Phase II study of biweekly cetuximab plus mFOLFOX6 or mFOLFIRI as second-line treatment for metastatic colorectal cancer and exploratory analysis of associations between DNA methylation status and the efficacy of the anti-EGFR antibody: T-CORE1201.

Background: Little is known about the biweekly combined use of cetuximab and chemotherapy as second-line treatment of metastatic colorectal cancer (mCRC). Recently, DNA methylation status has been reported to be a new possible predictor of the efficacy from the anti-epidermal growth factor receptor (EGFR) antibody treatment. The purpose of this study was to examine the efficacy and safety of biweekly cetuximab plus mFOLFOX6 or mFOLFIRI as a second-line treatment for exon 2 wild-type mCRC.

Albuminuria, C-reactive protein, and socioeconomic factors are associated with periodontal status in subjects with type 2 diabetes.

Diabetes and periodontitis may increase risk of cardiovascular disease. Whether albuminuria, C-reactive protein (CRP), and socioeconomic factors, known as cardiovascular risks in subjects with poorly controlled diabetes, are independently associated with periodontal status in well-controlled diabetes remains to be elucidated. In 503 subjects with type 2 diabetes, the cross-sectional associations of clinical and socioeconomic factors with periodontal parameters were investigated.

Predictive factors for tooth loss during supportive periodontal therapy in patients with severe periodontitis: a Japanese multicenter study.

Background: Supportive periodontal therapy (SPT) must take individual patient risk factors into account. We conducted a multicenter joint retrospective cohort study to investigate the value of modified periodontal risk assessment (MPRA) and therapy-resistant periodontitis (TRP) assessment as predictive factors for tooth loss due to periodontal disease in patients with severe periodontitis during SPT.

Methods: The subjects were 82 patients from 11 dental institutions who were diagnosed with severe periodontitis and continued SPT for at least 1 year (mean follow-up = 4.

Correction to: Effects of periodontal treatment on carotid intima-media thickness in patients with lifestyle-related diseases: Japanese prospective multicentre observational study.

Unfortunately, in Table-5 of the original article, the parameter in the 5th row was published incorrectly as "LDL-C (mg/dL)". The correct parameter should read as "HDL-C (mg/dL)".

Effects of periodontal treatment on carotid intima-media thickness in patients with lifestyle-related diseases: Japanese prospective multicentre observational study.

Atherosclerosis, a chronic inflammatory disease in arterial blood vessels, is one of the major causes of death in worldwide. Meanwhile, periodontal disease is a chronic inflammatory disease caused by infection with periodontal pathogens such as P. gingivalis (Porphyromonas gingivalis).

Oral infection control to assist infliximab therapy in a Behçet's disease patient with severe eye inflammation in response to dental treatment: a case report.

We report a case of Behçet's disease which was aggravated by psychological stress and oral infection. The control of oral infection under medical and dental collaboration is important for providing Behçet's disease patients with the optimal medical care and for facilitating the relief of the primary disease.

Analysis of the relationship between periodontal disease and atherosclerosis within a local clinical system: a cross-sectional observational pilot study.

It has been revealed that atherosclerosis and periodontal disease may have a common mechanism of "chronic inflammation". Several reports have indicated that periodontal infection is related to atherosclerosis, but none have yet reported such an investigation through the cooperation of local clinics. This study was performed in local Japanese clinics to examine the relationship between periodontal disease and atherosclerosis under collaborative medical and dental care.

Distribution of oral mucosal bacteria with mecA in patients undergoing hematopoietic cell transplantation.

Purpose: We recently reported frequent detection of antibiotic-resistant bacteria on the oral mucosa during the period of hematopoietic cell transplantation (HCT) and suggested an association between oral mucositis and antibiotic-resistant bacterial infection. Methicillin-resistant Staphylococcus spp. were frequently detected, and the oral cavity may be a reservoir of the gene mediating methicillin resistance, mecA.

Successful treatment of sepsis caused by Staphylococcus lugdunensis in an adult with 22q11.2 deletion syndrome.

A 27-year-old woman visited our hospital because of high fever. She had been diagnosed as 22q11.2 deletion syndrome (22q11.

Novel curcumin analogs, GO-Y030 and GO-Y078, are multi-targeted agents with enhanced abilities for multiple myeloma.

Background: Multiple myeloma remains an incurable malignancy despite of the recent approval of new molecular-targeted agents. The complex molecular mechanism, composed of various signal networks, including nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/AKT, Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), and interferon regulatory factor 4 (IRF4) pathways, is a major reason for treatment failure. Curcumin can regulate these molecules, but its low bioavailability prevents its clinical application.

Synthesis of 86 species of 1,5-diaryl-3-oxo-1,4-pentadienes analogs of curcumin can yield a good lead in vivo.

Background: Curcumin is known to possess many anti-tumor properties such as inhibition of tumor growth and induction of apotosis. However, limited bioavailability of curcumin prevents its clinical application. A synthesized curcumin analog, 1,5-diaryl-3-oxo-1,4-pentadiene such as GO-Y030, has the improved anti-tumor potential in vitro as well as in mouse model of colorectal carcinogenesis.

Curcumin analog GO-Y030 is a novel inhibitor of IKKβ that suppresses NF-κB signaling and induces apoptosis.

Curcumin is a dietary constituent with tumor-suppressing potential, inhibiting various pathways involved in carcinogenesis. However, because of its low bioavailability, the use of curcumin in in vivo trials has been limited. To overcome this problem, we synthesized more than 50 analogs and identified a monoketone analog, GO-Y030, which has a 30-fold higher potential to suppress tumor cell growth compared with curcumin.

Prognosis of periodontitis recurrence after intensive periodontal treatment using examination of serum IgG antibody titer against periodontal bacteria.

Chronic periodontitis is associated with systemic diseases such as atherosclerosis. In this study, we evaluated the efficacy of serum IgG antibody titer to periodontal bacteria for prognosis of periodontitis recurrence during supportive periodontal therapy (SPT) phase. The 139 patients during SPT phase were selected and divided to two groups as follows: "Stable" and "Recurrence" group at SPT phase for case-control study: "High IgG titer" and "Normal IgG titer" group before transition to SPT phase for cohort study.

KSRP/FUBP2 Is a Binding Protein of GO-Y086, a Cytotoxic Curcumin Analogue.

Bis(arylmethylidene)acetone derivatives are an important class of curcumin analogues that exhibit various biological and pharmacological activities. We herein report that GO-Y086, a biotinylated bis(arylmethylidene)acetone, inhibits cancer cell growth. We also show that GO-Y086 specifically interacts with the nuclear protein KSRP/FUBP2 by covalent modification.

Structure-activity relationship of C5-curcuminoids and synthesis of their molecular probes thereof.

A series of novel analogues of 1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-(1E,4E)-1,4-dien-3-one (C(5)-curcumin), which is a natural analogue of curcumin isolated from the rhizomes of Curcuma domestica Val. (Zingiberacea), were synthesized and evaluated for their cytotoxicities against human colon cancer cell line HCT-116 to conclude the SAR of C(5)-curcuminoids for further development of their use in cancer chemotherapy: (1) Bis(arylmethylidene)acetone serves as a promising skeleton for eliciting cytotoxicity. (2) The 3-oxo-1,4-pentadiene structure is essential for eliciting cytotoxicity.

Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo.

Curcumin (diferuloylmethane) has chemopreventive and chemotherapeutic potentials against various types of cancers. We have developed a series of curcumin analogs to improve its low bioavailability by enhancing its potentials. The newly synthesized analog GO-Y030 [(1E, 4E)-1,5-bis-(3,5(-bismethoxymethoxyphenyl) penta-1,4-dien-3-one] showed a 30-fold greater growth suppression in vitro via similar molecular mechanisms to curcumin.

Febrile neutropenia and periodontitis: lessons from a case periodontal treatment in the intervals between chemotherapy cycles for leukemia reduced febrile neutropenia.

Goals Of Work: Oral and systemic infections arising from the oral cavity are significant problems in clinical management of patients undergoing leukemia treatment. However, there is significant disparity in the reported incidences of development of periodontal infections. Evidence is limited to those showing the systemic influence of periodontal infection in neutropenic patients.

Appearance of multidrug-resistant opportunistic bacteria on the gingiva during leukemia treatment.

Background: Dentists generally recognize the importance of periodontal treatment in patients with leukemia, with the most attention paid to preventing the development of odontogenic infection. For physicians, the worst type of infection is one caused by multidrug-resistant bacteria. Here, we report a patient with an abnormal increase in multidrug-resistant opportunistic bacteria in the gingiva during hematopoietic cell transplantation (HCT).

Periodontal disease as part of the insulin resistance syndrome in diabetic patients.

Periodontal disease has been considered as a complication of diabetes mellitus. A recent epidemiological study revealed that obesity is an independent risk factor for periodontal disease. Obesity and type 2 diabetes mellitus are associated with many metabolic disorders including insulin resistance, dyslipidemia, hypertension and atherosclerosis.

BRAF point mutations in primary melanoma show different prevalences by subtype.

To elucidate the biological significance of activating mutations of BRAF in human malignant tumors, we performed a mutation analysis using 43 cell lines established from tumors that had developed in several kinds of human organs. Because the same V599E point mutation was observed in three of six melanoma cell lines and no such mutations were observed in other types of cancers, we focused further on melanoma, performed mutation analyses of NRAS, KRAS, CTNNB1, and p16/p14(ARF) in these cell lines, and found one NRAS mutation and three p16/p14(ARF) mutations. We further searched for mutations of BRAF and NRAS in 35 primary sporadic melanomas from 35 Japanese patients and detected the V599E BRAF point mutation in only nine (26%) of them.