Supplementary Legends 1-2 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Supplementary Figure 2 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Neuroleptic malignant syndrome (NMS) is an adverse effect of drugs, mainly neuroleptics. It is characterized by problems related to the autonomic nervous system (such as hyperthermia, diaphoresis, and tachycardia) and extrapyramidal symptoms (such as muscle rigidity and tremor). After onset, NMS progresses rapidly and without treatment, becomes life-threatening. In recent years, NMS has become better recognized, and treatment has improved; most cases are now curable before becoming dangerous. Most NMS reports are from psychiatrists or neurologists; few are from other specialized clinicians. However, nonpsychiatric clinicians, such as surgeons, emergency physicians, orthopedists, and oral surgeons, sometimes must administer neuroleptic drugs. Although NMS is rare, its effects on patients may be debilitating, and this places a heavy burden on clinicians. Thus, not only psychiatrists but also clinicians in various other fields should understand this illness. This article describes NMS in fields other than psychiatry and its diagnosis, risk factors, and treatment strategies.

Supplementary Figure 1 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Supplementary Legends 1-2 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Supplementary Legends 1-2 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Abstract Using proteomic selection, functional verification, and clinical validation, we identified specific down-regulation of Lin-7C/VELI3/MALS-3 (Lin-7C), which marks oral squamous cell carcinoma (OSCC) metastasis. Despite a rarity of sequence variations in the Lin-7C gene in both primary OSCC and OSCC-derived cells, a high prevalence of hypermethylation was detected in the CpG island region that strongly correlated with its down-regulation. Inducible Lin-7C mRNA by experimental demethylation was found in all OSCC cells tested. Overexpression of the Lin-7C gene in an OSCC cell clone does not contribute to underproliferation but results in a noninvasive phenotype with elevated β-catenin expression. Experimental metastases in multiple organs of immunodeficient mice were inhibited in cells expressing Lin-7C. Finally, the Lin-7C expression status in primary tumors afforded significantly (P < 0.001) high accuracy for predicting lymph node metastasis. These results establish Lin-7C as a novel target of early detection, prevention, and therapy for OSCC metastasis. [Cancer Res 2007;67(20):9643–8]

Supplementary Figure 1 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Supplementary Figure 2 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Surgical site infections (SSI) are associated with increased morbidity and mortality rates. This study aimed to investigate the ability of perioperative oral management (POM) to reduce the risk of SSI in abdominal surgery Real-world data collected from 16 university hospitals in Japan were reviewed. The medical records of consecutive 2782 patients (1750 men and 1032 women) who underwent abdominal surgery under general anesthesia at 16 university hospitals were retrospectively reviewed. Detailed information about SSI was assessed and compared between patients with and without POM in univariate and multivariate analyses. SSI were observed in 275 patients (incidence rate:9.9%), and POM was administered to 778 patients (28.0%). Univariate analyses revealed that diabetes mellitus, Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists classification, surgical site, preoperative Prognostic Nutritional Index score, POM, extent of surgery, operation time, and intraoperative blood loss were significantly associated with postoperative SSI (Chi-square or Mann–Whitney U test, P < .01). Multivariate analysis revealed that POM had significant preventive effects against postoperative SSI (estimate: −0.245, standard error: 0.080, P < .01). Surgical site, American Society of Anesthesiologists classification, and operation time were also significant and independent clinical predictors of SSI. The analysis of real-world data from 16 university hospitals revealed that, regardless of the content and degree of the problem, the addition of POM has significant beneficial effects in reducing the risk of SSI in patients who undergo abdominal surgery. Medical records from each hospital and data from the Health Care Payment Fund were collected and analyzed retrospectively.

Supplementary Information from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Supplementary Table 1 from Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

GTPases of immunity-associated protein 2 (GIMAP2) is a GTPase family member associated with T cell survival. However, its mechanisms of action in oral squamous cell carcinoma (OSCC) remain largely unknown. Therefore, the present study aimed to elucidate the possible role of GIMAP2 in OSCC development by investigating its expression levels and molecular mechanisms in OSCC. Reverse transcription quantitative PCR, immunoblotting and immunohistochemistry indicated that GIMAP2 expression was significantly upregulated (P<0.05) in OSCC-derived cell lines and primary OSCC specimens compared with that in their normal counterparts. GIMAP2-knockdown OSCC cells exhibited decreased cell growth, which was associated with cyclin-dependent kinase (CDK)4, CDK6 and phosphorylated Rb downregulation and p53 and p21 upregulation. In addition to cell cycle arrest, GIMAP2 affected anti-apoptotic functions in GIMAP2-knockdown cells by upregulating Bcl-2 and downregulating Bax and Bak. These findings indicated that GIMAP2 may significantly influence OSCC development and apoptosis inhibition and thus is a potential biomarker of OSCC.

Lysyl hydroxylase 2 (LH2) is an enzyme that catalyzes the hydroxylation of lysine (Lys) residues in fibrillar collagen telopeptides, a critical post-translational modification for the stability of intermolecular cross-links. Though abnormal LH2 activities have been implicated in various diseases including Bruck syndrome, the molecular basis of the pathologies is still not well understood. Since LH2 null mice die at early embryonic stage, we generated LH2 heterozygous (LH2+/-) mice in which LH2 level is significantly diminished, and characterized collagen and bone phenotypes using femurs. Compared to the wild-type (WT), LH2+/- collagen showed a significant decrease in the ratio of hydroxylysine (Hyl)- to the Lys-aldehyde-derived collagen cross-links without affecting the total number of aldehydes involved in cross-links. Mass spectrometric analysis revealed that, in LH2+/- type I collagen, the extent of hydroxylation of all telopeptidyl Lys residues was significantly decreased. In the helical domain, Lys hydroxylation at the cross-linking sites was either unaffected or slightly lower, but other sites were significantly diminished compared to WT. In LH2+/- femurs, mineral densities of cortical and cancellous bones were significantly decreased and the mechanical properties of cortical bones evaluated by nanoindentation analysis were compromised. When cultured, LH2+/- osteoblasts poorly produced mineralized nodules compared to WT osteoblasts. These data provide insight into the functionality of LH2 in collagen molecular phenotype and its critical role in bone matrix mineralization and mechanical properties.

The epithelial-stromal interaction 1 gene (EPSTI1) is known to play multiple roles in the malignant progression of breast cancer and also in some aspects of the immune responses to the tumor. However, the relevance of the gene in the onset/progression of oral squamous cell carcinoma (OSCC) and lung squamous cell carcinoma (LSCC) is not yet known. The present study was aimed at revealing the roles of EPSTI1 in conferring malignant characteristics to OSCC and LSCC, and the underlying mechanisms. Quantitative real-time polymerase chain reaction (PCR) and western blot analyses demonstrated significant upregulation of EPSTI1 in all four OSCC cell lines (HSC2, HSC3, HSC3-M3 and HSC4), and significant downregulation of EPST11 in all three LSCC cell lines (LK-2, EBC-1 and H226) used in the present study, as compared to the expression levels in the corresponding control cell lines. Both knockdown of EPST11 in OSCC and overexpression of the gene in LSCC suppressed cell proliferation, and induced cell-cycle arrest in the G1 phase, with upregulation of p21 and downregulation of CDK2 and cyclin D1. Furthermore, these alterations of EPST11 gene expression in the OSCC and LSCC cell lines suppressed the cell migration ability and reversed the EMT phenotype of the tumor cells. Collectively, while EPSTI1 appears to have oncogenic roles in OSCC, it appears to exert tumor-suppressive roles in LSCC. PCR array analyses revealed some genes whose expression levels were altered along with the modified EPSTI1 expression in both the OSCC and LSCC cell lines. These findings suggest that EPSTI1 may be a therapeutic target for both OSCC and LSCC.

We report a rare case of high-grade MEC developed in the palate. Myoepithelial carcinoma (MEC) is an uncommon malignant tumor, which is also known as malignant myoepithelioma. It generally occurs in major salivary glands. A 79-year-old female presented complaining a painless swelling on the left side palate which grew rapidly in 3 weeks. A soft and pendulous mass with approximately 42 x 30 mm in diameter with ulceration was observed in the palate.Radiological imaging analyses (e-CT, e-MRI and FDG-PETCT) showed an irregular mass of the left palate with bone invasion into the palatal bone and suggested potential metastases in submandibular lymph nodes. A biopsy was performed and diagnosed as MEC of the palate. Surgical tumor resection and radical neck dissection were performed under general anesthesia. Pathologic evaluation showed that the lesion was mainly consisted of atypical cells with abundant eosinophilic cytoplasm including a mixture of spindled or epithelioid cells. Immunohistochemically, the lesion included specifically and diffusely positive for S-100, CD10, calponin, GFAP, and p63. Cell proliferation activity assessed by the Ki67 labeling index was 55 %. From these findings, the lesion was finally diagnosed as MEC of the palate. The patient has been followed for 6years without a recurrence. (C) 2020 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.

Pneumatosis intestinalis (PI) is characterized by the presence of gas in the bowel wall and is associated with a wide range of clinical conditions, such as pulmonary, gastrointestinal, infectious, and autoimmune diseases, and an immunosuppressive state such as that resulting from cancer chemotherapy. It is not a distinct disease but rather a physical or radiographic finding and can be categorized into types: primary and secondary. Primary PI is idiopathic, while secondary PI occurs as a result of an underlying disease. Several theories were suggested for the etiology of this condition. Intestinal gas, mucosal integrity, intraluminal pressure, and bacterial flora play interactive roles in the development of PI; yet, the mechanisms involved remain unclear. PI can be seen in benign or life-threatening situations. Choosing an appropriate treatment owing to the various interpretations of the clinical significance of PI is difficult. An urgent surgical procedure is necessary for patients with signs of bowel perforation, peritonitis, or necrotizing enterocolitis. Potentially, these life-threatening conditions should be ruled out, based on the physical and radiographic findings of the patient. Herein, we report a rare case of PI in a 72-year-old woman who was administrated cisplatin and radiation as adjuvant chemoradiotherapy for oral cancer. During the therapy, free air was detected via chest radiography. Based on the physical and computed tomographic findings, the development of free air was considered as a non-life-threatening PI phenomenon caused by the cancer chemotherapy.

Exosomes are involved in a wide range of biological processes in human cells. Considerable evidence suggests that engineered exosomes (eExosomes) containing therapeutic agents can attenuate the oncogenic activity of human cancer cells. Despite its biomedical relevance, no information has been available for oral squamous cell carcinoma (OSCC), and therefore the development of specific OSCC-targeting eExosomes (octExosomes) is urgently needed. We demonstrated that exosomes from normal fibroblasts transfected with Epstein–Barr Virus Induced-3 (EBI3) cDNA were electroporated with siRNA of lymphocyte cytoplasmic protein 1 (LCP1), as octExosomes, and a series of experiments were performed to evaluate the loading specificity/effectiveness and their anti-oral cancer cell activities after administration of octExosomes. These experiments revealed that octExosomes were stable, effective for transferring siLCP1 into OSCC cells and LCP1 was downregulated in OSCC cells with octExosomes as compared with their counterparts, leading to a significant tumor-suppressive effect in vitro and in vivo. Here we report the development of a new valuable tool for inhibiting tumor cells. By engineering exosomes, siLCP1 was transferred to specifically suppress oncogenic activity of OSCC cells. Inhibition of other types of human malignant cells merits further study.

The purpose of the present study was to investigate the efficacy of perioperative oral managements (POMs) on perioperative nutritional conditions in patients undergoing surgery with general anesthesia. Medical records were retrospectively reviewed and the effects of POMs were investigated based on a large number of cases using a multicenter analysis. The profile of serum albumin levels was assessed and compared between patients with and without POMs using the multivariate analysis. Seventeen Eleven thousand and one hundred sixty patients (4,873 males and 6,287 females) were reviewed. Of these, 2710 patients (24.3%) had undergone POMs. The results of a multivariate analysis revealed the significant positive effect of POMs on perioperative serum albumin level (change between at admission and discharge, (Estimate: 0.022, standard error: 0.012, P < .0001). Patient gender, age, surgical site, performance status, the American Society of Anesthesiologists (ASA) physical status classification, operation time, amount of blood loss, and serum albumin level at admission were also significant predictors. Adjusted multivariate analysis of the effects of POMs on perioperative change of serum albumin level in all subjects reveled the significance of POMs intervention (estimate: 0.022, standard error: 0.012, P < .0001). These results suggest that POMs exerts significant positive effects on perioperative serum albumin levels in patients underwent surgery under general anesthesia.