Medical Record Survey after Comprehensive Health Checkup Referral and Its Contribution to the Early Detection of Cancer.

Comprehensive health checkups in Japan are a preventive method to detect cancer and metabolic diseases. Unlike group medical examinations, individual examinations in health checkups are possible, with additional tests possible for disease detection. However, it is difficult to accurately ascertain the results from only the report after referral to a medical institution in individuals suspected of having cancer who need to be examined. We aimed to conduct a medical record survey of patients referred to the Hospital after undergoing a comprehensive health checkup and investigate the contribution of comprehensive health checkups to the detection of cancer more accurately. The subjects were 1763 examinees who were referred to various departments of our hospital because of doubtful cancer from 23,128 examinees who underwent comprehensive health checkups in our center from January 2018 to December 2022 for 5 years. The medical record survey demonstrated that cancer was detected in more than twice as many individuals as reported and other sources. Early-stage cancers require a significantly longer time to establish a definitive diagnosis. In conclusion, short-term reports from the referring hospital are insufficient for a final diagnosis, and long-term follow-up is extremely important to increase the diagnosis rates of cancer for comprehensive health checkups.

Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis.

Previously, our group has demonstrated establishment of Cancer Stem Cell (CSC) models from stem cells in the presence of conditioned medium of cancer cell lines. In this study, we tried to identify the factors responsible for the induction of CSCs. Since we found the lipid composition could be traced to arachidonic acid cascade in the CSC model, we assessed prostaglandin E2 (PGE2) as a candidate for the ability to induce CSCs from induced pluripotent stem cells (iPSCs). Mouse iPSCs acquired the characteristics of CSCs in the presence of 10 ng/mL of PGE2 after 4 weeks. Since constitutive Akt activation and pik3cg overexpression were found in the resultant CSCs, of which growth was found independent of PGE2, chronic stimulation of the receptors EP-2/4 by PGE2 was supposed to induce CSCs from iPSCs through epigenetic effect. The bioinformatics analysis of the next generation sequence data of the obtained CSCs proposed not only receptor tyrosine kinase activation by growth factors but also extracellular matrix and focal adhesion enhanced PI3K pathway. Collectively, chronic stimulation of stem cells with PGE2 was implied responsible for cancer initiation enhancing PI3K/Akt axis.

Undifferentiated carcinoma of the oral tongue treated with cetuximab: A case report.

Undifferentiated carcinoma of the oral cavity is a rare and possibly fatal malignant neoplasm. We present here a case of undifferentiated carcinoma of the oral tongue, which responded well to chemotherapy with cisplatin, 5-fluorouracil, and cetuximab. A 59-year-old man was referred to our hospital for a large tumor of the tongue. Physical examination revealed an ulcerative tumor, approximately 50 mm in diameter, on the right edge of the tongue and swelling of multiple cervical lymph nodes; therefore, the clinical diagnosis was tongue cancer (T4aN2bM0). The histological diagnosis from a biopsy specimen was undifferentiated carcinoma; we tested the sample for human papilloma virus immunoreactivity, which was positive. The patient then underwent chemotherapy with cisplatin, 5-fluorouracil and cetuximab. The tumor's size decreased markedly after two courses of chemotherapy, but the treatment was stopped due to the patient' various mental problems and pneumonia; he died 6 months after the initial visit. Our encounter with this patient suggests that cetuximab treatment is a good option for HPV-positive undifferentiated carcinoma of the oral tongue.

Investigation of arterial-cardiac-pulmonary interaction.

Pulmonary function and arterial stiffness correlate significantly, attributing to the chronic inflammation of atherosclerosis. However, through the pulmonary or systemic circulation, pulmonary and vascular functions associate hemodynamically with cardiac morphology and function. In the present study, we investigated arterial-cardiac-pulmonary interaction by examining how the pulmonary and vascular functions correlate with the heart. This study investigated 55 consecutive subjects not suffering from pulmonary, vascular and cardiac disease who underwent health screening test at our medical center. First, the presence of atherosclerotic disease (hypertension, dyslipidemia and diabetes) and smoking status of the patients were determined. Next, pulmonary function test, vascular function test including cardio-ankle vascular index, and echocardiography were performed. Then, we examined the correlation among the pulmonary, vascular and the heart. Our results revealed many correlations among these three factors. Especially left atrial dimension (LAD) and E/A ratio (E/A) were important cardiac factors associated with both pulmonary and vascular functions independently. Conventionally, inflammatory responses are known to involve in the correlation between pulmonary and vascular functions. Our study demonstrated that cardiac function and morphology were also involved in this correlation, signifying that LAD and E/A plays important roles in the arterial-cardiac-pulmonary interaction.

Carcinoma Ex Pleomorphic Adenoma of the Tongue: Difficulty in Diagnosis Between Metastasis of Breast Cancer and Salivary Tumor.

Carcinoma ex pleomorphic adenoma (CEPA) is a carcinoma that shows histologic evidence of arising in or from a benign pleomorphic adenoma. Carcinoma ex pleomorphic adenoma often occurs in parotid glands, but is extremely rarely in the tongue. A 53-year-old Japanese woman was referred to the Department of Oral and Maxillofacial Surgery, Nagasaki University Hospital, because of tumor of the right dorsum tongue. She had a history of surgery of breast cancer (invasive ductal carcinoma) and it was disseminated to the lung and bone. Macroscopic examination revealed an oval tumor with a smooth mucosal surface of 10 mm in diameter in the right dorsum tongue. A clinical diagnosis was metastasis from breast cancer or primary salivary gland tumor. Histologic diagnosis of the biopsy specimen was CEPA. She underwent partial glossectomy under general anesthesia. The final diagnosis of surgical materials was CEPA based on the differential diagnosis from breast carcinoma. She is alive bearing disseminated breast carcinoma without recurrence of CEPA at 6 months after glossectomy.

Psychometric properties of the Japanese ADHD-RS in preschool children.

BACKGROUND: Children with ADHD show multiple difficulties in their lives. Its early detection is important to provide timely intervention. AIMS: To evaluate the psychometric properties of the Japanese version of the home and school form of the ADHD-Rating Scale-IV (P- and T-ADHD-RS) for screening five-year-olds with ADHD. METHODS: The parents and teachers of 838 children (452 boys, 386 girls; including 28 boys, 18 girls diagnosed ADHD) completed the ADHD-RS and the Strengths and Difficulties Questionnaire in a community health check-up. RESULTS: The P- and T-ADHD-RS confirmed the two-factor model (Inattention and Hyperactivity-Impulsivity) and internal consistencies (CFI=0.968, 980; RMSEA=0.049, 0.055; SRMR=0.030, 0.024; α=0.86-.93). Japanese boys and girls scored significantly lower in all scales of the P- and T-ADHD-RS (d=0.65-1.14, 0.36-0.59) than US children. The P-ADHD-RS showed higher accuracy in area under the curve (AUC), sensitivity, and positive predictive value (PPV) than the T-ADHD-RS (AUC=0.955, 0.692; sensitivity=89.13%, 30.23%; PPV=46.59%, 16.05%). IMPLICATIONS: The P-ADHD-RS shows good reliability and validity for screening children with possible ADHD in a community. Longitudinal studies are needed to examine its predictive validity of adaptation in their lives at school.

Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice.

To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticles, the liposomes containing curcumin, ranged from 60 to 100 nm. Flow cytometric analyses revealed that after intraperitoneal administration of the liposomes containing curcumin into mice, these were incorporated mainly by macrophages positive for F4/80, CD36, and CD11b antigens. Peritoneal cells prepared from mice injected in vivo with the liposomes containing curcumin apparently decreased interleukin-6-producing activities. Major changes in body weight and survival rates in the mice were not observed after administrating the liposomes containing curcumin. These results indicate that the liposomes containing curcumin are safe and useful for the selective suppression of macrophages in vivo in mice.

Potent synergy of dual antitumor peptides for growth suppression of human glioblastoma cell lines.

Molecular targeting agents have become formidable anticancer weapons, which show much promise against the refractory tumors. Functional peptides are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms a basis for potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. Here, we examine growth suppression efficiency of human glioblastomas by dual-peptide targeting. We did simultaneous introduction of two tumor suppressor peptides (p14(ARF) and p16(INK4a) or p16(INK4a) and p21(CIP1) functional peptides) compared with single-peptide introduction using Wr-T-mediated peptide delivery. Wr-T-mediated transport of both p14(ARF) and p16(INK4a) functional peptides (p14-1C and p16-MIS, respectively) into human glioblastoma cell line, U87DeltaEGFR, reversed specific loss of p14 and p16 function, thereby drastically inhibiting tumor growth by >95% within the first 72 h, whereas the growth inhibition was approximately 40% by p14 or p16 single-peptide introduction. Additionally, the combination of p16 and p21(CIP1) (p21-S154A) peptides dramatically suppressed the growth of glioblastoma line Gli36DeltaEGFR, which carries a missense mutation in p53, by >97% after 120 h. Significantly, our murine brain tumor model for dual-peptide delivery showed a substantial average survival enhancement (P < 0.0001) for peptide-treated mice. Wr-T-mediated dual molecular targeting using antitumor peptides is highly effective against growth of aggressive glioblastoma cells in comparison with single molecule targeting. Thus, jointly restoring multiple tumor suppressor functions by Wr-T-peptide delivery represents a powerful approach, with mechanistic implications for development of efficacious molecular targeting therapeutics against intractable human malignancies.