Utilization of novel lectin-conjugated Au nanoparticles as Thomsen-Friedenreich onco-antigen target for in vitro cytotoxicity and apoptosis induction in leukemic cell line.

Leukemia is a tumor of blood-forming tissues including bone marrow and lymphatic nodes, which comprise biologically distinct subgroups. In the present study, Au NPs-PEG-Lectin was prepared as a drug targeting system for potential Thomsen-Friedenreich antigen (TF-Ag) presented on the surface of leukemic cells to induce cytotoxicity. Gold nanoparticles were prepared using citrate reduction method and conjugated with lectin via SH-PEG-COOH. The conjugate was characterized using UV/Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Zeta potential, and Scanning electron microscopy (SEM) with subsequent applications for cytotoxicity, cell cycle analysis, and apoptosis. Immunophenotypically blood samples from patients with acute lymphoblastic leukemia (ALL) were positively expressed CD45, CD95 dim expression, and low CD176 (TF-Ag) expression. Samples of acute myeloid leukemia (AML) confirmed the expression of all markers. Au NPs-PEG-Lectin conjugate showed an average size of 35.82 nm with zeta potential of -27.33 with accelerated lectin release from the conjugate at acidic pH. Au NPs-PEG-Lectin demonstrated the highest and most significant cytotoxic activity against HL-60 and K562 with IC50 of 132.5 and 314.8 µg mL-1, respectively. Flow cytometric analysis revealed induction of HL-60 cell apoptosis upon conjugate treatment in a dose-dependent pattern up to 51.03 % with no sign of necrosis with cell cycle arrest at G0/G1 phase. HL-60 cells treated with Au NPs-PEG-Lectin exhibited inter-nucleosomal DNA fragmentation. Morphologically, Phospho-Histone/BrdU dual staining indicated that Au NPs-PEG-Lectin initiated HL-60 arrest at G0/G1 phase. Taken together, molecular docking verified the possible interaction between lectin amino acids and different hydroxy groups within TF-Ag forming hydrogen bonds.

Validation of a new three-dimensional imaging system using comparative craniofacial anthropometry.

BACKGROUND: The aim of this study is to validate a new three-dimensional craniofacial stereophotogrammetry imaging system (3dMDface) through comparison with manual facial surface anthropometry. The null hypothesis was that there is no difference between craniofacial measurements using anthropometry vs. the 3dMDface system. METHODS: Facial images using the new 3dMDface system were taken from six randomly selected subjects, sitting in natural head position, on six separate occasions each 1 week apart, repeated twice at each sitting. Exclusion criteria were excess facial hair, facial piercings and undergoing current dentofacial treatment. 3dMDvultus software allowed facial landmarks to be marked and measurements recorded. The same measurements were taken using manual anthropometry, using soluble eyeliner to pinpoint landmarks, and sliding and spreading callipers and measuring tape to measure distances. The setting for the investigation was a dental teaching hospital and regional (secondary and tertiary care) cleft centre. The main outcome measure was comparison of the craniofacial measurements using the two aforementioned techniques. RESULTS: The results showed good agreement between craniofacial measurements using the 3dMDface system compared with manual anthropometry. For all measurements, except chin height and labial fissure width, there was a greater variability with the manual method compared to 3D assessment. Overall, there was a significantly greater variability in manual compared with 3D assessments (p < 0.02). CONCLUSIONS: The 3dMDface system is validated for craniofacial measurements.

Outcome of combined orthodontic-surgical treatment in a United Kingdom university dental institute.

INTRODUCTION: This retrospective observational cohort study evaluated effectiveness of combined orthodontic-orthognathic surgical treatment in a UK University Dental Institute. METHODS: Patients were identified from a database maintained prospectively throughout a 5-year period of observation. Demographic and clinical data included age, malocclusion, Index of Treatment Need, Index of Orthognathic Functional Treatment Need, orthodontist, surgeon, surgical procedure and treatment-time. Peer Assessment Rating (PAR) scores were generated from pre- and post-treatment dental study casts by a single calibrated examiner. RESULTS: One hundred and sixty two subjects began treatment during the period of observation, 92 completed, 14 elected to discontinue before surgery and 56 remained in treatment. Outcome data were available for 73, 16 males and 57 females (mean age 23.28 [SD, 7.92] years). Within this sample, 33 (45.2%) presented with class II division 1, 6 (8.2%) with class II division 2 and 34 (46.6%) with class III malocclusion. Isolated maxillary and mandibular surgery was carried out in 3 (4.1%) and 24 cases (32.8%), respectively; bimaxillary surgery was performed in 46 (63.1%). Mean total treatment time in fixed appliances was 920.28 days (30.7 months). Mean pre-treatment PAR score was 39.09 [SD, 9.42] and post-treatment 5.86 [SD, 4.25] with a mean 83.7% PAR score reduction, representing a greatly improved occlusal result. Kruskal-Wallis testing found no evidence of any relationship between independent variables and percentage PAR reduction; however, surgeon identity did significantly influence treatment length (P = 0.007). CONCLUSIONS: This investigation demonstrates that in terms of static occlusion combined orthodontic-orthognathic surgery is effective in correcting severe malocclusion.

Interstitial PDT for vascular anomalies.

INTRODUCTION: Photodynamic therapy is a proven therapeutic modality in the management of variety of pathologies involving the human body. Our aim in this clinical study is to prospectively evaluate the outcome following interstitial photodynamic therapy for patients with vascular anomalies. Patients' reports on quality of life with clinical and radiological evaluation were the main end point parameters used to assess the outcome. MATERIALS AND METHODS: Forty-three patients were referred to the UCLH Head and Neck Centre for treatment of vascular anomalies of the head and neck, including: infantile and congenital haemangiomas, venous, lymphatic and arteriovenous malformations. After multidisciplinary discussion, all patients underwent interstitial photodynamic therapy under general anaesthesia, using 0.15 mg/kg mTHPC as the photosensitising agent. Following treatment, patients were followed-up for a mean of 21 months. RESULTS: Fifteen out of nineteen patients who presented with long-term pain reported improvement after treatment. Also, 7/8 reported significant reduction of bleeding related to their vascular anomaly. Improvement of swelling was reported by 28/35 patients; while reduction of infection episodes was evident in 8/11 patients and 31/36 reported reduction in the disfigurement caused by their pathology. Significant reduction of swallowing problems was reported in 9/12 patients, and breathing problems in 7/9 patients. Clinical assessment showed that half of the patients had 'good response' to the treatment. Moderate clinical response was reported by 13 (30.2%) patients. Radiological assessment comparing imaging 6-week post-PDT to the baseline showed moderate response in 11 (25.6%) patients and significant response in 15 (34.9%) patients. CONCLUSION: This study on 43 patients with vascular anomalies undergoing interstitial photodynamic therapy provided evidence that PDT is a successful modality in the management of these pathologies that are resistant to conventional modalities, with minimal side effects.

Photodynamic therapy: The minimally invasive surgical intervention for advanced and/or recurrent tongue base carcinoma.

INTRODUCTION: The management of tongue base carcinoma continues to be a major challenge in head and neck oncology. Our aim in this prospective study was to evaluate the outcome following ultrasound-guided interstitial photodynamic therapy (US-iPDT) of stage IV tongue base carcinoma patients. Patients' reports on quality of life with clinical and radiological evaluation were the main end point parameters used to assess the outcome. MATERIAL AND METHODS: Twenty-one consecutive patients referred to the UCLH Head and Neck Centre for treatment of advanced and/or recurrent tongue base cancer were included in this study. Two-thirds of the referred patients had not been offered further conventional therapeutic options apart from palliative treatment. It was decided, by the multidisciplinary team, that the only available option was to offer US-iPDT under general anesthesia, using mTHPC (Foscan®) as the photosensitizing agent. Following treatment, patients were followed-up for a mean of 36 months (min. 21, max. 45). RESULTS: Nine of the 11 patients who presented with breathing problems reported improvement after treatment. Also, 19 of the 21 patients reported improvement of swallowing. Improvement of speech was reported by 11 of 13 patients. Clinical assessment showed that more than half of the patients had "good response" to the treatment and about a third reported "moderate response." Radiological assessment comparing imaging 6-week post-PDT to the baseline showed stable pathology with no change in size in four patients, minimal response in seven patients, moderate response in six patients, and significant response in two patients. Eight patients died; four of which due to loco-regional disease; and two from distant tumor spread. Kaplan-Meir survival curve was generated from the survival and follow-up data. CONCLUSIONS: Photodynamic therapy is a successful palliative modality in the treatment of advanced and/or recurrent tongue base carcinoma.

Photodynamic therapy outcome for oral dysplasia.

INTRODUCTION: Photodynamic therapy (PDT) is a minimally invasive surgical intervention used in the management of tissue disorders. It can be applied before, or after, any of the conventional modalities, without compromising these treatments or being compromised itself. MATERIALS AND METHODS: In this prospective study, a total of 147 consecutive patients with oral potentially malignant disorders were treated with surface illumination PDT, using 5-ALA or mTHPC as the photosensitizer. The average age was 53 ± 8.9 years. The patients' recovery was uneventful and no complications reported. Comparisons with the clinical and histopathological features and rate of recurrence as well as malignant transformation were made. The patients were followed-up for a mean of 7.3 years. ANALYSIS AND RESULTS: Homogenous leukoplakias were identified in 55 patients, non-homogenous leukoplakias in 73 patients, whereas 19 patients had erythroplakias. Ex- and current lifelong smokers formed 84.4% of the recruited patients. While people who currently smoke and drink formed 38.1% (56 patients) of the cohort. Erythroplakias were mainly identified in heavy lifelong smokers. The most common identified primary anatomical locations were the lateral border of tongue, floor of mouth and retromolar area. Moderate dysplasia was identified in 33 patients while 63 patients had severe dysplasias; and 32 patients had a histopathological diagnosis of carcinoma in situ. The rate of recurrence in laser surgery was approximately 11.6%. Malignant transformation was observed in 11 patients (7.5%), in the tongue, floor of mouth and retromolar area. Recurrence and malignant transformation was mainly identified in erythroplakias and non-homogenous leukoplakias. The final outcome of the cohort showed that 11 (7.5%) suffered from progressive disease, 5 (3.4%) had stable disease, 12 (8.2%) were considered partially responsive to the therapy. Complete response was identified in 119/147 patients (81%). CONCLUSION: 5-ALA-PDT and/or mTHPC-PDT offer an effective alternative treatment for oral potentially malignant disorders.

Prospective evaluation of outcome after transoral CO(2) laser resection of T1/T2 oral squamous cell carcinoma.

OBJECTIVE: Oral cancer is the sixth most common cancer in the world. The incidence of oral squamous cell carcinoma (OSCC) continues to be high, if not increasing. This prospective study assessed the oncological outcomes following transoral CO(2) laser resection of T1/T2 N0 OSCC. Patients' 3-year disease-specific survival and disease-free survival were evaluated. MATERIAL AND METHODS: The patients' data included a range of clinical, operative, and histopathological variables related to the status of the surgical margins. Data collection also included recurrence, cause of death, date of death, and last clinic review. Ninety patients (64 males and 26 females) participated in this study. Their mean age at the first diagnosis of OSCC was 63.5 years. Two thirds of the patients were Caucasians. Usually patients present with an ulcer of the tongue, floor of mouth, or buccal mucosa. Current and ex-smokers represented 82.2% of the cohort, whereas current and ex-drinkers were 78.9%. Comorbidities included history of oral lichen planus, oral submucous fibrosis, immunodeficiency, oral dysplasia, or OSCC. Clinically, 81 patients had T1N0 disease and 9 had T2N0 disease. RESULTS: Pathologic analysis revealed that nearly half of the patients had moderately differentiated OSCC, 18 moderately to poorly differentiated, and 19 poorly differentiated carcinoma. Study of the tumor margins was carried out and showed a mean of 5.7-mm depth of invasion; tumor clearance was primarily achieved in 73 patients. Recurrence was identified in 11 (12%) patients. The mean age of first diagnosis of the recurrence group was 76.4 years. The most common clinical presentation in the recurrence group was an ulcer involving the tongue or buccal mucosa; most commonly were identified in current or ex-smokers or drinkers. Recurrence was associated with clinical N-stage disease. The surgical margins in this group were also evaluated following relaser excision or surgical excision ± neck dissection. Follow-up resulted in a 3-year survival of 86.7%. Twelve patients died: 9 from noncancer-related causes, 2 from locoregional disease spread, and 1 from distant metastasis to the lungs. CONCLUSIONS: Squamous cell carcinoma of the oral cavity has a poor overall prognosis with a high tendency to recur at the primary site and extend to involve the locoregional lymph nodes. The overall results of this study suggest that CO(2) laser is a comparable modality to other traditional interventions (surgery) in the management of low-risk (T1/T2) tumors of the oral cavity.

Metastatic renal cell carcinoma to the orofacial region: A novel method to alleviate symptoms and control disease progression.

Head and neck metastatic tumours are uncommon. The primary tumors most likely to metastasize are those of the thyroid, breast, and lungs. The management of metastatic carcinoma in the orofacial region is variable. Palliative and symptomatic approaches are the mainstay in the management. The purpose of this case report is to highlight the feasibility of using PDT to alleviate nasal and visual symptoms and control the growth of metastatic renal cell carcinoma to the orofacial region.

Implementing NICE Guidelines on Recall Intervals into General Practice.

The NICE guidelines require practitioners to ensure that each patient has a specific recall interval based on an oral health needs assessment. There appears to be a hesitancy in the profession to move away from the 'six-month recall'. In England and Wales, Primary Care Organizations (PCOs) monitor activity using quantitative data. One particular metric measures how many patients are seen by the practice within 3 months and also between 3 and 9 months from their last course of treatment. The purpose of this paper is to introduce a quick reference chart based on the NICE guidelines which, when used in combination with clinical judgement, can aid the clinician in selecting a tailored recall interval. This paper discusses the purpose and benefits for using the guidelines in relation to NHS contractual obligations.

Brain activity before an event predicts later recollection.

Neural activity elicited by an event can predict whether the event is successfully encoded into memory. Here we assessed whether memory encoding relies not only on neural activity that follows an event, but also on activity that precedes it. In two experiments we found that human brain activity elicited by a cue presented just before a word could predict whether the word would be recollected in a later memory test.