Endocrine response and resistance in breast cancer: a role for the transcription factor Fos

The concentration of the tumor marker CA 19-9 is influenced by the patient's secretor status and Lewis genotype. The aim of this study was to establish novel reference intervals for CA 19-9 in serum based on secretor and Lewis genotypes, to investigate the biological variation of CA 19-9, and to evaluate the utility of Lewis and secretor genotyping on a group of individuals with serologically defined Lewis phenotypes. CA 19-9 was measured in serum of 500 healthy individuals. Secretor and Lewis genotypes were determined by sequencing and PCR-cleavage methods. Significant differences were found between subgroups with different Lewis and secretor genotypes. Genotype-based reference intervals for CA 19-9 are presented. The upper reference limit for all individuals was 28.7 kilounits/L; for secretors and nonsecretors, the upper reference limits were 12.4 and 61.2 kilounits/L, respectively. The analytical imprecision (CVA) was 9.8%, the within-subject variability (CVI) was 15.8%, and the between-subject variability (CVG) was 102.2%. Good agreement was found between Lewis and secretor genotyping and conventional blood grouping. Genotype-based reference intervals may be a way to increase the clinical utility of CA 19-9. On the basis of the calculation of a critical difference for sequential values (significant at P 相似文献   

Methodological issues in the use of biological markers in cancer epidemiology: cohort studies

In this chapter we summarize the major strengths and weaknesses of cohort studies; consider how these characteristics influence the use of biomarkers in cohort studies; briefly review considerations of statistical power, design and the influence of measurement error in cohort studies; and discuss some of the emerging ethical considerations that relate to the use of biomarkers in prospective studies.     

Nodal tumour growth in breast cancer: the time-span of its biological progression

Malignant hyperthermia (MH) is a rare autosomally dominantly hereditary and potentially life-threatening disease. The prevalence of the genetic MH predisposition is estimated as 1:10,000 to 1:20,000. In Germany no data on the regional distribution are available. Therefore, the purpose of this investigation is to summarise and present the epidemiological data of all German MH laboratories. Nine German hospitals offer the specific in vitro contracture test to diagnose the MH predisposition. All German MH laboratories carry out the examination in accordance with the standardised protocol of the European Malignant Hyperthermia Group. The laboratories were asked to provide the number of all patients investigated, excluding those suffering from other neuromuscular diseases, separated according to diagnostic groups and their places of residence, the number of the identified MH-families as well as the number of the clinically suspected and investigated MH cases with their places of residence. Eight MH laboratories provided the requested data. Until September 1997 a total of 2620 patients were investigated. In 865 patients (34%) MH suspicion was confirmed (diagnosis: MHS). 1494 patients (56%) were released by investigation from MH-suspicion (diagnosis: MHN). In 261 patients (10%) the MH-predisposition remained unsolved (diagnosis: MHE). 580 MH families were identified. Among 2620 patients 757 were clinically suspected MH cases. 35% of these suspected MH cases were classified as MHS, 10% as MHE and 55% as MHN. The documentation of the patients places of residence classified as MHS and MHE into a map of Germany demonstrates an exhaustive distribution with an increased regional prevalence in the areas of the MH laboratories. This concentration in the area of the MH laboratories becomes even more evident, when the places of residence of the MH suspected cases are demonstrated. In conclusion, the distribution of the MH predisposition is uniform and exhaustive in Germany. The presented regional concentration of clinically suspected MH cases among the MH laboratories is mainly interpreted as an expression of effective regional education and information. Considering the overall incidence of the MH predisposition as described above only 15-20% of the MH patients have so far been identified. The MH laboratories have already released about 10,000 patients from the suspicion of MH predisposition. A preliminary prevalence of at least 1:60,000 to 1:80,000 in Germany can be estimated according to the presented data.     

乳腺癌抗血管生成治疗:现状与前景

Tumor angiogenesis plays an important role in the growth, invasion and metastasis of breast cancer, therefore recently a very active area of breast cancer research involves the addition of antiangiogenic therapy. Numerous clinical studies for several antiangiogenic agents have recently been conducted in breast cancer patients and have shown clinically significant improvement in outcomes. This review gives a brief background to breast cancer angiogenesis, also focusing on current progress in the field of antiangiogenic therapy for breast cancer and issues regarding future therapeutic development.     

IGF system components as prognostic markers in breast cancer

Device closure of oval fossa atrial septal defects with the Amplatzer Septal Occluder was performed in 26 patients ranging in age from 0.89 to 60.44 years. In eight additional patients no device implant was performed because of the presence of multiple defects or because the defect was of a size unsuitable for closure with the devices currently available. The stretched diameter of the defects that were closed ranged from 4 to 23 mm (mean 14+/-5.4 mm) and device sizes ranged from 4 to 24 mm. Two devices were unstable, of which one embolized to the right atrium after release. Both devices were retrieved at the same procedure. One of these patients subsequently underwent a successful device closure of his defect using a larger (24-mm) device. Three patients had multiple defects, which were successfully closed with a single device. At 1-month follow-up 23/26 (88%) and at 3-month follow-up 22/24 (92%) patients had complete closure of their defects, while two had residual shunts. One further patient who had complete closure of his defect at 1-month post-implant had his device removed and his atrial septal defect patched surgically 8 weeks after device closure. This was done as a result of the development of a vegetation affecting the device after an episode of septicaemia, which was not related to the cardiac problems. There was no procedure-related morbidity or mortality and all patients remain well at the present time.     

Proliferative disorders of the breast as risk factors for breast cancer in a self-selected screened population: pathologic markers

A study was done to quantify the pathologic risk of subsequent breast cancer in women whose biopsies demonstrated proliferative histologic conditions. Out of a total of 10,530 patients, 1,408 had biopsies which were classified as either bland fibrocystic or hyperplastic. The behavior of the disease in these patients was compared to that of the general screened population. It was concluded that women whose biopsies reveal hyperplastic disorder, primarily atypical hyperplasia and fibroadenoma, run the greatest risk of getting cancer. For women with atypical hyperplasia, the risk is 13 times that of the general population, and for those with fibroadenoma it is three times greater.     

Polyamines as markers of response and disease activity in cancer chemotherapy

One hundred twenty-four patients with hematological and solid neoplasms had pretreatment urinary polyamine determinations. Putrescine, spermidine, and spermine were all significantly increased as compared to normals (p less than 0.001). Polyamine levels were directly related to disease activity and tumor burden. In patients with multiple myeloma, putrescine levels were significantly correlated with clinical disease activity as well as the in vitro labeling index of marrow plasma cells. Spermidine values reflected tumor cell burden. Serial studies in 56 patients indicated that greater than twofold rise in urinary spermidine during treatment was highly correlated with cell kill and subsequent clinical response (p less than 0.001). Serum polyamine levels in 17 patients were found to be comparable to urinary values. Our data indicate that polyamine determinations can potentially be clinically useful, i.e., baseline values as indicators of tumor cell mass and growth fraction, and increases in spermidine during treatment as an excellent marker of tumor cell kill.     

Lymph node metastasis in breast cancer: common prognostic markers lack predictive value

Isoflavones are present in soybeans and its products in concentrations up to 300 mg/100 g, have estrogenic and antiestrogenic properties, and may be protective against hormone-related cancers. The purpose of this cross-sectional study was to investigate the association between urinary isoflavone excretion and self-reported soy intake. A total of 102 women of Caucasian, Native Hawaiian, Chinese, Japanese, and Filipino ancestry completed a dietary questionnaire for soy products consumed during the last year and during the 24-h period before urine collection. Overnight urine samples were analyzed for coumestrol and the soy isoflavones genistein, daidzein, and glycitein and their main human metabolites by reverse-phase high-pressure liquid chromatography. Soy protein and isoflavone intake (predominantly from tofu) were estimated using published nutritional databases. Wilcoxon's rank-sum test scores and Spearman rank correlation coefficients were computed. Japanese women excreted more daidzein, genistein, and glycitein than did Caucasian women, whereas Caucasian women excreted slightly more coumestrol. Soy intake differed significantly among ethnic groups. Dietary soy protein and isoflavone intakes during the previous 24 h were positively related to urinary isoflavone excretion [rs = 0.61 (P < 0.0001) and 0.62 (P < 0.0001), respectively]. Urinary excretion of isoflavones was also related to annual dietary soy protein and isoflavone intake [rs = 0.32 (P < 0.0012) and 0.31 (P < 0.0016), respectively]. The strong correlation between urinary isoflavone excretion and self-reported soy intake validates the dietary history questionnaire that is now used in a study exploring dietary risk factors for breast cancer.     

Predictive value of biological markers in etiopathogenesis of juvenile diabetes--reviewing the role of insulin antibodies

The lack of complete concordance for diseases in monozygotic twins prevents application of genetic markers for a thorough identification of the subjects who will develop the type I diabetes. Furthermore, the impact of the environmental factors precipitating beta cells destruction in genetically sensitive subjects has not been completely enlightened yet. The identification of high risk markers for the development of diabetes is aimed at detection of the early immune response activation markers. Islet cell antibodies are the most valuable markers, whose presence can be discovered even up to 7-8 years prior to the onset of symptoms. They are found in 50-80% of the newly discovered insulin-dependent diabetics. Their prevalence in the general population is 0.5-2%. These are commonly concomitant with insulin antibodies, found in 20-40% of the newly discovered diabetics, as reported in the literature. In our circumstances it was possible to determine the insulin antibodies only. We have concluded that they appear in 13.6% of children with a newly discovered diabetes, presenting a significant marker for predicting the course of the disease.     

Radical abdominopelvic lymphadenectomy: historic perspective and current role in the surgical management of rectal cancer

Radical abdominopelvic lymphadenectomy for rectal cancer is based on the tenet that removal of all potentially involved lymphatic tissue will yield a lower rate of locoregional failure and improve survival. At centers with extensive experience with the procedure, the operating time is only modestly prolonged compared with conventional resection. Blood loss and postoperative hospitalization are not significantly increased. Urinary dysfunction and impotence associated with radical abdominopelvic lymphadenectomy (as high as 80 percent and 76 percent, respectively, in recent series) have been major deterrents to its more routine application. Preservation of the hypogastric plexus and even selective preservation of a unilateral S4 nerve root have been shown to reduce the occurrence of genitourinary complications. Improved five-year survival of 68 percent and local recurrence rates of 5 to 20 percent for TNM Stage III cancers have been achieved with radical abdominopelvic lymphadenectomy. These results compare favorably with recent trials of adjuvant chemoradiation after conventional resection in stage-matched patients. The rationale, evolution, and application of radical abdominopelvic lymphadenectomy to the surgical management of rectal cancer are critically examined. The potential benefits of radical abdominopelvic lymphadenectomy, which have been demonstrated in nonrandomized trials, should be evaluated in a prospective and properly randomized study to clearly establish or refute its efficacy.     

Use of serum tumor markers for the diagnosis and follow-up of breast cancer

Human immunodeficiency virus (HIV) seroprevalence rates among rural trauma patients range between 0.15 and 1.32 per cent. A random sample of trauma patients treated at our rural trauma center between September 1994 and November 1995 was enrolled into a blind HIV serosurvey. Five hundred sixty-six of 1315 trauma patients (43%) were tested. Two of the 566 patients (0.35%) were HIV positive. A review of aggregate data for HIV infection among rural trauma patients in the United States show that 28 of the 4639 patients (0.60%) are HIV positive. We conclude that there was a low HIV incidence among our trauma patients from September 1994 to November 1995, and the cost-effectiveness of HIV testing for rural trauma patients is questionable with incidences between 0.5 and 1.0 per cent.     

The current role of radiotherapy in the treatment of invasive bladder cancer

Invasive bladder cancer remains a therapeutic challenge. Approximately 50% of patients treated with radical cystectomy die of metastatic disease. External beam radiation therapy when given alone has results inferior to that of surgery, and although it has shown some benefit when given in the preoperative setting, this was not verified by randomized trials. Altered fractionation radiation schemes and combined modality using a cisplatin-based combination chemotherapy with radiation have resulted in up to 60% bladder preservation.     

The role of ataxia-telangiectasia heterozygotes in familial breast cancer

The role of ataxia-telangiectasia (AT) heterozygotes in breast cancer has been controversial. We have found previously an overrepresentation (3.4%) of ATM mutations in a subset of 88 selected breast cancer patients with a family history of breast cancer, leukemia, and lymphoma. This prevalence is comparable to the estimated value (3.8%) from epidemiological study. To further examine the possibility that ATM is correlated to breast cancer, we screened for ATM germ-line mutations in another 100 breast cancer patients with a family history of breast cancer. We used the protein truncating test and found one new germ-line mutation. This figure (1%) is consistent with the observed 0.2-1% carrier frequency for AT. We also studied breast tumors from ATM mutants, and three showed retention of both alleles, whereas the fourth showed loss of the mutant allele. We conclude that the contribution of heterozygous ATM mutations to familial breast cancer is minimal. Even if the ATM gene were causative in these cases, it is not likely to act as a tumor suppressor.     

The emerging role of paclitaxel in breast cancer therapy

Bradykinin and thrombin caused a time- and dose-dependent stimulation of prostanoid biosynthesis in human dental-pulp fibroblasts, as assessed by the release of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (the stable breakdown product of prostacyclin). The stimulatory effect of bradykinin and thrombin on PGE2 biosynthesis was maximal within 5-10 min. The concentration of bradykinin producing half-maximal stimulation (EC50) of PGE2 and prostacyclin formation was 10 nM. EC50 for thrombin-induced formation of PGE2 and prostacyclin were 0.05 and 0.2 U/ml, respectively. Bradykinin analogues with affinity to the bradykinin B2 receptor, but not those with affinity to the B1 receptor, caused a burst of PGE2 formation. The stimulatory action of bradykinin and thrombin on PGE2 biosynthesis was abolished by two structurally different cyclo-oxygenase inhibitors and significantly reduced by two corticosteroids. Thrombin dose-dependently enhanced the incorporation of [3H]-thymidine into DNA in pulpal fibroblasts by a mechanism that was unrelated to the effect on prostanoid biosynthesis. Bradykinin did not affect thymidine incorporation. Thrombin, but not bradykinin, stimulated the biosynthesis of type 1 collagen in the pulpal fibroblasts. The stimulatory effect of thrombin on collagen biosynthesis was not affected by cyclo-oxygenase inhibitors. These data show that human dental-pulp fibroblasts are equipped with receptors for bradykinin and thrombin linked to enhanced prostanoid biosynthesis. Occupancy of the thrombin receptors also leads to a prostaglandin-independent stimulation of cell proliferation and collagen biosynthesis.     

Identification of metabolic bone disease in patients with endogenous hyperthyroidism: role of biological markers of bone turnover

Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 +/- 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2-L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease.     

The role of cell communication in the pathogenesis of breast cancer]

OBJECTIVE: The aim of the study is to analyse long-term results of patients with small cell lung cancer (SCLC) treated at the same institution according to a prospective study including surgery, chemotherapy, and radiotherapy. METHODS: From 1981 to 1995, 104 patients with a proven histology of SCLC underwent surgery, chemotherapy, and radiotherapy. Fifty-one patients with operable stage I or II lesion received surgical resection followed by adjuvant chemotherapy and radiotherapy. Fifty-three patients with proved SCLC and clinical stage III received induction chemotherapy followed by surgery and radiotherapy. All patients received from four to six courses of chemotherapy and 36 had prophylactic cranial irradiation (PCI). All patients had follow-up for at least 1 year, and survival time was calculated from the date of the diagnosis until death or most recent follow-up. RESULTS: Ninety-six patients were male and eight female. We performed 29 pneumonectomies, eight bilobectomies, 66 lobectomies and one no resection. Regarding the clinical stage, 35 patients (33.6%) had stage I, 16 patients (15.4%) had stage II and 53 (51%) had stage III. Post-operative pathologic staging revealed stage I in 37 patients (35.6%), stage II in nine patients (8.6%), stage III in 45 patients (43.3%), and in 13 patients (12.5%) there was no more tumor. The 30-day mortality was 2% (two patients). Fourteen patients (13.4%) had post-operative complications. Fifty-one patients (49%) had a relapse. The median follow-up was 55 months. Twenty-six patients remain alive and 78 patients have died. The overall 5-year survival rate was 32%, with an estimate median survival time of 28 months; according to the pathologic stage, the survival data were 52.2%, 30% and 15.3% for stage I, II and III, respectively (P < 0.001). The 5-year survival was 41% in patients without SCLC after chemotherapy. CONCLUSION: As with non-small cell lung cancer, survival following surgery and chemotherapy clearly correlates with the stage. At present, it is not clear whether surgery is truly effective for patients with SCLC. In our experience, the complete elimination of small cell lung cancer is associated with an improvement in survival (41% at 5 years).