Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC. @*Materials and Methods@#We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments. @*Results@#In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug. @*Conclusion@#This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

Prognostic Value of Serum Soluble Programmed Death-Ligand 1 and Dynamics During Chemotherapy in Advanced Gastric Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). @*Materials and Methods@#We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics. @*Results@#The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline. @*Conclusion@#sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.

Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC. @*Materials and Methods@#In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models. @*Results@#AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy. @*Conclusion@#Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

Erratum to: Prevention of Lower Eyelid Ectropion Using Nonincisional Suspension Sutures after Blepharoplasty

The name of author should be corrected as the following: from "Min Hwang" to "So Min Hwang".

Erratum to: Prevention of Lower Eyelid Ectropion Using Nonincisional Suspension Sutures after Blepharoplasty

In this article, on page 173, the title has been spelled incorrectly.

Prevention of Lower Eyelid Ectropion Using Noninsional Suspension Sutures after Blepharoplasty

Blepharoplasty is one of the most common anti-aging operations. Although rare, complications such as ectropion may occur. Thus, we introduced an operative technique to prevent ectropion of the lower lid after blepharoplasty. From January 2012 to August 2013, we performed a nonincisional suspension suture (NISS) technique for 30 patients who visited our clinic for lower blepharoplasty. These patients had a distance of greater than 7 mm on the distraction test and were suspected of having horizontal lid laxity. We performed a slit incision 3 mm superior to the junction between the lateral epicanthus and the orbital bone during lower blepharoplasty. We passed a 7-0 nylon suture through the subcutaneous layer and the orbicularis oculi muscle. Then, we punctured the tarsal plate at the lateral limbus and fixed it to the lateral orbital rim by puncturing the periosteum. We tied a suspension knot through the slit incision. Thirty patients had satisfactory results without major complications, such as scleral exposure or ectropion. The NISS technique could be an effective method by which to prevent postoperative ectropion in cases with a mild to moderate degree lower lid laxity. The use of a NISS procedure is also a simple surgical technique, which saves time and is minimally invasive.

Delayed Rupture of Flexor Pollicis Longus by Plate for Fracture of the Distal Radius

PURPOSE: Delayed rupture of flexor pollicis longus as a sequelae of the plate inserted for distal radius fracture is a very rare. This is the first case reported and published in Korea. METHODS: A 48 years old female patient visited hospital, complaining flexor disturbance of interphalangeal joint of left thumb, which suddenly occurred without any external wound. We found that she had received operation of fixing plate for fracture of left distal radius 10 years ago. As operational opinion, we have checked that flexor pollicis longus tendon has been ruptured with oblique ways being stimulated by extended plate to palmar side over long period. RESULTS: Authors performed tenorrhaphy of flexor pollicis longus without tendon graft and presented a successful active flexion of the left thumb interphalangeal joint 1 year after the operation. CONCLUSION: If the extruded part of the end plate is observed during the operation or follow-up, it is considered to be necessary to get rid of the plate as early as possible after the fracture healing.

Clinical Study of Lacrimal Fistulas in the Oculoplastic Surgery

Lacrimal fistula, a rare developmental disorder, may result from an abnormal budding of the epithelial cord of the lacrimal system. Most cases are unilateral, however, bilateral cases are still more rare, which are combined with other systemic diseases or accompanying disorders. This entity has so far been known only to ophthalmologist. We would like to illustrate lacrimal fistula in patients who were referred to our clinic for periorbital cosmetic surgery, such as blepharoptosis and epicanthus, from April 2005 to December 2007. Fistular orifices of all 6 patients were had been located inferomedial to medial canthi along the epicanthal fold. Out of 6 patients, 4 patients presented with unilateral lacrimal fistula; right side in 3 patients and left side in 1 patient, and bilateral lacrimal fistulas in 2 patients. Three cases were found to have positive connection between the nasolacrimal apparatus, and blind pouch type in 5 cases. Three out of six patients underwent fistulectomy with concurrent cosmetic periorbital surgery. In 2 patients who presented with connection with the nasolacrimal apparatus, fistulectomy and lacrimal sac or the common lacrimal canaliculi repair was performed as well. The remaining one patient with bilateral blind pouch type of lacrimal fistulas underwent a simple fistulectomy. There were no postoperative complications or any recurrences.

Atypical Giant Cell Tumor: A Case Report

PURPOSE: Giant cell tumor is the second most common benign neoplasm in upper extremity. Unlike usual chief complaint of painless mass, an atypical case with giant cell tumor presented a distinguishing characteristics of which accompany pain and tenderness and is histologically giant-cell free. METHODS: A 31-year-old male patient complained of a rapid growing painful mass on the proximal phalanx of the left ring finger. Under microscopic operation, a 1.6 x 1.3cm sized mass was found to be surrounded by areolar tissue and attached to a tendon sheath, encircling the digital nerve and artery. Diagnostic confirmation was assisted by positive finding in histologic immunohistochemical stain-CD68. Characteristic pathologic finding is an atypical distribution of spindle cells & histiocytes without giant cells in fascicular pattern. RESULTS: Giant cell tumor was carefully removed under microscopic approach, while preserving digital nerve & artery. In postoperative 13th month, the patient presented with a 6mm of static two-point discrimination test, similar to that of the adjacent fingers. CONCLUSION: We report an atypical case with painful mass on tendon sheath, surrounding the digital nerve and artery that was diagnosed of giant cell tumor, but without giant cells on pathology. This case provides broader understanding of the giant cell tumor that should not only rely its typical findings of the painless mass and positive sign on H&E stain.

Lower Face-Neck Lift by Periauricular Minimal Invasion & Suspension Suture

To reverse the wrinkling & sagging of the skin on lower face and neck, there are various surgical methods such as suspension suture method, classical cervicofacial lift, SMAS-platysmal facelift, deep-plane facelift and composite facelift. Aging of lower face and neck present not only with sagging skin, but also is aggravated due to loss of elasticity of the SMAS and platysmal muscle. Successful surgical outcome is expected when tugging of the SMAS and platysma is performed with proper skin excision of lower face. Practically, deep-plane facelift methods present more satisfying outcome than the subcutaneous dissection, but takes longer recovery period and higher risk of postoperative complication. The authors would like to present a new method of lower face and neck lift, with periauricular minimally invasive suspension suture method, which does not required hospitalization, and gives higher patient satisfaction. In this study, 30 patients(26 females, 4 males) were operated from December of 2004 to February of 2007. Minimal periauricular subcutaneous dissection was performed. While measuring the sagging of the soft tissue on lower face and neck, suspension suture was performed anchoring platysma muscle from the submandibular slit incision site to the fascia of the mastoid process and stretched SMAS of the lower face was suspended to the fascia of the mastoid process with PDS 3-0 sutures. Most of the patients were satisfied without specific problems. The procedure carries advantages of simple operative method, easier access under intravenous sedation, much lesser risk of hematoma formation or facial nerve injury, shorter recovery period, improvement on the cervicomental angle and jaw line, and minimal postoperative scar.

A Case of Ossifying Fibromyxoid Tumor on the Temple Region

Ossifying fibromyxoid tumor of soft parts is a rare soft tissue neoplasm of uncertain histogenesis. It occurs commonly as a subcutaneous or intramuscular mass in the extremities and trunk, but rarely in the head and neck region. Its biologic behavior is generally benign, but a locally aggressive clinical course due to a pseudocapsule containing nests of tumor cells. Herein we report a case of a benign ossifying fibromyxoid tumor which occurred in the right temple in 34-year-old woman. The tumor was located in the temporalis muscle and completely removed with clear margin through bicoronal approach. The lesion was 2.0 x 2.5 x 3.0cm sized white to tan colored, well demarcated, firm mass. The tumor was covered by a fibrous capsule, and there was incomplete shell of lamellar bone at the periphery of the nodule. The tumor cells were uniformly round, ovoid, or spindle-shaped in collagenous and myxoid stroma. During 1 year's postoperative follow-up, the patient had no local recurrence.