Delta-like canonical Notch ligand 3 as a potential therapeutic target in malignancies: A brief overview

Delta-like canonical Notch ligand 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) Notch receptor ligand family and plays a crucial role in Notch signaling, which influences various cellular processes including differentiation, proliferation, survival, and apoptosis. DLL3 is expressed throughout the presomitic mesoderm and is localized to the rostral somatic compartments; mutations in DLL3 induce skeletal abnormalities such as spondylocostal dysostosis. Recently, DLL3 has attracted interest as a novel molecular target due to its high expression in neuroendocrine carcinoma of the lung. Moreover, a DLL3-targeting Ab-drug conjugate, rovalpituzumab tesirine (ROVA-T), has been developed as a new treatment with proven antitumor activity. However, the development of ROVA-T was suspended because of shorter overall survival compared to topotecan, the second-line standard treatment. Thus, several studies on the mechanism and function of DLL3 in several malignancies are underway to find a new strategy for targeting DLL3. In this review, we discuss the roles of DLL3 in various malignancies and the future perspectives of DLL3-related research, especially as a therapeutic target.     

Fluorescence visualization of the intersegmental plane by bronchoscopic instillation of indocyanine green into the targeted segmental bronchus: determination of the optimal settings

ObjectiveTo determine the appropriate amount of indocyanine green for bronchial insufflation.MethodsWe enrolled 20 consecutive patients scheduled for anatomical segmentectomy in the Kochi Medical School Hospital. After inducing general anesthesia, 6 to 60 mL of 200-fold-diluted indocyanine green (0.0125 mg/mL) was insufflated into the subsegmental bronchi in the targeted pulmonary segmental bronchus. The volume of the targeted pulmonary segments was calculated using preoperative computed tomography. Fluorescence spread in the segmental alveoli was visualized using a dedicated near-infrared thoracoscope.ResultsThe targeted segment was uniformly visualized by indocyanine green fluorescence in 16/20 (80.0%) cases after insufflating indocyanine green. A receiver operating characteristic curve indicated that the area under the curve was 0.984; the optimal cut-off volume of diluted indocyanine green for insufflation was 8.91% of the calculated targeted pulmonary segment volume.ConclusionsThe setting for indocyanine green insufflation was optimized for near-infrared fluorescence image-guided anatomical segmentectomy. By injecting the correct amount of indocyanine green, fluorescence-guided anatomical segmentation may be performed more appropriately.     

The morphologic and biochemical effects of tensile force application to the interparietal suture of the Sprague-Dawley rat

The purpose of this study was to correlate the histologic and biochemical responses of the interparietal suture to a range of tensile forces. Stainless steel spring implants, calibrated to generate expansive forces from 50 to 250 g, were placed across the interparietal suture in 85 female Sprague-Dawley rats. After experimental periods from 2 hours to 14 days, the interparietal sutures were evaluated by radiography, histology, and biochemistry. An in vivo/in vitro system was used for the biochemical analysis; total protein, proline incorporated, percent collagen, and alkaline phosphatase activity were measured. The radiographs and histology showed that in vivo suture expansion was achievable with 50 to 70 g of force, but the heavier forces showed greater sutural opening, more cellular proliferation, and more bone formation. This increased biologic response by the heavier forces was substantiated by an increase in sutural protein and alkaline phosphatase activity but not in percent collagen. It was concluded that changes in the total protein content of the suture were not primarily caused by proliferation of osteogenic cells and fibroblasts but due to an influx of transudate. In contrast, the increase in incorporation of 3H-proline and alkaline phosphatase activity correlated with the observance of bone formation. This study indicated a positive correlation between the magnitude of tensile forces and osteogenic response.     

Factors associated with the stability of titanium screws placed in the posterior region for orthodontic anchorage.

Recently, implant anchors such as titanium screws have been used for absolute anchorage during edgewise treatment. However, there have been few human studies reporting on the stability of implant anchors placed in the posterior region. The purpose of this study was to examine the success rates and to find the factors associated with the stability of titanium screws placed into the buccal alveolar bone of the posterior region. Fifty-one patients with malocclusions, 134 titanium screws of 3 types, and 17 miniplates were retrospectively examined in relation to clinical characteristics. The 1-year success rate of screws with 1.0-mm diameter was significantly less than that of other screws with 1.5-mm or 2.3-mm diameter or than that of miniplates. Flap surgery was associated with the patient's discomfort. A high mandibular plane angle and inflammation of peri-implant tissue after implantation were risk factors for mobility of screws. However, we could not detect a significant association between the success rate and the following variables: screw length, kind of placement surgery, immediate loading, location of implantation, age, gender, crowding of teeth, anteroposterior jaw base relationship, controlled periodontitis, and temporomandibular disorder symptoms. We concluded that the diameter of a screw of 1.0 mm or less, inflammation of the peri-implant tissue, and a high mandibular plane angle (ie, thin cortical bone), were associated with the mobility (ie, failure) of the titanium screw placed into the buccal alveolar bone of the posterior region for orthodontic anchorage.     

A trigeminal neuralgia-like paroxysmal pain condition presumably due to buccal nerve compression in the temporalis muscle

We encountered three patients with trigeminal neuralgia-like paroxysmal pain in the buccal nerve region. In all cases, paroxysmal pain was felt spreading to the receptive field of the ipsilateral buccal nerve, and clear tenderness was observed during intraoral palpation at the inner side of the mandibular ramus where the temporalis muscle runs and attaches. It was assumed that the paroxysmal pain might be caused by nerve compression related to temporalis muscle hyperactivity. To lend support to this hypothesis, we also studied the anatomical relationship between the buccal nerve and the masticatory muscles. In this autopsy study, the buccal nerve pierced the temporalis muscle in six (12%) of 52 specimens from 26 cadavers. These findings support the hypothesis that peripheral buccal nerve compression could be an etiology of paroxysmal neuropathic pain in the unilateral orofacial region.