Akihito Arai

RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

RECQL1 and WRN proteins are RecQ DNA helicases that participate in suppression of DNA hyper-recombination and repair. In this study, we report evidence supporting their candidacy as cancer therapeutic targets. In hypopharyngeal carcinomas, which have the worst prognosis among head and neck squamous cell carcinomas (HNSCC) that are rapidly rising in incidence, we found that RECQL1 and WRN proteins are highly expressed and that siRNA-mediated silencing of either gene suppressed carcinoma cell growth in vitro. Similarly, siRNA administration in a murine xenograft model of hypopharyngeal carcinoma markedly inhibited tumor growth. Moreover, combining either siRNA with cis-platinum (II) diammine dichloride significantly augmented the in vivo anticancer effects of this drug that is used commonly in HNSCC treatment. Notably, we observed no recurrence of some tumors following siRNA treatment in this model. Our findings offer a preclinical proof of concept for RECQL1 and WRN proteins as novel therapeutic targets to treat aggressive HNSCC and perhaps other cancers.

RB1CC1 activates the p16 promoter through the interaction with hSNF5

RB1-inducible coiled-coil 1 (RB1CC1, also known as FIP200) is involved in dephosphorylation and increase of retinoblastoma tumor suppressor protein (RB1), but the RB1CC1 molecular mechanism in the dephosphorylation of RB1 is not fully understood. We determined that RB1CC1 activates the expression of p16 (also called INK4a/CDKN2a) through the activation of its promoter, using chromatin immunoprecipitation (ChIP) and p16 promoter-luciferase reporter assays. In addition, RB1CC1 essentially requires binding with hSNF5 (also known as BAF47/INI1, a chromatin-remodeling factor) to activate the p16 promoter, in order to enhance the RB1 pathway and acts as a tumor suppressor. Evaluation of the RB1CC1 mechanism of action is expected to provide useful information for clinical practice and future therapeutic strategies in human cancers.

Low-grade cribriform cystadenocarcinoma of the parotid gland: A case report

Low-grade cribriform cystadenocarcinoma is a rare tumor that is recognized as a variant of cystadenocarcinoma by the 2005 WHO classification. We report a case of low-grade cribriform cystadenocarcinoma. The patient was a 32-year-old woman who presented with a mass in the right parotid region. Computed tomography and magnetic resonance imaging revealed a polycystic mass in the right parotid gland. The preoperative fine needle aspiration biopsy showed no malignancy, however the frozen section during surgery showed carcinoma. The patient subsequently underwent total parotidectomy with preservation of the facial nerve. Microscopically, the tumor had a typical feature of intraductal proliferation. There was a golden brown pigment and PAS-positive/diastase-resistant cytoplasmic granules in the epithelium of the cysts. Immunohistochemically, smooth muscle actin highlighted the cells rimming the cystic spaces. The tumor cells were negative for S-100 protein. The patient has no recurrence and no facial palsy after the treatment.

Prognostic significance of RB1-inducible coiled-coil 1 in salivary gland cancers

No generally agreed‐upon method is available for predicting the prognosis of salivary gland cancers. RB1‐inducible coiled‐coil 1 (RB1CC1) is a positive regulator for the retinoblastoma tumor suppressor (RB1) pathway, and is a suitable marker for evaluating the clinical course of breast cancer. We investigated whether RB1CC1 predicts the prognosis of salivary gland cancers.

Use of systemic low-dose unfractionated heparin in microvascular head and neck reconstruction: Influence in free-flap outcomes

Abstract Background: Intravenous heparin administration is used to prevent thrombosis in free-flap transfer. However, it is unknown whether the use of heparin affects free-flap survival. The purpose of this study is to investigate the effect of heparin in free flap transfer. Methods: Two hundred and six patients who received ablative surgery for head and neck cancer were classified into three groups. Group A received ablative surgery, neck dissection, and free-flap reconstruction, and postoperatively they were administered continuous intravenous unfractionated heparin (5000–10 000 units/day) until postoperative day 7 (POD7); group B received the same procedures as group A but without heparin; group C received only ablative surgery and neck dissection without heparin. As indicators of coagulation time, the prothrombin time-international normalised ratio (PT-INR) and the activated partial thromboplastin time (APTT) were measured, before surgery and on POD1, 3, and 7. Flap failure, bleeding, haematoma formation, re-exploration, and thromboembolic events were recorded. Results: The PT-INR and APTT were 1.3–1.5-times longer in group A (p < 0.01), and 1.3-times longer (p < 0.01) in group B. The PT-INR and APTT were higher in groups A and B than C (p < 0.01). The free-flap success rate was not affected. Only the incidence of haematoma was increased in group A (p = 0.04). Conclusion: Heparin increased the haematoma formation, but did not change the incidence of free-flap failure. Thus, the intravenous low-dose heparin use does not affect microvascular flap survival.

Two cases of carotid blowout syndrome

We report two cases of carotid blowout syndrome. The first case, a 38-year-old man, suffered from common carotid artery rupture due to postoperative infection after thyroid surgery, and visited our emergency room. The site of rupture was identified under angiography, and was occluded with a balloon catheter. Then, carotid ligation was performed and the surgical site was covered with a deltopectoral skin flap. The second case, a 55-year-old woman, had undergone neck dissection and Co60 irradiation for oral tongue cancer 30 years before. Subsequently, she developed a cervical fistula, and suffered a hemorrhage from the fistula. Pseudoaneurysm of the external carotid artery was found by CT, so we tried to perform coil embolization, but could not control the bleeding. Thereafter, we confirmed necrosis around the carotid bifurcation, ligated the common carotid artery, and covered the surgical site with a pectoralis major myocutaneous flap. The triggers of both ruptures were inflammation, and, fortunately, ligating the carotid artery enabled both cases to survive without cerebrovascular disorder.