis") in which early lymph node biopsies have not allowed clear separation from benign histiocytic disorders have been observed. Nine such cases in which only a follow-up lymph node biopsy documented their malignant nature are reported. Seven of the nine patients were under 21 years of age; there was an even sex distribution. All had localized or generalized lymphadenopathy and three had hepatosplenomegaly at initial presentation. Histologically, the initial lymph node biopsy specimens showed an atypical sinusoidal proliferation, often with hemophagocytosis, but without sufficient atypia to allow a diagnosis of malignancy. The analysis of the follow-up biopsies, performed from 6 weeks to 5 years after the initial biopsy, showed a progression in histology with an increase in atypia, a greater tendency to efface lymph node architecture, and a decrease in hemophagocytosis. All patients were treated with chemotherapy. Six patients ultimately died; at autopsy, these patients showed a pattern of organ involvement typical of what has been described for malignant histiocytosis.

Adolescent↗

PubMed2006

Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential.

BACKGROUND: Methylation-mediated suppression of detoxification, DNA repair, and tumor suppressor genes has been implicated in cancer development and progression. Studies also have indicated that concordant methylation of multiple genes (methylator phenotypes), rather than a single gene, may predict cancer prognosis. The current study was designed to determine whether a methylator phenotype exists in ovarian cancer, whether methylation frequencies differ between malignant ovarian tumors and ovarian tumors with low malignant potential (LMP or borderline), and whether methylation of multiple genes affects patient survival. METHODS: The current study included 234 consecutively diagnosed patients with either LMP (n = 19 patients) or malignant (n = 215 patients) ovarian tumors. DNA samples were extracted from fresh frozen tissues and were analyzed for methylation in the promoter region of 6 genes (p16, breast cancer 1 [BRCA1], insulin-like growth factor-binding protein 3 [IGFBP-3], glutathione S-transferase pi 1 [GSTP1], estrogen receptor-alpha [ER-alpha], and human MutL homologue 1 [hMLH1]) by using methylation-specific polymerase chain reaction analysis. RESULTS: The frequencies of methylation in malignant tumors and LMP tumors were 0% and 0% for GSTP1, respectively; 9% and 0% for hMLH1, respectively; 21% and 5% for BRCA1, respectively; 42% and 21% for p16, respectively; 44% and 26% for IGFBP-3, respectively; and 57% and 42% for ER-alpha, respectively. A methylator phenotype was not detected, but a calculated methylation index (MI) that was based on the total number of genes methylated in each tumor was associated with ovarian cancer risk and progression. A higher MI was associated with malignant tumors (odds ratio, 10.11; 95% confidence interval [95% CI], 1.19-85.75) and disease progression (hazards ratio, 6.53; 95% CI, 1.39-30.65). CONCLUSIONS: Although a methylator phenotype was not identified, the current results suggested that methylation of multiple genes may play an important role in ovarian cancer development and progression and may have clinical implications in prognosis.

Adaptor Proteins, Signal Transducing↗

PubMed1983

Characterization of malignant and non-neoplastic cell phenotypes in highly malignant non-Hodgkin lymphomas.

Malignant and non-neoplastic cells in 38 cases of highly malignant non-Hodgkin lymphomas: 3 centrocytic anaplastic, 18 centroblastic, 13 immunoblastic and 4 lymphoblastic (according to the Kiel classification) were immunophenotyped in cryosections and cell suspensions by means of monoclonal antibodies. Additionally, cell cycle analysis on cell suspensions was performed by DNA flow cytofluorometry. In 33 (87%) lymphomas the malignant cells expressed monoclonal surface immunoglobulin (Ig), which indicated B-cell origin of tumors. In 7 of the 19 B-cell lymphomas tested by the peroxidase-antiperoxidase method, cytoplasmic Ig was found. Four lymphomas were of T-cell and one of non-B/non-T-cell origin. In II B-cell and 2 lymphoblastic non-B-cell tumors, common acute lymphoblastic leukemia antigen (CALLA) was found. In 25 of 30 studied NHL the malignant cells expressed receptor for transferrin and in 19 of 28 cases a high percentage of cells in S-phase (greater than 10.85%) was found. Number and distribution as well as type of non-B-cells infiltrating B-cell-derived lymphomas varied considerably from case to case. Among these cells Leu 3+ (T helper/inducer) cells predominated. Leu 2+ (T suppressor/cytotoxic) and Leu 7+ (natural killer and killer) cells constituted less numerous groups. Correlation of cytodiagnostic analyses with clinical observations indicates that high content of infiltrating T cells may be a favorable prognostic feature in highly malignant B-cell lymphomas.

Adolescent↗

PubMed1990

Transcription of biliary glycoprotein I gene in malignant and non-malignant human liver tissues.

Biliary glycoprotein I (BGP I) is a member of carcinoembryonic antigen (CEA) gene family consisting of at least 11 related genes. The transcription of BGP I gene was analysed in malignant and non-malignant human liver tissues with a 396-bp 3'-untranslated region probe from a cDNA clone 4-13 which was newly isolated from an adult human colon cDNA library. Among 21 tissue samples from 14 patients with hepatocellular carcinoma, 16 samples were clearly shown to express a single 3.9-kb message. This message was also found in the hepatoma cell line HuH-7. When the malignant tissues were compared to the non-malignant ones for the intensity of the band, no significant difference was observed. mRNAs of CEA and non-specific cross-reacting antigen (NCA) were not detected in 5 samples which were shown to have the message of the BGP I gene. These data suggest that the human hepatocyte and its malignant transformant produce BGP I, and that this could correspond to the cross-reacting antigen previously detected in the liver.

Antigens, CD↗

PubMed1987

Precocious puberty associated with malignant thoracic teratoma and malignant histiocytosis in a child with Klinefelter's syndrome.

A 10-year-old boy with precocious puberty of 2 1/2 years' duration presented with a malignant thoracic teratoma with elevated levels of beta human chorionic gonadotropin (beta-HCG) and alpha fetoprotein (alpha FP). The mediastinal tumor was completely excised and adjuvant chemotherapy commenced. Within 3 weeks of commencing chemotherapy he developed hematologic abnormalities that, with the subsequent clinical illness, led to a diagnosis of malignant histiocytosis. Death occurred a few days after start of therapy for malignant histiocytosis. Cytogenic studies showed the somatic karyotype to be that of Klinefelter's syndrome, while the malignant cells in marrow and lymph node carried an additional marker chromosome. This case, with others reported, suggest that the XXY karyotype may influence the development of mediastinal germ cell tumors, which in themselves appear to be associated with the early onset of a malignancy of the hemopoietic system.

Child↗

PubMed1986

The utilization of [3H] sugars by non-malignant and malignant human breast.

The utilization of [3H] sugars and leucine by non-malignant and malignant human breast has been assessed using an organ culture technique with subsequent tissue autoradiography. The uptake of sugars by normal and hyperplastic breast was generally constant, with some differences observed in the utilization of galactose by acini of normal and hyperplastic tissues. After 24 h incubation localization was predominantly at the luminal cell periphery. The utilization of sugars by carcinomas was much more variable. Differences were observed between adjacent cells and cell groups of the same tumour. The uptake of individual sugars within a carcinoma was also varied being either similar to, or greater or lesser than normal breast. Variation between carcinomas was also present. No correlation between type and differentiation was noted in this respect, but there was between localization of sugars and differentiation. Better differentiated areas in tumours showed patterns similar to non-malignant breast whilst localization in poorly differentiated cell groups was cytoplasmic. The uptake of leucine was more constant and proved to be a useful indicator of viability. While this approach cannot give information with regard to differences in glycoprotein structure between non-malignant and malignant breast, it has been of value in determining the heterogeneity of tumour cells with regard to the enzymes involved in glycosylation. As such it would be of use in assessing the uniformity of response to agents modifying glycosylation.

Breast↗

PubMed1995

Multiple (five) synchronous primary malignant neoplasms of dissimilar histogenesis including a malignant fibrous histiocytoma of the bladder.

A unique case was recently encountered involving the synchronous presentation of five primary malignancies of different histology. Malignant neoplasms of the colon, kidney, prostate and bladder were treated surgically. Bladder was affected by two separate tumours: a transitional cell carcinoma and a malignant fibrous histiocytoma. The latter constitutes an extremely rare malignant lesion of the organ. The pathologic characteristics, histogenesis, differential diagnosis and treatment considerations of this soft tissue sarcoma, and the incidence, terminology and incriminating factors of multiple primary malignant neoplasms, as well as their association with the genitourinary system are reviewed.

Aged↗

PubMed1996

Triple primary malignant neoplasms including a malignant brain tumor: report of two cases and review of the literature.

BACKGROUND: Two rare cases of triple primary malignant neoplasms (PMN), including malignant brain tumors, which were glioblastoma multiformes, are described. METHODS: The clinical characteristics and underlying genetic alterations in triple or more PMN, including malignant brain tumors are discussed with intensive review of the literature. RESULTS: The first patient, a 77-year-old male, suffered metachronously from tubular adenocarcinoma of the stomach, transitional cell carcinoma of the bladder, and glioblastoma in the brain. This glioblastoma had loss of heterozygosity in exons 7-8 in p53 gene. The second patient, a 68-year-old male, developed papillary adenocarcinoma of the lung, adenocarcinoma of the rectum, and glioblastoma in the brain during a period of 7 years. In 42 such cases described in the literature, age distribution demonstrated two characteristic peaks, one in the third decade and the other over 50 years of age. The younger group consisted mainly of Turcot's syndrome, and of a case of Li-Fraumeni familial cancer syndrome. On the other hand, neither of these hereditary cancer syndromes were contained in the elder group. Regarding the site of PMN, colorectal cancers were associated most frequently with malignant brain tumors, followed by stomach cancers, and thyroid cancers. Malignant brain tumors, mostly glioblastoma multiforme, tend to occur as the last tumor of triple or more PMN. CONCLUSIONS: These results suggest that genetic background might play an important role in tumorigenesis of PMN in the younger group, whereas epigenetic factors would be more important in the older group. Characteristic organ association and factors influencing carcinogenesis, such as aging, environmental carcinogens, and underlying genetic alterations in these tumors are further discussed.

Adenocarcinoma↗

PubMed1993

Cytotoxic effect of interferon on primary malignant tumour cells. Studies in various malignancies.

It is a well established fact that interferon (IFN) can inhibit cell growth, but only recently has it been found that IFN can exert a direct cytotoxic effect on primary tumour cells. This was shown in malignant cells from patients with multiple myeloma. In this study the influence of IFN on the viability of primary malignant cells from patients with different malignancies was studied. As previously described a direct cytotoxic effect of IFN on multiple myeloma cells was observed. No major effects on cell viability could be found in malignant cells from patients with lymphoma, chronic lymphocytic leukaemia, hairy cell leukaemia, chronic myelogenous leukaemia and carcinoma. This indicates that the direct cytotoxic effect of IFN in multiple myeloma may be relatively specific for this malignancy. It could be due to a specific differentiation stage in the myeloma cells, specific genetic alterations and/or abrogation of an autocrine/paracrine loop.

Cell Count↗

PubMed2005

Breakthrough pain in malignant and non-malignant diseases: a review of prevalence, characteristics and mechanisms.

Breakthrough pain or transient worsening of pain in patients with an ongoing steady pain is a well known feature in cancer pain patients, but it is also seen in non-malignant pain conditions with involvement of nerves, muscles, bones or viscera. Continuous and intermittent pain seems to be a general feature of these different pain conditions, and this raises the possibility of one or several common mechanisms underlying breakthrough pain in malignant and non-malignant disorders. Although the mechanisms of spontaneous ongoing pain and intermittent flares of pain (BTP) may be difficult to separate, we suggest that peripheral and/or central sensitization (hyperexcitability) may play a major role in many causes of BTP. Mechanical stimuli (e.g. micro-fractures) changes in chemical environments and release of tumour growth factors may initiate sensitization both peripherally and centrally. It is suggested that sensitization could be the common denominator of BTP in malignant and non-malignant pain.

Humans↗

PubMed2006

Atypical foci suspicious but not diagnostic of malignancy in prostate needle biopsies (also referred to as "atypical small acinar proliferation suspicious for but not diagnostic of malignancy").

OBJECTIVE: To review atypical focus suspicious but not diagnostic of malignancy in needle biopsies of the prostate, also referred to as "atypical small acinar proliferation suspicious for but not diagnostic of malignancy." METHODS: A number of descriptive and somewhat confusing terms have been used to refer to a prostate tissue biopsy with small focus of atypical glands. Based on MEDLINE database searches, all aspects, including the synonymous terms, of atypical focus suspicious but not diagnostic of malignancy were examined. RESULTS: An average of 5% of needle biopsy pathology reports show a diagnosis of atypical focus suspicious for malignancy. It may be composed of acini of small size, that is, smaller than normal ducts and acini, but may also include glands with a diameter similar to that of normal ducts and acini. It encompasses a variety of lesions, including benign mimickers of cancer and small foci of carcinoma that, for a variety of reasons, cannot be accurately diagnosed. Maximal diagnostic information should be gained on section stained with haematoxylin and eosin, with immunohistochemical stains used for confirmation. Its presence in a biopsy set is a strong predictor for concurrent or subsequent adenocarcinoma. The values range from 17% to 60%, the mean being 40.7%. The precise labelling of the initial biopsies is mandatory so that rebiopsy of patients with atypical foci can be directed in a more concentrated fashion into the region of the initial biopsy. CONCLUSION: The presence of atypical focus suspicious but not diagnostic of malignancy in needle biopsies is an important predictor of cancer compared with biopsies from patients who lack this finding.

Biopsy, Needle↗

PubMed2001

Malignant cells, directors of the malignant process: role of transforming growth factor-beta.

Malignant cells survive and thrive by expressing growth and invasion 'programs' that many normal cell types recognize and respond to in 'programmed' patterns. An early event in the molecular evolution of many malignancies loss of response to growth control by transforming growth factor-beta (TGF-beta) frequently due to mutation in the type I or type II TGF-beta receptor or a Smad protein. The malignant cells secrete TFG-beta that acts on the host to suppress antitumor immune responses, to enhance extracellular matrix production and to augment angiogenesis. These activities resemble those induced by TGF-beta during embryonic development and account in part for the 'de-differentiated' nature of malignant disease. Clinically, TGF-beta1 is often elevated in the plasma of breast cancer patients, lung cancer patients, hepatocellular carcinoma patients, and prostate cancer patients. Preclinically, several breast cancer models and prostate cancer models in vivo have demonstrated a connection between TGF-beta expression and increased tumorigenicity, increased invasion and drug resistance. In other diseases such as colon, gastric, endometrial, ovarian, and cervical cancers and gliomas and melanoma, loss of response to TGF-beta as a growth inhibitor and increased expression of TGF-beta have been associated with malignant conversion and progression. Elevated levels of TGF-beta are measurable in nude mice bearing a wide variety of human tumor xenografts; thus, these tumor models may serve as useful mimics of the human disease with respect to the TGF-beta pathway. Cancer cure may be approached by blocking several of the major normal pathways used for tumor growth and survival in combination with cytotoxic therapies.

Animals↗