A peptide derived from adaptor protein STAP-2 inhibits tumor progression by downregulating epidermal growth factor receptor signaling.

Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signals. We previously demonstrated that STAP-2 binds to epidermal growth factor receptor (EGFR) and facilitates its stability and activation of EGFR signaling in prostate cancer cells. Inhibition of this interaction may be a promising direction for cancer treatment. Here, we found that 2D5 peptide, a STAP-2-derived peptide, blocked STAP-2-EGFR interactions and suppressed EGFR-mediated proliferation in several cancer cell lines. 2D5 peptide inhibited tumor growth of human prostate cancer cell line DU145 and human lung cancer cell line A549 in murine xenograft models. Additionally, we determined that EGFR signaling and its stability were decreased by 2D5 peptide treatment during EGF stimulation. In conclusion, our study shows that 2D5 peptide is a novel anticancer peptide that inhibits STAP-2-mediated activation of EGFR signaling and suppresses prostate and lung cancer progression.

Identification of RPL15 60S Ribosomal Protein as a Novel Topotecan Target Protein That Correlates with DAMP Secretion and Antitumor Immune Activation.

Damage-associated molecular patterns (DAMPs) contribute to antitumor immunity during cancer chemotherapy. We previously demonstrated that topotecan (TPT), a topoisomerase I inhibitor, induces DAMP secretion from cancer cells, which activates STING-mediated antitumor immune responses. However, how TPT induces DAMP secretion in cancer cells is yet to be elucidated. Here, we identified RPL15, a 60S ribosomal protein, as a novel TPT target and showed that TPT inhibited preribosomal subunit formation via its binding to RPL15, resulting in the induction of DAMP-mediated antitumor immune activation independent of TOP1. TPT inhibits RPL15-RPL4 interactions and decreases RPL4 stability, which is recovered by CDK12 activity. RPL15 knockdown induced DAMP secretion and increased the CTL population but decreased the regulatory T cell population in a B16-F10 murine melanoma model, which sensitized B16-F10 tumors against PD-1 blockade. Our study identified a novel TPT target protein and showed that ribosomal stress is a trigger of DAMP secretion, which contributes to antitumor immunotherapy.

Osteochondral Lesion of the Tibial Plafond Induced by Malposition of Soft Suture Anchors Used for the Deltoid Ligament Repair: A Case Report.

CASE: A 24-year-old elite female rugby player complained of prolonged symptoms after a surgical repair of the deltoid ligament performed 2 years previously. Ankle arthroscopy revealed an osteochondral lesion in the tibial plafond at the medial gutter, with the fibers of the soft suture anchor exposed in the joint. The anchors were removed, and the cysts were filled with autogenous cancellous bone. The patient returned to the elite-level rugby games 5 months after the operation without any symptoms. CONCLUSION: We must be aware that even soft anchors can cause arthritis if improperly positioned.

Fibrocartilaginous Bed Injury of the Posterior Tibial Tendon Sheath: A Report of 3 Cases.

CASES: Three athletes (2 female gymnasts and 1 male rugby player) complained of persistent posteromedial ankle pain after an ankle injury. Arthroscopy of the ankle and tendoscopy of the posterior tibial tendon (PTT) were performed in 2 patients with prolonged symptoms and in 1 patient with acute severe pain. A small rupture at the fibrocartilaginous bed of the PTT with pinhole communication between the PTT sheath and the ankle joint cavity was detected, and open repair of the fibrocartilaginous bed was performed. CONCLUSION: All patients returned to their respective sports without any residual symptoms after open repair of the fibrocartilaginous bed.

Severe complication subsequent to surgical site infection after cervical laminoplasty: a case report.

INTRODUCTION: Surgical site infections (SSI) following spinal surgery can result in serious complications. Although early detection and intensive care are essential to minimize possible sequelae, more than one surgical intervention is required to alleviate the infection in some cases. CASE PRESENTATION: A 66-year-old man with long-standing Parkinson's disease (PD) developed SSIs after cervical laminoplasty. Despite surgical debridement and irrigation, his neurological status worsened severely and anterior infectious involvement at the C4-5 level was identified by magnetic resonance imaging. He underwent another urgent surgery for anterior debridement and iliac bone grafting. His laboratory results gradually normalized with antibiotic therapy, and his neurological status improved. One year after surgery, he was ambulatory with walker assistance. However, his right hand remained difficult to control with significant sensory loss and numbness. DISCUSSION: To our knowledge, this is the first case of SSI that extended rapidly to the anterior side despite immediate and intensive treatment in a patient with PD after laminoplasty. During SSI treatment, meticulous observation should be performed to check for exacerbations.

Visualization of the photodegradation of a therapeutic drug by chemometric-assisted fluorescence spectroscopy.

The fluorescence spectral fingerprint, also known as the excitation-emission matrix (EEM), is used to assess and visualize therapeutic drug photodegradation in combination with chemometrics. Examination of EEM-parallel factor analysis (PARAFAC) data showed that an individual component was easily separated from a mixture of photogenerated products of a heterocyclic pharmacophore, in this case, phenothiazine drugs (PTZs). Detailed investigations of both structure-EEM relationships and kinetics revealed that the components extracted from EEM-PARAFAC could be quantitatively attributed to such photogenerated products as phenothiazine sulfoxide and carbazole derivatives. EEM in combination with principal component analysis (PCA) could be used as a mapping tool to visualize information of the photodegradation process of PTZs. We also assessed the photostability of various types of PTZs containing side chains by using validated EEM-PARAFAC methodology.

A nonsense nucleotide substitution in the oculocutaneous albinism II gene underlies the original pink-eyed dilution allele (Oca2(p)) in mice.

The original pink-eyed dilution (p) on chromosome 7 is a very old spontaneous mutation in mice. The oculocutaneous albinism II (Oca2) gene has previously been identified as the p gene. Oca2 transcripts have been shown to be absent in the skin of SJL/J mice with the original p mutant allele (Oca2(p)); however, the molecular genetic lesion underlying the original Oca2(p) allele has never been reported. The NCT mouse (commonly known as Nakano cataract mouse) has a pink-eyed dilution phenotype, which prompted us to undertake a molecular genetic analysis of the Oca2 gene of this strain. Our genetic linkage analysis suggests that the locus for the pink-eyed dilution phenotype of NCT is tightly linked to the Oca2 locus. PCR cloning and nucleotide sequence analysis indicates that the NCT mouse has a nonsense nucleotide substitution at exon 7 of the Oca2 gene. Examination of three mouse strains (NZW/NSlc, SJL/J, and 129X1/SvJJmsSlc) with the original Oca2(p) allele revealed the presence of a nonsense nucleotide substitution identical to that in the NCT strain. RT-PCR analysis revealed that the Oca2 transcripts were absent in the skin of NCT mice, suggesting intervention of the nonsense-mediated mRNA decay pathway. Collectively, the data in this study indicate that the nonsense nucleotide substitution in the Oca2 gene underlies the Oca2(p) allele. Our data also indicate that the NCT mouse can be used not only as a cataract model, but also as a model for human type II oculocutaneous albinism.