A5028206592- Colorectal and Anal Carcinomas
- Colorectal Cancer Surgical Treatments
- Pancreatic and Hepatic Oncology Research
- Gastric Cancer Management and Outcomes
- Glioma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Advanced Radiotherapy Techniques
- Cancer Immunotherapy and Biomarkers
- Colorectal Cancer Treatments and Studies
- PI3K/AKT/mTOR signaling in cancer
- Brain Metastases and Treatment
- Colorectal Cancer Screening and Detection
- Cancer, Hypoxia, and Metabolism
- Chemical Reactions and Isotopes
- Radiation Therapy and Dosimetry
- Radiomics and Machine Learning in Medical Imaging
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer, Lipids, and Metabolism
- Head and Neck Cancer Studies
- Cancer Research and Treatments
- Inflammatory mediators and NSAID effects
- Peptidase Inhibition and Analysis
- Meningioma and schwannoma management
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
Goethe University Frankfurt
2016-2025
Frankfurt Cancer Institute
2017-2025
Heidelberg University
2016-2025
German Cancer Research Center
2016-2025
University Hospital Cologne
2023-2025
Heinrich Heine University Düsseldorf
2024-2025
Düsseldorf University Hospital
2024-2025
University of Cologne
2024-2025
University Hospital Heidelberg
2017-2025
Deutschen Konsortium für Translationale Krebsforschung
2015-2024
Total neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy (CRT) and chemotherapy remains to be established. We conducted multicenter, randomized, phase II trial using pick-the-winner design on the basis hypothesis an increased pathologic complete response (pCR) 25% after total compared with standard 15% CRT. Patients stage or III were assigned group A induction three cycles fluorouracil, leucovorin, oxaliplatin before...
We previously described the prognostic impact of tumor regression grading (TRG) on outcome patients with rectal carcinoma treated preoperative chemoradiotherapy (CRT) in CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up 132 months.TRG CRT was determined 386 surgical specimens by amount viable cells versus fibrosis, ranging from TRG 4 (no cells) to 0 signs regression). Clinicopathologic parameters and were correlated cumulative incidence local recurrence, distant...
Combined radiochemotherapy is the currently used therapy for locally advanced pancreatic ductal adenocarcinoma (PDAC), but normal tissue toxicity limits its application. Here we test hypothesis that inhibition of ATR (ATM-Rad3-related) could increase sensitivity cancer cells to radiation or chemotherapy without affecting cells. We tested VE-822, an inhibitor, in vitro and vivo radiosensitization. Chk1 phosphorylation was indicate activity, γH2AX 53BP1 foci as evidence DNA damage Rad51...
We aimed to investigate the prognostic value of tumour-infiltrating lymphocytes’ (TILs) expression in pretreatment specimens from patients with head and neck squamous cell carcinoma (HNSCC) treated definitive chemoradiotherapy (CRT). The prevalence CD3+, CD8+, CD4+ FOXP3+ TILs was assessed using immunohistochemistry tumour tissue obtained 101 before CRT correlated clinicopathological characteristics as well local failure-free- (LFFS), distant metastases free- (DMFS), progression-free (PFS)...
DNA damaging agents such as radiotherapy and gemcitabine are frequently used for the treatment of pancreatic cancer. However, these treatments typically provide only modest benefit. Improving low survival rate cancer patients therefore remains a major challenge in oncology. Inhibition key damage response kinase ATR has been suggested an attractive approach sensitization tumor cells to agents, but specific inhibitors have remained elusive. Here we investigated potential first highly selective...
Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. To report the long-term results secondary end points prespecified in Randomized Phase 2 Trial Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) Locally Advanced Rectal Cancer. This analysis a randomized clinical trial included 311 patients who were...
Abstract Tumour hypoxia renders cancer cells resistant to therapy, resulting in markedly worse clinical outcomes. To find candidate compounds that reduce tumours, we conduct a high-throughput screen for oxygen consumption rate (OCR) reduction and identify number of drugs with this property. For study focus on the anti-malarial, atovaquone. Atovaquone rapidly decreases OCR by more than 80% wide range cell lines at pharmacological concentrations. In addition, atovaquone eradicates FaDu, HCT116...
Standard cancer therapy targets tumor cells without considering possible damage on the microenvironment that could impair response. In rectal patients we find inflammatory cancer-associated fibroblasts (iCAFs) are associated with poor chemoradiotherapy Employing a murine model or patient-derived organoids and primary stroma cells, show that, upon irradiation, interleukin-1α (IL-1α) not only polarizes toward phenotype but also triggers oxidative DNA damage, thereby predisposing iCAFs to...
We examined the prognostic value of tumour-infiltrating lymphocytes (TILs) in patients with squamous cell carcinoma head and neck (SCCHN) after surgery postoperative cisplatin-based chemoradiotherapy. FFPE-tissue originating from 161 treated 8 DKTK partner sites was immunohistochemically stained for CD3 CD8. Their expression correlated clinicopathological characteristics as well overall survival (OS), local progression-free (LPFS) distant metastases free-survival (DMFS), also context...
Research Article8 December 2016Open Access Source DataTransparent process PD-L1 blockade enhances response of pancreatic ductal adenocarcinoma to radiotherapy Abul Azad Department Oncology, CRUK/MRC Oxford Institute for Radiation University Oxford, UK Search more papers by this author Su Yin Lim Zenobia D'Costa Keaton Jones Angela Diana Owen J Sansom orcid.org/0000-0001-9540-3010 CRUK Beatson Cancer Institute, Glasgow, Philipp Kruger Sir William Dunn School Pathology, Stanley Liu Sunnybrook...
We investigated tumor regression grading (TRG) as a prognostic marker and individual-level surrogate for disease-free survival (DFS) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial.TRG was recorded prospectively using Dworak classification 1179 after preoperative fluorouracil-based chemoradiotherapy (CRT) or without oxaliplatin. Multivariable...
The aberrant vascular architecture of solid tumors results in hypoxia that limits the efficacy radiotherapy. Vascular normalization using antiangiogenic agents has been proposed as a means to improve radiation therapy by enhancing tumor oxygenation, but only short-lived effects for this strategy have reported so far. Here, we show NVP-BEZ235, dual inhibitor phosphoinositide-3-kinase (PI3K) and mTOR, can oxygenation structure over prolonged period achieves aim effective normalization. Because...
Hepatic metastases are amenable to ablation; however, many patients not suitable candidates for such therapy and recurrence is common. The tumor microenvironment known be essential metastatic growth, yet identification of plausible targets cancer in the has proven elusive. We found that human colorectal liver murine gastrointestinal experimental infiltrated by neutrophils. Plasticity neutrophils recently been shown lead both protumor antitumor effects. Here, promoted growth hepatic...
// Lai Mun Wang 1, * , Michael A. Silva 2, Zenobia D’Costa 3, Robin Bockelmann Zahir Soonawalla 2 Stanley Liu 4 Eric O’Neill 3 Somnath Mukherjee W. Gillies McKenna Ruth Muschel Emmanouil Fokas 1 Department of Pathology, Oxford University Hospital NHS Trust, Oxford, UK Surgery, Oncology, CRUK/MRC Institute for Radiation Sunnybrook Research Institute, Health Sciences Centre, Toronto, Canada These authors contributed equally to this work Correspondence to: Fokas, e-mail:...
We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8+ tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs phosphorylated Caspase-8 (T273) in patients with anal squamous cancer (ASCC) treated standard chemoradiotherapy (CRT). The baseline immunohistochemical expression was correlated clinicopathologic characteristics, cumulative incidence local failure, disease-free survival (DFS) overall (OS) 150 patients, also context human...
We examined the prognostic role of PD-1+ and CD8+ tumor infiltrating lymphocytes (TILs), PD-L1+ cells in patients with squamous cell carcinoma head neck (SCCHN) treated surgery postoperative chemoradiotherapy (CRT). FFPE samples from 161 were immunohistochemically stained for PD-1, CD8 PD-L1. The immune marker expression was correlated clinicopathologic characteristics, overall survival (OS), local progression-free (LPFS) distant metastases free-survival (DMFS), also context HPV16 DNA/p16...
Previous retrospective studies have shown that surgical quality affects local control in rectal cancer..In this secondary end point analysis, we evaluated the prognostic effect of total mesorectal excision (TME) plane CAO/ARO/AIO-04 phase 3 randomized clinical trial.The trial enrolled 1236 patients with cT3-4 and/or node-positive adenocarcinoma from 88 centers Germany between July 25, 2006, and February 26, 2010.Patients were to receive treatment standard fluorouracil-based preoperative...