The present invention is directed to secreted and transmembrane polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Secreted and Transmembrane Polypeptides and Nucleic Acids Encoding the Same

Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival ...

/pdf/mechanisms-of-cancer-cachexia-26gc7sv3fx.pdf

Mechanisms of Cancer Cachexia

Cancer cachexia: mediators, signaling, and metabolic pathways.

Anti-cancer drugs

High-throughput sequencing of circulating tumor DNA (ctDNA) promises to facilitate personalized cancer therapy. However, low quantities of cell-free DNA (cfDNA) in the blood and sequencing artifacts currently limit analytical sensitivity. To overcome these limitations, we introduce an approach for integrated digital error suppression (iDES). Our method combines in silico elimination of highly stereotypical background artifacts with a molecular barcoding strategy for the efficient recovery of cfDNA molecules. Individually, these two methods each improve the sensitivity of cancer personalized profiling by deep sequencing (CAPP-Seq) by about threefold, and synergize when combined to yield ∼15-fold improvements. As a result, iDES-enhanced CAPP-Seq facilitates noninvasive variant detection across hundreds of kilobases. Applied to non-small cell lung cancer (NSCLC) patients, our method enabled biopsy-free profiling of EGFR kinase domain mutations with 92% sensitivity and >99.99% specificity at the variant level, and with 90% sensitivity and 96% specificity at the patient level. In addition, our approach allowed monitoring of NSCLC ctDNA down to 4 in 10(5) cfDNA molecules. We anticipate that iDES will aid the noninvasive genotyping and detection of ctDNA in research and clinical settings.

Integrated digital error suppression for improved detection of circulating tumor DNA

Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss.

Using an optical biosensor based on a dual-peak long-period fiber grating, we have demonstrated the detection of interactions between biomolecules in real time. Silanization of the grating surface was successfully realized for the covalent immobilization of probe DNA, which was subsequently hybridized with the complementary target DNA sequence. It is interesting to note that the DNA biosensor was reusable after being stripped off the hybridized target DNA from the grating surface, demonstrating a function of multiple usability.

/pdf/real-time-detection-of-dna-interactions-with-long-period-4t55g6fjh8.pdf

Real-time detection of DNA interactions with long-period fiber-grating-based biosensor.

Removing the redundancy from randomised gene libraries.

Muscle protein degradation is thought to play a major role in muscle atrophy in cancer cachexia. To investigate the importance of the ubiquitin-proteasome pathway, which has been suggested to be the main degradative pathway mediating progressive protein loss in cachexia, the expression of mRNA for proteasome subunits C2 and C5 as well as the ubiquitin-conjugating enzyme, E214k, has been determined in gastrocnemius and pectoral muscles of mice bearing the MAC16 adenocarcinoma, using competitive quantitative reverse transcriptase polymerase chain reaction. Protein levels of proteasome subunits and E214k were determined by immunoblotting, to ensure changes in mRNA were reflected in changes in protein expression. Muscle weights correlated linearly with weight loss during the course of the study. There was a good correlation between expression of C2 and E214k mRNA and protein levels in gastrocnemius muscle with increases of 6–8-fold for C2 and two-fold for E214k between 12 and 20% weight loss, followed by a decrease in expression at weight losses of 25–27%, although loss of muscle protein continued. In contrast, expression of C5 mRNA only increased two-fold and was elevated similarly at all weight losses between 7.5 and 27%. Both proteasome functional activity, and proteasome-specific tyrosine release as a measure of total protein degradation was also maximal at 18–20% weight loss and decreased at higher weight loss. Proteasome expression in pectoral muscle followed a different pattern with increases in C2 and C5 and E214k mRNA only being seen at weight losses above 17%, although muscle loss increased progressively with increasing weight loss. These results suggest that activation of the ubiquitin-proteasome pathway plays a major role in protein loss in gastrocnemius muscle, up to 20% weight loss, but that other factors such as depression in protein synthesis may play a more important role at higher weight loss.

/pdf/expression-of-the-ubiquitin-proteasome-pathway-and-muscle-4c81vgcnzv.pdf

Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia

Bacteriophage T7 DNA primase recognizes 5'-GTC-3' in single-stranded DNA The primase contains a single Cys4 zinc-binding motif that is essential for recognition Biochemical and mutagenic analyses suggest that the Cys4 motif contacts cytosine of 5'-GTC-3' and may also contribute to thymine recognition Residues His33 and Asp31 are critical for these interactions Biochemical analysis also reveals that T7 primase selectively binds CTP in the absence of DNA We propose that bound CTP selects the remaining base G, of 5'-GTC-3', by base pairing Our deduced mechanism for recognition of ssDNA by Cys4 motifs bears little resemblance to the recognition of trinucleotides of double-stranded DNA by Cys2His2 zinc fingers

https://www.pnas.org/content/pnas/96/8/4295.full.pdf

Anna V. Hine

Papers

Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss.

Real-time detection of DNA interactions with long-period fiber-grating-based biosensor.

Removing the redundancy from randomised gene libraries.

Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia

The Cys4 zinc finger of bacteriophage T7 primase in sequence-specific single-stranded DNA recognition