| 1. |
- Bruns, F, et al.
(författare)
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Complementary and alternative medicine experience in radiation oncology patients : first results of a multi-center approach
- 2006
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Ingår i: Trace elements and electrolytes. - 0946-2104. ; 23:4, s. 318-325
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Tidskriftsartikel (refereegranskat)abstract
- In recent years the demand and use of complementary and alternative medicine (CAM) in malignant diseases has increased noticeably. Since the general knowledge about CAM use is scant and CAM could potentially interact with standard therapies the German Working group “Trace Elements and Electrolytes in Oncology” performed a multi-centric study to comprehensively evaluate the use of CAM therapies in cancer patients treated with radiotherapy. Methods: 1,013 patients receiving consecutively radiotherapy for malignant diseases were interviewed using a standardized questionnaire including clinical and pathological tumor parameters as well as the type of CAM and reasons for CAM use. A self-assessment of patients’ personal conditions was performed in order to evaluate the subjective impact of CAM on quality of life. Results: A total of 59% of patients reported using CAM therapies. CAM use was more common in female patients, generally higher in advanced stages of disease and most common in breast cancer patients. Most frequently reported CAM therapies were vitamins (18%), mistletoe extracts (15%), selenium (10%), and other trace element preparations (7%). Multivariate logistic regression showed age, gender, tumor type and stage, and smoking behavior to be significant predictors for CAM use. A subjective improvement in quality of life due to the use of CAM was accounted for in 30% of patients. Conclusions: More than half of patients undergoing RT for cancer are using CAM therapies. Therefore, radiation oncologists should be asking for respective obtaining information about CAM use in order to avoid harmful interactions with conventional therapies. The value and potential hazards of such combined treatments have yet to be tested in further clinical studies.
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| 2. |
- Micke, O., et al.
(författare)
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Complementary and alternative medicine in lung cancer patients : a neglected phenomenon?
- 2010
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Ingår i: Frontiers of radiation therapy and oncology. - : S. Karger AG. - 0071-9676 .- 1662-3789. ; 42, s. 198-205
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Tidskriftsartikel (refereegranskat)abstract
- Study on the use of complementary and alternative medicine (CAM) in lung cancer patients has been widely neglected. Therefore, we initiated a study on the use of CAM in lung cancer patients in addition to radiation treatment. Overall, 120 patients from 3 institutions were interviewed by a standardized questionnaire. Besides the tumor parameters and the use of CAM, the reason for the use, patient information of the medication, the information sources and the subjective condition of the patient. Altogether, 54% of the patients reported using CAM (66% of female patients, 52% of male patients). The most frequently used CAM measures were vitamin combinations (17%), mistletoe (15%), and selenium (12%). A total of 52% reported the wish to support the tumor treatment as a reason for using CAM and 27% had a 'better feeling' using CAM. 50% of CAM was bought by the patients themselves and 50% were prescribed by their family physicians. The use of CAM is frequent in lung cancer patients. Our results suggest that it is very important to obtain information on the CAM use of patients and, particularly in controlled clinical trials, to prospectively document it.
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| 3. |
- Micke, Oliver, et al.
(författare)
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Predictive factors for the use of complementary and alternative medicine (CAM) in radiation oncology
- 2009
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Ingår i: European Journal of Integrative Medicine. - : Elsevier BV. - 1876-3820. ; 1:1, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A multi-center study was performed to identify factors predicting the use of complementary and alternative medicine (CAM) in radiotherapy patients, giving patients the information and the support they request. Methodology: A total of 1013 consecutive patients receiving radiotherapy for malignant diseases were interviewed using a structured questionnaire. Multivariate logistic stepwise backward regression was used to analyze the replies. Results: A total of 59% of patients reported using CAM therapies. CAM use was more common in female patients, generally higher in advanced stages, and most common in breast cancer, followed by Hodgkin's disease, other gynecologic malignancies, renal cell carcinoma, rectal cancer, and prostate cancer. The most frequently reported CAM therapies were vitamins, mistletoe, selenium, and other trace elements. Multivariate logistic stepwise backward regression showed that age, gender, tumor type and stage, and smoking behavior were significant predictors of CAM use. The highest relative risk (RR) was calculated for breast cancer patients, while the lowest RR was calculated for head and neck cancer patients. Discussion: This study represents the largest analysis of CAM use among radiotherapy cancer patients. More than half of the patients undergoing radiotherapy for cancer were using CAM. In general, the typical CAM user was a female patient suffering from breast cancer, a non-smoker and non-drinker, had an advanced stage of disease, and was treated with curative intentions.
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| 4. |
- Micke, O., et al.
(författare)
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Traditional European Medicine : Hildegard von Bingen and beyond
- 2011
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Ingår i: Trace elements and electrolytes. - 0946-2104. ; 28:3, s. 150-155
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Tidskriftsartikel (refereegranskat)abstract
- The term Traditional European Medicine (TEM) was coined analogous to Traditional Chinese Medicine (TCM). In the German-speaking areas, the so called Hildegard Medicine (HM) is very popular and according to a national survey, about 3% of German residents believe in HM. Their thoughts of unity and holistic care are based on the belief that cure and salvation are only possible in the devotion to God, who is the "great healer". Disease is an imbalance and health a balance of the soul. Her works are written in Latin and a visionary language and are therefore not intended for use by laymen. They are difficult to understand and leave a lot of room for interpretation. The currently popular term "Hildegard Medicine" cannot be found in her original writings. About 30 years ago, the ideas of Hildegard von Bingen have been readdressed by two physicians, Gottfried Hertzka and Wighard Strehlow. They are suggesting the drugs as well as Hildegard's dietary recommendations as an appropriate medical healing system for today. Hertzka and Strehlow follow a highly commercialized attempt while suggesting that the medical recommendations by Hildegard are of divine origin. This, however, cannot be true as the medical texts compiled by Hildegard are not relying on her visionary experiences as do their religious treatises. In conclusion, HM represents a typical example of current complementary and alternative medicine (CAM). Thus, one should state that the actual importance of the remarkable person Hildegard must not be seen as a recommendation for today's therapy but in the fact that she compiled medieval medical knowledge. Under the name of HM, poorly defined overpriced preparations are distributed. Treatment following the principles of HM for serious or malignant disorders is strongly discouraged.
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| 5. |
- Sarhan, Dhifaf, et al.
(författare)
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Antibody targeting of tumor associated macrophages in lung cancer remodel the tumor microenvironment and revives immune targeting of tumor cells
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Immunotherapy for cancer has revolutionized clinical practice and enabled cures for previously lethal cancers. However, the clinical responses are variable and highly influenced by immune regulatory compartments in the tumor microenvironment. This is especially true for immune-excluded tumors, where clinical trials aiming to recover T cell anti-tumor activity have been disappointing. Thus, in NSCLC and other cancers there is a clinical need for additional and combinatory treatments. We have previously shown that antibodies targeting scavenger receptors expressed on tumor-associated macrophages (TAMs), reduces tumor growth and impair metastasis in murine cancer models. Here we investigated targeting of the scavenger receptor MARCO on human TAMs in NSCLC. We found that expression of this receptor in the tumor correlated with immune-exclusion phenotype. Also, we found that lung cancer cell lines converted healthy myeloid cells towards TAM like cells with high expression of MARCO. These human MARCO+ myeloid cells stopped cytotoxic T cells and natural killer (NK) cells from killing tumors and inhibited their overall activity. We then generated anti-human MARCO antibodies and found that these could repolarize TAMs leading to augmented cytolytic ability of NK cells and T cells to kill tumor cells and recovered their proliferation and IFNγ production capacity. Overall, our data demonstrate that it is feasible to use antibodies to alter human TAM immune suppression of NK and T cell anti-tumor activities.
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| 6. |
- Ali, Abir Salwa, 1986-, et al.
(författare)
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PD-L1 expression in gastroenteropancreatic neuroendocrine neoplasms grade 3
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- Gastroenteropancreatic neuroendocrine neoplasms grade 3 (GEP-NENs G3) are rare tumors. These highly aggressive neoplasms are traditionally treated with platinum-based chemotherapy in combination with etoposide. Immune checkpoint proteins such as programmed cell death ligand (PD-L1) may have a role in different cancers allowing them escape the immune system and hence, progress. We aimed to investigate the immunohistochemical expression of PD-L1 in GEP-NEN G3 and evaluate its correlation to clinical parameters. In a cohort of 136 patients, 14 (10%) expressed PD-L1 immunoreactivity; four (3%) patients in the tumor cells and 10 (7%) had immunoreactive immune cells. PD-L1 expression did not correlate to clinical parameters, progression-free survival or overall survival. We conclude that PD-L1 expression is present only in a subset of GEP-NEN G3 patients. Further studies are needed to fully understand the role of PD-L1 in patients with GEP-NEN G3, including the future possibility for treatment with immune checkpoint inhibitors.
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| 7. |
- Augsten, Martin, et al.
(författare)
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CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:9, s. 3414-3419
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Tidskriftsartikel (refereegranskat)abstract
- This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts over-expressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic studies demonstrated that autocrine CXCL14-stimulation of fibroblasts stimulate migration and ERK-dependent proliferation of fibroblasts. CXCL14-stimulation of monocyte migration was also demonstrated. Furthermore, CXCL14-producing fibroblasts, but not recombinant CXCL14, enhanced in vitro proliferation and migration of prostate cancer cells and in vivo angiogenesis. These studies thus identify CXCL14 as a novel autocrine stimulator of fibroblast growth and migration, with multi-modal tumor-stimulatory activities. In more general terms, our findings suggest autocrine stimulation of fibroblasts as a previously unrecognized mechanism for chemokine-mediated stimulation of tumor growth, and suggest a novel mechanism whereby cancer-associated fibroblasts achieve their pro-tumorigenic phenotype.
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| 8. |
- Backman, Max, et al.
(författare)
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Extending the immune phenotypes of lung cancer: Oasis in the desert
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Tumor infiltrating immune cells are key elements of the tumor microenvironment and mediate the anti-tumor effects of immunotherapy. The aim of the study was to characterize patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to tumor mutations and clinicopathological parameters. Methods: Lymphocytes (CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+) and PD-L1+ were annotated on a tissue microarray including 357 operated NSCLC cases. Somatic mutations and tumor mutational burden were analyzed by targeted sequencing for 82 genes, and transcriptomic immune patterns were established in 197 patients based on RNAseq data. Results: We identified somatic mutations (TP53, NF1, KEAP1, CSMD3, LRP1B) that correlated with specific immune cell infiltrates. Hierarchical clustering revealed four immune classes: with (1) high immune cell infiltration (“inflamed”), (2) low immune cell infiltration (“desert”), (3) a mixed phenotype, and (4) a new phenotype with an overall muted inflammatory cell pattern but with an imprint of NK and plasma cells. This latter class exhibited low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, TGFB1), but was linked to better survival and therefore designated “oasis”. Otherwise, the four immune classes were not related to the presence of specific mutations (EGFR, KRAS, TP53) or histologic subtypes. Conclusion: We present a compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC and identified the novel immune class “oasis”. The immune classification helps to better define the immunogenic potency of NSCLC in the era of immunotherapy.
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| 9. |
- Backman, Max, et al.
(författare)
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Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
- 2021
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 255:3, s. 243-256
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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| 10. |
- Backman, Max, 1987-
(författare)
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Spatial immune analyses in clinical cancer tissue
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is a leading cause of premature death and lung cancer is the deadliest cancer type, with non-small cell lung cancer (NSCLC) representing 85% of lung cancer cases. Despite promising development in cancer treatment in recent decades, overall prognosis is poor. The aim of this thesis was to explore novel techniques in protein visualization in clinical cancer tissue to better our understanding of cancer immunity and to discover new biomarkers for improved cancer diagnostics.In Paper I traditional immunohistochemistry (IHC) was compared to the in-situ proximity ligation assay (isPLA). Both techniques were applied to stain 12 proteins in 39 cell lines and 37 tissue types. Two different antibodies were used in the IHC assay and in the isPLA, where binding by both antibodies is required to generate detection signals. The comparison of staining patterns showed that the isPLA presents a valuable alternative to traditional IHC.In Paper II cancer tissue from 357 NSCLC patients was immunophenotyped through IHC annotations of 11 different immune markers. A distinct group of cases with a signature of NK cells and/or plasma cells had favorable prognosis despite significantly lower T-cell activation signatures. This study provides a detailed description of the immune landscape in NSCLC, extending previous concepts, and highlights plasma and NK-cells as potential biomarkers for further validation.In Paper III a multiplex-multispectral pipeline was established to explore three immune marker panels in a NSCLC cohort, spatially quantifying 13 immune cell types. The immune composition of NSCLC was analyzed for the prognostic relevance of immune cell coordination. Cell densities and distances were found to contribute independently to prognosis, indicating that spatial information on local immune cell infiltration is crucial for understanding tumor immunity.In Paper IV an extensive characterization of the immune cell landscape of colon cancer identified a prognostic signature based on the ratio of CD8+ lymphocytes to CD68+CD163+ macrophages. This signature was superior to the state-of-the-art ‘Immunoscore’, and was also associated with longer survival when analyzed in other common cancer types. This presents a promising immunological biomarker that warrants further validation as a prognostic and predictive signature in common cancers.In summary, this thesis presents an in-depth study of immune cell infiltration in several cancer types to better understand cancer immunity. Through novel techniques and spatial metrics, we describe immunophenotypes that might contribute to cancer classification and prognostication. The identified immune phenomena may also present alternative treatment targets to overcome resistance to immunotherapy.
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