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- Brezicka, Thomas, 1961
(författare)
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Expression of epithelial-cell adhesion molecule (Ep-CAM) in small cell lung cancer as defined by monoclonal antibodies 17-1A and BerEP4
- 2005
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Ingår i: Acta Oncol. ; 44:7, s. 723-7
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Tidskriftsartikel (refereegranskat)abstract
- Small cell lung cancer (SCLC) comprises 15-20% of all lung cancer. Despite high initial response to chemotherapy chemoresistance at relapse leads to a less than 5% five-year survival rate. Adjuvant treatment with monoclonal antibodies (Mabs) against SCLC antigens may offer a therapeutic option. Mab 17-1A directed against the epithelial-cell adhesion molecule (Ep-CAM) has been extensively tested for therapy in patients with colorectal carcinoma. Expression of Ep-CAM in SCLC has been earlier described. However, reactivity of Mab 17-1A and another Ep-CAM-binding Mab BerEP4 has not yet been described for SCLC. Using immunohistology first with BerEP4 and confirmatory with 17-1A a homogenous and strong expression of Ep-CAM was seen in all SCLC specimens tested (n = 10). For comparison, heterogenous expression was seen in the non-SCLC tumors tested (n = 15). These findings strongly suggest that Mab 17-1A can be useful for adjuvant immunotherapy in patients with SCLC. For detection of Ep-CAM in tumor tissue in patients that might be considered for immunotherapy with Mab 17-1A, Mab BerEP4 appears to be preferred.
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| 2. |
- Enarsson, Karin, 1975, et al.
(författare)
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CD4+ CD25high regulatory T cells reduce T cell transendothelial migration in cancer patients.
- 2007
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Ingår i: European journal of immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 37:1, s. 282-91
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Tidskriftsartikel (refereegranskat)abstract
- Cell-mediated immunity is thought to be the main mechanism of anti-tumour responses of the host, but it is not known if cancer disease affects T cell recruitment from blood to tissues. Therefore, we compared Heliobacter pylori-induced T cell transendothelial migration (TEM) in H. pylori-infected gastric carcinoma patients, colon and lung carcinoma patients and healthy volunteers. H. pylori induced significant T cell migration from all groups. However, there was a dramatic reduction of T cell TEM in gastric carcinoma patients (80%) compared to healthy individuals. A similarly reduced transmigration was also seen in colon and lung carcinoma patients. We found significantly increased frequencies of T(reg) cells in the blood of gastric carcinoma patients compared to healthy individuals, and depletion of T(reg) cells from the blood of these patients prior to TEM restored T cell migration. The effect of T(reg) cells was largely dependent on cell-cell contact, but not on IL-10 or TGF-beta. In addition, the presence of T(reg) cells led to reduced T cell attachment to endothelium and decreased production of T cell-recruiting chemokines during TEM. In conclusion, T(reg) cell-mediated reduction of T cell TEM may reduce T cell recruitment in patients with epithelial malignancies, thereby hampering anti-tumour responses.
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| 3. |
- Fredman, Pam, 1950, et al.
(författare)
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Gangliosides as therapeutic targets for cancer
- 2003
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Ingår i: BioDrugs. ; 17:3, s. 155-67
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Tidskriftsartikel (refereegranskat)abstract
- Gangliosides, sialic acid-containing glycosphingolipids, have engendered great interest for more than 20 years in the search for target molecules of relevance for tumour growth and formation of metastases and as potential targets for immunotherapy. These molecules show large quantitative and structural variability, which is related to cell type and developmental stage. Their potential role in the formation of tumour metastases was suggested from data supporting that they are involved in cell growth regulation and in cell-cell and cell-matrix adhesion. Moreover, gangliosides are expressed on the cell surface and thereby are accessible for antibodies or other ganglioside-binding molecules to induce cell death, inhibit cell growth and/or inhibit formation of tumour metastasis.All tumours exhibit aberrant ganglioside expression. This includes overexpression of normal ganglioside constituents, which appears to be common among various tumours, and expression of gangliosides not found in normal adult tissue but often found during fetal development. The ganglioside composition of melanoma cells has been found to correlate with their metastatic potential and also to be selectively expressed in cells of a tumour mass and invading tumour cells. Passive immunotherapy using murine or murine/human chimeric monoclonal antiganglioside antibodies in their native form or combined with various effector molecules has been investigated. However, the vaccination strategy using native or structurally modified tumour-associated gangliosides in combination with adjuvants is currently the dominant method in clinical trials. The outcomes reported so far vary between type of tumour and treatment strategies. However, we believe that targeting gangliosides is as promising as any other immune therapeutic strategy, and basic research as well as clinical trials utilising new aspects is encouraged.
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| 4. |
- Gerlee, Philip, 1980, et al.
(författare)
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Predicting regional COVID-19 hospital admissions in Sweden using mobility data.
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The transmission of COVID-19 is dependent on social mixing, the basic rate of which varies with sociodemographic, cultural, and geographic factors. Alterations in social mixing and subsequent changes in transmission dynamics eventually affect hospital admissions. We employ these observations to model and predict regional hospital admissions in Sweden during the COVID-19 pandemic. We use an SEIR-model for each region in Sweden in which the social mixing is assumed to depend on mobility data from public transport utilisation and locations for mobile phone usage. The results show that the model could capture the timing of the first and beginning of the second wave of the pandemic 3weeks in advance without any additional assumptions about seasonality. Further, we show that for two major regions of Sweden, models with public transport data outperform models using mobile phone usage. We conclude that a model based on routinely collected mobility data makes it possible to predict future hospital admissions for COVID-19 3weeks in advance.
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| 5. |
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| 6. |
- Livingston, P. O., et al.
(författare)
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Selection of GM2, fucosyl GM1, globo H and polysialic acid as targets on small cell lung cancers for antibody mediated immunotherapy
- 2005
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Ingår i: Cancer Immunol Immunother. ; 54:10
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Tidskriftsartikel (refereegranskat)abstract
- Glycolipids GM2, GD2, GD3, fucosyl GM1, sialyl Lewis a (sLe(a)) and globo H, and polysialic acid on embryonal NCAM, are cell-surface antigens expressed on small cell lung cancer (SCLC) biopsy specimens. They are all candidates for inclusion in a polyvalent, antibody-inducing vaccine or for adoptive therapy with monoclonal antibodies (mAbs) against SCLC. To identify the minimum optimal combination of target antigens on SCLC and to confirm that antibodies against this combination might be able to mediate complement activation and lysis in the majority of cases, we tested ten SCLC cell lines with fluorescence activated cell sorter (FACS) and complement dependent cytotoxicity (CDC) assays using mAbs against these seven target antigens individually or pooled in different combinations. We find that (1) none of these mAbs demonstrated strong FACS reactivity with more than 6 of the 10 cell lines, (2) no mAb had strong CDC reactivity with more than 4 of the cell lines, (3) when the mAbs were pooled, nine cell lines were strongly positive by FACS and nine cell lines were strongly positive by CDC, and (4) mAbs against GM2, FucGM1, globo H and polysialic acid was the minimum optimal combination for inducing FACS reactivity. The addition of mAbs against sLe(a), GD2 and GD3 had no additional impact by FACS and only minimal additional impact in CDC assays. H345, the only cell line that had less than 30% CDC with the four mAb pool was strongly positive by FACS. To understand the lack of correlation between FACS and CDC in the case of H345, the ten cell lines were screened for expression of complement resistance factors CD55 and CD59. Three cell lines were strongly positive for CD55 and eight were strongly positive for CD59. Overall, no correlation was seen between expression of either of these factors on the ten cell lines and sensitivity to CDC. In the case of H345 however, complement resistance of H345 is demonstrated to be mediated primarily by CD59, and in the presence of mAb against CD59, the four mAb MEM-43 pool induced strong (94%) CDC. CD59 inhibits membrane attack complex formation but not activation of earlier complement components. Consequently, all ten cell lines are good targets for complement activation by the four antibody pool and for elimination by effector mechanisms including complement mediated inflammation and opsonization. These findings support our plan to develop a tetravalent vaccine against SCLC targeting GM2, fucosyl GM1, globo H and polysialic acid.
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| 7. |
- Saguti, Fredy, et al.
(författare)
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Surveillance of wastewater revealed peaks of SARS-CoV-2 preceding those of hospitalized patients with COVID-19
- 2021
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Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 189
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 was discovered among humans in Wuhan, China in late 2019, and then spread rapidly, causing a global pandemic. The virus was found to be transmitted mainly by respiratory droplets from infected persons or by direct contact. It was also shown to be excreted in feces, why we investigated whether the virus could be detected in wastewater and if so, to which extent its levels reflects its spread in society. Samples of wastewater from the city of Gothenburg, and surrounding municipalities in Sweden were collected daily from mid-February until June 2020 at the Rya wastewater treatment plant. Flow proportional samples of wastewater were collected to ensure that comparable amounts were obtained for analysis. Daily samples were pooled into weekly samples. Virus was concentrated on a filter and analyzed by RT-qPCR. The amount of SARS-CoV-2 varied with peaks approximately every four week, preceding variations in number of newly hospitalized patients by 19-21 days. At that time virus testing for COVID-19 was limited to patients with severe symptoms. Local differences in viral spread was shown by analyzing weekly composite samples of wastewater from five sampling sites for four weeks. The highest amount of virus was found from the central, eastern, and northern parts of the city. SARS-CoV-2 was also found in the treated effluent wastewater from the WWTP discharged into the recipient, the Göta River, although with a reduction of 4-log10. The viral peaks with regular temporal intervals indicated that SARS-CoV-2 may have a cluster spread, probably reflecting that the majority of infected persons only spread the disease during a few days. Our results are important for both the planning of hospital care and to rapidly identify and intervene against local spread of the virus.
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