Cancer detection and prevention最新文献

P-glycoprotein (P-gp) acts as an active efflux mechanism for a large number of cytostatics and seems to be involved in the frequent failure of cancer chemotherapy. The molecular events of substrate recognition and transport still are not understood completely. We show here that the percentage of P-gp epitopes available for labeling with UIC2 monoclonal antibody is increased significantly after methanol permeabilization/fixation of cells. At the same time, binding of the MRK16 and 4E3 anti-P-gp antibodies is changed only moderately. Confocal microscopical images of UIC2-PE-labeled cells show that the epitopes becoming available after fixation are situated mainly in the plasma membrane. Thus, only a minority of P-gp molecules are accessible for UIC2 in the cell membrane of live cells, and methanol treatment can expose a large pool of previously plasma membrane-embedded, cryptic UIC2 epitopes. The UIC2-reactive P-gp molecules do not appear to be sequestered spatially, as suggested by the high fluorescence resonance energy transfer efficiency measured between the fluorescently labeled competing UIC2 and MRK16 antibodies, suggestive of P-gp dimerization and oligomerization on live cells.

The aim of this study was to evaluate the relationship between renal function and the blood level of some tumor markers that are low molecular weight proteins, that is, tumor-associated trypsin inhibitor (TATI), squamous cells carcinoma antigen (SCC), cytokeratin 19 fragments (CYFRA 21-1), tissue polypeptide antigen (TPA), and M3-specific epitope of tissue polypeptide antigen (TPS). In 41 adult patients without evidence of neoplastic disease, glomerular filtration rate (GFR) and the blood levels of creatinine and of the tumor markers were determined. The decrease in GFR was accompanied by an increase in serum levels of TATI, SCC, CYFRA 21-1, and TPA. The serum level of tumor markers increased particularly when GFR fell below 40 ml/min. On the basis of these results, the renal function must be taken into account for the clinical evaluation of the studied tumor markers.

The issue of minimal residual disease (MRD) manifesting itself by the presence of undetected disseminated isolated tumor cells in both tissues and hematopoietic autografts from patients with early-stage malignancies or from patients in clinical complete remission has been discussed widely during the last decade. Based on the current understanding of the pathogenesis of malignancy, disseminated tumor cells persisting after conventional oncologic treatment modalities or after reinfusion of contaminated autologous hematopoietic cells constitute the source of subsequent recurrence of disease. Accordingly, much emphasis is placed on the detection and characterization of disseminated isolated tumor cells in both basic and clinical research. This effort is aimed at a better understanding of the processes of metastasis and tumor dormancy and, ultimately, the estimation of prognosis, molecular monitoring, and the design of new therapeutic agents in oncology. In our review, we used computerized (MEDLINE, Embase) and manual searches to summarize laboratory and clinical data concerning MRD focusing on the issue of MRD in solid malignancies. We give a detailed overview of the methods used for the detection and molecular characterization of disseminated tumor cells and of the prevalence and prognostic significance of the detection of MRD in patients and hematopoietic autografts. Finally, we discuss the emerging therapeutic consequences of the detection of disseminated tumor cells, with special emphasis on the therapeutic potential of antibodies. We conclude that the detection of MRD represents a hallmark for the diagnosis, monitoring, and treatment of malignant conditions in future clinical trials.

This study was undertaken to assess the role of fine-needle aspiration biopsy in the evaluation of palpable peripheral lymphadenopathy in pediatric and adolescent patients. A 15-year experience in aspiration of patients younger than age 21 was reviewed. These cases were taken from four large university hospitals and clinics. Data included clinical information, anatomic site, cytologic diagnosis, and any follow-up surgical excision at these institutions. From a total of 1,302 lymph node fine-needle aspirates, a subset of 106 aspirates from patients 21 years or younger was selected. This group formed the basis for this study, and these aspirates were obtained from 103 patients. Most of these aspirates (88.7%) were from the head and neck; 11 were from sites other than head and neck; and the site was not stated in one case. One hundred and one of the aspirates produced adequate samples, and only five (4.72%) were unsatisfactory. Of the 106 fine-needle aspirates, 88 (83.0%) were diagnosed as negative for malignancy, five (4.7%) were inconclusive, and three (2.8%) were interpreted as suspicious but not diagnostic of malignancy. Five cases (4.7%) were diagnosed as positive for malignancy, including two cases of metastatic papillary carcinoma of the thyroid, two cases of Hodgkin's disease, and a single case of high-grade non-Hodgkin's lymphoma. No false-positive or false-negative diagnoses occurred, excluding the aspirates classified as inconclusive or suspicious but not diagnostic of malignancy (six cases). Results of aspirates from near adolescent and adolescent patients (ages 11-21 years) were compared with those of younger pediatric patients (age < 10 years). Eighty-one (76%) of the 106 aspirates were obtained from the older group. The percentage of unsatisfactory specimens was smaller and the percentage of inconclusive or suspicious or malignant diagnoses was greater in the older group. Fine-needle aspiration biopsy is reliable in the evaluation of palpable peripheral lymphadenopathy. As most fine-needle aspirates in children and adolescents proved to indicate benign reactive conditions that failed to respond to antibiotics rather than proving to be malignant tumors, we advocate a larger role for the fine-needle aspiration biopsy technique in the evaluation of peripheral lymphadenopathy in this age group. Its early use can direct further testing, saving time, expense, and morbidity for the patient and reducing anxiety for the parents.

The purpose of this study was to use population-based sources to estimate the frequency and characteristics of first inpatient hospital admission through an emergency department (ED) among 11,023 patients with diagnosed colorectal cancer between 1992 and 1996. Patients were identified from the population-based Connecticut Tumor Registry. Linkage with a statewide hospital discharge database (inpatient only) disclosed that 20% had a first hospital inpatient admission through an ED. Inpatient admission through an ED was statistically significantly associated with older age and race and was a statistically significant risk factor for distant stage at diagnosis. Studies are needed of the roles of patient delay and lack of screening in influencing ED presentation, especially in the elderly.

The aim of this study was to measure the total sialic acid (TSA) content in endometrial cancer tissue and to assess its relationship to clinicopathologic features of the malignancy. Tissue TSA content was measured in 42 women with endometrial cancer, 14 women with endometrial hyperplasia, and 45 women with normal endometrium in the proliferative phase (n = 16) and secretory phase (n = 29) of the menstrual cycle using the Warren procedure. The mean TSA content in endometrial cancer (2.16 micromol/gm) was significantly higher in comparison to normal endometrium in both proliferative (1.23 micromol/gm) and secretory (1.51 micromol/gm) phases. TSA content in the hyperplastic endometrium (1.56 micromol/gm) was higher as compared to the normal endometrium, but the differences were not statistically significant. An increased TSA content in the neoplastic endometrium in relation to the normal endometrium supports the view that the development of endometrial cancer is associated with the increasing content of sialic acid in the tumor tissue.

Unlabelled: Esophageal carcinoma frequently occurs in patients with long-standing achalasia.

Aim: To examine the role of p53 alterations and PCNA in patients with megaesophagus.

Methods: Sections of four tumors, and corresponding adjacent areas, from patients with achalasia due to Chagas' disease were examined by immunohistochemistry for p53 and PCNA proteins. Furthermore, 128 biopsies from 16 advanced achalasic patients were prospectively collected and evaluated for grades of inflammation, hyperplasia, dysplasia and also for p53 and PCNA proteins. All specimens showing p53 immunoreactivity were topographically genotyped using microdissection, PCR amplification and direct sequencing of p53 exons 5-8.

Results: Diffuse strong immunoreactivity of p53 was observed in 2/4 tumors. In one patient, the adjacent mucosa also showed strong p53. In the adjacent mucosa, the same areas showing p53 overexpression also had PCNA positive cells. In the prospective group, 7/16 (43.7%) patients or 53/128 (41.4%) biopsies expressed p53. The grade of inflammation was significantly correlated with the presence of positive p53, in patients, p = 0.004 and in biopsies, p < 0.00001. PCNA expression was found in the basal layer of the mucosa, and increased PCNA was associated with p53 overexpression, p = 0.00018. Genotyping detected mutation in exon 6, codon 213 RG, in one patient (1/16, 6.2%).

Conclusions: (1.) p53 alterations, overexpression and mutational change, are an early event in patients with achalasia; (2.) The inflammation frequently seen in these patients appears to be associated with alterations of the p53 protein; (3.) Expression of the tumor suppressor gene is increased in areas showing proliferation.

The relationship between expression of p53 protein in bladder cancer and tumor progression is known. In this paper, we attempt to study this phenomenon by molecular-genetic techniques. One hundred thirty-seven bladder tumor tissues were obtained from transurethral resection (TURB). Urine sediments were collected from 72 patients suffering from transitional cell carcinoma and tumor recurrence. These patients were followed up for at least three months. Separate polymerase chain reactions (PCR) were carried out for exons 5, 6, 7, and 8 of the Tp53 gene. Temperature gradient gel electrophoresis (TGGE) was used to screen mutations in the PCR products. Sequencing from reamplified mutant and wildtype bands was excised from the TGGE. Tp53 mutation frequency is 43.1% in 137 bladder cancer specimens, but already 32.7% of Ta-tumors (16/49) were Tp53 mutated. Four of 25 patients with Tp53 wild-type tumors suffered from progression. In the group of patients with Tp53 mutated cancer, seven of 12 had a tumor progression. In 11 of 14 patients with Tp53 mutation in cancer tissue, the same mutation was also found in urine sediments. In such patients, successful tumor treatment by TURB results in loss of their Tp53 mutation in urine sediment, and tumor recurrency resulted in reappearance.

Nuclear grade (NG) was studied in cytologic material obtained from 120 fine-needle aspiration biopsies of breast lesions and compared with the NG observed in the nuclear grade of surgical biopsies of the same lesions. All lesions included were invasive breast carcinomas diagnosed cytologically and confirmed histologically. Cytologic aspirates and tissue sections were graded by cytologists and pathologists, respectively, using a multiheaded microscope. Fisher's modification of Black's NG scheme was used. An agreement was observed between the NG of cytologic material and that of surgical biopsies in 93.33% of tumors, and an interesting exercise would be to correlate the NG with other significant factors for the prognosis of breast carcinomas. The purpose of this study was to assign and correlate the NG of ductal carcinomas of the breast in fine-needle aspiration biopsies and tissue specimens from the same patients.

We evaluated the usefulness of carcinoembryonic antigen (CEA) concentrations in colonic effluent as a high-risk marker for colorectal carcinoma (CRC). After 213 patients ingested 1,800 ml of a 5% isotonic solution of magnesium citrate, colonic effluent was collected from them before routine colonoscopy from February through June 1992. Of these patients, 27 who had undergone colonoscopy after a mean of 2.6 years were selected as subjects. The relationship between the CEA concentration in the colonic effluent and the occurrence of new colorectal tumors was examined. The CEA concentration in colonic effluent was adjusted on the basis of alkaline phosphatase activity. New colorectal tumors were noted significantly more frequently (P = .006) in patients with a high CEA level in colonic effluent (5 of 5; 100%) than in those with low a CEA level (6 of 22; 27%). The CEA concentration in colonic effluent is a simple and practical biomarker for identification of patients at high risk for CRC.