The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision medicine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individual’s particular drug response. In this article, we review the contributions of genetic polymorphisms to major individual variations in drug pharmacotherapy, focusing specifically on the pharmacogenomics of phase-I drug metabolizing enzymes and transporters. Substantial frequency differences in key variants of drug metabolizing enzymes and transporters, as well as their possible functional consequences, have also been discussed across geographic regions. The current effort illustrates the common presence of variability in drug responses among individuals and across all geographic regions. This information will aid health-care professionals in prescribing the most appropriate treatment aimed at achieving the best possible beneficial outcomes while avoiding unwanted effects for a particular patient.

The therapeutic efficacy of antibodies can be successfully improved through targeted delivery of potent cytotoxic drugs in the form of antibody-drug conjugates. However, conventional conjugation strategies lead to heterogeneous conjugates with undefined stoichiometry and sites, even with considerable batch-to-batch variability. In this study, we have developed a chemo-enzymatic strategy by equipping the C-terminus of anti-CD20 ofatumumab with a click handle using Sortase A, followed by ligation of the payload based on a strain-promoted azide-alkyne cycloaddition to produce homogeneous conjugates. The resulting antibody-drug conjugates fully retained their antigen binding capability and proved to be internalized and trafficked to the lysosome, which released the payload with a favorable efficacy in vitro and in vivo. Thus, this reported method is a versatile tool with maximum flexibility for development of antibody-drug conjugates and protein modification.

Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient’s HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM.

BACKGROUND:Gemcitabine/cisplatin (GP) resistance displays a negative role in treating advanced and metastatic non-small cell lung cancer (NSCLC). Several studies found that the association existed between platelets and cancer antigen 125 (CA125) with...

In the present study, the efficacy of unilateral transverse process‑pedicle and bilateral puncture techniques in percutaneous kyphoplasty (PKP) for Kummell disease was compared. Between March 2015 and June 2017, 63 patients with Kummell disease were recruited and underwent PKP with two different puncture techniques: A total of 38 patients were treated by unilateral transverse process‑pedicle PKP and 25 patients were treated by bilateral PKP. The operative time, intra‑operative fluoroscopy time, volume of bone cement injection and bone cement leakage were recorded. Prior to surgery and 1 day post‑surgery, the visual analogue scale (VAS) pain score and Oswestry disability index (ODI) were determined, and the vertebral body height and Cobb angle were measured. The results indicated that the incidence of bone cement leakage in the unilateral group was similar with the bilateral group (15.79% vs. 16.00%), with no statistically significant difference between the two groups. None of the patients in the two groups had any obvious damage of the spinal cord. The operative time, intra‑operative fluoroscopy time and volume of bone cement injection in the unilateral group were lower than those in the bilateral group. A chest X‑ray examination at 1 day post‑surgery revealed no pulmonary embolism in the two groups. The VAS score, ODI, vertebral body height and Cobb angle were significantly improved in the unilateral and bilateral groups at 1 day post‑surgery and at the last follow‑up (12 months post‑surgery) as compared with these parameters prior to surgery. In conclusion, the unilateral transverse process‑pedicle and bilateral puncture techniques in PKP exhibited good efficacy as a treatment for Kummell disease. The operative time, intra‑operative fluoroscopy time and volume of bone cement injection were lower in the unilateral group.