The role of parotidectomy in Sjögren's syndrome.

Sjögren's syndrome, a chronic and progressive autoimmune disorder mainly characterized by xerophthalmia, xerostomia, and parotid enlargement, is primarily managed medically, but some patients will require surgical management. Patients with Sjögren's syndrome have an increased risk of non-Hodgkin lymphoma. Superficial parotidectomy is indicated for diagnostic purposes and can be therapeutic in limited circumstances. Surgical indications for parotidectomy in Sjögren's syndrome include recurrent parotitis refractory to medical management; salivary gland malignancy; and severe, refractory pain. Surgical complications include transient or permanent facial nerve injury, post-operative pain, persistent inflammation of remnant parotid tissue, Frey syndrome, and facial scarring.

Small molecule tolfenamic acid inhibits PC-3 cell proliferation and invasion in vitro, and tumor growth in orthotopic mouse model for prostate cancer.

BACKGROUND: Specificity protein (Sp) transcription factors are implicated in critical cellular and molecular processes associated with cancer that impact tumor growth and metastasis. The non-steroidal anti-inflammatory drug, tolfenamic acid (TA) is known to inhibit Sp proteins in some human cancer cells and laboratory animal models. We evaluated the anti-cancer activity of TA using in vitro and in vivo models for prostate cancer. METHODS: The anti-proliferative efficacy of TA was evaluated using DU-145, PC-3, and LNCaP cells. PC-3 cells were treated with DMSO or 50 µM TA for 48 hr. Whole cell lysates were evaluated for the expression of Sp1, survivin, c-PARP, Akt/p-Akt, c-Met, cdk4, cdc2, cyclin D3, and E2F1 by Western blot analysis. Cell invasion was assessed by Boyden-chamber assay and flow cytometry analysis was used to study apoptosis and cell cycle distribution. An orthotopic mouse model for prostate cancer with PC-3-Luc cells was used to study the in vivo effect of TA. RESULTS: TA inhibited the expression of Sp1, c-Met, p-Akt, and survivin; increased c-PARP expression and caspases activity in PC-3 cells. TA caused cell arrest at G(0) /G(1) phase accompanied by a decrease in cdk4, cdc2, cyclin D3, and E2F1 and an increase in critical apoptotic markers. TA augmented annexin-V staining, caspase activity, and c-PARP expression indicating the activation of apoptotic pathways. TA also decreased PC-3 cell invasion. TA significantly decreased the tumor weight and volume which was associated with low expression of Sp1 and survivin in tumor sections. CONCLUSION: TA targets critical pathways associated with tumorigenesis and invasion. These pre-clinical data strongly demonstrated the anti-cancer activity of TA in prostate cancer.

Harnessing nanoparticles to improve toxicity after head and neck radiation.

This article reports the evaluation of cerium oxide (CeO(2)) nanoparticles' ability to decrease xerostomia and radiation-induced dermatitis in mice after head and neck radiation. Mice were irradiated using an IC160 x-ray system. Two cohorts were included: (A) No-radiation and (B) 30 Gy/6 fractions, and were randomized into three groups: (1) saline, (2) 15 nM CeO(2) and (3) 15 µM CeO(2). Stimulated salivary flow and radiation-induced dermatitis were evaluated post radiation. Stimulated sialometry demonstrated improved salivary production in all CeO(2) groups in comparison with controls (flow: 204 vs. 115 µL/10 minutes, P = 0.0002). One week post radiation, G-III dermatitis decreased in the 15 µM group in comparison with controls (10% versus 100% incidence, respectively). There was decreased skin hyperpigmentation at 12 weeks in the 15-µM group in comparison with 15-nM and non-CeO(2) groups (50%, 70%, and 90% G-II, respectively). This study suggests that CeO(2) may be radioprotective for salivary production and reduces G-III dermatitis and skin hyperpigmentation incidence. CeO(2) as radioprotectant may be a feasible concept during radiotherapy. FROM THE CLINICAL EDITOR: This study demonstrates in a mouse model that cerium oxide (CeO(2)) nanoparticles may provide an important mechanism in preventing radiation induced xerostomia, a common complication of head and neck radiation treatments.

Bioluminescence imaging correlates with tumor progression in an orthotopic mouse model of lung cancer.

BACKGROUND AND OBJECTIVES: To determine whether bioluminescence imaging of human lung cancer cells growing in an orthotopic murine model provides a sensitive tool for monitoring tumor progression in athymic nude mice. METHODS: Human lung cancer (A549) cells were stably transfected with the firefly luciferase gene and inoculated into the right lung of athymic nude mice. Seven days after inoculation tumor growth was evaluated using the Kodak in-vivo Imaging System FX and continued to be monitored on a weekly basis. RESULTS: In duplicate experiments, human lung cancer tumors formed in 90% of animal's injected orthotopically. The mean intensity of the bioluminescence signal emitted from the lung cancer cells increased logarithmically during the course of study. Mice with positive bioluminescence signaling had confirmed tumors by microscopic histological analysis. Bioluminescence activity had a strong correlation with the tumor volume as determined histologically. CONCLUSIONS: Bioluminescence intensity directly correlates with tumor volume and therefore offers a reliable approach for detecting and monitoring the growth of human lung cancer cells in orthotopic murine models.

Quality indicators in head and neck operations: a comparison with published benchmarks.

OBJECTIVE: To investigate the reproducibility of quality indicators in the care of patients undergoing operations for head and neck cancer. DESIGN: A review of specialty-specific surgical quality indicators in a cohort undergoing procedures for definitive treatment of head and neck cancer, stratified by high and low acuity of the surgical procedures and compared with established benchmarks. SETTING: A large tertiary care institution and an associated multidisciplinary cancer center. PATIENTS: Fifty randomly selected patients with evaluable data who were diagnosed as having head and neck cancer that was definitively treated using any of the 3 modalities (surgical procedures, chemotherapy, and/or radiotherapy) during a 15-month period at our center. Twenty-one patients who underwent operations form the basis of this report. MAIN OUTCOME MEASURES: Procedures were stratified by acuity on the basis of the extent of the operation. Data were centered on quality indicators designed to reflect length of stay, readmission within 30 days postoperatively, return to the operating room within 7 days of surgery, use of blood products, 30-day mortality, adequacy of reports on surgical pathologic findings, and surgical site infection. RESULTS: Diagnoses in the cohort included carcinoma of the oral cavity in 19 patients (39%), oropharynx in 14 (29%), larynx in 13 (27%), and hypopharynx in 3 (6%). High- and low-acuity surgical procedures were performed in 12 and 7 patients, respectively. No statistically significant differences in the measures for quality indicators were found between the cohort and the calculated benchmarks. CONCLUSION: Our findings demonstrate the applicability of quality indicators to the care of patients with head and neck cancer treated by surgical intervention stratified by acuity and compared with established benchmarks.

Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice.

The nonsteroidal anti-inflammatory drug (NSAID), tolfenamic acid (TA) is emerging as a new anti-cancer agent. TA induces the degradation of specific Specificity protein (Sp) transcription factors, Sp1, Sp3 and Sp4 which are associated with tumor growth and metastasis. In this study we have evaluated the effect of TA on lung cancer using both in vitro and in vivo models. TA in a dose dependent manner inhibited proliferation and cell viability of two different lung cancer cells, A549 and CRL5803. TA treatment for 48 h significantly decreased the expression of Sp1, Sp3 and Sp4. The hepatocyte growth factor receptor, c-Met is overexpressed in a variety of cancers including lung cancer and Sp proteins mediate the regulation of c-Met. TA diminished the expression of c-Met protein and modulates its downstream signaling pathway. Furthermore, TA treatment significantly increased the number of apoptotic cells and pro-apoptotic markers c-PARP and Bax confirming the activation of apoptotic pathways. In vivo studies using the orthotopic mice model for lung cancer showed that TA (25 mg/kg/2 days and 50 mg/kg/2 days) resulted in a dose dependent decrease in tumor formation. The immunohistochemical staining of lung tissue showed high expression of Sp1, Sp3, Sp4, c-Met and phospho Met in control group and a dose dependent decrease in TA treated groups. The crucial findings of this study support that targeting c-Met with a potent inhibitor of Sp proteins is a robust strategy for the implications in lung cancer treatment and TA can serve as a therapeutic agent for this devastating disease.

Novel murine model for colon cancer: non-operative trans-anal rectal injection.

BACKGROUND: This study was conducted to develop a modified murine model of colon cancer that is non-operative. Currently, the most accurate orthotopic murine model of colon cancer requires an invasive procedure involving cecal injection of colon cancer cells and therefore limits the ability to perform immunological studies subsequent to cecal resections. MATERIALS AND METHODS: Murine colon cancer (CT26) cells were injected submucosally into the distal, posterior rectum of BALB/c mice. Care was taken not to pass transmurally into the pelvic cavity. Different magnifications (10x versus 100x) were used for injection, and primary tumor growth and metastatic disease were studied. RESULTS: In the initial study, 3/7 mice injected using 10x magnifications had notable, large tumor originating from the rectal wall, and histology revealed that all excised tumors were poorly differentiated adenocarcinoma. In the second study, 8/10 mice injected using 100x magnifications had notable tumor originating from the rectal well, and 4/8 mice had abnormal lung tissue with pathological evidence of hemorrhagic pulmonary edema. The use of 10x magnification resulted in 43% tumor take. In sharp contrast, 80% tumor take was observed with 100x magnification. The overall success of tumor take was 65% using the trans-anal rectal injection model. CONCLUSIONS: Our modified orthotopic murine model of colon cancer offers an alternative non-operative murine model for colon cancer and is less invasive than the traditional orthotopic model (i.e., cecal injection). This model may allow for more accurate investigations of inflammation and immune responses to surgical intervention without the influence of previous abdominal surgery.