Very Early Pulsed Dye Laser Intervention for Optimal Cosmetic Outcome in Post-Thyroidectomy Scars.

Purpose: Early intervention of surgical scars with a pulsed dye laser is known to effectively prevent pathologic scars. Despite multiple reports on the effectiveness of the treatment, very few studies have demonstrated its appropriate initiation timing. In this study, our objective was to determine the optimal timing for initiating laser treatment following thyroidectomy. Methods: This study retrospectively analyzed 91 patients undergoing pulsed dye laser treatment post-thyroidectomy, grouping them by treatment initiation timing. The patients underwent treatment at intervals of 3-4 weeks with at least five sessions. Those with a high pliability score were injected with intralesional corticosteroids. The Antera 3D® skin imaging analyzer was used to assess biophysical parameters. Results: The total Vancouver Scar Scale score significantly reduced after treatment in all groups. The Vancouver Scar Scale score reduction rate was significantly higher after treatment in the group for which the treatment was initiated within 3 weeks of surgery. The pigmentation and erythema score analyzed by Antera 3D® was also lower in this group. Conclusion: Early intervention using a pulsed dye laser within 3 weeks of thyroidectomy can substantially inhibit pathological scar development, providing physicians with a guide for optimal treatment commencement.

Comparison of Various Thyroidectomy Approaches: A Retrospective Cross-sectional Study.

BACKGROUND: To avoid anterior neck scarring, numerous remote-access techniques to approach the thyroid gland (Remote access approach) have been described, including the transaxillary approach (TA), bilateral axillo-breast approach (BABA), and transoral robotic thyroidectomy (TORT). Popular worldwide, Remote access approachs have unique characteristics, advantages, and disadvantages. Herein, we investigated the characteristics of these distinct thyroidectomy approaches to aid surgeons in selecting the most appropriate method for patients. PATIENTS AND METHODS: In total, 2351 cases of patients who underwent thyroidectomy between 2019 and 2021 were reviewed, including 1973, 281, 66, and 31 patients who underwent the conventional transcervical approach (TCA), TA, BABA, and TORT, respectively. Demographic characteristics, outcomes, and complications associated with these procedures were compared. The data were analyzed using the Student t test and the χ 2 test. Kruskal-Wallis and Mann-Whitney U tests were used if normality was not found. RESULTS: Central lymph nodes (LNs) were retrieved mostly in patients who underwent lobectomy through TORT (mean: 9.4, P < 0.001). Metastatic central LNs were found more frequently (mean: 1.9 in lobectomy, 3.7 in total thyroidectomy) in patients who underwent lobectomy through TCA and TORT than in those who underwent lobectomy through other approaches (mean: 1.4 and 2.4, respectively, P < 0.05). BABA group patients had significantly fewer central LNs retrieved than those in other groups in lobectomy and total thyroidectomy (mean: 4.8 and 6.2, respectively, P < 0.05). Stimulated thyroglobulin levels did not differ among the 4 groups. The incidence of transient vocal cord palsy was statistically higher in the BABA group (5 cases, 7.5%) than in the other groups; however, all patients recovered. No difference was found in permanent vocal cord palsy (0.4% in TCA) or hypoparathyroidism (1.3% to 3.1%) among the 4 groups. The tumor size was significantly larger in the BABA group than in the other groups, with 10.6% of the patients having tumors larger than 4 cm. Total thyroidectomy was performed more frequently in the BABA group (51.8%) than in the other groups ( P = 0.005). The path of the external branch of the superior laryngeal nerve was more evident in TA, and the Cernea type was confirmed and preserved in 90.6% of TA cases. CONCLUSIONS: Owing to the differences in working space and direction of the surgical field, TA was advantageous for preserving the external branch of the superior laryngeal nerve, whereas BABA was effective for total thyroidectomy and excision of large goiters. TORT was beneficial for central compartment neck dissection. These characteristics should be considered when choosing the best approach to improving cosmesis, function, and recurrence.

Therapeutic role of 2-stearoxyphenethyl phosphocholine targeting microtubule dynamics and Wnt/ß-catenin/EMT signaling in human colorectal cancer cells.

The inhibition of cell death, perturbation of microtubule dynamics, and acceleration of Wnt/ß-catenin/epithelial-mesenchymal transition (EMT) signaling are fundamental processes in the progression and metastasis of colorectal cancer (CRC). To explore the role of 2-stearoxyphenethyl phosphocholine (stPEPC), an alkylphospholipid-based compound, in CRC, we conducted an MTT assay, cell cycle analysis, western blot analysis, immunoprecipitation, immunofluorescence staining, Annexin V/propidium iodide double staining, small interfering RNA gene silencing, a wound-healing assay, an invasion assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the human CRC cell lines HT29 and HCT116. stPEPC showed anti-proliferative properties and mitotic cell accumulation via upregulated phosphorylation of BUBR1 and an association between mitotic arrest deficiency 2 (MAD2) and cell division cycle protein 20 homolog (CDC20). These results suggest that activation of the mitotic checkpoint complex and tubulin polymerization occurred, resulting in mitotic catastrophe in HT29 and HCT116 cells. In addition, stPEPC attenuated cell migration and invasion by regulating proteins mediated by EMT, such as E-cadherin and occludin. stPEPC altered the protein expression of Wnt3a and phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase 3ß (GSK3ß), and ß-catenin as well as their target genes, including cMyc and cyclin D1, in CRC cells. Thus, stPEPC may be useful for developing new drugs to treat human CRC.

NQO1 regulates cell cycle progression at the G2/M phase.

Rationale: Overexpression of NAD(P)H:quinone oxidoreductase 1 (NQO1) is associated with tumor cell proliferation and growth in several human cancer types. However, the molecular mechanisms underlying the activity of NQO1 in cell cycle progression are currently unclear. Here, we report a novel function of NQO1 in modulation of the cell cycle regulator, cyclin-dependent kinase subunit-1 (CKS1), at the G2/M phase through effects on the stability of c­Fos. Methods: The roles of the NQO1/c-Fos/CKS1 signaling pathway in cell cycle progression were analyzed in cancer cells using synchronization of the cell cycle and flow cytometry. The mechanisms underlying NQO1/c-Fos/CKS1-mediated regulation of cell cycle progression in cancer cells were studied using siRNA approaches, overexpression systems, reporter assays, co-immunoprecipitation, pull-down assays, microarray analysis, and CDK1 kinase assays. In addition, publicly available data sets and immunohistochemistry were used to investigate the correlation between NQO1 expression levels and clinicopathological features in cancer patients. Results: Our results suggest that NQO1 directly interacts with the unstructured DNA-binding domain of c-Fos, which has been implicated in cancer proliferation, differentiation, and development as well as patient survival, and inhibits its proteasome-mediated degradation, thereby inducing CKS1 expression and regulation of cell cycle progression at the G2/M phase. Notably, a NQO1 deficiency in human cancer cell lines led to suppression of c-Fos-mediated CKS1 expression and cell cycle progression. Consistent with this, high NQO1 expression was correlated with increased CKS1 and poor prognosis in cancer patients. Conclusions: Collectively, our results support a novel regulatory role of NQO1 in the mechanism of cell cycle progression at the G2/M phase in cancer through effects on c­Fos/CKS1 signaling.

Effect of withdrawal of thyroid hormones versus administration of recombinant human thyroid-stimulating hormone on renal function in thyroid cancer patients.

This study was conducted to investigate the effects of thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH) administration on renal function in patients with thyroid cancer after total thyroidectomy. This study included 202 patients who discontinued thyroid hormone therapy and/or received rhTSH after total thyroidectomy. Creatinine (Cr), blood urea nitrogen (BUN) levels, and estimated glomerular filtration rate (eGFR) were assessed at the following three time points: before thyroidectomy, at least 3 weeks after THW, and 1 day after the second injection of rhTSH. The median serum Cr level was significantly higher following THW compared to that before thyroidectomy (0.95 versus 0.70). In contrast, the median BUN level was significantly lower after THW compared to that before thyroidectomy (9.8 versus 11.3). Over a fifth (22.2%) of patients had abnormal eGFR values after THW, which was significantly greater than that before thyroidectomy. In contrast, renal parameter values after rhTSH administration were not significantly different than those before thyroidectomy. In conclusion, THW affects renal function in patients with thyroid cancer who have undergone total thyroidectomy. However, renal function in such patients is not affected by rhTSH administration.

Thyroid-Stimulating Hormone as a Biomarker for Stress After Thyroid Surgery: A Prospective Cohort Study.

BACKGROUND Thyroid-stimulating hormone (TSH), which is regulated by the negative feedback of triiodothyronine (T3) and thyroxine (T4), is affected by cortisol (a stress hormone) and cytokines during allostasis. Thus, we assessed changes in TSH levels under stress and its potential as a stress marker in patients lacking T3 or T4 feedback after thyroid surgery. MATERIAL AND METHODS Three stress questionnaires (Korean version of the Daily Stress Inventory, Social Readjustment Rating Scale, and Stress Overload Scale-Short [SOSS]), an open-ended questionnaire (OQ), and thyroid function tests were administered twice to 106 patients enrolled from January 2019 to October 2020. RESULTS In a multiple generalized linear mixed-effect model (GLMM) involving 106 patients, the T3 and free T4 levels, OQ, body weight, extent of thyroidectomy, and preoperative TSH levels were significantly correlated with log-transformed TSH (lnTSH). The modified SOSS (category) based on recent stressors on OQ interview was significantly associated with lnTSH. In the GLMM with modified SOSS (category), the lnTSH increased by 2.3 and 0.56 in the unconscious high- and high-risk groups, respectively, compared to that in the low-risk group (P<0.05). The calculated power of this study was 0.92 based on alpha=0.05. CONCLUSIONS TSH had a significant relationship with stress and the extent of thyroidectomy. An OQ supported the SOSS to help detect unrecognized stressors. TSH has potential utility as a stress marker combined with the modified SOSS (category) with sufficient power. However, questionnaires on social environments and research on coping strategies for stress are necessary for future studies.

Tuning of Peptide Cytotoxicity with Cell Penetrating Motif Activatable by Matrix Metalloproteinase-2.

Although diverse cell penetrating motifs not only from naturally occurring proteins but also from synthetic peptides have been discovered and developed, the selectivity of cargo delivery connected to these motifs into the desired target cells is generally low. Here, we demonstrate the selective cytotoxicity tuning of an anticancer KLA peptide with a cell penetrating motif activatable by matrix metalloproteinase-2 (MMP2). The anionic masking sequence introduced at the end of the KLA peptide through an MMP2-cleavable linker is selectively cleaved by MMP2 and the cationic cell penetrating motif is activated. Upon treatment of the peptide to H1299 cells (high MMP2 level), it is selectively internalized into the cells by MMP2, which consequently induces membrane disruption and cell death. In contrast, the peptide shows negligible cytotoxicity toward A549 cancer cells with low MMP2 levels. Furthermore, the selective therapeutic efficacy of the peptide induced by MMP2 is also corroborated using in vivo study.

Complete Genome Sequence of a Novel Monopartite Mastrevirus, Soybean Geminivirus B, Isolated from Soybean (Glycine max (L.) Merrill).

Soybean is one of the most important crops in Korea. To identify the viruses infecting soybean, we conducted RNA sequencing with samples displaying symptoms of viral disease. A contig displaying sequence similarity to the known Geminivirus was identified. A polymerase chain reaction (PCR) using two different pairs of back-to-back primers and rolling circle amplification (RCA) confirmed the complete genome of a novel virus named soybean geminivirus B (SGVB), consisting of a circular monopartite DNA genome measuring 2616 nucleotides (nt) in length. SGVB contains four open reading frames (ORFs) and three intergenic regions (IRs). IR1 includes a nonanucleotide origin of replication in the stem-loop structure. Phylogenetic and BLAST analyses demonstrated that SGVB could be a novel virus belonging to the genus Mastrevirus in the family Geminiviridae. We generated infectious clones for SGVB by adding a copy of the IR1 region of SGVB, comparing the V-ori in addition to the full-length genome of SGVB. Using the infectious clones, we observed chlorosis and leaf curling with a latent infection in the inoculated Nicotiana benthamiana plants, while none of the inoculated soybean plants showed any visible symptoms of disease. This study provides the complete genome sequence and infectious clones of a novel Mastrevirus referred to as SGVB from soybean in Korea.

Identification of highly selective type II kinase inhibitors with chiral peptidomimetic tails.

Identification of highly selective type II kinase inhibitors is described. Two different chiral peptidomimetic scaffolds were introduced on the tail region of non-selective type II kinase inhibitor GNF-7 to enhance the selectivity. Kinome-wide selectivity profiling analysis showed that type II kinase inhibitor 7a potently inhibited Lck kinase with great selectivity (IC50 of 23.0 nM). It was found that 7a and its derivatives possessed high selectivity for Lck over even structurally conserved all Src family kinases. We also observed that 7a inhibited Lck activation in Jurkat T cells. Moreover, 7a was found to alleviate clinical symptoms in DSS-induced colitis mice. This study provides a novel insight into the design of selective type II kinase inhibitors by adopting chiral peptidomimetic moieties on the tail region.

Regulation of ROS-Dependent JNK Pathway by 2'-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells.

The present study demonstrated that 2'-hydroxycinnamaldehyde (2'-HCA) induced apoptosis in human promyelocytic leukemia HL-60 cells through the activation of mitochondrial pathways including (1) translocation of Bim and Bax from the cytosol to mitochondria, (2) downregulation of Bcl-2 protein expression, (3) cytochrome c release into the cytosol, (4) loss of mitochondrial membrane potential (ΔΨm), and (5) caspase activation. 2'-HCA also induced the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase1/2 (ERK1/2) in HL-60 cells. The pharmacological and genetic inhibition of JNK effectively prevented 2'-HCA-induced apoptosis and activator protein-1 (AP-1)-DNA binding. In addition, 2'-HCA resulted in the accumulation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH) and protein thiols (PSH) in HL-60 cells. NAC treatment abrogated 2'-HCA-induced JNK phosphorylation, AP-1-DNA binding, and Bim mitochondrial translocation, suggesting that oxidative stress may be required for 2'-HCA-induced intrinsic apoptosis. Xenograft mice inoculated with HL-60 leukemia cells demonstrated that the intraperitoneal administration of 2'-HCA inhibited tumor growth by increasing of TUNEL staining, the expression levels of nitrotyrosine and pro-apoptotic proteins, but reducing of PCNA protein expression. Taken together, our findings suggest that 2'-HCA induces apoptosis via the ROS-dependent JNK pathway and could be considered as a potential therapeutic agent for leukemia.

AKF-D52, a Synthetic Phenoxypyrimidine-Urea Derivative, Triggers Extrinsic/Intrinsic Apoptosis and Cytoprotective Autophagy in Human Non-Small Cell Lung Cancer Cells.

Previously, we discovered that 1-(3,5-dimethoxyphenyl)-3-(4-(3-methoxyphenoxy)-2-((4-morpholinophenyl)amino)pyrimidin-5-yl)urea (AKF-D52), a synthetic phenoxypyrimidine urea derivative, acts as a growth inhibitor of various cancer cell types. In this study, we elucidated the antiproliferative properties of AFK-D52 and underlying mechanisms in non-small cell lung cancer (NSCLC) cells and an A549 xenograft animal model. AKF-D52 was found to induce both caspase-dependent and -independent apoptotic cell death. Furthermore, the mitochondrial component of the AKF-D52-induced apoptosis mechanism involves a reduction in mitochondrial membrane potential and regulation in B cell lymphoma-2 family protein expression. Moreover, AKF-D52 activates the extrinsic pathway through up-regulated expression of death receptor 3 and Fas and then the formation of a death-inducing signaling complex. AKF-D52 also induced autophagy by increasing acidic vesicular organelle formation and microtubule-associated protein 1A/1B-light chain 3-II levels and reducing p62 levels. Notably, pretreatment with autophagy inhibitors enhanced AKF-D52-induced cell death, indicating that the induced autophagy is cytoprotective. AKF-D52 treatment also triggered reactive oxygen species (ROS) production in NSCLC cells, whereas the antioxidant α-tocopherol abolished AKF-D52-induced cell death. In a xenograft lung cancer mouse model, AKF-D52 administration attenuated tumor growth by inducing apoptosis and autophagy in tumor tissues. Collectively, our data indicate that AKF-D52-induced ROS production plays a role in mediating apoptosis and cytoprotective autophagy in NSCLC.

Medical X-band linear accelerator for high-precision radiotherapy.

PURPOSE: Recently, high-precision radiotherapy systems have been developed by integrating computerized tomography or magnetic resonance imaging to enhance the precision of radiotherapy. For integration with additional imaging systems in a limited space, miniaturization and weight reduction of the linear accelerator (linac) system have become important. The aim of this work is to develop a compact medical linac based on 9.3 GHz X-band RF technology instead of the S-band RF technology typically used in the radiotherapy field. METHODS: The accelerating tube was designed by 3D finite-difference time-domain and particle-in-cell simulations because the frequency variation resulting from the structural parameters and processing errors is relatively sensitive to the operating performance of the X-band linac. Through the 3D simulation of the electric field distribution and beam dynamics process, we designed an accelerating tube to efficiently accelerate the electron beam and used a magnetron as the RF source to miniaturize the entire linac. In addition, a side-coupled structure was adopted to design a compact linac to reduce the RF power loss. To verify the performance of the linac, we developed a beam diagnostic system to analyze the electron beam characteristics and a quality assurance (QA) experimental environment including 3D lateral water phantoms to analyze the primary performance parameters (energy, dose rate, flatness, symmetry, and penumbra) The QA process was based on the standard protocols AAPM TG-51, 106, 142 and IAEA TRS-398. RESULTS: The X-band linac has high shunt impedance and electric field strength. Therefore, even though the length of the accelerating tube is 37 cm, the linac could accelerate an electron beam to more than 6 MeV and produce a beam current of more than 90 mA. The transmission ratio is measured to be approximately 30% ~ 40% when the electron gun operates in the constant emission region. The percent depth dose ratio at the measured depths of 10 and 20 cm was approximately 0.572, so we verified that the photon beam energy was matched to approximately 6 MV. The maximum dose rate was measured as 820 cGy/min when the source-to-skin distance was 80 cm. The symmetry was smaller than the QA standard and the flatness had a higher than standard value due to the flattening filter-free beam characteristics. In the case of the penumbra, it was not sufficiently steep compared to commercial equipment, but it could be compensated by improving additional devices such as multileaf collimator and jaw. CONCLUSIONS: A 9.3 GHz X-band medical linac was developed for high-precision radiotherapy. Since a more precise design and machining process are required for X-band RF technology, this linac was developed by performing a 3D simulation and ultraprecision machining. The X-band linac has a short length and a compact volume, but it can generate a validated therapeutic beam. Therefore, it has more flexibility to be coupled with imaging systems such as CT or MRI and can reduce the bore size of the gantry. In addition, the weight reduction can improve the mechanical stiffness of the unit and reduce the mechanical load.

Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells.

We previously reported the anticancer activity of 4-(4-fluorobenzylcarbamoylmethyl)-3-(4-cyclohexylphenyl)-2-[3-(N,N-dimethylureido)-N'-methylpropylamino]-3,4-dihydroquinazoline (OZ-001), a T-type calcium channel (TTCC) blocker, against non-small cell lung cancer (NSCLC) in vitro and in vivo. Here, we evaluated the synergistic effect of OZ-001 and cisplatin on A549 human lung cancer cells and A549 xenograft mice. Our study demonstrated that treatment with OZ-001 and cisplatin sensitized A549 cells to cisplatin and significantly inhibited cell growth, increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, and induced poly (ADP-ribose) polymerase (PARP) cleavage in A549 cells and an A549 xenograft tumor mouse model. Moreover, our findings showed that mechanistic target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and signal transducer and activator of transcription (STAT3) inactivation was required for apoptosis induced by the combination of OZ-001 and cisplatin in in vitro and in vivo experiments. Our results suggest that combined treatment with OZ-001 and cisplatin could potentiate antiproliferative effects via suppression of the mTOR/p70S6K and STAT3 pathways and may be considered a potential therapeutic agent for NSCLC.

Presence of TERT ± BRAF V600E mutation is not a risk factor for the clinical management of patients with papillary thyroid microcarcinoma.

BACKGROUND: The management of papillary thyroid microcarcinomas with TERT ± BRAF V600E mutations remains controversial owing to their potential associations with tumor aggressiveness. This study evaluated the clinical implications of these mutations in management of patients with papillary thyroid microcarcinomas. METHODS: Between June 2019 and October 2020, surgical specimens from 504 consecutive patients with papillary thyroid microcarcinomas were obtained at a tertiary hospital. The mutation statuses of TERT promoter and BRAF V600E were assessed by polymerase chain reaction. The prevalence and relationships of TERT ± BRAF V600E mutations with clinical, radiological, and pathological characteristics were evaluated. RESULTS: Of 504 patients with papillary thyroid microcarcinomas, TERT ± BRAF V600E mutations were found in 3.2% (16/504). Of these 16 patients, 93.8% (15/16) of papillary thyroid microcarcinomas with TERT promoter mutations also harbored BRAF V600E mutations. Correlation analysis showed that TERT ± BRAF V600E mutations were not associated with aggressive clinical, radiological, or pathological features (P > .05). The presence of lymph node metastasis was not associated with mutation status (P = .834). CONCLUSION: TERT ± BRAF V600E mutations in patients with papillary thyroid microcarcinomas are not associated with any unfavorable clinicopathological features, including lymph node metastasis status.

Development of a compact X-band linear accelerator system mounted on an O-arm rotating gantry for radiation therapy.

A compact X-band linear accelerator (LINAC) system equipped with a small and lightweight magnetron was constructed to develop a high-precision image-guided radiotherapy system. The developed LINAC system was installed in an O-ring gantry where cone-beam computed tomography (CBCT) was embedded. When the O-arm gantry is rotated, an x-ray beam is stably generated, which resulted from the stable transmission of radio frequency power into the X-band LINAC system. Quality assurance (QA) tests, including mechanical and dosimetry checks, were carried out to ensure safety and operation performance according to the American Association of Physicists in Medicine's TG-51, 142, an international standard protocol established by accredited institutions. In addition, delivery QA of the radiotherapy planning system was conducted to verify intensity-modulated radiotherapy techniques. Therefore, it was demonstrated that the developed X-band LINAC system mounted on the O-arm gantry proved to be valid and reliable for potential use in CBCT image-guided radiation therapy.

Tumor-Targeting H2O2-Responsive Photosensitizing Nanoparticles with Antiangiogenic and Immunogenic Activities for Maximizing Anticancer Efficacy of Phototherapy.

Phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) uses photosensitizers and light to kill cancer cells and has become a promising therapeutic modality because of advantages such as minimal invasiveness and high cancer selectivity. However, PTT or PDT as a single treatment modality has insufficient therapeutic efficacy. Moreover, oxygen consumption by PDT activates angiogenic factors and leads to cancer recurrence and progression. Therefore, the therapeutic outcomes of phototherapy would be maximized by employing photosensitizers for concurrent PTT and PDT and suppressing angiogenic factors. Therefore, integrating photosensitive agents and antiangiogenic agents in a single nanoplatform would be a promising strategy to maximize the therapeutic efficacy of phototherapy. In this study, we developed hyaluronic acid-coated fluorescent boronated polysaccharide (HA-FBM) nanoparticles as a combination therapeutic agent for phototherapy and antiangiogenic therapy. Upon a single near-infrared laser irradiation, HA-FBM nanoparticles generated heat and singlet oxygen simultaneously to kill cancer cells and also induced immunogenic cancer cell death. Beside their fundamental roles as photosensitizers, HA-FBM nanoparticles exerted antiangiogenic effects by suppressing the vascular endothelial growth factor (VEGF) and cancer cell migration. In a mouse xenograft model, intravenously injected HA-FBM nanoparticles targeted tumors by binding CD44-overexpressing cancer cells and suppressed angiogenic VEGF expression. Upon laser irradiation, HA-FBM nanoparticles remarkably eradicated tumors and increased anticancer immunity. Given their synergistic effects of phototherapy and antiangiogenic therapy from tumor-targeting HA-FBM nanoparticles, we believe that integrating the photosensitizers and antiangiogenic agents into a single nanoplatform presents an attractive strategy to maximize the anticancer therapeutic efficacy of phototherapy.

Diarylurea derivatives comprising 2,4-diarylpyrimidines: Discovery of novel potential anticancer agents via combined failed-ligands repurposing and molecular hybridization approaches.

A series of diarylurea derivatives comprising 2,4-diarylpyrimidines were synthesized based on a combination of postulated molecular hybridization design and failed-ligands repurposing approaches, which enabled the discovery of novel potential antiproliferative agents. Towards credible biological evaluation, an in vitro anticancer activity assay was conducted employing a library of 60 cancer cell lines constituting nine panels representing blood, lung, colon, CNS, skin, ovary, renal, prostate, and breast cancers. The results revealed high effectiveness and broad-spectrum anticancer activity of compounds 4m and 4g. Five-dose assay of compounds 4m and 4g proved their high potency that surpassed that of four standard kinase inhibitors FDA-approved anticancer drugs against many cancer cells. Towards the identification of their molecular target, screening of kinase inhibitory profile employing a panel of 51 kinases involved in cancer revealed inhibition of several kinases from the platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) kinase family, which might mediate, at least in part, the antiproliferative activity. Molecular docking of 4g into the crystal structure of the Feline McDonough Sarcoma (FMS) kinase predicted that it binds to a pocket formed by the juxtamembrane domain, the catalytic loop, and the αE helix, thus stabilizing the inhibited conformation of the kinase. Flow cytometric study of the cytotoxic effects of compound 4g in A549 cells showed it induces dose- and time-dependent apoptotic events leading to cell death. Collectively, this work presents compound 4g as a potential broad-spectrum anticancer agent against multiple cancer types.

Reoperations for structurally persistent or recurrent disease after thyroidectomy: analysis via preoperative CT.

The incidence rates of structural persistent disease (PD) and recurrent disease (RD) after thyroidectomy, and their clinicoradiological (CT) characteristics, remain poorly understood. Therefore, we characterized differentiated thyroid cancer (DTC) patients who underwent re-operations, with a focus on preoperative CT scans. We examined neck CT scans obtained prior to initial surgery and reoperation, and classified the disease into four categories according to the persistence/recurrence and neck dissection/non-dissection status. In total, 121 of 9,173 DTC patients underwent reoperations to treat PD or RD; the mean time to reoperation was 25.5 and 54.1 months, respectively. Of all reoperations, 19% (23/121) were performed to treat RD; 81% (98/121) were performed to treat PD. Compared to RD, PD was commonly detected in the non-dissected neck. Tumor multiplicity and the number of pathologically positive lymph nodes were greater in the non-dissected than dissected neck. A review of the CT data revealed more false-negative findings on the 60-s- versus 30-40-s-delay scans of PD patients with non-dissected necks. In conclusion, most of the reoperations performed on DTC patients were for management of PD. Improved preoperative CT assessments and initial surgery, based on the information of clinico-radiological characteristics, are required in the care of DTC patients.

A Rare Granular Cell Tumor with a Center Ulcer of the Rectum.

We report a very rare case of granular cell tumor with a center ulcer of the rectum, which was detected in a 47-year-old man during screening colonoscopy. It is difficult to distinguish granular cell tumor from other subepithelial tumors. However, our case had a center ulcer unlike previous cases. We confirmed the diagnosis using histological and immunohistochemical examinations. In addition to our case report, we discuss the morphology, size, layer of invasion, and treatment of rectal granular cell tumors based on a literature review.