Novel Antibody Exerts Antitumor Effect through Downregulation of CD147 and Activation of Multiple Stress Signals.

CD147 is an immunoglobulin-like receptor that is highly expressed in various cancers and involved in the growth, metastasis, and activation of inflammatory pathways via interactions with various functional molecules, such as integrins, CD44, and monocarboxylate transporters. Through screening of CD147-targeting antibodies with antitumor efficacy, we discovered a novel rat monoclonal antibody #147D. This humanized IgG4-formatted antibody, h4#147D, showed potent antitumor efficacy in xenograft mouse models harboring the human PDAC cell line MIA PaCa-2, HCC cell line Hep G2, and CML cell line KU812, which featured low sensitivity to the corresponding standard-of-care drugs (gemcitabine, sorafenib, and imatinib, respectively). An analysis of tumor cells derived from MIA PaCa-2 xenograft mice treated with h4#147D revealed that cell surface expression of CD147 and its binding partners, including CD44 and integrin α3ß1/α6ß1, was significantly reduced by h4#147D. Inhibition of focal adhesion kinase (FAK), activation of multiple stress responsible signal proteins such as c-JunN-terminal kinase (JNK) and mitogen-activated protein kinase p38 (p38MAPK), and expression of SMAD4, as well as activation of caspase-3 were obviously observed in the tumor cells, suggesting that h4#147D induced tumor shrinkage by inducing multiple stress responsible signals. These results suggest that the anti-CD147 antibody h4#147D offers promise as a new antibody drug candidate.

A case of generalized lipodystrophy-associated progeroid syndrome treated by leptin replacement with short and long-term monitoring of the metabolic and endocrine profiles.

We herein report a case of a 28-year-old man with generalized lipodystrophy-associated progeroid syndrome treated by leptin replacement. He showed symptoms of generalized lipodystrophy around onset of puberty. His body mass index was 11.9 kg/m2, and he had a short stature, birdlike facies, dental crowding due to micrognathia, partial graying and loss of hair, and a high-pitched voice, all of which are typical features of the progeroid syndrome. Laboratory examinations and abdominal ultrasonography revealed diabetes mellitus, insulin-resistance, dyslipidemia, decreased serum leptin levels (2.2 ng/mL), elevated serum hepatobiliary enzyme levels and fatty liver. Whole exome sequencing revealed de novo heterozygous LMNA p.T10I mutation, indicating generalized lipodystrophy-associated progeroid syndrome, which is a newly identified subtype of atypical progeroid syndrome characterized by severe metabolic abnormalities. Daily injection of metreleptin [1.2 mg (0.04 mg/kg)/day] was started. Metreleptin treatment significantly improved his diabetes from HbA1c 11.0% to 5.4% in six months. It also elevated serum testosterone levels. Elevated serum testosterone levels persisted even 1 year after the initiation of metreleptin treatment. To the best of our knowledge, this is the first Japanese case report of generalized lipodystrophy-associated progeroid syndrome. Furthermore, we evaluated short and long-term effectiveness of leptin replacement on generalized lipodystrophy by monitoring metabolic and endocrine profiles.

Anterior interosseous nerve palsy mimicking rupture of the index flexor digitorum profundus after volar locking plate fixation of a distal radius fracture.

We describe the case of a patient with distal radius fracture who became unable to flex the distal interphalangeal joint of the index finger after internal fixation using a volar locking plate. There was palpable crepitus with active thumb motion, and wrist radiographs showed prominence of the volar plate at the watershed line. Therefore, our initial diagnosis was plate-induced closed rupture of the flexor digitorum profundus tendon of the index finger. However, upon surgical removal of the plate, no tendon rupture was found. Magnetic resonance imaging after plate removal showed diffuse increased signal intensity in the index flexor digitorum profundus on T2-weighted fat-suppressed images, which indicated muscle denervation. Based on the above findings, we changed the diagnosis to anterior interosseous nerve palsy with isolated paralysis of the flexor digitorum profundus of the index finger. Finger flexion disability following volar plate fixation of distal radius fracture should always be investigated carefully..

[Perioperative Oral Management of Lung Cancer Patients; Medical, Dental, and Regional Dental Clinic Collaboration].

PURPOSE: To prevent oral problems in lung cancer patients, dental intervention should be performed in conjunction with cancer treatment in cancer base hospitals. This paper reports on the perioperative oral care management of lung cancer patients. PATIENTS AND METHODS: From January 2013 to August 2015, perioperative oral management was performed in 123 patients undergoing pulmonary lobectomy. We ensure cooperation between the departments of medicine and dentistry. First, the dentist plans oral management based on the patient's individual oral status. Then, the actual oral management is performed by an in-hospital dentist and at the regional dental clinic. RESULTS: The patients comprised 70 males and 53 females with an average age of 69.4 years;118 had primary lung cancer and 5 had metastatic lung cancer. Abnormal findings were detected in approximately 50% of the patients, of whom 6 received oral treatment before starting their cancer treatment. Two patients(1.3%)had postoperative complications. In all cases, the oral care support team provided both tooth and oral mucosal care. CONCLUSION: About half of the referred patients required oral treatment. There were no serious adverse events due to the oral care intervention. Further investigation is necessary to establish appropriate treatment policy guidelines for dental disease requiring oral maintenance.

Radial osteotomy for Kienböck disease.

Of various surgical treatments, radial shortening for patients with negative ulnar variance and radial wedge osteotomy (radial closing osteotomy) for patients with 0 or positive ulnar variance are widely accepted for the treatment of Kienböck disease. Long-term follow-up studies have shown more than 10 years lasting satisfactory pain relief, as well as an increase in wrist range of motion and grip strength. As representative surgical procedures, the techniques of radial shortening by transverse osteotomy, using a locking compression plate for internal fixation, and radial wedge osteotomy by step-cut osteotomy, using a small dynamic compression plate or locking compression plate, are described. One important point of radial wedge osteotomy is that resection of simple wedge bone yields a decrease in ulnar variance; therefore, we recommend trapezoidal bone resection with ulnar height of 1 mm for transverse osteotomy at the metaphysis and ulnar height of 2 mm for step-cut osteotomy at the distal fourth of the radius.