Search PubMed⌕ Search

Biomedical subjects

J Lundin

Publications and source records attributed to J Lundin.

At least 19 recordsLinked to original sources
PubMed2006

Using high-power lasers for detection of elastic photon-photon scattering.

The properties of four-wave interaction via the nonlinear quantum vacuum is investigated. The effect of the quantum vacuum is to generate photons with new frequencies and wave vectors, due to elastic photon-photon scattering. An expression for the number of generated photons is derived, and using state-of-the-art laser data it is found that the number of photons can reach detectable levels. In particular, the prospect of using the high-repetition Astra Gemini system at the Rutherford Appleton Laboratory is discussed. The problem of noise sources is reviewed, and it is found that the noise level can be reduced well below the signal level. Thus, detection of elastic photon-photon scattering may for the first time be achieved.

Journal Article↗
PubMed2005

Epithelial syndecan-1 expression is associated with stage and grade in colorectal cancer.

OBJECTIVES: Loss of epithelial heparan sulfate proteoglycan syndecan-1 has been associated with a more aggressive behavior in various cancer forms, but the prognostic significance of syndecan-1 expression in colorectal cancer is unclear. The aim of this study was to evaluate the prognostic value of immunohistochemical syndecan-1 expression in a series of 237 patients with colorectal cancer. METHODS: Paraffin-embedded formalin-fixed specimens were stained with a syndecan-1-specific monoclonal antibody, and both the epithelial and stromal expression were analyzed. RESULTS: Epithelial expression of syndecan-1 was seen in 222 tumors (94%), and it was associated with low stage of disease (p = 0.002) and low histological differentiation grade (p = 0.048). The cumulative 5-year survival of patients with weak and strong syndecan-1 expression was 49 and 54 %, respectively (p = 0.234). Syndecan-1 stromal immunoreactivity was observed in 138 tumors (58%), but lacked prognostic significance. Staining pattern and distribution can be viewed from digitized representative microscope slides (virtual slides) at http://www.webmicroscope.net/supplements/syndecan. CONCLUSIONS: The results are in line with previous reports in that low epithelial syndecan-1 expression was associated with a higher histological grade and a more advanced clinical stage of the patients. This study shows that syndecan-1 is expressed also in stromal tissue of colorectal cancer, but it does not support the proposed role of stromal syndecan-1 expression as a marker of poor clinical outcome.

Adult↗
PubMed2005

High tissue expression of tumour-associated trypsin inhibitor (TATI) associates with a more favourable prognosis in gastric cancer.

AIMS: The tumour-associated trypsin inhibitor (TATI) is a 6-kDa protease inhibitor with potential inhibitory effects on tissue degradation. In serum, increased levels have been associated with adverse prognosis in different forms of cancer. We assessed the tumour tissue expression and prognostic value of TATI in a surgically treated, single-institution series of patients with gastric cancer. METHODS AND RESULTS: Using a monoclonal anti-TATI antibody, immunohistochemistry was performed on formalin-fixed paraffin-embedded tumour specimens from 336 patients. TATI expression was observed in 265 (79%) of the tumours. There was a significant association between high TATI expression and low stage (P = 0.007), superficial tumours (P = 0.005), and absence of nodal (P = 0.015) and of distant metastases (P = 0.022). In univariate analysis, patients with high TATI expression had a significantly more favourable 5-year cumulative survival compared with patients with negative to moderate immunostaining (43% and 28%, respectively, P = 0.006). On multivariate survival analysis stratified for estimated cure of surgery, stage (P < 0.0001) and age (P = 0.022) at the time of surgery were independent prognostic factors. CONCLUSIONS: High TATI expression in tumour tissue was detected more frequently in patients with early-stage gastric cancer and seems to correlate with a favourable outcome.

Adenocarcinoma↗
PubMed2004

Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia.

Little information is available on long-term immune reconstitution after therapy with alemtuzumab in B-CLL patients. We present long-term follow-up data for blood lymphocyte subsets analysed by flow cytometry in previously untreated B-CLL patients who received alemtuzumab subcutaneously as first-line therapy. All lymphoid subsets were significantly (P<0.001) and profoundly reduced; the median end-of-treatment counts for CD4(+), CD8(+), CD3(-)56(+) (natural killer (NK)), CD3(+)56(+) (NK-T) and CD19(+)5(-) (normal B) cells were 43, 20, 4, 1 and 8 cells/microl, respectively. The median cell count of all subsets remained at <25% of the baseline values for >9 months post-treatment. CD4(+) and CD8(+) levels in blood had reached >100 cells/microl in >50% of the patients at 4 months after the end of treatment. One patient had a cytomegalovirus reactivation and one patient developed Pneumocystis carinii pneumonia during therapy. No opportunistic or other major infections were recorded during unmaintained, long-term follow-up. There was no correlation between the cumulative dose of alemtuzumab and the severity or length of immunosuppression. CD52(-) T-cell subsets occurred during the treatment and comprised >80% of all CD4(+) and CD8(+) cells in the blood at the end of therapy. These subpopulations declined gradually during unmaintained follow-up. The relationship between these observations and the safety/antitumour effects of alemtuzumab is discussed.

Adult↗
PubMed2004

Apoptotic tumor cells are superior to tumor cell lysate, and tumor cell RNA in induction of autologous T cell response in B-CLL.

B cell chronic lymphocytic leukemia (B-CLL) is a chronic leukemia manifested by increased numbers of B cells in circulation. The slow, smouldering nature of the disease in a significant proportion of the cases makes it an ideal target for immunotherapy. Dendritic cell (DC)-based immunotherapy is emerging as an exciting modality with significant clinical potential. In this study, three strategies for delivering antigens to DC, namely apoptotic bodies (Apo-DC), tumor lysates, and tumor RNA were studied in an autologous setting. In all six CLL patients, Apo-DC induced higher HLA-restricted, T cell responses than DC pulsed with tumor lysate or RNA. Real-time PCR confirmed higher expression of genes for IL-2 and IFN-gamma in T cells stimulated with Apo-DC. Concurrently, no IL-10 and low IL-4 responses indicated that the immune response was primarily of the Th1 type. Enzyme-linked immunospot assay revealed high IFN-gamma secretion by T cells when Apo-DC was used to stimulate autologous T cells in all patients. Our data suggest that cellular vaccines with DC loaded with apoptotic bodies may be a suitable approach for immunotherapy of B-CLL.

Aged↗
PubMed2004

Tenascin C expression is upregulated in pancreatic cancer and correlates with differentiation.

BACKGROUND: Tenascin C is a large, hexameric, extracellular matrix protein that is present during embryonic development but essentially absent in adult tissues. It is involved in remodelling processes, such as wound healing and tumour development. Tissue expression of tenascin C correlates with prognosis in colorectal, cervical, and breast cancer and in carcinoma of the papilla of Vater. AIM: To study the expression of tenascin C in pancreatic cancer and to compare the staining results with the patients' clinicopathological data. MATERIAL AND METHODS: Formalin fixed, paraffin wax embedded specimens from 146 patients with pancreatic adenocarcinoma were stained with an anti-tenascin C monoclonal antibody. RESULTS: Tenascin C immunoreactivity was seen in most samples of pancreatic carcinoma: staining was weak in 72 (49%), moderate in 52 (36%), strong in 10 (7%), and negative in 12 (8%) samples. Tenascin C expression correlated with age (< or = 66 v >66 years) and poor differentiation (grades 1-2 v 3). There was no correlation between tenascin C expression and survival, clinical stage, tumour size, nodal status, distant metastasis, tumour location, or sex. CONCLUSION: Tenascin C expression was increased in most pancreatic carcinomas, but contrary to the results in other cancers, it is not a prognostic factor in pancreatic cancer.

Adenocarcinoma↗
PubMed2004

A digital atlas of breast histopathology: an application of web based virtual microscopy.

AIMS: To develop an educationally useful atlas of breast histopathology, using advanced web based virtual microscopy technology. METHODS: By using a robotic microscope and software adopted and modified from the aerial and satellite imaging industry, a virtual microscopy system was developed that allows fully automated slide scanning and image distribution via the internet. More than 150 slides were scanned at high resolution with an oil immersion x 40 objective (numerical aperture, 1.3) and archived on an image server residing in a high speed university network. RESULTS: A publicly available website was constructed, http://www.webmicroscope.net/breastatlas, which features a comprehensive virtual slide atlas of breast histopathology according to the World Health Organisation 2003 classification. Users can view any part of an entire specimen at any magnification within a standard web browser. The virtual slides are supplemented with concise textual descriptions, but can also be viewed without diagnostic information for self assessment of histopathology skills. CONCLUSIONS: Using the technology described here, it is feasible to develop clinically and educationally useful virtual microscopy applications. Web based virtual microscopy will probably become widely used at all levels in pathology teaching.

Breast↗
PubMed2003

Loss of p27 expression is associated with poor prognosis in stage I-II pancreatic cancer.

OBJECTIVE: p27 is a cyclin-dependent kinase inhibitor that prevents progression of the cell cycle from G1 phase. Postranscriptional loss of p27 correlates with poor prognosis in various solid tumors. In pancreatic cancer, the loss of p27 expression has been correlated with high tumor grade and advanced clinical stage, but data on its prognostic value are lacking. METHOD: In this retrospective study, the association between immunohistochemical p27 expression and prognosis was evaluated in 147 patients with pancreatic cancer using a commercial anti-Kip1/p27 monoclonal antibody. RESULT: p27 expression was generally low; in 103 of the 147 pancreatic cancer tumors examined, no nuclear staining was observed and in only 5 specimens did more than 50% of the nuclei stain, probably reflecting the aggressive nature of the disease. Loss of p27 expression was associated with poor prognosis in stage I-II pancreatic adenocarcinoma; the 5-year survival for p27 negative patients was 3.6% compared with 20% for p27-positive patients (p = 0.03). In a multivariate survival analysis in patients with stage I-II disease, p27 (HR 1.8) was a significant prognostic factor, independent of grade (RR 2.9). There was no association between p27 and other clinical variables. In conclusion, tissue expression of p27 is a significant predictor of 5-year survival in stage I-II pancreatic adenocarcinoma.

Aged↗
PubMed2001

Tissue expression of human chorionic gonadotropin beta predicts outcome in colorectal cancer: a comparison with serum expression.

Production of the glycoprotein hormone human chorionic gonadotropin beta (hCGbeta) has been associated with more aggressive behavior in non-trophoblastic tumors. In this study, the prognostic value of immunohistochemical hCGbeta expression was evaluated in 239 patients with colorectal cancer. Paraffin-embedded, formalin-fixed specimens were stained with hCGbeta-specific monoclonal antibody, and the results were compared with serum levels determined with an assay based on the same antibody. hCGbeta immunoreactivity was seen in 52 of 239 tumors (22%). The difference in survival time between patients with histologically hCGbeta-negative (median survival 94 months) and -positive (median survival 27 months) tumors was statistically significant (p = 0.014). The risk ratio during follow-up for patients with positive hCGbeta tissue expression was 1.65 (95% CI 1.11-2.46). In a Cox multivariate analysis, Dukes' stage, hCGbeta and age remained independent prognostic factors. There was moderate agreement between immunohistochemical and serum expression levels of hCGbeta (kappa = 0.30). Using a combination of histological and serum levels of hCGbeta, the difference between survival rates was highly significant (p < 0.001). The accuracy when predicting 5-year survival status with the combined results of serum and tissue expression was 1.3% higher compared to hCGbeta tissue expression alone. Our results show that hCGbeta expression in both tumor tissue and serum has prognostic significance independent of other clinicopathological variables. Positive tumor staining does not always occur together with elevated serum levels, and the prognostic accuracy can slightly be increased by combining the results.

Adult↗
PubMed2001

Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer.

The prognostic value of the immunohistochemical expression of epithelial and stromal syndecan-1 was evaluated in 296 patients with gastric carcinoma. Formalin-fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with mouse monoclonal antibody B-B4 against human syndecan-1. Loss of immunoreactivity (syndecan-1 immunoreactivity correlated with a higher stage of disease (stages II-IV), tumour location in the upper third of the stomach, nodal metastases (N1 or N2), positive stromal syndecan-1 staining, deep tumour penetration (to subserosa or deeper = T2-T4), larger tumour size (> or = 5 cm) and intestinal type of cancer. No correlation between epithelial syndecan-1 immunoreactivity and age, gender, distant metastases, grade of differentiation or Borrmann classification was observed. Positive stromal syndecan-1 immunoreactivity correlated with decreased epithelial syndecan-1 expression, intestinal type of cancer and Borrmann type I. Patients with low epithelial syndecan-1 expression in cancer cells had worse overall survival than patients with strong epithelial syndecan-1 staining (p = 0.0012). Stromal syndecan-1-positive patients had a worse outcome than patients with syndecan-1-negative stroma (p = 0.0193). In Cox multivariate analysis, stromal syndecan-1 immunoreactivity was a prognostic factor independent of TNM stage, surgery for cure and tumour size. Thus, the immunohistochemical expression of syndecan-1 might be a predictor of outcome in patients with gastric adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Omission of histologic grading from clinical decision making may result in overuse of adjuvant therapies in breast cancer: results from a nationwide study.

PURPOSE: To investigate the influence of routinely performed histologic grading on breast cancer outcome prediction and patient selection for adjuvant therapy. PATIENTS AND METHODS: The analysis is based on a cohort of 2,842 women diagnosed with breast cancer and comprising 91% of all breast cancers diagnosed in five defined geographical regions in Finland in 1991 through 1992. Data on clinicopathologic factors and follow-up were collected from hospital case records and national registries. Histologic grade assessed at diagnosis and other clinicopathologic data were available for 1,554 operable unilateral invasive carcinomas. The relative value of grade with respect to competing prognostic factors was estimated with the Cox proportional hazards model and logistic regression. Interactions and nonlinearity of factors were accounted for by using an artificial neural network. RESULTS: Histologic grade was correlated strongly with survival in the entire series and in all subgroups studied. Women with well-differentiated node-negative cancer had a 97% 5-year distant disease-free survival rate as compared with 78% for women with poorly differentiated cancer. Grade was an independent prognostic factor in multivariate models and increased the predictive accuracy of a neural network model. Inclusion of grade data in a Cox multivariate model based on tumor size and hormone receptor status in node-negative cancer increased the proportion of patients with 5% or less risk for distant recurrence at 5 years from 15% to 54%. CONCLUSION: Even when assessed by pathologists who have no special training in breast cancer pathology, histologic grade has substantial and independent prognostic value in breast cancer. Omission of grading from clinical decision making may result in considerable overuse of adjuvant therapies.

Adult↗
PubMed2001

p27 expression correlates with short-term, but not with long-term prognosis in breast cancer.

UNLABELLED: New prognostic and predictive factors are needed to adjust more appropriate therapy for individual patients after operation. p27 is a cell cycle regulator, and a low tissue expression of this protein has been shown to correlate with poor prognosis in colorectal, lung, gastric, prostate, and breast cancer. In this study on 197 breast cancer patients with a median follow-up of 17 years, the prognostic value of immunohistochemical p27 expression was evaluated. After 5 years of follow-up patients with a p27 expression in less than 50% of the tumor cells had a significantly lower survival rate than those with an expression above this level (p = 0.01). However, after longer follow-up the difference decreased and was no longer significant at 7 years (p = 0.1) or when the entire follow-up period was examined (p=0.67). Tests for associations showed that a low p27 expression correlated with a high histologic grade, a high S-phase fraction (SPF), an advanced TNM stage and negative hormone receptor status. IN CONCLUSION: Tissue expression of p27 is a significant predictor of 5-year, but not of 10- or 15-year breast cancer specific survival.

Adult↗
PubMed2001

Amplification of c-myc oncogene by chromogenic and fluorescence in situ hybridization in archival breast cancer tissue array samples.

Fluorescence in situ hybridization (FISH) is currently considered to be the most specific and sensitive method for detection of oncogene amplifications in human tumor samples. However, FISH requires fluorescence microscopy, which is tedious and does not allow histopathologic evaluation of the cells and tissues examined. Here we compared FISH with the newly developed chromogenic in situ hybridization (CISH), which uses peroxidase enzyme for probe detection instead of fluorescent dyes. CISH was found to be highly concordant with FISH in a tissue array series of 177 archival breast cancer samples. This was true both when comparing CISH with single-color and two-color FISH, the latter including the chromosome 8 centromere probe as reference (the kappa coefficients were 0.67 and 0.76, respectively). Clinicopathologic correlations of c-myc amplification as detected by FISH and CISH were generally the same. By both methods, c-myc amplification was significantly associated with high histologic grade, negative progesterone receptor status, DNA aneuploidy, and high S-phase fraction. c-myc amplification was strongly associated with poor distant metastasis-free survival when amplification was detected by CISH (p = 0.0013), but this association was weaker when FISH was used (p = 0.16 for two-color FISH and p = 0.065 for single-color FISH). These data suggest that CISH is at least as sensitive and specific as FISH in the detection of oncogene amplification in human tumor samples. The possibility for concomitant tissue architecture evaluation using an ordinary transmitted light microscope may favor the use of CISH over FISH in oncogene amplification detection in large tumor series, and tissue arrays and, ultimately, in routine clinical diagnostics.

Archives↗
PubMed2001

Amplification of c-myc by fluorescence in situ hybridization in a population-based breast cancer tissue array.

A total of 261 primary breast carcinomas were analyzed for amplification of the c-myc oncogene by fluorescence in situ hybridization performed on tumor tissue array samples. Results were compared with individual clinicopathologic and follow-up data. Thirty-eight (14.6%) of the tumors showed c-myc gene amplification (defined as two or more additional copies of c-myc gene in relation to the number of chromosome 8 centromere). The reproducibility of fluorescence in situ hybridization assay (defined by hybridization with two different myc probes) was good (kappa coefficient 0.402). Statistically significant associations were found between c-myc amplification and DNA aneuploidy (P =.0011), and progesterone receptor negativity (P =.0071), and c-myc amplification also tended to be associated with high histologic grade (P =.064), positive axillary nodal status (P =.080), and a high S-phase fraction (P =.052). c-myc amplification was not significantly associated with overall survival of patients with invasive cancer (P =.32). These data from a population-based tumor material suggest that c-myc amplification is a feature of aggressive breast cancers, but that it is unlikely to be a clinically useful prognostic factor.

Aneuploidy↗
PubMed2001

Variability in B-cell antigen expression: implications for the treatment of B-cell lymphomas and leukemias with monoclonal antibodies.

OBJECTIVES: Antigen expression intensity is becoming important for decision-making in relation to monoclonal antibody therapy. By quantifying CD20, CD22 and CD52 expression on chronic lymphocytic leukemia and normal (control) B cells, over time. The effect of Interleukin-4 therapy on CD20 antigen intensity on B-CLL cells in vivo was also determined. METHODS: Lymphocytes were purified at weeks 0, 4 and 8 from five B-CLL patients, five healthy volunteers and seven B-CLL patients receiving IL-4 therapy. The number of antigen receptor sites was calculated in molecules of equivalent soluble fluorochrome using flow cytometry. RESULTS: The mean number of CD20 receptors at baseline was significantly lower on B-CLL cells compared to normal B cells (8160 vs 87 046; P<0.0001). Similar results were obtained for CD22 (8630 vs 27 647; P<0.01), but not for CD52 (371 303 vs 409 484; P = 0.54). When soluble fluorochrome values at weeks 4 and 8 were analysed as change in per cent from baseline (delta%), there was <10 delta% variability in CD20 expression on control B cells, but considerable variability (22.5-67.5 delta%) on B-CLL cells. Expression of CD22 in CLL and control B cells varied by <15 delta%. CD52 on CLL B cells showed slightly greater variability (+/-35 delta%) than that of CD22 (+/-15delta%), but less than that of CD20. IL-4 therapy did not consistently increase the CD20 expression on B-CLL cells in vivo. CONCLUSION: Our data confirm differences in intensity between different target antigens on B-CLL cells, and draws attention to the fact that a substantial variability may occur over time, which may influence clinical decision-making. Caution must be taken when interpreting in vitro results on cytokine-mediated receptor intensity up-regulation.

Adult↗
PubMed2001

Interleukin 4 therapy for patients with chronic lymphocytic leukaemia: a phase I/II study.

Interleukin 4 (IL-4) is a pleiotropic type II cytokine which has been shown to have a direct killing effect on lymphoma and B-cell chronic lymphocytic leukaemia (B-CLL) cells in vitro. The clinical effects and toxicity of IL-4 treatment in patients with B-CLL were evaluated. Fourteen patients with B-CLL who were in partial remission after chemotherapy received one, two or three 8-week cycles of escalating doses (2, 4 or 6 microg/kg/d s.c.) of IL-4 for 3 d/week. Clinical response was analysed after each treatment cycle and toxicity was monitored continuously. Ten patients (71%) had progressive disease (PD) during IL-4 treatment. This was mainly attributable to an increase (two- to fourfold) of the blood lymphocyte count during IL-4 therapy. After cessation of IL-4 treatment, the lymphocytosis decreased spontaneously in 8 out of 12 evaluable patients. Splenomegaly remained unchanged in 7/7 patients, whereas enlarged lymph nodes were reduced by > 50% in 1/13 patients and by 25-50% in 4/13 patients. None of the patients achieved an objective tumour regression (complete or partial remission). A temporary increase (16-60%) of the platelet count was observed during IL-4 treatment. The platelet count decreased in 8/11 patients after the end of IL-4 therapy. World Health Organization (WHO) grade I/II fever, arthralgia and fatigue was observed in one-third of the patients and was more commonly seen with the highest dose (6 microg/kg/d). One patient developed pulmonary oedema and WHO grade III neutropenia was recorded in three patients. IL-4 was well tolerated by most patients in an outpatient setting. The anti-tumour activity observed in previous in vitro studies was not verified by the present in vivo trial which showed that IL-4 may instead increase the number of CLL cells in blood, indicating that IL-4 may have induced a stimulatory or antiapoptotic effect on the CLL cells in blood. These results may have important implications for the development of immunotherapy of CLL. In addition, the potential platelet-stimulatory effect of IL-4 warrants further studies.

Aged↗
PubMed2001

Redo bypass surgery to the infrapopliteal arteries for critical leg ischaemia.

OBJECTIVES: to evaluate the results of redo bypass surgery to the infrapopliteal artery and the value of adjuvant arteriovenous fistula (AVF) in this setting. DESIGN: retrospective study. MATERIALS: fifty-one redo reconstructions to the infrapopliteal arteries were done for critical leg ischaemia in 45 patients who have had primary infrainguinal reconstructions to the popliteal artery in 20 cases (39%), the crural arteries in 18 (35%), and the pedal arteries in 13 (25%). METHODS: a PTFE prosthesis was used in 21 cases (41%). A Miller cuff was used in 16 prosthetic grafts. Adjuvant AVF was added to three autogenous vein and 12 prosthetic grafts. RESULTS: at 2 years, the primary patency rate was 42%, the secondary patency was 43%, the limb salvage was 67%, the survival was 77%, and 53% of patients were alive with salvaged leg. The primary patency rate with a vein graft was 44% at 1 year, with prosthesis plus AVF 67%, but with prosthesis without AVF only 19%. Secondary patency rates were similar. Prosthetic graft with AVF and those without AVF achieved a 1-year leg salvage rate of 100% and 51%, respectively (p =0.01). Patients with adjuvant AVF had a worse 2-year survival rate that those without AVF (31% vs 89%) (p =0.007; RR: 8.87, CI 95%: 1.62-48.42). CONCLUSIONS: redo bypass surgery using autogenous vein graft may achieve satisfactory long-term results. The use of adjuvant AVF may improve patency of redo infrapopliteal prosthetic bypass grafts.

Aged↗