Therapeutic Effect of Regional Chemotherapy in Diffuse Metastatic Cholangiocarcinoma

Background: Current therapeutic options in diffuse metastatic cholangiocarcinoma (CCC) are limited with unsatisfactory results. We evaluated the efficacy of regional chemotherapy (RegCTx) using arterial infusion (AI), hypoxic stop-flow abdominal perfusion (HAP), upper abdominal perfusion (UAP) and isolated-thoracic perfusion (ITP) in 36 patients with metastatic perihilar and intrahepatic CCC. Methods: Ten patients had previously undergone a liver resection and in 14 patients the previous systemic chemotherapy (sCTx) approach had failed. A total of 189 RegCTx cycles (90 AI, 74 UAP, 13 HAP and 12 ITP) were applied using cisplatin alone or with Adriamycin and Mitomycin C. A minimum of three cycles were applied in 75% of the study population. The response was evaluated using RECIST criteria with MediasStat 28.5.14. Mortality, morbidity and survival analysis were performed using a prospective follow-up database and SPSS–28.0. Results: No procedure related mortality occurred. The overall morbidity was 56% and dominated by lymph fistulas at the inguinal access site. No grade III or IV haematological complication occurred. The overall response rate was 38% partial response, 41% stable and 21% progressive disease. Median overall survival was 23 months (95%CI 16.3–29.7). The RegCTx specific survival was 12 months (95%CI 6.5–17.5) in completely therapy naive patients but also in patients who had failed a sCTx attempt previously. Conclusion: RegCTx is feasible, safe and superior to the current proposed therapeutic options in metastatic CCC. The role of RegCTx should be determined in a larger cohort of diffuse metastatic CCC patients but also at early stages especially in initially not resectable but potentially resectable patients

Basics of oncology/ Stephens

xxiv, 375 hal.: ill.; tab.; 24 cm

From an electrophoretic mobility shift assay to isolated transcription factors: a fast genomic-proteomic approach

Abstract Background Hypocrea jecorina (anamorph Trichoderma reesei) is a filamentous ascomycete of industrial importance due to its hydrolases (e.g., xylanases and cellulases). The regulation of gene expression can influence the composition of the hydrolase cocktail, and thus, transcription factors are a major target of current research. Here, we design an approach for identifying a repressor of a xylanase-encoding gene. Results We used streptavidin affinity chromatography to isolate the Xylanase promoter-binding protein 1 (Xpp1). The optimal conditions and templates for the chromatography step were chosen according to the results of an electrophoretic mobility shift assay performed under repressing conditions, which yielded a DNA-protein complex specific to the AGAA-box (the previously identified, tetranucleotide cis-acting element). After isolating AGAA-box binding proteins, the eluted proteins were identified with Nano-HPLC/tandem MS-coupled detection. We compared the identified peptides to sequences in the H. jecorina genome and predicted in silico the function and DNA-binding ability of the identified proteins. With the results from these analyses, we eliminated all but three candidate proteins. We verified the transcription of these candidates and tested their ability to specifically bind the AGAA-box. In the end, only one candidate protein remained. We generated this protein with in vitro translation and used an EMSA to demonstrate the existence of an AGAA-box-specific protein-DNA complex. We found that the expression of this gene is elevated under repressing conditions relative to de-repressing or inducing conditions. Conclusions We identified a putative transcription factor that is potentially involved in repressing xylanase 2 expression. We also identified two additional potential regulatory proteins that bind to the xyn2 promoter. Thus, we succeeded in identifying novel, putative transcription factors for the regulation of xylanase expression in H. jecorina.</p

Current standards of surgical management of gastric cancer: an appraisal.

PURPOSE Gastric cancer (GC) is the fifth most common malignancy worldwide and portends a grim prognosis due to a lack of appreciable improvement in 5-year survival. We aimed to analyze the available literature and summarize the current standards of surgical care for curative and palliative intent treatment of GC. METHODS We conducted a systematic search on the PubMed database for studies on the management of GC. RESULTS Endoscopic resection is an acceptable treatment option for T1a tumors. The role of optimal resection margin for GC remains unclear. D2 lymph node dissection remains the standard of care with splenectomy needed selectively for splenic hilum involvement. A distal pancreatic resection should be avoided. The advantage of bursectomy and omentectomy in GC surgery is not clear. Multi-visceral resection may be considered for locally advanced GC in carefully selected patients. Minimally invasive approaches are non-inferior to open surgery. Surgery should be abandoned prior even in metastatic GC within the frame of multimodal therapy approach. CONCLUSION Various trials have conclusively shown improved patient outcomes when well-established surgical standards are followed

A nuclear magnetic resonance biomarker for neural progenitor cells: is it all neurogenesis?

In vivo visualization of endogenous neural progenitor cells (NPCs) is crucial to advance stem cell research and will be essential to ensure the safety and efficacy of neurogenesis-based therapies. Magnetic resonance spectroscopic imaging (i.e., spatially resolved spectroscopy in vivo) is a highly promising technique by which to investigate endogenous neurogenesis noninvasively. A distinct feature in nuclear magnetic resonance spectra (i.e., a lipid signal at 1.28 ppm) was recently attributed specifically to NPCs in vitro and to neurogenic regions in vivo. Here, we demonstrate that although this 1.28-ppm biomarker is present in NPC cultures, it is not specific for the latter. The 1.28-ppm marker was also evident in mesenchymal stem cells and in non-stem cell lines. Moreover, it was absent in freshly isolated NPCs but appeared under conditions favoring growth arrest or apoptosis; it is initiated by induction of apoptosis and correlates with the appearance of mobile lipid droplets. Thus, although the 1.28-ppm signal cannot be considered as a specific biomarker for NPCs, it might still serve as a sensor for processes that are tightly associated with neurogenesis and NPCs in vivo, such as apoptosis or stem cell quiescence. However, this requires further experimental evidence. The present work clearly urges the identification of additional biomarkers for NPCs and for neurogenesis

Does Technological Innovation Really Reduce Marginal Abatement Costs? Some Theory, Algebraic Evidence, and Policy Implications

Marginal abatement costs, Production process innovations, Technological change, O38, Q28,