Immune stimulatory effect of anti-EpCAM immunotoxin - improved overall survival of metastatic colorectal cancer patients.

In a recent phase I trial in a heterogeneous group of carcinoma patients with advanced disease, we did not observe objective responses by CT at 8 weeks in patients treated with either the anti-EpCAM immunotoxin MOC31PE alone or administered in combination with the immunosuppressor cyclosporin (CsA). We have now assessed overall survival (OS) data for the two groups to reveal potential differences, and to elucidate putative underlying mechanisms. The OS time of MOC31PE monotherapy (34 patients) and MOC31PE in combination with CsA (23 patients), was assessed.

Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastoma.

Background: Protein tyrosine phosphatases (PTPs) regulate neuronal differentiation and survival, but their expression patterns and functions in human neuroblastoma (NB) are scarcely known. Here, we have investigated the function and expression of the non-receptor PTPN1 on human NB cell lines and human NB tumor samples.

Material/methods: NB tumor samples from 44 patients were analysed by immunohistochemistry using specific antibodies against PTPN1, PTPRH, PTPRZ1, and PTEN.

JASPAR 2020: update of the open-access database of transcription factor binding profiles.

JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups.

GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients.

Background: In breast cancer, activation of bone morphogenetic protein (BMP) signaling and elevated levels of BMP-antagonists have been linked to tumor progression and metastasis. However, the simultaneous upregulation of BMPs and their antagonist, and the fact that both promote tumor aggressiveness seems contradictory and is not fully understood.

Methods: We analyzed the transcriptomes of the metastatic 66cl4 and the non-metastatic 67NR cell lines of the 4T1 mouse mammary tumor model to search for factors that promote metastasis.

Beware the Jaccard: the choice of similarity measure is important and non-trivial in genomic colocalisation analysis.

The generation and systematic collection of genome-wide data is ever-increasing. This vast amount of data has enabled researchers to study relations between a variety of genomic and epigenomic features, including genetic variation, gene regulation and phenotypic traits. Such relations are typically investigated by comparatively assessing genomic co-occurrence.

MirGeneDB 2.0: the metazoan microRNA complement.

Small non-coding RNAs have gained substantial attention due to their roles in animal development and human disorders. Among them, microRNAs are special because individual gene sequences are conserved across the animal kingdom. In addition, unique and mechanistically well understood features can clearly distinguish bona fide miRNAs from the myriad other small RNAs generated by cells.

Publisher Correction: Shared heritability and functional enrichment across six solid cancers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Interfocal heterogeneity challenges the clinical usefulness of molecular classification of primary prostate cancer.

Prostate cancer is a highly heterogeneous disease and typically multiple distinct cancer foci are present at primary diagnosis. Molecular classification of prostate cancer can potentially aid the precision of diagnosis and treatment. A promising genomic classifier was published by The Cancer Genome Atlas (TCGA), successfully classifying 74% of primary prostate cancers into seven groups based on one cancer sample per patient.

Precise Immunodetection of PTEN Protein in Human Neoplasia.

PTEN is a major tumor-suppressor protein whose expression and biological activity are frequently diminished in sporadic or inherited cancers. gene deletion or loss-of-function mutations favor tumor cell growth and are commonly found in clinical practice. In addition, diminished PTEN protein expression is also frequently observed in tumor samples from cancer patients in the absence of gene alterations.

Two truncating variants in FANCC and breast cancer risk.

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies.

Targeted Killing of Monocytes/Macrophages and Myeloid Leukemia Cells with Pro-Apoptotic Peptides.

Several cells of myeloid origin, such as monocytes and macrophages are involved in various human disorders, including cancer and inflammatory diseases. Hence, they represent attractive therapeutic targets. Here we developed three lytic hybrid peptides, by fusing a monocyte- and macrophage-binding peptide to pro-apoptotic peptides, and investigated their killing potency on blood monocytes, macrophages, and leukemia cells.

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: long-term follow-up of a multicentre, randomised trial.

Background: The optimal surgical excision margins are uncertain for patients with thick (>2 mm) localised cutaneous melanomas. In our previous report of this multicentre, randomised controlled trial, with a median follow-up of 6·7 years, we showed that a narrow excision margin (2 cm vs 4 cm) did not affect melanoma-specific nor overall survival. Here, we present extended follow-up of this cohort.

The coexpression of fibroblast activation protein (FAP) and basal-type markers (CK 5/6 and CD44) predicts prognosis in high-grade invasive urothelial carcinoma of the bladder.

High-grade urothelial carcinoma (UC) of the bladder is a heterogeneous disease with dismal prognosis. Bladder tumors with basal phenotype are intrinsically aggressive, and morphological parameters that define disease staging remain main prognosticators. We intend to evaluate the role of cancer-associated fibroblasts (CAFs) in the prognosis of bladder cancer and its association with basal and luminal phenotypes.

High OGT activity is essential for MYC-driven proliferation of prostate cancer cells.

O-GlcNAc transferase (OGT) is overexpressed in aggressive prostate cancer. OGT modifies intra-cellular proteins via single sugar conjugation (O-GlcNAcylation) to alter their activity. We recently discovered the first fast-acting OGT inhibitor OSMI-2.

Chimeric antigen receptor preparation from hybridoma to T-cell expression.

The successful use of chimeric antigen receptor (CAR) for hematological cancer treatment has influenced the direction taken in translational research toward an increasing focus on personalized targeted immunotherapy. Thus, a growing number of labs worldwide are now interested in testing their old antibody collections in this format to broaden the spectrum of utility and improve safety and efficacy. We herein present a straightforward protocol for the identification of an antibody from a hybridoma and the design of the single chain fragment that will be placed on the extracellular part of the CAR construct.

Induction of neoantigen-reactive T cells from healthy donors.

The identification of immunogenic neoantigens and their cognate T cells represents the most crucial and rate-limiting steps in the development of personalized cancer immunotherapies that are based on vaccination or on infusion of T cell receptor (TCR)-engineered T cells. Recent advances in deep-sequencing technologies and in silico prediction algorithms have allowed rapid identification of candidate neoepitopes. However, large-scale validation of putative neoepitopes and the isolation of reactive T cells are challenging because of the limited availablity of patient material and the low frequencies of neoepitope-specific T cells.

B7-H3 Immune Checkpoint Protein in Human Cancer.

B7-H3 belongs to the B7 family of immune checkpoint proteins, which are important regulators of the adaptive immune response and emerging key players in human cancer. B7-H3 is a transmembrane protein expressed on the surface of tumor cells, antigen presenting cells, natural killer cells, tumor endothelial cells, but can also be present in intra- and extracellular vesicles. Additionally, B7-H3 may be present as a circulating soluble isoform in serum and other body fluids.

Precise definition of PTEN C-terminal epitopes and its implications in clinical oncology.

Anti-PTEN monoclonal antibodies (mAb) are arising as important tools for immunohistochemistry (IHC) and protein quantification routine analysis in clinical oncology. Although an effort has been made to document the reliability of tumor tissue section immunostaining by anti-PTEN mAb, and to standardize their IHC use in research and in the clinical practice, the precise topological and biochemical definition of the epitope recognized by each mAb has been conventionally overlooked. In this study, six commercial anti-PTEN mAb have been validated and characterized for sensitivity and specificity by IHC and FISH, using a set of prostate and urothelial bladder tumor specimens, and by immunoblot, using PTEN positive and PTEN negative human cell lines.

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function.

p38 MAPK activation through B7-H3-mediated DUSP10 repression promotes chemoresistance.

Immunoregulatory protein B7-H3 is involved in the oncogenic and metastatic potential of cancer cells, as well as in drug resistance. Resistance to conventional chemotherapy is an important aspect of melanoma treatment, and a better understanding of how B7-H3 enhances drug resistance may lead to the development of more effective therapies. We investigated the in vitro and in vivo sensitivity of chemotherapeutic agents dacarbazine (DTIC) and cisplatin in sensitive and drug resistant melanoma cells with knockdown expression of B7-H3.

Electrosurgery and Temperature Increase in Tissue With a Passive Metal Implant.

During monopolar electrosurgery in patients, current paths can be influenced by metal implants, which can cause unintentional tissue heating in proximity to implants. Guidelines concerning electrosurgery and active implants such as pacemakers or implantable cardioverter defibrillators have been published, but most describe interference between electrosurgery and the active implant rather than the risk of unintended tissue heating. Tissue heating in proximity to implants during electrosurgery may cause an increased risk of patient injury.

Antigen-delivery through invariant chain (CD74) boosts CD8 and CD4 T cell immunity.

Eradication of tumors by the immune system relies on the efficient activation of a T-cell response. For many years, the main focus of cancer immunotherapy has been on cytotoxic CD8 T-cell. However, stimulation of CD4 helper T cells is critical for the promotion and maintenance of immune memory, thus a good vaccine should evoke a two-dimensional T-cell response.