TEST:

Sema4 Signal®

SEMA4D knockdown prevented the migration and promoted the apoptosis of HCT116 cells in vitro. In summary, Epi-11 cells, an important subset of epithelial cells, may drive the LM of CRC and act by crosstalk with immune cells through the PLXNB1/SEMA4D signalling axis.

"We identified GCBs as B cell-specific prognostic biomarkers for the first time. The MEF2B+ GCB score fills the research gap in the genetic prognostic prediction model of HNSCC and is expected to provide a theoretical basis for finding new therapeutic targets for HNSCC."

The KEYNOTE-B84 study (NCT04815720) evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC. Biomarker studies conducted in patients with surgically resectable metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) received neoadjuvant treatment with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone...Increased density and maturity of lymphoid aggregates correlated with disease control and longer progression-free survival (PFS). Conclusions Pepinemab, a Semaphorin 4D (SEMA4D) blocking antibody, in combination with ICB converts 'Cold' tumors to 'Hot' by inducing organized lymphoid aggregates.

Screening and on-treatment tumor biopsies were collected from several clinical trials: the KEYNOTE-B84 study (NCT04815720), that evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC, and biomarker neoadjuvant studies conducted in metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) patients with surgically resectable disease treated with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone. When SEMA4D is blocked from binding to its receptors, suppression is reduced, leading to increased penetration and organization of antigen presenting cells (APC) and lymphoid cells in the tumor microenvironment. It is expected that this would facilitate interaction and communication among these cell populations, accounting for improved immune responses in otherwise "cold" tumors.

Additionally, gene expression analysis revealed that relaxin 3 (RLN3), gastrin-releasing peptide (GRP), and cocaine- and amphetamine regulated transcripts (CART, also known as CARTPT) may function as novel endocrine hormones, influencing the HPO axis through autocrine, paracrine, and endocrine pathways. Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP, RLN3, CARTPT, LHCGR, FSHR, and GRPR in the ovaries of Lohmann layers, potentially contributing to their superior reproductive performance. In conclusion, this study provides a detailed molecular characterization of the HPO axis, offering novel insights into the regulatory mechanisms underlying reproductive biology.

Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

By examining the clustering and colocalization of presynaptic and postsynaptic molecules, we seek to determine whether the unique transmembrane domains of Plexin-B1 and Plexin-B2 may direct distinct steps of GABAergic and glutamatergic synapse development. Uncovering the functions of specific Plexin-B domains in synapse development will enhance our understanding of the signaling mechanisms that govern different steps in this process, as well as provide insight on how those processes differ between GABAergic and glutamatergic synapse development.

"Avera Health...and Sema4...announced the Avera/Sema4 Oncology and Analytics Protocol (ASAP) study, a five-year commitment to population health for precision oncology care...Avera and Sema4 will leverage Sema4 Signal® Whole Exome/Transcriptome Sequencing (WES/WTS), which captures data from approximately 18,500 genes, to enable comprehensive molecular profiling of a patient’s tumor tissue. The ASAP study will also include Sema4 Signal® Hereditary Cancer, one of the most comprehensive hereditary cancer testing panels available, to inform better care decisions for individuals with and without a concurrent cancer diagnosis."

There were no FDA-approved SDTs in prostate cancer (PCa) until 2020, when PARP inhibitors olaparib and rucaparib were approved for tumors bearing homologous recombination repair (HRR) genes. Increases in NGS test volume and olaparib use coincided with approval of PARP inhibitors for HRR-mutated PCa patients. Notably, NGS was used to match patients to off-label/investigational olaparib before its FDA approval.

"Sema4...announced the nationwide expansion of its disparities in cancer care study. The study, launched in 2021, enables access to comprehensive genetic and genomic testing for advanced cancer patients in underserved communities...The REsearch to advance PREciSion medicine and health Equity in oNcology Treatment (REPRESENT) study, which is already enrolling patients at five locations across two sites, will run nationally in collaboration with community oncologists caring for patients with advanced cancer in diverse and traditionally understudied and underserved populations."