Personalized medicine最新文献

accepted at SABCS 2023, poster presented at SABCS 2023We report the efficacy of trastuzumab deruxtecan (T-DXd) in treating human epidermal growth factor receptor 2 (HER2) low, type ID leptomeningeal breast cancer (LMD) (with positive cerebrospinal fluid [CSF] cytology and hydrocephalus as the only abnormal imaging finding) and the diagnostic and monitoring utilization of a novel microfluidic platform called CNSide™. Breast cancer LMD is associated with poor prognosis, and effective treatments are lacking. Our case highlights two crucial aspects related to the treatment and monitoring of breast cancer LMD. First, T-DXd was chosen based on immunocytochemistry (IHC) data from CSF malignant cells and follow-up revealed effectiveness of T-DXd in treating HER2-low LMD. While the efficacy of T-DXd has been established in treating metastatic HER2-low breast cancer, our case represents, to our knowledge, the first demonstration of T-DXd's effectiveness in HER2-low breast cancer LMD. Second, since this is type 1D LMD with absence of unequivocal measurable radiological disease in both the central nervous system (CNS) and extra-CNS, we employed a novel microfluidic CSF assay to monitor disease response. This novel assay outperformed standard CSF cytology in our case. There is an urgent need to develop CSF tumor cell assessment tool that surpasses the capabilities of conventional CSF cytology.

Lung cancer has the highest mortality rate among all the highly prevalent neoplasia globally. The major concern with its frontline treatment-cisplatin, is the rapid progression of chemoresistance and multi-organ-based toxicities including hearing loss and tinnitus, nephrotoxicity, hepatotoxicity and myelosuppression including anemia and neutropenia. In this review, studies concluding the association of single nucleotide polymorphisms (SNP) in disparate genes with aforementioned toxicity points are summarized to observe the pharmacogenomic pattern. Especially, SNPs in ATP7B, ERCC-1, ERCC-2, MATE-1, OCT-2, ABCB-1, ABCC-1, ABCG-2, ABCC-2, SLC22A, ERCC-5, BRCA-1, GSTM-3, GSTM-4 and GSTM-5 genes appear to be associated with the therapeutic response and/or adverse effects of cisplatin. We recommend utilizing this information to minimize the risk of treatment failure due to chemoresistance and adverse effects on other organs.

Aim: Nonalcoholic fatty liver disease (NAFLD) is a significant health issue worldwide. This study investigated the effect of the adiponectin receptor 1 gene (ADIPOR1) polymorphism on susceptibility to NAFLD.Methods: Data from 330 participants, including 165 biopsy-proven NAFLD patients and 165 healthy controls, were collected. The PCR-RFLP method was used to detect the genotypes of ADIPOR1 rs2275738 or T-106C variant.Results: The "CC" genotype of the ADIPOR1 rs2275738 polymorphism, compared with the "TT" genotype and the "C" allele, compared with the "T" allele, are markers of increased NAFLD susceptibility (p = 0.018; OR = 2.07, 95% CI = 1.43-2.01 and p = 0.041; OR = 1.52, 95% CI = 1.24-2.35, respectively).Conclusion: This research suggests, for the first time, that the ADIPOR1 rs2275738 "CC" genotype is associated with a 107% increased risk for biopsy-proven NAFLD.

Aim: Rs16851030, a single-nucleotide variant located in the 3'-untranslated region of the ADORA1 gene, has been proposed as a potential marker of caffeine sensitivity in apnea of prematurity. Besides, it is associated with aspirin-induced asthma and the development of acute chest syndrome. However, its functional significance is still unconfirmed. This study aimed to elucidate the functional impact of rs16851030 by using CRISPR/Cas9 approach to induce the DNA variant and attendant physiological changes.Methods: Rs16851030 was introduced into HEK293 cells via homology-directed repair (HDR). Edited cells were fluorescence-enriched, sorted, isolated, and expanded into single-cell-derived clones. The edit was confirmed by Sanger sequencing. RNA sequencing was used to analyze affected pathways.Results: Rs16851030-mutant cells showed increased susceptibility to hypoxia, a condition related to apnea of prematurity. After 24 h of hypoxia, the viability of mutant clones 1 and 2 was low compared with wild-type cells (75.45% and 74.47% vs. 96.34%). RNA sequencing revealed transcriptomic changes linked to this increased vulnerability.Conclusion: Rs16851030 impairs cellular resistance to hypoxia, suggesting its role in conditions like apnea of prematurity. Further research should investigate the molecular mechanisms and transcriptomic alterations caused by rs16851030 under hypoxic conditions.

High altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema. In recent years, association studies have become the main method for identifying HAPE genetic loci. A genome-wide association study (GWAS) of HAPE risk-associated loci was performed in Chinese male Han individuals (164 HAPE cases and 189 healthy controls) by the Precision Medicine Diversity Array Chip with 2,771,835 loci (Applied Biosystems Axiom™). Eight overlapping candidate loci in CCNG2, RP11-445O3.2, NUPL1 and WWOX were finally selected. In silico functional analyses displayed the PPI network, functional enrichment and signal pathways related to CCNG2, NUPL1, WWOX and NRXN1. This study provides data supplements for HAPE susceptibility gene loci and new insights into HAPE susceptibility.

Background: Statins are commonly used medications. Variants in SLCO1B1, CYP2C9, and ABCG2 are known predictors of muscle effects when taking statins. More exploratory genes include RYR1 and CACNA1S, which can also be associated with disease conditions. Methods: Patients with pathogenic/likely pathogenic variants in RYR1 or CACNA1S were identified through an elective genomic testing program. Through chart review, patients with a history of statin use were assessed for statin-associated muscle symptoms (SAMS) along with collection of demographics and other known risk factors for SAMS. Results: Of the 23 patients who had a pathogenic or likely pathogenic RYR1 or CACNA1S variant found, 12 had previous statin use; of these, SAMS were identified in four patients. Conclusion: These data contribute to previous literature suggesting patients with RYR1 variants may have an increased SAMS risk. Additional research will be helpful in further investigating this relationship and providing recommendations.

Background: Colorectal cancer (CRC) is a prominent form of cancer globally, ranking second in terms of prevalence and serving as a leading cause of cancer-related deaths, but the underlying biological interpretation remains largely unknown. Methods: We used the summary data-based Mendelian randomization method to integrate CRC genome-wide association studies (n_case = 7062; n_control = 195,745) and expression quantitative trait loci summary data in peripheral whole blood (Consortium for Architecture of Gene Expression: n = 2765; Genotype-Tissue Expression [v8]: n = 755) and colon tissue (colon-transverse: n = 406; colon-sigmoid: n = 373) and identified related genes. Results: Genes ABTB1, CYP21A2, NLRP1, PHKG1 and PIP5K1C have emerged as significant prognostic markers for CRC patient survival. Functional analysis revealed their involvement in cancer cell migration and invasion mechanisms, providing valuable insights for the development of future anti-CRC drugs. Conclusion: We successfully identified five CRC risk genes, providing new insights and research directions for the effective mechanisms of CRC.

Multi-cancer early detection tests are emerging as a revolutionary technology for the early detection of dozens of cancers from a single blood sample, including cancers without proven screening methods. However, they also come with challenges, including false-positive and false-negative results. To help patients make informed decisions, patient education materials are crucial. A review of available materials reveals that, while some materials provide understandable and actionable information, most lack a balanced presentation of the current benefits and risks of multi-cancer early detection testing. The dynamic nature of this field necessitates continuous updates to educational materials, incorporating current evidence and uncertainties.