Nicole Fink-Neuboeck

The influence of elevated levels of C-reactive protein and hypoalbuminemia on survival in patients with advanced inoperable esophageal cancer undergoing palliative treatment

Inflammation perpetuates individual tumor progression resulting in decreased survival in cancer patients. The aim of our study was to evaluate the influence of elevated levels of C‐reactive protein (CRP) as well as low levels of albumin on patients with inoperable esophageal carcinoma.

Frequency and clinical impact of preoperative circulating tumor cells in resectable non-metastatic lung adenocarcinomas

OBJECTIVES Despite successful surgery, 30-50% of patients with resectable non-small cell lung cancer develop tumor recurrence within 5 years of surgery. MATERIALS AND METHODS In this prospective study, we performed CTC enumerations in 40 patients with non-metastatic lung adenocarcinoma (NMLA) using a size-based microfilter. Additionally, cfDNA isolated from plasma was analyzed in 35 out of 40 patients. RESULTS CTCs were identified in 15 out of 40 patients (37.5%) with a range of 1-44 cells, whereas mutated cfDNA was only detected in 3 out of 35 patients (8.6%). Disease-free survival (DFS) was significantly associated with CTC positivity (log-rank p=0.025), grading (log-rank p=0.019), tumor stage (log-rank p=0.025) and lymph node status (log-rank p=0.029). Multivariate analysis, including tumor stage and grading, showed that CTC positivity (p=0.006), grading (0.039) and tumor stage (p=0.022) were independently associated with DFS. CONCLUSION Our study found that microfilter-based CTC enumeration in NMLA patients is an independent predictor of worse DFS. The used NGS-based cfDNA characterization had limited sensitivity to be clinically informative in our study cohort. CTC assessment before surgery can thus identify NMLA patients at high risk of disease recurrence.

Influence of eukaryotic translation initiation factor 6 on non–small cell lung cancer development and progression

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Dysregulation of protein synthesis plays a major role in carcinogenesis, a process regulated at multiple levels, including translation of mRNA into proteins. Ribosome assembly requires correct association of ribosome subunits, which is ensured by eukaryotic translation initiation factors (eIFs). eIFs have become targets in cancer therapy studies, and promising data on eIF6 in various cancer entities have been reported. Therefore, we hypothesised that eIF6 represents a crossroad for pulmonary carcinogenesis. High levels of eIF6 are associated with shorter patient overall survival in adenocarcinoma (ADC), but not in squamous cell carcinoma (SQC) of the lung. We demonstrate significantly higher protein expression of eIF6 in ADC and SQC than in healthy lung tissue based on immunohistochemical data from tissue microarrays (TMAs) and on fresh frozen lung tissue. Depletion of eIF6 in ADC and SQC lung cancer cell lines inhibited cell proliferation and induced apoptosis. Knockdown of eIF6 led to pre-rRNA processing and ribosomal 60S maturation defects. Our data indicate that eIF6 is upregulated in NSCLC, suggesting an important contribution of eIF6 to the development and progression of NSCLC and a potential for new treatment strategies against NSCLC.

Photodynamic Therapy for Esophageal Cancer: Functional, Clinical, and Immunological Aspects

Patients suffering from esophageal cancer ineligible for curative surgery still have a poor prognosis. Endoscopic photodynamic therapy (PDT) represents a feasible and effective approach beneath the different treatment options for this aggressive malignancy. The mechanism of function is based on the illumination of malignant tumor tissue with laser light after selective accumulation of the specific photosensitizer in these tumor cells. As a result of this photochemical reaction, distinct necrosis of the endoluminal tumor develops quickly resulting in reducing tumor load and increasing quality of life. In case of esophageal cancer, PDT is performed endoscopically under general anesthesia. Moreover, PDT does not only represent a local anticancer therapy limited to the carcinoma. By inducing a considerable systemic inflammatory response, PDT is able to interfere with the human immune system. On the one hand, PDT induces the synthesis of tumor-specific cytotoxic T cells which are able to eliminate distant untreated tumor cells. On the other hand, PDT leads to the development of antitumor memory immunity that may sustainably prevent tumor recurrence.