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Estimation of the usefulness of neoplastic markers TPS and CA 125 in diagnosis and monitoring of ovarian cancer.

PURPOSE: We have undertaken an attempt to compare the suitability of tumor markers TPS (tissue polypeptide specific antigen) and CA125 for diagnosis and monitoring of ovarian cancer patients. METHODS AND MATERIAL: The studies were performed on 33 patients treated for ovarian cancer in the Department of Oncology, Karol Marcinkowski School of Medicine, Poznań from 1995-1996, Serum levels of TPS and CA125 were determined before surgery and at each chemotherapy course. CONCLUSION: Estimation of the neoplastic markers TPS and CA125 is suitable for diagnosis of ovarian cancer. Parallel use of TPS and CA125 in ovarian cancer patients increases sensitivity of the diagnosis. Estimation of TPS is highly suitable and estimation of CA125 is of low value in detection of mucinous ovarian cancer. Serum levels of the neoplastic markers TPS and CA125 decrease after total or debulking surgery for ovarian cancer. Serum TPS and CA125 levels reflect the course of the neoplastic process during chemotherapy.

Adult↗

[Primary tumors of heart].

The analysis of 36 years' experience in surgical treatment of 162 patients with benign and malignant primary tumors of the heart, verified by morphological examination, is presented. The possibility of their timely and intra vital revealing is noted in cases of clinical alertness which makes possible to suspect this disease and purposefully examine these patients using preferably echocardiography and computed tomography. The scope of the operations and their success depend on morphological characteristics of the tumors and the extent of neoplastic process. However, by now short- and long-term results of surgical treatment evidence, that predominant part of this category of patients is potentially curable, provided that these neoplasms of the heart were revealed at an initial stage.

Adolescent↗

Stem cell factor is not essential for cell survival and proliferation of soft tissue sarcoma of neuroectodermal origin.

BACKGROUND AND OBJECTIVE: Stem cell factor (SCF), and its receptor (c-kit) play key roles in the expansion and differentiation of hematopoietic progenitor cells, in melanoblasts and primordial germ cells, making it possible that SCF and c-kit are involved in neoplastic processes deriving from these cells. C-kit has been described to be expressed at different levels in neuroblastoma and in soft tissue sarcoma of neuroectodermal origin, and seems to be required for survival processes. In this study we investigate how c-kit expression is regulated and whether a SCF autocrine loop is essential for survival of sarcoma cell lines. DESIGN AND METHODS: C-kit modulation and internalization was evaluated incubating cells with rhSCF. Cell differentiation and proliferation experiments were performed to test whether c-kit expression is related to cell cycle progression or to differentiation processes. Cell cultures were treated with neutralizing antibody and antisense oligonucleotides in order to assess the possible significance of the SCF autocrine loop. RESULTS: In vitro SCF stimulation induces c-kit down-regulation; this phenomenon could be connected with receptor internalization, and new protein synthesis is necessary for its re-expression. The cell proliferation arrest in G0/G1 does not modify c-kit expression while down-regulation of c-kit was demonstrated after cells had been treated with differentiating agents. SCF neutralization does not influence either the S phase or apoptosis in sarcoma cell lines. INTERPRETATION AND CONCLUSIONS: In sarcoma cell lines, c-kit is regulated by differentiation processes; moreover our results suggest that c-kit activity, but probably not the SCF autocrine loop, is essential for survival of these cell lines.

Antibodies, Monoclonal↗

[Pharmacologic and toxicologic results in genetic polymorphisms (review)].

Paper provides a survey of the basic knowledge on the genetic polymorphism of enzymes involved in the metabolism of medicinal drugs and other xenobiotics. The major implications of this phenomenon have been described, namely the interindividual variability in the therapeutic effect of drugs differently metabolised by the polymorphically determined enzymes, or the interindividual variability in the susceptibility to neoplastic processes related to the polymorphically determined enzymes metabolising xenobiotics. Recent advances in the understanding of the molecular genetics of enzymes metabolising drugs and other xenobiotics (particularly cytochrome P-450, glutathione S-transferase, N-acetyltransferase, UDP-glucoronosyltransferases and others), help to understand the molecular basis of several genetic polymorphisms. Present article reviews the current status of studies on polymorphism of xenobiotics-metabolising enzymes and brings a discussion to their pharmacotherapeutical relevance and to their significance for identification of susceptible individuals/subgroups in the carcinogen exposed population.

Enzymes↗

Postauricular approach for surgery of the temporomandibular articulation.

The adaptation of a postauricular approach for surgical exposure of the temporomandibular articulation is presented. The ease, safety, and predictability of extensive exposure have led us to use this approach exclusively for surgical intervention in this region. It has been effectively used in cases of trauma, pathologic conditions, and reconstruction involving the TMJ. In addition to the cases reported in this series, the procedure may be adapted to oblique subcondylar oestotomies and to the treatment of a variety of regional neoplastic processes and other forms of TMJ dysfunctions that may be encountered.

Humans↗

Disseminated coccidioidomycosis. The role of cytology in multidisciplinary clinical approach and diagnosis.

A case of clinically unsuspected disseminated coccidioidomycosis diagnosed by different cytologic approaches and confirmed by mycological culture is reported. An African-American man presented with a clinical picture of pneumonia not responding to antibiotics. He subsequently developed a large neck mass and was found to have mediastinal and hilar adenopathy highly suspicious of a neoplastic process. Fine needle aspiration biopsy of the neck mass, followed by flexible bronchoscopy, was performed. Various cytologic approaches and techniques in rapid diagnosis of suspicious masses are discussed.

Biopsy, Needle↗

[Urogenital amyloidosis: clinico-pathological study of 8 cases].

Amyloidosis of the genito-urinary tract is uncommon. We report 8 cases, often misdiagnosed as a neoplastic process (6/8). Amyloidosis was localized in the bladder (3 cases), in the ureter (1 case) and in the prostate and/or seminal vesicles (4 cases). The amyloid protein was characterized in 7 cases by immunohistochemistry. Among the bladder and ureter amyloidosis, 2 cases were classified as AL lambda amyloidosis and one case as AA amyloidosis in a patient with long history of chronic arthritis. In the fourth case, the deposits could not be identified. Nevertheless an AL amyloidosis might be suggested. Two cases of prostate and/or seminal vesicles amyloidosis were stained with an anti-B2M antibody, in hemodialyzed patients. The 2 others, positive with the anti-Transthyretina antibody, were classified as senile amyloidosis. This small series illustrated the heterogeneous pathogenic types of amyloidosis in the urogenital tract and emphasized the interest of immunohistochemistry to identify the chemical composition of these deposits.

Adult↗

[The evaluation of cell proliferation in gliomas].

INTRODUCTION: The homeostasis of tissues depends on a strict control of cell growth, differentiation and death. Several proteins, which are involved on the regulation of the cell cycle, can suffer diverse alterations and produce an uncontrolled cell proliferation and the genesis of a neoplastic process. The assessment of cell proliferation is an useful method applied to Neuro-oncology in order to know the behavior of gliomas. DEVELOPMENT: This work is focussed on the analysis of different methods, all of them employed to study the cell proliferation: immunostaining of proliferating cell nuclear antigen (PCNA) and Ki-67, DNA content and ploidy by flow cytometry, in vitro incorporation of bromodeoxyuridine (BrdU) and the identification of apoptotic cells. The study of the DNA by flow cytometry establishes a relationship between ploidy and the prognostic of gliomas. The assessment of PCNA provides us with objective data about the proliferative activity of gliomas. Both Ki-67 expression and BrdU incorporation are also useful methods in the study of gliomas. CONCLUSIONS: In short, the most malignant gliomas are characterized by a high frequency of aneuploidies and high PCNA, Ki-67 and BrdU labelling indexes. All of these described methods can be used as prognostic markers complementary to the classic criteria employed nowadays.

Apoptosis↗

[Myelopoiesis--a kinetic approach].

The mechanisms of haemopoietic cellular proliferation are more clearly understood when the granylocytic, monocytic and macrophagic elements of the bone marrow are studied by means of in vitro cultures. Better physiological insight into stimulating and inhibitory factors is obtained in this way. These studies are of diagnostic, therapeutic and prognostic importance in the clinical handling of myeloid leukaemia dn neutropenia. It can be accepted today that the concept of myeloid leukaemia as a neoplastic process with an increased production of autonomous cell populations is to a large extent outdated, and these cells can be induced in vitro to differentiate into mature polymorphs. In the past it has been demonstrated that in vitro successes are followed by in vivo results, and in particular it is hoped that with the development of techniques for concentration of colony-stimulating factor, that this might be of therapeutic advantage in selected leukaemia patients in the future.

Antineoplastic Agents↗

[The long-term results in complicated colorectal cancer (survival for over 3 and 5 years)].

Colorectal cancer survival depends on: stage of primary neoplastic process development, clinical complication pattern and clinical course of the disease, type (radicalism) of the surgical intervention done and histological verification of blastoma. As shown by the results, postoperative lethality in complicated colorectal carcinoma cases amounts to 17.1 per cent, whereas in those undergoing radical surgery for uncomplicated carcinoma it amounts to 6.8 per cent. Patients presenting complicated colorectal carcinoma are admitted to the clinic with diagnosis advanced stage of development of the disease which explains the lower survival rate. The studies performed show that five-year survivorship in patients with complicated colorectal carcinoma amounts to 33.3 per cent, while among those operated for uncomplicated colorectal carcinoma it is 62.7 per cent in the average.

Actuarial Analysis↗

[The relationship between the clinical picture and course of acoustic nerve tumors and the direction of their growth in the cerebellopontine angle].

The data of clinical, surgical and post-mortem studies in 95 patients with neurinomas of the acoustic nerve permitted to eliminate 3 variants in the growth of neoplastical process into the ponto-cerebellar angle: 1) subtentorial (the upper variant) -- 27 cases; 2) the middle line of the brain stem (middle variant) -- 15 cases; 3) the lower parts of the angle (lower variant)--52 cases. Depending upon the direction of the growth into this space and upon the stage of the disease there were differences in the succession, frequency and expressiveness of focal and general brain symptoms. The development of the disease also differed.

Adult↗

[Breast tuberculosis--a case report].

The authors report a case of breast tuberculosis in a 58-year-old patient in which the diagnosis was made with difficulty, initially the case being interpreted as a neoplastic process. This diagnosis should be considered in such cases. In our area, in the present tuberculosis endemic, the cases of tuberculosis with extrapulmonary localisation are more and more frequent.

Antitubercular Agents↗

Telomerase, cervical cancer, and human papillomavirus.

Review of the available data indicates that telomerase is activated in the majority of cervical squamous cell carcinomas as it is in most malignant neoplasms. Telomerase activity can also be detected in some preneoplastic cervical lesions, but the significance of this in unclear, because nonneoplastic, proliferating epithelial cells also can have telomerase activity. The bias introduced by cytologic sampling methods can complicate the interpretation of results. Quantitative telomerase assays may be useful in distinguishing nonmalignant, physiologic activation of telomerase from malignant activation. Studies evaluating telomerase component (hTR or hTERT) expression by evaluation of RNA, mRNA, or antigen have yielded conflicting results, but the observation that many nonmalignant, nontelomerase active cells have detectable hTR and hTERT suggests that many cells express telomerase RNA and catalytic components, but do not have active telomerase. The implication is that a regulatory overlay must exist that controls telomerase activation. Activation of the enzyme in carcinogenesis could conceivably be a physiologic activation that normally accompanies cellular proliferation, a direct appropriation of telomerase activity by the neoplastic process, or both. The presence of inactive telomerase in many cells also raises the possibility of a noncatalytic function for the telomerase complex. An understanding of telomerase interaction with HPV infection in the pathogenesis of cervical neoplasia must await a further elaboration of telomerase regulation. Likewise, application of telomerase detection in cervical cancer screening programs must await a better integration of telomerase regulation in normal and specifically in HPV-infected squamous epithelial cells.

Female↗

[The diagnostic approach in hepatic lesions--the role and place of laparoscopy with laparoscopic echography].

The study is designed to cases the potentials of laparoscopy with laparoscopic echography, and the role they play in the diagnostic algorithm, with the purpose to develop an optimal therapeutic approach to hepatic lesions. Laparoscope R. Wolf and 7.5 MHz linear transducer, obtained from the Aloka Company are employed in work. A total of 303 patients presenting primary and metastatic carcinoma of liver (58 and 145, respectively), cholangiocarcinoma (11), hemangioma(28), adenomatous hyperplasia (38) and other lesions (23) are studied. Morphologic verification of the diagnosis is done in over one third of cases. In 30 to 40 per cent of the series reviewed laparoscopic echography supplements the laparoscopic finding depending on the type of lesion. Without pretending to create a diagnostic algorithm in individual hepatic lesions, abiding to the following diagnostic approach is strongly recommended: stage one--echography (a noninvasive, not irradiating, cheap, readily accessible and often resolving method), stage two--noninvasive, stage three--invasive, stage four--preoperative or final (laparoscopy plus laparoscopic echography). In the event of properly established indications, the invasive methods of study (thin-needle biopsy under ultrasonographic control plus laparoscopy) may be considered as a second stage, without any need to apply the complete spectrum of examination accessible. Not infrequently, laparoscopy with laparoscopic ultrasonography play a crucial role in diagnosing liver lesions, exact determination of the stage and resectability of the neoplastic process, planning and shortening the duration of operation with simultaneous identification of intractable patients.

Algorithms↗

Effect of heparin and liver heparan sulphate on interaction of HepG2-derived transcription factors and their cis-acting elements: altered potential of hepatocellular carcinoma heparan sulphate.

Proteoglycan assembly in malignant tumours is subject to profound changes. The significance of these alterations is not well understood; especially, their role in nuclear regulation is a topic for debate. The capacity of heparin and liver carcinoma heparan sulphate (HS) to alter DNA-transcription factor interactions has been studied to provide further evidence concerning the regulatory potential of glycosaminoglycan (GAG) in the nucleus. Experiments both in vitro and in vivo indicated that heparin and HS are capable of inhibiting the interaction of transcription factors with their consensus oligonucleotide elements. Among five transcription factors studied, AP-1, SP-1, ETS-1 and nuclear factor kappaB proved to be sensitive to heparin and heparan sulphate, whereas TFIID was hardly inhibited in either in vitro or in vivo systems. Interestingly, HS from peritumoral liver was five times more effective than heparin. Liver carcinoma HS was less effective than liver HS, but its activity was comparable with that of heparin. These results indicate that the structural differences of GAG chains strongly influence their biological behaviour. The loss of their recognized functional activity in malignant tumours might promote the development of uncontrolled growth and gene expression favouring the neoplastic process.

Carcinoma, Hepatocellular↗

Analysis of the DNA "mismatch-repair" enzyme human mut-S-homologon-2 in endometrial cancer on protein- and RNA-level.

BACKGROUND: Microsatellite instability seems to be important in the development of various human cancers including sporadic endometrial cancer and is characterized by length changes at repetitive loci scattered throughout the genome. It has been shown that cancer predisposition is attributable to defects in any one of four genes, all of which encode homologs of the microbial mismatch repair proteins mutS and mutL. The human Mut-S-Homologon-2 gene (hMSH-2) specifies a mutS homolog, whereas hMLH-1, hPMS-1 and hPMS-2 encode homologs of mutL. MATERIAL AND METHODS: Freshly excised endometrial specimens (malignancies of the uterine corpus: n=50; normal endometrial tissue: n=20) were examined by immunohistochemistry (mAb FE 11, Dianova, Germany) and RT-PCR to analyze the expression of human MUT-S-Homologon-2 on protein- and mRNA-level. Most of the neoplasms of the uterine corpus were sporadic endometrial. RESULTS: In the immunohistochemical study, 25% of normal endometrial tissues were human Mut-S-Homologon-2 negative, while the remaining 75% revealed weak human Mut-S-Homologon-2 immunoreactivity (mean human Mut-S-Homologon-2 IRS: 1.52; SD: +/-1.42; mean human Mut-S-Homologon-2-PP: 12.12; SD: +/-10.31; mean human Mut-S-Homologon-2 IS: 0.98; SD: +/-0.81). All malignancies of the uterine corpus revealed strong nuclear immunoreactivity for human Mut-S-Homologon-2 (mean human Mut-S-Homologon-2-IRS: 9.12, SD: +/-3.34; mean human Mut-S-Homologon-2-PP: 81.82, SD: +/-15.67; mean human Mut-S-Homologon-2-IS: 2.58, SD: +/-0.71). In addition, expression of human Mut-S-Homologon-2 protein was statistically significantly upregulated in tumor cells of malignancies of the uterine corpus as compared to normal endometrial tissue on the protein level. In the RT-PCR study, the hMSH-2 gene was highly expressed in endometrial neoplasms on the mRNA-level. hMSH-2 expression was consistently increased in endometrial neoplasms compared to normal endometrial tissue. CONCLUSION: The expression of the human MUT-S-Homologon-2 is increased both on the protein- and on mRNA-level in endometrial neoplasms compared to normal endometrial tissue possibly caused by the neoplastic process driven by an increase in the rate of mutations in oncogenes and tumor suppressor genes.

DNA Repair↗

[The interphase fluorescence in situ hybridization (I-FISH) technique in patients with chronic lymphatic leukemia (CLL)].

BACKGROUND: Trisomy 12 was found to be the most frequent chromosomal aberration identified by conventional cytogenetic studies of bone marrow cells and peripheral lymphocytes of patients with CLL. Molecular-cytogenetic techniques which enable examination of dividing and/or non-diving interphase nuclei (I-FISH), proved existence of other chromosomal abnormalities, mainly deletions, which could have in CLL patients relation to the origin, course and prognosis of the disease. METHODS AND RESULTS: During the last two years bone marrow chromosomes of all patients with CLL were examined by G-banding and by I-FISH. The numerical changes of chromosome 12 were followed by centromeric DNA probe in dividing and non-dividing cells. The small deletions were ascertained by locus specific probes for 13q14 (Rb gene), 17p13 (p53 protein) and 11q23 (MLL gene). These genes are responsible for cell division and their function is probably in connection with neoplastic process. It is of interest whether numerical and structural chromosomal rearrangements are primary or secondary changes and what is their impact on etiology of CLL. 93 patients were examined by DNA prove CEP12 and trisomy 12 was found in 24 of them (25.8%), the range of the clone was 2.5-75.5% of the screened cells. Deletion del(13)(q14) was examined by probe D13S319 in 73 patients and proved in 24 of them (32.8%), pathological clone ranged 2.5-80.0% of the cells. Deletion del(17)(p13) was found in 14 patients out of 61 examined by probe LSI p53 (22.9%). The extent of the clone was 2.5-34.0% of examined cells. Deletion 11q23 was not ascertained in any of 11 patients by means of probe LSI 11q23 (MLL). All probes used for FISH were manufactured by VYSIS. CONCLUSIONS: FISH is very sensitive method, suitable for molecular-cytogenetic examination of leukemic patients. With I-FISH the deletion of 13q14 was ascertained as the most frequent chromosomal aberration in series of 73 patients with CLL. We continue to increase the number of patients screened by I-FISH with all eligible DNA probes and start the prospective study on patients with chromosomal pathology. We will correlate the immunophenotype, morphology, clinical course and prognosis with karyotypic findings.

Adult↗

Loss of heterozygosity in gastric neuroendocrine tumor.

The MEN1 gene locus is known to be partly responsible for the tumorigenesis of sporadic gastric neuroendocrine tumors, but the genetic events that drive the neoplastic process of this tumor remain largely unknown. In order to screen the tumor suppressor genes associated with the tumorigenesis of gastric neuroendocrine tumors, 15 neuroendocrine carcinomas and three carcinoid tumors in the stomach were analyzed for loss of heterozygosity (LOH) using 22 microsatellite markers. In our study, the gastric neuroendocrine tumors showed a high rate of LOH in chromosomes 8p (82%), 15q (58%), 17p (57%), llp (50%), 12p (50%) and 13q (50%). The mean fractional allelic loss (FAL) was higher in the neuroendocrine carcinoma components than in the adenocarcinoma components (0.42 versus 0.33, respectively). In four cases, the adenocarcinoma components showed discordant LOH patterns from those of the neuroendocrine counterparts in half of the informative chromosomes analyzed. Comparably, the gastric neuroendocrine carcinomas exhibited a higher LOH frequency on 8p and a lower LOH on 7q than did the gastric adenocarcinomas. It is suggested that chromosome 8p is the possible location of the tumor suppressor genes associated with the tumorigenesis of gastric neuroendocrine tumors.

Aged↗