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R Rosenberg

Publications and source records attributed to R Rosenberg.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer.

The gene SASH1 (SAM- and SH3-domain containing 1) has originally been identified as a candidate tumour suppressor gene in breast cancer. SASH1 is a member of the SH3-domain containing expressed in lymphocytes (SLY1) gene family that encodes signal adapter proteins composed of several protein-protein interaction domains. The other members of this family are expressed mainly in haematopoietic cells, whereas SASH1 shows ubiquitous expression. We have used quantitative real-time PCR to investigate the expression of SASH1 in tissue samples from 113 patients with colon carcinoma, and compared the expression with 15 normal colon tissue samples. Moreover, nine benign adenomas and 10 liver metastases were analysed. Expression levels of SASH1 were strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in liver metastases. Moreover, SASH1 was also found to be downregulated on protein levels by immunoblot analysis. However, SASH1 expression was not significantly deregulated in precancerous adenomas and in earlier stage lesions (UICC I). Overall, 48 out of 113 primary colon tumours showed SASH1 expression that was at least 10-fold lower than the levels found in normal colon tissue. Downregulation of SASH1 expression was correlated with the formation of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival. This study demonstrates for the first time that expression of a member of the SLY1-gene family has prognostic significance in human cancer.

Adenoma↗
PubMed2006

Menopausal-type symptoms in young breast cancer survivors.

BACKGROUND: There has been little previous information available about menopausal-type symptoms in very young breast cancer survivors. METHODS: In collaboration with the Young Survival Coalition, we conducted an Internet-based survey of women with a history of breast cancer diagnosed at age 40 years or younger using items derived from the Breast Cancer Prevention Trial symptom checklist. RESULTS: A total of 371 respondents were eligible for analysis. Mean age at diagnosis was 32.8 years and mean age at follow-up 36.2 years; 89% of women received chemotherapy, 49% tamoxifen, 15% ovarian suppression, 4% aromatase inhibitors. At the time of survey, 37% were taking tamoxifen and 9% ovarian suppression. Excluding women on ovarian suppression, 77% of women were premenopausal at follow-up. Many women reported bothersome menopausal-type symptoms. In particular, 46% of women reported hot flashes and 39% reported dyspareunia. In a linear regression model of symptom scores, current ovarian suppression, postmenopausal status, baseline anxiety before the diagnosis, pregnancy after the diagnosis, prior chemotherapy, and lower perceived financial status were associated with more bothersome symptoms. CONCLUSION: A substantial number of young breast cancer survivors experience bothersome menopausal symptoms. While the women who responded to our survey may represent a select group of survivors, these findings may have important implications for treatment decision making and long-term quality of life of young women with breast cancer.

Adult↗
PubMed2006

Free peritoneal tumour cells are an independent prognostic factor in curatively resected stage IB gastric carcinoma.

BACKGROUND: Several studies have shown that the cytological detection of free peritoneal tumour cells (FPTCs) in patients with gastric cancer indicates the presence of metastatic disease. The immunocytochemical detection of FPTCs, especially in early-stage tumours, has not been examined comprehensively. METHOD: Peritoneal lavage was performed in 351 patients before curative resection of a gastric carcinoma between 1987 and 2001, and an adequate sample was obtained from 346 patients. FPTCs were detected immunocytochemically using Ber-EP4 antibody. Median follow-up time was 70 months. RESULTS: FPTCs were detected in the lavage fluid of 74 patients (21.4 per cent) and correlated with increasing pathological tumour depth (pT) and lymph node (pN) status (P < 0.001). The 5-year overall survival of patients with FPTCs was significantly worse than that of patients without FPTCs (35 versus 71.9 per cent; P < 0.001). FPTCs were present in 14 (8.5 per cent) of 164 patients with stage IA or IB tumours. Although the detection of FPTCs had no prognostic significance for stage IA tumours, the presence of FPTCs in those with stage IB tumours was associated with a worse prognosis (P < 0.001). Multivariate analysis identified the presence of FPTCs as an independent prognostic factor in the whole cohort and in the stage IB subgroup. CONCLUSION: Detection of FPTCs is associated with poor prognosis even in patients with early-stage gastric cancer and should be used for risk-group stratification.

Adult↗
PubMed2006

[Curative vs palliative strategies in locoregional recurrence of gastrointestinal malignancies].

Locoregional recurrence is a relevant problem in surgical oncology. Intraluminal local relapse only occurs when the primary resection is carried through with inappropriate safety margins. If possible, a second surgical resection with wider margins is the treatment of choice. When the primary resection was appropriately done, extraluminal relapse in the original tumor bed indicates the primary tumor was already in an advanced stage. The indication for a second resection must be considered carefully. A realistic prospect of long-term tumor control exists only when the second resection yields tumor-free margins and is combined with chemo- and radiotherapy. There is usually no curative treatment option for recurrences in the draining lymph node region, the so-called fourth dimension.

Combined Modality Therapy↗
PubMed2004

Thrombin generation in non-cardioembolic stroke subtypes: the Hemostatic System Activation Study.

BACKGROUND: The association between hemostatic activation, stroke mechanism, and outcome is poorly defined. The Hemostatic System Activation Study (HAS) investigators measured serial levels of prothrombin fragment F1.2, a marker of thrombin generation, in patients enrolled in the Warfarin Aspirin Recurrent Stroke Study (WARSS). METHODS: HAS enrolled 631 of the 2,206 patients in WARSS. Strokes were subtyped according to inferred mechanism. Plasma was collected for F1.2 at randomization (within 30 days of stroke), 3 months, 12 months, and 18 months. The 3 to 6 month samples in aspirin-treated patients were used for the primary analysis. RESULTS: The authors analyzed 3 to 6 month samples on 320 patients. Higher F1.2 levels were associated with older age, female sex, and hypertension. There was no difference between mean F1.2 levels in 56 cryptogenic (0.9 +/- 0.32 nmol/L) and 114 non-cryptogenic (1.13 +/- 0.74 nmol/L) patients or across specific stroke subtypes. There was an 8.8%/year (p = 0.006) increase in mean F1.2 levels. There was a trend toward higher risk of recurrent stroke or death as F1.2 levels increased in aspirin (RR: 1.30, 95% CI: 0.57 to 2.94, p = 0.53) and warfarin treated patients (RR: 1.68, 95% CI: 0.48 to 5.94, p = 0.42). F1.2 levels were reduced on average 70% in warfarin-treated patients in a dose-dependent fashion. CONCLUSION: F1.2 levels did not appear to differ by stroke subtype, suggesting that factors other than underlying stroke pathophysiology influence thrombin generation in the post-acute stroke period. F1.2 levels were suppressed by warfarin in a dose-dependent fashion. Additional research is needed to determine the predictive value of F1.2 after stroke.

Aged↗
PubMed2004

Combined chronic treatment with citalopram and lithium does not modify the regional neurochemistry of nitric oxide in rat brain.

A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentation strategy. Also inhibitors of nitric oxide synthase (NOS) have been used as an augmentation strategy, while inhibitors of NOS exhibit antidepressant-like properties in various animal models. Therefore, we hypothesized that modulation of NOS may be involved in the long-term effects of antidepressants and lithium, and studied the influence of acute and chronic administration of citalopram, alone or in combination with lithium, on NOS activity in hippocampus, cerebellum, and frontal cortex, by determination of L-citrulline being formed. We found that administration of acute or chronic citalopram (5 mg/kg and 20 mg/kg/24h, respectively) alone or in combination with subchronic lithium (60 mmol/kg chow pellet) did not influence the activity of NOS ex vivo in all regions compared to control. In contrast, high doses of lithium caused a significant decrease in NOS activity in vitro. We conclude that basal conditions are unsuitable for the study of antidepressant effects on NOS, and that the neurochemistry of nitric oxide remains unaltered following chronic citalopram or subchronic lithium under normal physiological conditions.

Animals↗
PubMed2003

Identification of occult tumor cells in node negative lymph nodes of colorectal cancer patients by cytokeratin 20 gene and protein expression.

BACKGROUND AND AIMS: Evaluation of cytokeratin 20 (CK20) specific quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) and immunohistochemistry (IHC) for detection of occult tumor cells in lymph nodes of 72 patients with colorectal carcinoma (UICC stage I and II). METHODS: Serial sections of formalin-fixed, paraffin-embedded lymph nodes (mean 14.3/case) were used for microdissection, RNA isolation and QRT-PCR and for CK20 IHC using routine protocols. Results of QRT-PCR and IHC were compared and correlated to the CK20 expression pattern of the primary tumors and clinical follow-up. RESULTS: IHC revealed CK20-positive tumor cells in lymph nodes of 14.5% (10/69) and 0% (0/3) cases with a CK20-positive and CK20-negative primary tumor, respectively. CK20 mRNA was detected in the lymph nodes of 36.8% (7/19) cases by QRT-PCR with all 7 cases also expressing CK20 mRNA in the primary tumor. CK20 mRNA (QRT-PCR) and protein (IHC) detection in serial sections did not agree in 25% (5/20) of cases. A trend was seen towards a worse disease course for patients with CK20-positive lymph nodes by IHC (incidence of recurrent disease) and QRT-PCR (disease-free survival, incidence of recurrent disease). CONCLUSION: CK20-specific IHC and QRT-PCR are supportive tools to conventional histology for detection of occult tumor cells in archival tissues, with the restriction that a laborious QRT-PCR procedure is necessary to achieve appropriate specificity. A prognostic value of CK20 IHC or QRT-PCR for stratification of UICC stage I and II patients into those likely to develop recurrent disease was not evident.

Biomarkers, Tumor↗
PubMed2003

Reliability of quantitative reverse-transcriptase-PCR-based detection of tumour cells in the blood between different laboratories using a standardised protocol.

Differences in methods of reverse-transcriptase (RT)-polymerase chain reaction (PCR)-based detection of tumour cells in the blood gives rise to conflicting results, and standardisation is urgently needed. This pilot study aimed to assess the variation of RT-PCR-based detection of tumour cells in blood between four different laboratories using a commercially available kit with a standardised protocol. This kit allows comparison of results from different laboratories and facilitates the investigation of the influence of pre-analytical parameters. All laboratories analysed identical sets of blood samples spiked with tumour cells in a concentration range of 1-100 tumour cells/ml. To study at which level variation was introduced, three kinds of sample sets were generated in which (i) tumour cell RNA was spiked in the RNA of mononuclear cells (MNC), (ii) tumour cells were spiked in isolated MNC, and (iii) tumour cells were spiked in blood. Real-time quantitative RT-PCR was used to detect and quantify cytokeratin 20 (CK20) expression, which is indicative for the presence of epithelial tumour cells. All laboratories were able to detect CK20 expression in all spiked-RNA samples with limited variation in expression levels between laboratories. There was a positive correlation between the amount of spiked tumour cell RNA and CK20 expression level. RT-PCR analysis of spiked-MNC samples resulted in more variation in the CK20 expression levels between laboratories, however again all spiked samples were reported to be positive by all of the laboratories. The evaluation of spiked-blood samples gave rise to considerable quantitative and qualitative variation between the laboratories. Our results underline the importance and need for standardisation and extended quality control studies in the field of pre-analytics.

HT29 Cells↗
PubMed2003

The Danish PET/depression project: cognitive function and regional cerebral blood flow.

OBJECTIVE: To clarify the relationship between cognitive functions and regional cerebral blood flow (rCBF) in a large group of depressed patients compared with healthy controls. METHOD: A set of principal components was extracted from scores of a battery of neuropsychological tests of 40 patients suffering from major depression and 49 healthy controls. The components were correlated by multiple linear regression analyses to selected regions of interest in the brain obtained from positron emission tomography images. RESULTS: In contrast to findings in the healthy controls, cognitive functions in the depressed patients correlated significantly with rCBF in specified regions of interest in only a few instances. CONCLUSION: Our study indicates that disturbed cognitive functions in depression do not relate to specific areas of the brain in the same way as normal cognitive functioning, suggesting that the abnormalities of brain function in major depression may be qualitative, rather than quantitative, in nature.

Adolescent↗
PubMed2002

Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood.

BACKGROUND: The detection of disseminated tumor cells in peripheral blood is limited by the presence of very few tumor cells within a large number of blood cells. Therefore, tumor cell detection calls for enrichment systems with effective depletion of blood cells and high tumor cell recovery. METHODS: We compared the new density gradient centrifugation method OncoQuick with the standard method of Ficoll. The enriched cell fractions were quantified. Tumor cell spiking experiments examined the recovery of tumor cells as detected by immunocytochemistry and cytokeratin-20 reverse transcriptase-polymerase chain reaction (RT-PCR). Clinical application of OncoQuick was evaluated in 37 peripheral blood samples of patients with gastrointestinal carcinomas. RESULTS: The depletion of mononuclear cells (MNCs) in the enriched cell fraction after OncoQuick centrifugation was 632-fold, with an average cell number of 9.5 x 10(4), compared with Ficoll, with a depletion factor of 3.8 and a mean number of 1.6 x 10(7) MNCs. The mean tumor cell recovery rates were 87% for OncoQuick and 84% for Ficoll. The increased depletion of MNCs with OncoQuick centrifugation further simplified immunocytochemical evaluation by reducing the number of cytospins and increasing the tumor cell density. Due to the reduced number of co-enriched MNCs by OncoQuick, the blood volume, which could be analyzed in one RT-PCR reaction, was increased up to 30 ml. Examination of peripheral blood samples from 37 patients with gastrointestinal tumors showed a cytokeratin-20 detection rate of 30% and a significant correlation with the presence of distant metastases (P < 0.02). CONCLUSIONS: OncoQuick significantly reduced the co-enriched number of MNCs, with a high tumor cell recovery rate. Processing blood from tumor patients with OncoQuick increased the chance of detecting circulating tumor cells.

Cell Count↗
PubMed2002

The Danish PET/depression project: clinical symptoms and cerebral blood flow. A regions-of-interest analysis.

OBJECTIVE: We wanted to explore associations between clinical symptoms of depression and the blood flow to specific regions of the brain. Furthermore, we wanted to compare the regions-of-interest (ROI) method with the functions-of-interest (FOI) approach. METHOD: The resting blood flow to 42 ROI in the brain was obtained with positron emission tomography (PET) imaging in 42 representative in-patients with major depression and 47 matched healthy controls. RESULTS: The patients had increased blood flow to hippocampus, cerebellum, anterior cingulate gyrus, and the basal ganglia. A strong negative correlation was found between the degree of psychomotor retardation of the patients and the blood flow to the dorsolateral and supraorbital prefrontal cortices. The total Hamilton score was correlated with the blood flow to the hippocampus. CONCLUSION: Our findings support the notion that depressed patients have disturbances in the loops connecting the frontal lobes, limbic system, basal ganglia, and cerebellum.

Adult↗
PubMed2002

Zn metabolism affects apoptosis rate and proliferative responsiveness of PBMC from patients on chronic hemodialysis.

Patients with end-stage renal failure suffer from severe plasma trace metal deficiency that is not corrected by dialysis. Trace metals, including Zn(2+), are critical for cell differentiation and replication. Zn(2+)also plays important role in cell apoptosis. Both processes are known to be impaired in uremia. The present study was undertaken to evaluate the effect of Zn(2+) supplementation on apoptosis of cultured peripheral blood mononuclear cells (PBMC) from patients on chronic hemodialysis versus those from healthy control subjects, concomitantly with assessment of mitogen-induced cell proliferation. The results showed that (1) basal total cell-associated Zn(2+) was elevated in uremic PBMC, compared to normal controls (23.9 +/- 5.64 v 10.5 +/- 2.64 micromol/L/mg protein). The gap persisted following incubation in Zn(2+)-enriched medium (63.3 +/- 26.12 v 81.6 +/- 13.4 micromol/L/mg protein, P <.005). (2) Basal proliferative response to phytohemagglutinin (PHA) was significantly decreased in uremic PBMC compared to normal controls (12,000 +/- 1,560 cpm v 16,600 +/- 1,460 cpm, P <.01). Incubation of uremic PBMC in Zn(2+)-enriched medium improved their proliferative response to PHA, yielding counts per minute significantly higher compared to their normal counterparts (37,000 +/- 7,500 cpm v 22,000 +/- 3,000 cpm, P <.001). (3) Basal apoptosis rate in uremic PBMC was significantly elevated compared to normal control cells (7.6% v 2.6%, P <.05). Following incubation in Zn(2+)-enriched medium, apoptosis was increased both in normal and uremic PBMC. Percent apoptosis of uremic PBMC remained significantly elevated compared to control cells (11.7% v 5.7%). We conclude that uremic PBMC are more responsive to exogenous Zn(2+) in culture than their normal counterparts. This, among other abnormalities, might reflect an abnormal regulation of Zn(2+) transport by uremic mononuclear cell membranes. The resultant increase in total cell-associated Zn(2+) content improves poor proliferative responsiveness of uremic PBMC. On the other hand, increased total cell-associated Zn(2+) stimulates enhanced apoptosis in uremic PBMC, which, probably by eliminating defective cells, contributes to the functional capability of the population as a whole. The net effect of the 2 processes is still augmentation of cell proliferation.

Apoptosis↗
PubMed2002

[Importance of occult metastatic cells in the treatment of patients with breast and gastrointestinal cancers].

Early and clinically non-apparent hematogenous dissemination of tumor cells is considered an important prognostic factor and marker of tumor progression. This phenomenon is reported for tumor entities differing as much as breast and gastrointestinal cancers. First prospective studies point to the unique opportunity of therapy monitoring utilizing follow-up bone marrow aspirations before and after adjuvant therapy. First results of these studies further indicate that currently used treatment strategies such as chemotherapy may not be efficient enough to eliminate all metastatic cells in all of the cases studied. Apart from improved tumor staging, such screening efforts may not only help to improve planning and monitoring of adjuvant therapy (which at present is only possible retrospectively) but also help to design individualized targeted biological treatment. This review summarizes the currently available data on the importance of disseminated tumor cells for the treatment of patients with breast or gastrointestinal cancer.

Bone Marrow↗
PubMed2002

[Minimal residual disease in gastrointestinal tumors: tumor detection in bone marrow, blood and lymph nodes].

The cure of a tumor patient with gastrointestinal cancer is dependent on the extension of the primary tumor (TNM-classification) and the option of curative resection (R0-resection) at the time of operation. The additional application of multimodal therapy approaches has lead to an improvement of prognosis in different advanced tumor stages. Nevertheless, despite curative tumor resection about 50% of patients with locally advanced gastrointestinal cancer develop recurrent tumor disease or distant metastases and die tumor-related. A possible explanation is the seed of disseminated tumor cells in blood, bone marrow or lymph nodes pre-, intra- or postoperatively, but also during diagnostic procedures. Several studies have shown in the last years that the presence of minimal residual disease (MRD) influences the course of disease and the patient's prognosis after curative tumor resection. Although several groups have reported the prognostic impact of disseminated tumor cells in the different compartments of bone marrow, lymph nodes and blood, the phenomenon of minimal residual disease is not acknowledged as an established prognostic factor and is not integrated into the classification of the UICC. Therefore, no therapeutic consequences were drawn at present from the detection of disseminated tumor cells in patients with gastrointestinal cancer. A possible explanation are missing multi-center-studies, which confirm the results of the several single-center-studies. Standardization of study designs and methodical procedures and the evidence of reproduction are mandatory in order to value and interpret the multitude of studies and the available data in this field. Only these results will allow to decide if the presence and detection of disseminated tumor cells can alter the tumor staging and individualize or possibly minimize further oncological therapy strategies.

Biomarkers, Tumor↗