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Resistance to chemoimmunotherapy in non-small-cell lung cancer

Cancer Drug Resistance 2020年第3期3卷 445-453页

作者： Maximilian Johannes Hochmair Respiratory Oncology Unit Vienna North Hospital-Klinik FloridsdorfVienna 1210Austria.

Recent clinical trials evaluating the combination of chemotherapy with immune checkpoint inhibition for the primary treatment of lung cancer showed increased progression-free and overall survival compared with chemotherapy alone.However,the combination of these two modalities is less than additive and the mechanisms of resistance to this therapeutic intervention are discussed here.So far,the conventional biomarkers for immunotherapy,namely programmed death-ligand 1 expression or tumor mutational burden are poor predictors of the efficacy of immunochemotherapy,and the optimal sequence of chemotherapy and immunotherapy has yet to be defined.

关键词： Lung cancer chemotherapy immunotherapy combination pembrolizumab resistance

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Protection of small-cell lung cancer circulating tumor cells by cellular fragmentation

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 345-354页

作者： Barbara Rath Adelina Plangger Doris Moser Maximilian Hochmair Ernst Ulsperger Gerhard Hamilton Department of Vascular Surgery Medical University of ViennaVienna A-1190Austria Department of Cranio-Maxillofacial and Oral Surgery Medical University of ViennaVienna A-1090Austria hospital floridsdorf Vienna A-1210Austria hospital Horn Horn A-3580Austria

Aim:Small-cell lung cancer(SCLC)disseminates aggressively and may exhibit high chemoresistance and poor survival rates.In this study,we aimed to investigate a new mechanism of drug resistance for SCLC circulating tumor cells(CTCs).Methods:SCLC CTC cell lines(n=4)which shed cellular fragments(MAT),as demonstrated by light and scanning electron microscopy,are compared to permanent SCLC lines.Selected proteins are detected by proteome arrays and the functional impact of MAT is studied using cytotoxicity tests involving cisplatin and Topotecan.Results:The SCLC CTC lines revealed layers of attached cellular fragments with a range of decreasing sizes from intact cells(approximately 12μm)down to small debris(approximately 2μm)which are not detectable in permanent SCLC lines.Intact SCLC CTC clusters represent cores of these fragment-coated spheroids.Proteome profiling of MAT revealed a protein pattern similar to intact cells.Chemosensitivity tests employing SCLC and SCLC CTC lines with chemotherapeutics used in therapy of SCLC demonstrated an inhibitory activity of MAT on the resulting cytotoxicity.Conclusion:Generation of cell-associated debris by SCLC CTCs offers protective effects against cytotoxic drugs,representing a novel mechanism allowing survival of SCLC CTCs in patients.

关键词： Small cell lung cancer circulating tumor cells shedding topotecan

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Recurrent abscess after primary successful endo-sponge treatment of anastomotic leakage following rectal surgery

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World Journal of Gastroenterology 2010年第36期16卷 4570-4574页

作者： Stefan Riss Anton Stift Caroline Kienbacher Bernhard Dauser Ingrid Haunold Stefan Kriwanek Wolfgang Radlsboek Michael Bergmann Division of General Surgery Department of SurgeryMedical University of ViennaA-1090 ViennaAustria Department of Surgery Floridsdorf HospitalA-1210 ViennaAustria Department of Surgery Barmherzige Brüder WienA-1020 ViennaAustria Department of Surgery Barmherzige Schwestern WienA-1060 ViennaAustria Department of Surgery Rudolfstiftung HospitalA-1030 ViennaAustria Department of Surgery G-ttlicher Heiland WienA-1170 ViennaAustria

AIM:To assess long-term efficacy of initially successful endo-sponge assisted therapy.METHODS:Between 2006 and 2009,consecutive patients who had undergone primary successful endo-sponge treatment of anastomotic leakage following rectal cancer surgery were enrolled in the study.Patients were recruited from 6 surgical departments in Vienna.Clinical and oncologic outcomes were assessed through routine endoscopic and radiologic follow-up examination.RESULTS:Twenty patients(7 female,13 male)were included.The indications for endosponge treatment were anastomotic leakage(n=17)and insufficiency of a rectal stump after Hartmann's procedure(n=3).All patients were primarily operated for rectal cancer.The overall mortality rate was 25%.The median followup duration was 17 mo(range 1.5-29.8 mo).Five patients(25%)developed a recurrent abscess.Median time between last day of endosponge therapy and occurrence of recurrent abscess was 255 d(range 21-733 d).One of these patients was treated by computed tomography-guided drainage and in 3 patients Hartmann's procedure had to be performed.Two patients(10%)developed a local tumor recurrence and subsequently died.CONCLUSION:Despite successful primary outcome,patients who receive endo-sponge therapy should be closely monitored in the first 2 years,since recurrence might occur.

关键词： Rectal surgery Anastomotic leakage Endo-sponge Endo-vacuum treatment

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