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1. COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing

Author

Peto, T., Affron, D., Afrough, B., Agasu, A., Ainsworth, M., Allanson, A., Allen, K., Allen, C., Archer, L., Ashbridge, N., Aurfan, I., Avery, M., Badenoch, E., Bagga, P., Balaji, R., Baldwin, E., Barraclough, S., Beane, C., Bell, J., Benford, T., Bird, S., Bishop, M., Bloss, A., Body, R., Boulton, R., Bown, A., Bratten, C., Bridgeman, C., Britton, D., Brooks, T., Broughton-Smith, M., Brown, P., Buck, B., Butcher, E., Byrne, W., Calderon, G., Campbell, S., Carr, O., Carter, P., Carter, D., Cathrall, M., Catton, M., Chadwick, J., Chapman, D., Chau, K.K., Chaudary, T., Chidavaenzi, S., Chilcott, S., Choi, B., Claasen, H., Clark, S., Clarke, R., Clarke, D., Clayton, R., Collins, K., Colston, R., Connolly, J., Cook, E., Corcoran, M., Corley, B., Costello, L., Coulson, C., Crook, A., Crook, D.W., D'Arcangelo, S., Darby, M-A, Davis, J., de Koning, R., Derbyshire, P., Devall, P., Dolman, M., Draper, N., Driver, M., Dyas, S., Eaton, E., Edwards, J., Elderfield, R., Ellis, K., Ellis, G., Elwell, S., Evans, R., Evans, B., Evans, M., Eyre, D., Fahey, C., Fenech, V., Field, J., Field, A., Foord, T., Fowler, T., French, M., Fuchs, H., Gan, J., Gernon, J., Ghadiali, G., Ghuman, N., Gibbons, K., Gill, G., Gilmour, K., Goel, A., Gordon, S., Graham, T., Grassam-Rowe, A., Green, D., Gronert, A., Gumsley-Read, T., Hall, C., Hallis, B., Hammond, S., Hammond, P., Hanney, B., Hardy, V., Harker, G., Harris, A., Havinden-Williams, M., Hazell, E., Henry, J., Hicklin, K., Hollier, K., Holloway, B., Hoosdally, S.J., Hopkins, S., Hughes, L., Hurdowar, S., Hurford, S-A, Jackman, J., Jackson, H., Johns, R., Johnston, S., Jones, J., Kanyowa, T., Keating-Fedders, K., Kempson, S., Khan, I., Khulusi, B., Knight, T., Krishna, A., Lahert, P., Lampshire, Z., Lasserson, D., Lee, K., Lee, L.Y.W., Legard, A., Leggio, C., Liu, J., Lockett, T., Logue, C., Lucas, V., Lumley, S.F., Maripuri, V., Markham, D., Marshall, E., Matthews, P.C., Mckee, S., McKee, D.F., McLeod, N., McNulty, A., Mellor, F., Michel, R., Mighiu, A., Miller, J., Mirza, Z., Mistry, H., Mitchell, J., Moeser, M.E., Moore, S., Muthuswamy, A., Myers, D., Nanson, G., Newbury, M., Nicol, S., Nuttall, H., Nwanaforo, J.J., Oliver, L., Osbourne, W., Osbourne, J., Otter, A., Owen, J., Panchalingam, S., Papoulidis, D., Pavon, J.D., Peace, A., Pearson, K., Peck, L., Pegg, A., Pegler, S., Permain, H., Perumal, P., Peto, L., Peto, T.E.A., Pham, T., Pickford, H.L., Pinkerton, M., Platton, M., Price, A., Protheroe, E., Purnell, H., Rawden, L., Read, S., Reynard, C., Ridge, S., Ritter, T.G., Robinson, J., Robinson, P., Rodger, G., Rowe, C., Rowell, B., Rowlands, A., Sampson, S., Saunders, K., Sayers, R., Sears, J., Sedgewick, R., Seeney, L., Selassie, A., Shail, L., Shallcross, J., Sheppard, L., Sherkat, A., Siddiqui, S., Sienkiewicz, A., Sinha, L., Smith, J., Smith, E., Stanton, E., Starkey, T., Stawiarski, A., Sterry, A., Stevens, J., Stockbridge, M., Stoesser, N., Sukumaran, A., Sweed, A., Tatar, S., Thomas, H., Tibbins, C., Tiley, S., Timmins, J., Tomas-Smith, C., Topping, O., Turek, E., Neibler, T., Trigg-Hogarth, K., Truelove, E., Turnbull, C., Tyrrell, D., Vaughan, A., Vertannes, J., Vipond, R., Wagstaff, L., Waldron, J., Walker, P., Walker, A.S., Walters, M., Wang, J.Y., Watson, E., Webberley, K., Webster, K., Westland, G., Wickens, I., Willcocks, J., Willis, H., Wilson, S., Wilson, B., Woodhead, L., Wright, D., Xavier, B., Yelnoorkar, F., Zeidan, L., Zinyama, R., Peto, T., Affron, D., Afrough, B., Agasu, A., Ainsworth, M., Allanson, A., Allen, K., Allen, C., Archer, L., Ashbridge, N., Aurfan, I., Avery, M., Badenoch, E., Bagga, P., Balaji, R., Baldwin, E., Barraclough, S., Beane, C., Bell, J., Benford, T., Bird, S., Bishop, M., Bloss, A., Body, R., Boulton, R., Bown, A., Bratten, C., Bridgeman, C., Britton, D., Brooks, T., Broughton-Smith, M., Brown, P., Buck, B., Butcher, E., Byrne, W., Calderon, G., Campbell, S., Carr, O., Carter, P., Carter, D., Cathrall, M., Catton, M., Chadwick, J., Chapman, D., Chau, K.K., Chaudary, T., Chidavaenzi, S., Chilcott, S., Choi, B., Claasen, H., Clark, S., Clarke, R., Clarke, D., Clayton, R., Collins, K., Colston, R., Connolly, J., Cook, E., Corcoran, M., Corley, B., Costello, L., Coulson, C., Crook, A., Crook, D.W., D'Arcangelo, S., Darby, M-A, Davis, J., de Koning, R., Derbyshire, P., Devall, P., Dolman, M., Draper, N., Driver, M., Dyas, S., Eaton, E., Edwards, J., Elderfield, R., Ellis, K., Ellis, G., Elwell, S., Evans, R., Evans, B., Evans, M., Eyre, D., Fahey, C., Fenech, V., Field, J., Field, A., Foord, T., Fowler, T., French, M., Fuchs, H., Gan, J., Gernon, J., Ghadiali, G., Ghuman, N., Gibbons, K., Gill, G., Gilmour, K., Goel, A., Gordon, S., Graham, T., Grassam-Rowe, A., Green, D., Gronert, A., Gumsley-Read, T., Hall, C., Hallis, B., Hammond, S., Hammond, P., Hanney, B., Hardy, V., Harker, G., Harris, A., Havinden-Williams, M., Hazell, E., Henry, J., Hicklin, K., Hollier, K., Holloway, B., Hoosdally, S.J., Hopkins, S., Hughes, L., Hurdowar, S., Hurford, S-A, Jackman, J., Jackson, H., Johns, R., Johnston, S., Jones, J., Kanyowa, T., Keating-Fedders, K., Kempson, S., Khan, I., Khulusi, B., Knight, T., Krishna, A., Lahert, P., Lampshire, Z., Lasserson, D., Lee, K., Lee, L.Y.W., Legard, A., Leggio, C., Liu, J., Lockett, T., Logue, C., Lucas, V., Lumley, S.F., Maripuri, V., Markham, D., Marshall, E., Matthews, P.C., Mckee, S., McKee, D.F., McLeod, N., McNulty, A., Mellor, F., Michel, R., Mighiu, A., Miller, J., Mirza, Z., Mistry, H., Mitchell, J., Moeser, M.E., Moore, S., Muthuswamy, A., Myers, D., Nanson, G., Newbury, M., Nicol, S., Nuttall, H., Nwanaforo, J.J., Oliver, L., Osbourne, W., Osbourne, J., Otter, A., Owen, J., Panchalingam, S., Papoulidis, D., Pavon, J.D., Peace, A., Pearson, K., Peck, L., Pegg, A., Pegler, S., Permain, H., Perumal, P., Peto, L., Peto, T.E.A., Pham, T., Pickford, H.L., Pinkerton, M., Platton, M., Price, A., Protheroe, E., Purnell, H., Rawden, L., Read, S., Reynard, C., Ridge, S., Ritter, T.G., Robinson, J., Robinson, P., Rodger, G., Rowe, C., Rowell, B., Rowlands, A., Sampson, S., Saunders, K., Sayers, R., Sears, J., Sedgewick, R., Seeney, L., Selassie, A., Shail, L., Shallcross, J., Sheppard, L., Sherkat, A., Siddiqui, S., Sienkiewicz, A., Sinha, L., Smith, J., Smith, E., Stanton, E., Starkey, T., Stawiarski, A., Sterry, A., Stevens, J., Stockbridge, M., Stoesser, N., Sukumaran, A., Sweed, A., Tatar, S., Thomas, H., Tibbins, C., Tiley, S., Timmins, J., Tomas-Smith, C., Topping, O., Turek, E., Neibler, T., Trigg-Hogarth, K., Truelove, E., Turnbull, C., Tyrrell, D., Vaughan, A., Vertannes, J., Vipond, R., Wagstaff, L., Waldron, J., Walker, P., Walker, A.S., Walters, M., Wang, J.Y., Watson, E., Webberley, K., Webster, K., Westland, G., Wickens, I., Willcocks, J., Willis, H., Wilson, S., Wilson, B., Woodhead, L., Wright, D., Xavier, B., Yelnoorkar, F., Zeidan, L., and Zinyama, R.

Abstract

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.

Published
2021

4. The Value of Fine-Needle Aspiration Biopsy in Patients With Nodular Thyroid Disease Divided Into Groups of Suspicion of Malignant Neoplasms on Clinical Grounds

Author

Hamming, J. F., Goslings, B. M., van Steenis, G. J., van Ravenswaay Claasen, H., Hermans, J., and van de Velde, C. J. H.

Abstract

• The accuracy of clinical diagnosis and fine-needle aspiration biopsy (FNAB) was evaluated in 169 patients surgically treated for nodular thyroid disease. Patients were divided into three groups with high, moderate, or low suspicion of malignant neoplasms on clinical grounds without previous knowledge of cytologic or histologic results. Histologic examination revealed an overall malignant neoplasm rate of 23%; the rate was 71%, 14%, and 11%for the groups with high, moderate, and low suspicion, respectively. The FNAB diagnostic interpretations of malignant and uncertain were considered positive. Overall sensitivity, specificity, and accuracy for FNAB were 92%, 71%, and 75%, respectively. Sensitivity in the high-, moderate-, and low-suspicion groups was 95%, 89%, and 88%, respectively; specificity was 88%, 72%, and 67%, respectively; and accuracy was 93%, 75%, and 69%, respectively. In our opinion, all patients in the group with high clinical suspicion need surgical treatment whatever the FNAB result; those with lower degrees of clinical suspicion should also undergo surgery.(Arch Intern Med. 1990;150:113-116)

Published
1990
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9. [Clinical reasoning and decision-making in practice. A patient with fever and pancytopenia].

Author

Lam-Tse WK, van den Berg L, Dawson L, van Ravenswaay Claasen HH, Hart W, and Maartense E

Subjects
Aged, 80 and over, C-Reactive Protein analysis, Epstein-Barr Virus Infections blood, Epstein-Barr Virus Infections complications, Fatal Outcome, Fever of Unknown Origin etiology, Humans, Lymphohistiocytosis, Hemophagocytic blood, Lymphohistiocytosis, Hemophagocytic complications, Male, Pancytopenia etiology, Epstein-Barr Virus Infections diagnosis, Herpesvirus 4, Human isolation & purification, Lymphohistiocytosis, Hemophagocytic diagnosis
Abstract

An 82-year-old man was admitted with a 1-week history of chilling fever and dry cough. Laboratory tests revealed pancytopenia and elevated levels of C-reactive protein and lactic dehydrogenase (LDH). Screening for infectious diseases was negative. A bone marrow biopsy showed aspecific findings. The combination of pancytopenia, persistent fever, elevated LDH and hepatomegaly (demonstrated by ultrasound examination of the abdomen) was suggestive of the haemophagocytic syndrome. This was confirmed by very high levels of ferritin and soluble interleukin-2 receptor in the blood. In addition, re-examination of the bone marrow showed several haemophagocytic histiocytes. A polymerase chain reaction for Epstein-Barr virus (EBV) revealed a very high viral load. Since the patient had a history of an increased level of anti-EBV immunoglobulin-G, this was explained by a reactivation of the EBV infection. On the sixth day in hospital the patient developed signs of bilateral pneumonia and subsequent multiple organ failure. Despite intensive treatment the patient died. Autopsy revealed no haematological or other malignancies, but did show haemophagocytosis in many organs. It was then concluded that the patient had a virus-associated haemophagocytic syndrome, due to a reactivation of EBV, for which no underlying cause was found.

Published
2008

10. Cerebral involvement in two patients with Wegener's granulomatosis.

Author

Bajema IM, Hagen EC, Weverling-Rijnsburger AW, van der Pijl H, van Dorp WT, van Ravenswaay Claasen HH, and Bruijn JA

Subjects
Aged, Brain pathology, Brain Diseases diagnosis, Brain Diseases mortality, Female, Granulomatosis with Polyangiitis mortality, Humans, Male, Middle Aged, Vasculitis diagnosis, Vasculitis etiology, Vasculitis mortality, Brain Diseases etiology, Granulomatosis with Polyangiitis complications
Abstract

Two cases of cerebral involvement in Wegener's granulomatosis (WG) are described. The course of the disease in both patients was characterized by sudden onset and fatal outcome, despite maximum immunosuppressive therapy. Cerebral involvement is a rare complication of WG. Over the past two decades, only a small number of case-reports appeared of patients with WG who showed this complication. Since the era of cyclophosphamide therapy, it is commonly assumed that cerebral involvement in WG has no influence on patient survival. However, the two patients described here both died shortly after the occurrence of central neurological symptoms.

Published
1997

12. The influence of combination chemotherapy on antigen expression in ovarian cancer.

Author

van Ravenswaay Claasen HH and Fleuren GJ

Subjects
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antigens, Neoplasm immunology, Biomarkers, Tumor immunology, Female, Humans, Middle Aged, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Antigens, Neoplasm biosynthesis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor biosynthesis, Ovarian Neoplasms drug therapy
Abstract

The best treatment results for advanced-stage ovarian cancer patients are obtained with cytoreductive surgery followed by combination chemotherapy. However, the 5-year survival rate of only 20% clearly shows a need for new treatment modalities. At present several modes of immunotherapy for cancer are being explored such as the use of monoclonal antibodies, bispecific antibodies, or specific cytotoxic effector cells, all making use of the presence of tumor-associated antigens remaining, necessary for tumor cell recognition. The antigenic phenotype of human epithelial ovarian cancer after chemotherapy treatment is an important issue in planning potential immunotherapeutic strategies for ovarian cancer. Therefore, we compared the antigen expression in tumor specimens obtained during operation for primary epithelial ovarian tumors and tissue biopsies taken during second-look operations after the administration of combination chemotherapy. A total of 60 ovarian tumors, including 44 serous, 3 mucinous, 2 endometrioid, 1 clear cell, 6 mixed, 2 undifferentiated, and 2 granulosa cell tumors, was studied. Frozen sections of the tumor specimens were stained with 15 different monoclonal antibodies by the indirect immunoperoxidase technique and graded semiquantitatively. The results showed only limited differences in antigenic expression in tumor tissue obtained before and after chemotherapy. Because antigen expression was not altered, immunotherapy making use of these antigenic determinants will not be hampered by prior chemotherapy.

Published
1995
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13. Immunotherapy in a human ovarian cancer xenograft model with two bispecific monoclonal antibodies: OV-TL 3/CD3 and OC/TR.

Author

van Ravenswaay Claasen HH, Eggermont AM, Nooyen YA, Warnaar SO, and Fieuren GJ

Subjects
Animals, Antibodies, Bispecific immunology, Antibodies, Monoclonal, Carcinoma mortality, Carcinoma pathology, Cell Division, Cell Separation, Female, Flow Cytometry, Humans, Immunohistochemistry, Lymphocytes physiology, Mice, Mice, Inbred Strains, Mice, Nude, Neoplasm Transplantation, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Survival Analysis, Transplantation, Heterologous, Antibodies, Bispecific therapeutic use, Carcinoma therapy, Immunotherapy, Ovarian Neoplasms therapy
Abstract

The bispecific antibodies (bs-mAbs) OV-TL 3/CD3 and OC/TR (MOv18/CD3) efficiently mediate ovarian tumor cell lysis by cytotoxic T cells and activated peripheral blood lymphocytes (PBL) in vitro. OV-TL 3/CD3 and OC/TR are reactive with tumor-associated antigens on ovarian carcinoma cells (OA3 and CA-MOv18, respectively), and CD3 on activated PBL, bridging both cells and simultaneously inducing activation of the effector cells. In a comparative study we investigated the therapeutic efficacy of OV-TL 3/CD3 and OC/TR by targeting activated PBL with the bs-mAbs against intraperitoneally growing NIH:OVCAR-3 human ovarian carcinoma cells. As they have good tumor localization characteristics, HPLC-purified bispecific F(ab')2 fragments were used to target highly active PHA and IL-2-stimulated PBL effector cells. The efficacy of OV-TL 3/CD3 was compared to OC/TR with respect to tumor-associated antigen (TAA) binding on NIH:OVCAR-3 ascites cells and NIH:OVCAR-3 tumor cell lysis in vitro. In this report we show that ip ovarian cancer-bearing nude mice treated with IL-2 and activated PBL coated with bispecific F(ab')2 had a significantly longer survival than the untreated mice. No significant difference in survival was found between the OC/TR or OV-TL 3/CD3 bispecific antibody, although MOv18 expression was higher on NIH:OVCAR-3 ascites cells and PBL targeted with OC/TR induced slightly higher tumor cell lysis in vitro. Thus, the therapeutic efficacy of these bs-mAbs in vivo could not be predicted by TAA expression or bs-mAb-mediated tumor cell lysis in vitro.

Published
1994
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14. Association between HLA-expression and infiltration of immune cells in cervical carcinoma.

Author

Hilders CG, Houbiers JG, van Ravenswaay Claasen HH, Veldhuizen RW, and Fleuren GJ

Subjects
Female, Humans, Immunohistochemistry, Immunophenotyping, Carcinoma immunology, HLA Antigens immunology, Lymphocytes, Tumor-Infiltrating immunology, Uterine Cervical Neoplasms immunology
Abstract

Background: To determine the degree of specificity of the cellular immune response in cervical carcinoma, that is known to be human papillomavirus-related, we investigated the exact relationship between in situ tumor-infiltrating immune cells and the monomorphic/allele-specific HLA expression on the tumor cells., Experimental Design: Attention was focussed on the type, location and number of in situ immunocompetent cells in malignant cervical tissue (N = 30). Immune cell distribution was quantitatively assessed by morphometry for stromal and tumor tissue separately. These results were related to the degree of expression of monomorphic- and allele-specific HLA I and II antigens on the cervical tumor cells., Results: In monomorphic HLA class I downregulated cervical tumors, a significant decrease in tumor-infiltrating CD8+ T cells was observed. However, allele-specific downregulation of respectively HLA-A2, HLA-A3, HLA-Bw4, and HLA-Bw6, did not correlate significantly with a decrease in tumor-infiltrating immune cells. For HLA class II-positive cervical tumors, HLA-DR expression significantly correlated with an increase in the presence of tumor-infiltrating CD3+/CD4+/CD8+ T cells, CD56+ natural killer cells and CD16+ macrophages. No significant correlations were found between alterations in HLA class I or II expression on the tumor cells and stromal infiltrating immune cells., Conclusions: Our observations provide in situ immunomorphologic evidence that in cervical carcinoma, de novo expression of HLA class II antigens on the tumor cells resulted in an increase of tumor-infiltrating immune cells. In addition, the tumor-infiltrating CD8+ T lymphocytes correlated with monomorphic HLA class I expression on the tumor cells, which stresses the existence of a HLA-restricted immune response of T lymphocytes in cervical carcinoma. These findings might have implications for the biologic behavior of this disease and have to be taken into account in strategies concerning immunotherapy of cervical carcinoma.

Published
1993

15. Analysis of production, purification, and cytolytic potential of bi-specific antibodies reactive with ovarian-carcinoma-associated antigens and the T-cell antigen CD3.

Author

van Ravenswaay Claasen HH, van de Griend RJ, Mezzanzanica D, Bolhuis RL, Warnaar SO, and Fleuren GJ

Subjects
Antibodies, Monoclonal immunology, Antibodies, Monoclonal isolation & purification, Antibody Specificity, Chromatography, High Pressure Liquid, Cytotoxicity, Immunologic, Female, Humans, Hybridomas immunology, Immunoglobulin Fab Fragments immunology, Tumor Cells, Cultured, Antibodies, Monoclonal biosynthesis, Antigens, Neoplasm immunology, Ovarian Neoplasms immunology, Receptor-CD3 Complex, Antigen, T-Cell immunology
Abstract

OV-TL3 and MOv 18 MAbs, due to their restricted specificity, have been successfully used to visualize ovarian cancer in patients and might therefore be used to develop therapies for ovarian cancer. The bi-specific MAbs alpha T3/OC2 and alpha OC/TR (both being combinations of MOv18 and alpha CD3) have been shown to lyse ovarian tumor cells in vitro. To evaluate the relative merits of MOv18/CD3 and OV-TL 3/CD3, the present study was undertaken in which the bi-specific MAbs alpha T3/OC2 and alpha OC/TR, and a newly developed bi-specific MAb, OV-TL 3/CD3, were highly purified and compared for specificity, stability, purification and cytolytic potential. The dual specificity of the hybrid-hybridoma supernatants was analyzed by immunohistochemistry, and by testing bi-specific MAb-mediated cytotoxicity against relevant target cells in the presence of effector cells. Stability testing of bi-specific MAb-producing hybridomas showed that, after sub-cloning, clones stably produced up to 40% bi-specific MAb even after prolonged in vitro culture. The purification of the bi-specific fractions was performed with protein A and by ion-exchange high-pressure liquid chromatography, depending on the sub-class combination of the bi-specific MAb. The purified bi-specific MAbs were tested for their ability to mediate target-cell lysis with the use of cytotoxic T-cell clones and activated peripheral-blood lymphocytes. The purified alpha T3/OC2, alpha OC/TR, and OV-TL3/CD3 were all able to mediate highly specific lysis of various ovarian-carcinoma cell lines. No correlation was found between the level of antigen expression and bi-specific MAb-mediated cytolysis.

Published
1993
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16. Establishment and characterization of 7 ovarian carcinoma cell lines and one granulosa tumor cell line: growth features and cytogenetics.

Author

van den Berg-Bakker CA, Hagemeijer A, Franken-Postma EM, Smit VT, Kuppen PJ, van Ravenswaay Claasen HH, Cornelisse CJ, and Schrier PI

Subjects
Chromosome Aberrations pathology, Chromosome Banding, Chromosome Disorders, DNA, Neoplasm analysis, Female, Flow Cytometry, Humans, Carcinoma pathology, Granulosa Cell Tumor pathology, Ovarian Neoplasms pathology, Tumor Cells, Cultured
Abstract

The characteristics of 7 newly established ovarian carcinoma cell lines and one granulosa tumor cell line obtained from tumor samples of 7 patients with varying histology of the primary tumor are reported. The cell lines were isolated from 5 serous carcinomas, a mucinous carcinoma, an endometrioid carcinoma and a granulosa cell tumor. All cell lines were passaged at least 25 times and showed stable growth rates. Colony-forming efficiency varied on plastic from 2 to 57% and in agar from 0.01 to 9.30%. The DNA index of the granulosa tumor cell line was diploid, while the ovarian carcinoma cell lines were all aneuploid. In 2 cell lines polyploidisation occurred during culturing. A thorough cytogenetic analysis of 7 cell lines revealed that the granulosa tumor cell line has only minor cytogenetic abnormalities (+5, 22q+). In contrast, the epithelial ovarian-cancer cell lines gave very complex karyotypes with numerous markers and structurally rearranged chromosomes. The chromosomes most often in excess were 15 and 20. Structural rearrangements of chromosomes 1, 3, 7 and 11 were prominent in all ovarian cell lines. In addition, we found changes in chromosomes X, 5, 8 and 13 that have rarely been described before.

Published
1993
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17. Tumor infiltrating cells in human cancer. On the possible role of CD16+ macrophages in antitumor cytotoxicity.

Author

van Ravenswaay Claasen HH, Kluin PM, and Fleuren GJ

Subjects
Antigens, CD analysis, Cytotoxicity, Immunologic, Humans, Immunoenzyme Techniques, Immunophenotyping, Immunotherapy, Neoplasms pathology, Lymphocytes, Tumor-Infiltrating immunology, Macrophages immunology, Neoplasms immunology
Abstract

Background: To obtain a better understanding of the mechanism underlying different modalities of immunotherapy, we investigated the types of tumor-infiltrating cells present at the tumor site, with special attention to the presence of macrophages., Experimental Design: Frozen sections of carcinomas of the kidney, colon, breast, lung, ovary, and thyroid gland, as well as malignant melanoma were investigated with a panel of monoclonal antibodies against macrophage, T cell and NK cell associated antigens. Both type and pattern of the tumor-infiltrating cells were analyzed., Results: All tumor-infiltrating cells accumulated preferentially in the stromal bands between tumor cells. In all types of tumor, CD11c+, CD14+, CD68+ and alpha-naphthyl-acetate-esterase positive monocytes/macrophages accounted for most tumor-infiltrating cells. Next in frequency were T lymphocytes (CD2+, CD3+, TCR alpha beta +). Only a few B lymphocytes (CD22+), and T cells expressing the T cell receptor gamma delta (TCR gamma delta) were found. Hardly any lymphoid cells with an NK phenotype (CD3-, CD56+) were present in the tumors studied. Large numbers of CD16+ cells were found, which could be identified as macrophages on the basis of their morphology, positive staining with a panel of monocyte/macrophage markers, and the results of double staining with CD11c., Conclusions: We have demonstrated the presence of a large number of macrophages in the cellular infiltrates of several types of tumors. The largest numbers of CD16+ macrophages were found in renal cancer, melanoma, and colonic-carcinoma. These are the tumors that are most susceptible to immunotherapy with lymphokine activated killer cells, suggesting that these CD16+ macrophages may be involved in antitumor cytotoxicity. Furthermore, these findings suggest that new strategies of immunotherapy aimed at the use of macrophages present in many tumors could be developed.

Published
1992

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