Publications by authors named "Kurreck A"
Background: Minimally Invasive Esophagectomy (MIE) is a complex surgical procedure that has become a cornerstone in the management of esophageal cancer. This study aims to delineate the learning curve associated with MIE and its impact on patient outcomes.
Methods: A retrospective analysis was conducted on 191 patients who underwent MIE between 2015 and 2022.
Background: Despite remarkable clinical efficacy, little is known about the system-wide immunological alterations provoked by PD1 blockade. Dynamics of quantitative immune composition and functional repertoire during PD1 blockade could delineate cohort-specific patterns of treatment response and therapy-induced toxicity.
Methods: We longitudinally assessed therapy-induced effects on the immune system in fresh whole blood using flow cytometry-based cell quantifications, accompanied by analyses of effector properties of all major immune populations upon cell-type specific stimulations.
Background: Esophagectomy is central to curative therapy for esophageal cancer (EC). Perioperative outcomes affect both disease-free survival (DFS) and overall survival (OS) in patients undergoing oncologic esophageal surgery. The adoption of robotic techniques may improve surgical outcomes; however, the complex nature of perioperative outcomes is not adequately captured by individual quality measures.
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- Multimodal two-stage hepatectomy (mTSH) is a surgical approach for patients with bilobar colorectal liver metastases (CRLM) who can't be treated with a single operation due to limited liver function.
- A narrative review of clinical studies shows that interval chemotherapy is used in mTSH and might improve disease control, though only a few studies have specifically reported its effects.
- Current data suggest that interval chemotherapy does not negatively impact liver growth during mTSH or lead to serious complications, but more randomized clinical trials are needed for definitive conclusions.
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- Preclinical studies suggest that combining MEK inhibition with autophagy or CDK4/6 targeting may be beneficial for pancreatic cancer (PDAC) patients.
- A retrospective analysis of 34 patients treated with trametinib combined with hydroxychloroquine (THCQ) or palbociclib (TP) was conducted to evaluate the effectiveness of these regimens.
- Results showed that both combinations were ineffective, with most patients experiencing disease progression within a short time frame, highlighting the need for better treatment strategies for advanced PDAC with specific genetic mutations.
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- Hepatitis E virus (HEV) affects around 20 million people each year, causing serious health risks, especially for pregnant women and those with liver issues.
- Researchers developed small interfering RNAs (siRNAs) aimed at specific regions in the HEV genome to reduce viral replication and prevent mutations.
- The study demonstrated that siRNAs could effectively inhibit HEV in lab cell lines, and a modification to the siRNA could enhance the body's immune response against the virus, paving the way for potential new treatments.
Background: The key endpoints for the assessment of the effect of maintenance therapy for metastatic colorectal cancer (mCRC) are survival and quality-of-life outcomes. We aimed to compare dermatology-related quality of life (DRQOL) in patients with RAS wild-type (wt) mCRC treated with fluorouracil and folinic acid (FU/FA) + panitumumab (Pmab) versus FU/FA alone as maintenance therapy after folinic acid, fluorouracil and oxaliplatin + Pmab induction.
Patients And Methods: The phase II randomized PanaMa (AIO KRK 0212; NCT01991873) trial included 387 patients at 70 community/academic sites in Germany.
Purpose: In patients with metastatic pancreatic cancer, after failure of gemcitabine/nab-paclitaxel, this trial compares the efficacy of second-line therapy with FOLFIRI vs. OFF (1:1 randomisation) with cross-over to the vice-versa regimen as third-line therapy.
Patients And Methods: The primary endpoint was PFS (progression-free survival: time from randomization until progression or death) of second-line therapy.
Article Synopsis
- Nucleoside and nucleotide analogues, particularly those with a sulfur atom replacing the ribose oxygen, show promise in treating viral infections and cancer.
- A new method combines biocatalytic nucleobase diversification and chemical functionalization to create a wide variety of nucleoside analogues from 4'-thiouridine.
- The approach successfully produced 5-iodo-4'-thiouridine enzymatically and led to a novel nucleoside analogue probe, 5-ethynyl-4'-thiouridine, which can monitor RNA synthesis in HeLa cells as a new tool for metabolic RNA labeling.
Modern, highly evolved nucleoside-processing enzymes are known to exhibit perfect regioselectivity over the glycosylation of purine nucleobases at N9. We herein report an exception to this paradigm. Wild-type nucleoside phosphorylases also furnish N7-xanthosine, a "non-native" ribosylation regioisomer of xanthosine.
View Article and Find Full Text PDFAutomated high-throughput liquid handling operations in biolabs necessitate miniaturised and automatised equipment for effective space utilisation and system integration. This paper presents a thermal segment microwell plate control unit designed for enhanced microwell-based experimentation in liquid handling setups. The development of this device stems from the need to move towards geometry standardization and system integration of automated lab equipment.
View Article and Find Full Text PDFPurpose: We evaluated additional mutations in RAS wild-type (WT) metastatic colorectal cancer (mCRC) as prognostic and predictive biomarkers for the efficacy of added panitumumab to a 5-fluorouracil plus folinic acid (FU/FA) maintenance as pre-specified analysis of the randomized PanaMa trial.
Patients And Methods: Mutations (MUT) were identified using targeted next-generation sequencing (NGS; Illumina Cancer Hotspot Panel v2) and IHC. RAS/BRAF V600E/PIK3CA/AKT1/ALK1/ERBB2/PTEN MUT and HER2/neu overexpressions were negatively hyperselected and correlated with median progression-free survival (PFS) and overall survival (OS) since start of maintenance treatment, and objective response rates (ORR).
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- Nucleoside analogues are key pharmaceuticals used in cancer and viral infection treatment, but none are currently used for bacterial infections, despite some having antibiotic properties.
- The rise in antibiotic resistance creates an urgent need for new antibiotics, and natural product-derived nucleoside analogues could offer new therapeutic options.
- This overview highlights recent advancements from 2019 to 2023 in developing natural purine nucleoside antibiotics by combining synthetic chemistry, biosynthetic knowledge, and recombinant enzyme applications.
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- Esophagogastric adenocarcinoma (EGA) is a growing global health concern, with current treatment for localized cases involving a triplet chemotherapy regimen (FLOT) followed by surgery, while HER2-targeted therapies and PD-1 inhibitors have shown promise in metastatic cases.
- The PHERFLOT study is a phase II clinical trial evaluating the effectiveness and safety of combining pembrolizumab, FLOT, and trastuzumab in treating localized HER2-positive EGA, involving 30 patients and focusing on key endpoints like complete response rate and disease-free survival.
- Preliminary findings suggest that adding trastuzumab to perioperative therapy improves outcomes, and ongoing research is exploring how immune responses and other biomarkers can further
Despite molecular selection, patients (pts) with RAS wildtype mCRC represent a heterogeneous population including diversity in metastatic spread. We investigated metastatic patterns for their prognostic and predictive impact on maintenance therapy with 5-fluorouracil/folinic acid ± panitumumab. The study population was stratified according to (1) number of involved metastatic sites (single vs multiple organ metastasis), liver-limited disease vs (2) liver metastasis plus one additional site, and (3) vs liver metastasis plus ≥two additional sites.
View Article and Find Full Text PDFProstate cancer (PCa) is one of the most prevalent cancers in men worldwide. For its detection, serum prostate-specific antigen (PSA) screening is commonly used, despite its lack of specificity, high false positive rate, and inability to discriminate indolent from aggressive PCa. Following increases in serum PSA levels, clinicians often conduct prostate biopsies with or without advanced imaging.
View Article and Find Full Text PDFNucleoside phosphorylases are important biocatalysts for the chemo-enzymatic synthesis of nucleosides and their analogs which are, among others, used for the treatment of viral infections or cancer. S-methyl-5'-thioadenosine phosphorylases (MTAP) are a group of nucleoside phosphorylases and the thermostable MTAP of Aeropyrum pernix (ApMTAP) was described to accept a wide range of modified nucleosides as substrates. Therefore, it is an interesting biocatalyst for the synthesis of nucleoside analogs for industrial and therapeutic applications.
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- The PanaMa trial showed that adding panitumumab (Pmab) to fluorouracil and folinic acid (FU/FA) significantly improves progression-free survival in patients with RAS wild-type metastatic colorectal cancer after initial treatment.
- Health-related quality of life (HRQOL) was monitored using the EORTC QLQ-C30 questionnaire throughout therapy, revealing that most aspects of HRQOL remained stable or improved during treatment.
- Maintenance therapy with Pmab helped enhance HRQOL dimensions that worsened during initial therapy, supporting the idea that this treatment prolongs survival without adversely affecting quality of life.
Background: Anti-EGFR antibodies plus doublet chemotherapy is the standard of care in RAS/BRAF wild-type metastatic colorectal cancer (mCRC). No phase-3 level of evidence is available to guide treatment de-escalation after anti-EGFR-based first-line. Several randomised clinical trials investigated de-intensification strategies with 5-fluorouracil/leucovorin (5-FU/LV) and/or anti-EGFR.
View Article and Find Full Text PDFBackground: Clinical trials in metastatic colorectal cancer (mCRC) are usually conducted irrespective of sex. Sex-associated differences relating to safety and efficacy in the treatment of mCRC, however, are gaining interest.
Methods: PanaMa investigated the efficacy of panitumumab (Pmab) plus fluorouracil and folinic acid (FU/FA) versus FU/FA alone after induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab in patients with RAS wild-type mCRC.
Enzymes from thermophilic organisms are interesting biocatalysts for a wide variety of applications in organic synthesis, biotechnology, and molecular biology. Next to an increased stability at elevated temperatures, they were described to show a wider substrate spectrum than their mesophilic counterparts. To identify thermostable biocatalysts for the synthesis of nucleotide analogs, we performed a database search on the carbohydrate and nucleotide metabolism of Thermotoga maritima.
View Article and Find Full Text PDFNucleoside analogues are important compounds for the treatment of viral infections or cancers. While (chemo-)enzymatic synthesis is a valuable alternative to traditional chemical methods, the feasibility of such processes is lowered by the high production cost of the biocatalyst. As continuous enzyme membrane reactors (EMR) allow the use of biocatalysts until their full inactivation, they offer a valuable alternative to batch enzymatic reactions with freely dissolved enzymes.
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- - Lung cancer remains a leading cause of death and its incidence is rising, particularly in developing countries, demonstrating an urgent need for new treatment options despite advancements in targeted therapies.
- - A novel non-small cell lung cancer model was developed using digital light processing (DLP), incorporating simulated human blood vessels to facilitate drug testing in a more relevant environment.
- - Initial studies showed that the bioprinted 3D model had significantly higher cell viability and drug response compared to traditional 2D cultures, indicating its potential for testing new anticancer drugs, although further refinement is needed for comprehensive drug characterization.
Purpose: Consensus molecular subtypes (CMSs) were evaluated as prognostic and predictive biomarkers of patients with wild-type metastatic colorectal cancer (mCRC) receiving fluorouracil and folinic acid (FU/FA) with or without panitumumab (Pmab) after Pmab + mFOLFOX6 induction within the randomized phase II PanaMa trial.
Methods: CMSs were determined in the safety set (ie, patients that received induction) and full analysis set (FAS; ie, randomly assigned patients who received maintenance) and correlated with median progression-free survival (PFS) and overall survival (OS) since the start of induction or maintenance treatment and objective response rates (ORRs). Hazard ratios (HRs) and 95% CI were calculated by univariate/multivariate Cox regression analyses.