Cough induced rib fracture, rupture of the diaphragm and abdominal herniation

Cough can be associated with many complications. In this article, we present a 59 year old male patient with a very rare combination of a cough related stress fracture of the ninth rib, a traumatic rupture of the diaphragm, and an abdominal wall herniation. The hernia was repaired through surgical treatment without bowel resection, the diaphragm and the internal and oblique abdominal muscle were adapted, and the abdomen was reinforced with a prolene net. Although each individual injury is well documented in the literature, the combination of rib fracture, abdominal herniation and diaphragm rupture has not been reported

Frequency, symptoms and outcome of intestinal metastases of bronchopulmonary cancer. Case report and review of the literature

BACKGROUND: We report a new case of small bowel metastases from primary lung cancer. Such metastases are not exceptional, but their clinical manifestations are rare. CASE PRESENTATION: The case involved a 56-year-old man with a squamous cell carcinoma of the lung (stage IV) that had been treated with chemotherapy. He presented fourteen months after diagnosis with an acute abdominal pain. Abdominal CT-scan demonstrated a perforated jejunum and he underwent emergency surgery. Postoperative pathologic analysis confirmed the diagnosis of metastatic pulmonary carcinoma. The patient was discharged after ten days, but died 8 weeks after surgery at home on tumor progression. CONCLUSION: We were able to find 58 documented similar cases in the literature. Most cases presented with bowel perforation or obstruction. Squamous cell carcinoma was the most common histological cell type followed by large cell carcinoma. Other metastases are often present, and the prognosis is mostly fatal at short term

Protein kinase CK1 interacts with and phosphorylates RanBPM in vitro

Members of the casein kinase 1 (CK1) family of serine/threonine kinases are highly conserved from yeast to mammals and are involved in the regulation of various cellular processes. Specifically, the CK1 isoforms δ and ε have been shown to be involved in the regulation of proliferative processes, differentiation, circadian rhythm, as well as in the regulation of nuclear transport. In this report we show that CK1δ and ε interact with murine RanBPM in the yeast two-hybrid system (YTH) and that the putative CK1δ-interacting domains of RanBPM are located between aa 155-386 and aa 515-653. Furthermore, in mammalian cells CK1δ partially co-localizes with RanBPM and can be co-immunoprecipitated with RanBPM. In addition, CK1δ strongly phosphorylates RanBPM within aa 436-514 in vitro. The identification of the interacting and scaffolding protein RanBPM as a new substrate of CK1δ points towards a possible function for CK1δ in modulating RanBPM specific functions

Newly Developed CK1-Specific Inhibitors Show Specifically Stronger Effects on CK1 Mutants and Colon Cancer Cell Lines

Protein kinases of the CK1 family can be involved in numerous physiological and pathophysiological processes. Dysregulated expression and/or activity as well as mutation of CK1 isoforms have previously been linked to tumorigenesis. Among all neoplastic diseases, colon and rectal cancer (CRC) represent the fourth leading cause of cancer related deaths. Since mutations in CK1δ previously found in CRC patients exhibited increased oncogenic features, inhibition of CK1δ is supposed to have promising therapeutic potential for tumors, which present overexpression or mutations of this CK1 isoform. Therefore, it is important to develop new small molecule inhibitors exhibiting higher affinity toward CK1δ mutants. In the present study, we first characterized the kinetic properties of CK1δ mutants, which were detected in different tumor entities. Subsequently, we characterized the ability of several newly developed IWP-based inhibitors to inhibit wild type and CK1δ mutants and we furthermore analyzed their effects on growth inhibition of various cultured colon cancer cell lines. Our results indicate, that these compounds represent a promising base for the development of novel CRC therapy concepts

Choledochal cyst as a diagnostic pitfall: a case report

<p>Abstract</p> <p>Introduction</p> <p>Choledochal cysts are rare congenital anomalies. Their diagnosis is difficult, particulary in adults.</p> <p>Case presentation</p> <p>This case report demonstrates the diagnostic and therapeutic pitfalls.</p> <p>Conclusion</p> <p>To prevent cost-intensive and potentially life-threating complications, a choledochal cyst must be considered in the differential diagnosis whenever the rather common diagnosis of a hepatic cyst is considered.</p

CD44 SNPrs187115: A Novel Biomarker Signature that Predicts Survival in Resectable Pancreatic Ductal Adenocarcinoma

Purpose: Although pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor, like other common cancers, it displays a wide range of biology. However, at present, there are no reliable tests to predict patients' cancer-specific outcomes and guide personalized treatment decisions. In this study, we aim to identify such biomarkers in resectable PDAC by studying SNPs in the CD44 gene, which drives the progression of pancreatic cancer. Experimental Design: A total of 348 PDAC patients from three independent cohorts [Switzerland, Germany, The Cancer Genome Atlas (TCGA)] who underwent pancreatic resection are included in the study. Information on the haplotype structure of the CD44 gene is obtained using 1000 Genomes Project data, and the genotypes of the respective tagging SNPs are determined. Cox proportional hazards models are utilized to analyze the impact of SNP genotype on patients' survival. Results: We identify an SNP in the CD44 gene (SNPrs187115) that independently associates with allelic differences in prognosis in all study cohorts. Specifically, in 121 Swiss patients, we observe an up to 2.38-fold (P = 0.020) difference in tumor-related death between the genotypes of SNPrs187115. We validate those results in both the German (HR = 2.32, P = 0.044, 101 patients) and the TCGA cohort (HR = 2.36, P = 0.044, 126 patients). Conclusions: CD44 SNPrs187115 can serve as a novel biomarker readily available at the time of PDAC diagnosis that identifies patients at risk for faster tumor progression and guide personalized treatment decisions. It has the potential to significantly expand the pool of patients that would benefit from tumor resection

TRAILblazing Strategies for Cancer Treatment

In the late 1990s, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF-family, started receiving much attention for its potential in cancer therapy, due to its capacity to induce apoptosis selectively in tumour cells in vivo. TRAIL binds to its membrane-bound death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) inducing the formation of a death-inducing signalling complex (DISC) thereby activating the apoptotic cascade. The ability of TRAIL to also induce apoptosis independently of p53 makes TRAIL a promising anticancer agent, especially in p53-mutated tumour entities. Thus, several so-called TRAIL receptor agonists (TRAs) were developed. Unfortunately, clinical testing of these TRAs did not reveal any significant anticancer activity, presumably due to inherent or acquired TRAIL resistance of most primary tumour cells. Since the potential power of TRAIL-based therapies still lies in TRAIL's explicit cancer cell-selectivity, a desirable approach going forward for TRAIL-based cancer therapy is the identification of substances that sensitise tumour cells for TRAIL-induced apoptosis while sparing normal cells. Numerous of such TRAIL-sensitising strategies have been identified within the last decades. However, many of these approaches have not been verified in animal models, and therefore potential toxicity of these approaches has not been taken into consideration. Here, we critically summarise and discuss the status quo of TRAIL signalling in cancer cells and strategies to force tumour cells into undergoing apoptosis triggered by TRAIL as a cancer therapeutic approach. Moreover, we provide an overview and outlook on innovative and promising future TRAIL-based therapeutic strategies