Diagnostic utility of CD205 in breast cancer: Simultaneous detection of myoepithelial cells and dendritic cells in breast tissue by CD205

Background. CD205 can be used to detect myoepithelial cells (MECs) and dendritic cells (DCs) in breast tissue. However, the usefulness of CD205 immunostaining in the pathological diagnosis of breast tumors is not fully understood. The objective of this study was to re-evaluate CD205 co-expression with other MEC markers, such as p63 and CD10, in nonneoplastic and neoplastic breast tissue and to evaluate its pathological diagnostic utility in these types of breast cancer. Material and methods. Nonneoplastic breast tissue samples with a terminal duct lobular unit and duct were obtained from fibroadenoma and mastopathy patients. Neoplastic breast tissue samples included ductal carcinoma in situ (DCIS) (n=43) and invasive ductal carcinoma (IDC) (n=60), including the tubule-forming type (n=20). These specimens were investigated by CD205, p63, and CD10 immunostaining. Results. In addition to p63 and CD10, CD205 was expressed on MECs in nonneoplastic breast and DCIS tissue samples; CD205 was simultaneously detected on DCs that had infiltrated DCIS and IDC tumor nests. CD205 was expressed on cancer cells themselves in only 7.3% of the breast cancer samples. The number of intratumoral CD205 + DCs in tubular IDC was significantly higher than that in DCIS (P<0.01

Development of an orally available inhibitor of CLK1 for skipping a mutated dystrophin exon in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a fatal progressive muscle-wasting disease. Various attempts are underway to convert severe DMD to a milder phenotype by modulating the splicing of the dystrophin gene and restoring its expression. In our previous study, we reported TG003, an inhibitor of CDC2-like kinase 1 (CLK1), as a splice-modifying compound for exon-skipping therapy; however, its metabolically unstable feature hinders clinical application. Here, we show an orally available inhibitor of CLK1, named TG693, which promoted the skipping of the endogenous mutated exon 31 in DMD patient-derived cells and increased the production of the functional exon 31-skipped dystrophin protein. Oral administration of TG693 to mice inhibited the phosphorylation of serine/arginine-rich proteins, which are the substrates of CLK1, and modulated pre-mRNA splicing in the skeletal muscle. Thus, TG693 is a splicing modulator for the mutated exon 31 of the dystrophin gene in vivo, possibly possessing therapeutic potential for DMD patients

Differentiation of astrocytoma between grades II and III using a combination of methionine positron emission tomography and magnetic resonance spectroscopy

Objective: This study aimed to establish a method for differentiating between grades II and III astrocytomas using preoperative imaging. Methods: We retrospectively analyzed astrocytic tumors, including 18 grade II astrocytomas (isocitrate dehydrogenase (IDH)-mutant: IDH-wildtype = 8:10) and 56 grade III anaplastic astrocytomas (37:19). We recorded the maximum methionine (MET) uptake ratios (tumor-to-normal: T/N) on positron emission tomography (PET) and three MRS peak ratios: choline (Cho)/creatine (Cr), N-acetyl aspartate (NAA)/Cr, and Cho/NAA, between June 2015 and June 2020. We then evaluated the cut-off values to differentiate between grades II and III. We compared the grading results between contrast enhancement effects on MR and combinational diagnostic methods (CDM) on a scatter chart using the cutoff values of the T/N ratio and MRS parameters. Results: The IDH-mutant group showed significant differences in the Cho/NAA ratio between grades II and III using univariate analysis; however, multiple regression analysis results negated this. The IDH-wildtype group showed no significant differences between the groups. Contrast enhancement effects also showed no significant differences in IDH status. Accordingly, regardless of the IDH status, no statistically independent factors differentiated between grades II and III. However, CDMs showed higher sensitivity and negative predictive value in distinguishing them than MRI contrast examinations for both IDH statuses. We demonstrated a significantly higher diagnostic rate of grade III than of grade II with CDM, which was more striking in the IDH-mutant group than in the wild-type group. Conclusions: CDM could be valuable in differentiating between grade II and III astrocytic tumors