Assessing the effects of Kampo medicine on human skin texture and microcirculation.

In this study, we verified the effectiveness of Kampo medicine by evaluating the changes in the feature values of facial skin texture and microcirculation at two distinct tissue depths (subcutaneous 2 mm and 8 mm). A total of 80 patients who took the Kampo formula participated in this study, and the changes in the feature values of facial skin texture and microcirculation were measured before and after Kampo treatment. The treatment period lasted 6-18 months, according to the doctor's judgment. The total area of the sulci cutis and the average thickness of the sulci cutis significantly decreased (P < 0.05), and the pixels of the grayscale image increased after Kampo treatment (P < 0.05). Moreover, the blood flow velocity at 8 mm depth significantly increased after Kampo treatment (P < 0.05). In this study, we specifically noted changes in the skin texture and microcirculation after Kampo treatment.

Study protocol for daiobotanpito combined with antibiotic therapy for treatment of acute diverticulitis: a study protocol for a randomized controlled trial.

BACKGROUND: Colonic diverticular disease has been increasing in prevalence due to the rapidly aging global population, but standard treatment has not changed dramatically in recent years. Daiobotanpito (DBT; Da Huang Mu Dan Tang in Chinese) has been used in medical treatment of acute abdominal abscesses, such as appendicitis or diverticulitis in traditional Japanese (Kampo) medicine for many years, based on more than 3000 years of experience. Prior to this study, a retrospective open-label trial was conducted to compare patients with acute diverticulitis who received oral DBT combined with intravenous antibiotics with those who received intravenous antibiotic alone; it showed a positive effect of DBT on acute diverticulitis. We aim to investigate whether moderate to severe acute diverticulitis shows greater improvement with intravenous antibiotics plus orally administered DBT compared with intravenous antibiotics plus placebo. METHODS: This is a two-group, randomized, double-blind, placebo-controlled, multi-center trial, which is designed to evaluate the efficacy and safety of DBT in patients with moderate to severe diverticulitis treated with intravenous antibiotics. Eligible participants will be randomized to either a treatment group receiving a 10-day oral DBT regimen plus conventional therapy or a control group receiving a 10-day placebo regimen plus conventional therapy. The primary outcome will be success in treating diverticulitis: the success rate will be defined as elimination of abdominal pain within 4 days in all patients, and in patients with fever (body temperature ≧ 37.5 °C) on inclusion into this study, fever relief with reduction in body temperature to < 37.5 °C within 3 days. Secondary endpoints will include the number of hospitalization days, changes in inflammatory response (C-reactive protein (CRP), white blood cell (WBC) and neutrophil counts), fever type, number of days before beginning food intake, recurrence rate (observation for 1 year after registration), and adverse event expression rate. Assessments will be performed at baseline and on the day of discharge. The recurrence rate will be recorded at 1 year after registration. DISCUSSION: This study is expected to provide evidence to support the clinical benefits of DBT in the treatment of acute diverticulitis. It may also provide evidence on the efficacy and safety of DBT in the recurrence of acute diverticulitis. TRIAL REGISTRATION: UMIN-CTR: UMIN000027381. Registered on 27 April 2017. https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000031377, and changed to jRCTs041180063, registered on 30 July 2019; as a result of the revision of the domestic law in 2018 in Japan.

The effect of contact needle therapy on fatigue in patients with cancer in palliative care: A study protocol for a randomized controlled trial.

INTRODUCTION: Almost all patients with end-of-life cancer experience cancer-related fatigue; however, there are only a few known effective coping methods. OBJECTIVES: We will conduct a prospective, multi-center, single-blinded randomized controlled study to evaluate the efficacy of acupuncture for cancer-related fatigue in patients with end-of-life cancer. METHODS: We will enroll 120 patients with cancer hospitalized in a palliative care unit or receiving consultation from a palliative care team in four hospitals. We will add acupuncture treatment; specifically, contact needle therapy (CNT), consisting of an intervention per week period to the usual care. The primary outcome measure will be the Cancer Fatigue Scale (CFS) score while the secondary outcome measures will be the Numerical Rating Scale (NRS) score for fatigue, pain, and salivary amylase levels. CONCLUSION: We will evaluate the possibility of using acupuncture therapy, that is, CNT, in relieving fatigue sensation in patients with advanced cancer. TRIAL REGISTRATION: UMIN000028304, registered on July 21st, 2017; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032401.

A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer.

OBJECTIVE: Matrix metalloproteinase-1 (MMP-1) and interleukin-8 (IL-8) play an important role in cancer development and metastasis. There is a single nucleotide polymorphism (SNP) located in the promoter region of MMP-1 and IL-8 that regulates gene expression. MMP-1 -1607 2G/2G and IL-8 -251 A/A genotypes enhance transcriptional activity and may be associated with increased risk in malignant tumors. We therefore evaluated the impact of these SNPs in tongue squamous cell carcinoma (SCC). METHODS: In this study, we genotyped 69 tongue SCC patients. The expression of MMP-1 and IL-8 in tongue SCC patients was analyzed by immunohistochemistry. RESULTS: We found a significant difference in IL-8 A/A genotypes with nodal recurrence (P=0.0068). An analysis of disease-free survival rates showed that the presence of both MMP-1 2G/2G and IL-8 A/A genotypes was associated with a particularly poor prognosis (P=0.0032) and was an independent prognostic factor (P=0.001). The expression of MMP-1 was significantly correlated with the frequency of MMP-1 2G/2G genotypes (P=0.049). CONCLUSION: These results suggest that SNP in the promoter region of MMP-1 and IL-8 plays an important role in tumor progression and recurrence through its expression in tongue SCC.

Prognostic value of cell motility activation factors in patients with tongue squamous cell carcinoma.

Cell motility plays a crucial role in invasion and metastasis of malignant tumors. Both AMFR and c-Met, known as key factors in up-regulation of cell motility, are overexpressed in a variety of malignant solid tumors. This study was designed to analyze the role of cell motility and its prognostic value in tongue squamous cell carcinoma (SCC). In addition, the expression of Ets-1, known as a transcription factor that regulates cell motility, was also studied to elucidate its relationship with c-Met and AMFR expression. The expression of c-Met, AMFR, and Ets-1 protein was analyzed by immunohistochemistry in 99 patients with tongue SCC. Then, the expression score of these proteins and their association with clinical factors was retrospectively evaluated. The expression level of both c-Met and AMFR was significantly correlated with local and distant metastatic tumor recurrence. Moreover, patients with increased expression of both c-Met and AMFR had significantly worse disease-free survival. The expression score of Ets-1 was also strongly correlated with that of c-Met, whereas it was weakly correlated with AMFR. Pathologically advanced tumor status (pT4), advanced node (pN2 and pN3), stage IV, c-Met and AMFR were significant hazards in univariate analysis. In multivariate analysis among stage IV, c-Met, and AMFR, AMFR expression remained a significant prognostic factor. This study suggests that Ets-1 contributes to the invasive phenotype through overexpression of c-Met. The evaluation of AMFR and c-Met in tongue SCC is valuable in identifying patients at high risk for recurrences and who should be treated as more advanced cases.

Splicing of Friend Murine Leukemia Virus env-mRNA Enhances Its Ability to Form Polysomes.

Friend murine leukemia virus (MLV) belongs to the gamma retroviruses of the Retroviridae family. The positive-sense RNA of its genome contains a 5' long terminal repeat (LTR), 5' leader sequence, gag, pol, env, and 3' LTR. Transcription from proviral DNA begins from the R region of the 5' LTR and ends at the polyadenylation signal located at the R region of the other end of the 3' LTR. There is a 5' splice site in the 5' leader sequence and a 3' splice site at the 3' end of the pol region. Both full-length unspliced mRNAs and a singly spliced mRNA (env-mRNA) are produced in MLV-infected cells. The MLV Env protein plays important roles both in viral adsorption to host cells and in neuropathogenic disease in MLV-infected mice and rats. Understanding the regulatory mechanisms controlling Env expression is important for determining the functions of the Env protein. We have previously shown that splicing increases env-mRNA stability and translation efficiency. Generally, mRNA polysome formation correlates with translation efficiency. Therefore, here we investigated the effects of env-mRNA splicing on polysome formation to identify mechanisms for Env up-regulation due to splicing. We performed polysome profile analyses using Env-expression plasmids producing spliced or unspliced env-mRNA and showed that the former formed polysomes more efficiently than the latter. Thus, splicing of env-mRNA facilitated polysome formation, suggesting that this contributes to up-regulation of Env expression. We replaced the env region of the expression plasmids with a luciferase (luc) gene, and found that in this case both unspliced and spliced luc-mRNA formed polysomes to a similar extent. Thus, we conclude that whether mRNA polysome formation is affected by splicing depends on the structure of gene in question.

Expression of intercellular adhesion molecule (ICAM)-1 in adenoid cystic carcinoma of the head and neck.

OBJECTIVES/HYPOTHESIS: Adenoid cystic carcinoma of the head and neck (ACCHN) is characterized by late recurrence and frequent distant metastasis. Tumor attack by cytotoxic T lymphocytes and macrophages is mediated by the interaction of leukocyte function-associated antigen (LFA)-1 on lymphocytes with intercellular adhesion molecule (ICAM)-1 on the tumor surface. Thus, the reduced expression of ICAM-1 on tumor cells could contribute to their escape from host immune surveillance. To investigate the relationship between the clinical features of ACCHN and host immune surveillance, the expression of ICAM-1 and infiltration of T/natural killer (NK) cells and macrophages were immunohistochemically examined. STUDY DESIGN: Retrospective analysis of immunohistochemical tumor characteristics and clinical outcome. METHODS: Immunohistochemical study of ICAM-1, T/NK cells, and macrophages was performed on paraffin sections of 42 patients with ACCHN. The expression of T/NK cells and macrophages was represented by T-cell-restricted antigen (TIA)-1 and CD68 expression, respectively. The expression of these molecules and clinical features were analyzed. RESULTS: Of 42 ACCHN cases, 15, 9, and 15 patients were classified as ICAM-1 high, TIA-1 high, and CD68 high, respectively. The TIA-1 expression scores in ICAM-1-low patients were significantly lower than those in ICAM-1-high patients (1.3 +/- 3.7 vs. 8.3 +/- 12.7, P =.0031). The CD68 expression scores in ICAM-1-low patients were also significantly lower than those in ICAM-1-high patients (9.6 +/- 9.6 vs. 21.1 +/- 17.6, P =.0047). Moreover, ICAM-1-high patients had a significantly better disease-free survival rate (P =.043). CONCLUSIONS: Reduced expression of ICAM-1 may promote immune evasion and metastasis, resulting in poor prognosis in ACCHN.

Identification of various types of α2-HS glycoprotein in sera of patients with pancreatic cancer: Possible implication in resistance to protease treatment.

α2-Heremans-Schmid glycoprotein (human fetuin) is one of numerous serum proteins produced in the liver. Recently, the biological functions of fetuin, such as calcification and insulin resistance, have been clarified. However, these effects appear to be indirect, occurring through binding to other molecules. When equal amounts of fetuin in sera were treated with chymotrypsin, resistance to the protease treatment was observed in patients with pancreatic cancer, but not in normal volunteers. To investigate the molecular mechanism behind this resistance, gel-filtration chromatography was performed. The results revealed that high molecular types of fetuin showed a resistance to protease treatment. When fetuin was purified from sera of patients with pancreatic cancer and normal volunteers, certain types of proteins, including haptoglobin (which binds to fetuin derived from pancreatic cancer patients), were identified using mass spectrometry. Furthermore, the oligosaccharide structures of fetuin analyzed with lectin microarray differed between pancreatic cancer patients and normal volunteers. This macro/micro heterogeneity of fetuin might contribute to pancreatic cancer resistance to chymotrypsin treatment.