Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stage III colorectal cancer.

The safety and immunological responsiveness of a peptide vaccine of ring finger protein 43 and 34-kDa translocase of the outer mitochondrial membrane combined with uracil-tegafur/leucovorin (UFT/LV) was previously demonstrated in metastatic colorectal cancer (CRC) in a phase I clinical trial. To clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment, a phase II clinical trial was conducted involving patients with stage III CRC. All enrolled patients, whose human leukocyte antigen (HLA)-A status was double-blinded, were administered the same regime of a peptide vaccine and UFT/LV chemotherapy.

Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.

We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34-kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil-tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination-induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA-masked fashion.

Prognostic factors for patients with advanced colorectal cancer and symptomatic brain metastases.

Background: Increased rates of long-term survival after CRC diagnosis are accompanied by increases in the incidence of BMs. Here, we retrospectively evaluated the outcomes of patients with BMs from CRC.

Materials And Methods: We reviewed the records of 1364 patients with CRC treated between January 1999 and December 2010 at Kinki University Hospital in Japan.

[Clinical trial of a seven-peptide vaccine and tegafur-uracil/leucovorin as combination therapy for advanced colorectal cancer].

We conducted a clinical trial of a seven-peptide vaccine in combination with tegafur-uracil/Leucovorin for advanced colorectal cancer. These antigenic peptides were derived from 5 proteins identified as cancer-testis antigens(ring finger protein 43 [RNF43], translocase of outer mitochondrial membrane 34[TOMM34], maternal embryonic leucine zipper kinase[MELK], forkhead box M1[FOXM1], and holliday junction recognition protein[HJURP])and 2 vascular endothelial growth factor receptors(VEGFR1 and VEGFR2). Thirty patients with advanced colorectal cancer were enrolled.

Clinical efficacy of abatacept, tocilizumab, and etanercept in Japanese rheumatoid arthritis patients with inadequate response to anti-TNF monoclonal antibodies.

The aim of this study was to compare the efficacy and retention rates of three biologics (abatacept, tocilizumab, and etanercept) after switching from first-course anti-TNF monoclonal antibody therapy. We performed a retrospective multicenter study of 89 patients who underwent second-course biologic therapy for 52 weeks after switching from first-course anti-TNF monoclonal antibody therapy. Patients at baseline had a mean age of 58.

Clinical trial of a 7-peptide cocktail vaccine with oral chemotherapy for patients with metastatic colorectal cancer.

Aim: The combination of a peptide vaccine and tegafur-uracil plus leucovorin (UFT/LV) were evaluated in patients with metastatic colorectal cancer refractory to standard chemotherapy.

Patients And Methods: Thirty human leukocyte antigen (HLA)-A2402-positive patients were enrolled in the study. In a cycle of treatment, a vaccine comprising of seven synthetic peptides (five tumor antigen-derived and two vascular endothelial growth factor receptor-derived) was injected weekly, and oral chemotherapy, UFT/LV was given daily for four weeks followed by one week of rest.

A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study).

Background: We previously conducted a phase I trial for advanced colorectal cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, and confirmed safety and immunological responses. To evaluate clinical benefits of cancer vaccination treatment, we conducted a phase II trial using the same peptides in combination with oxaliplatin-based chemotherapy as a first-line therapy.

Methods: The primary objective of the study was the response rates (RR).

[Treatment outcome of peptide vaccination for advanced colorectal cancer].

Complementary DNA( cDNA) microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen (HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different cancer-testis antigens, ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34( TOMM34). We conducted a clinical trial of colorectal cancer-specific peptide( RNF43, TOMM34) vaccines with uracil/tegafur( UFT)+Leucovorin( LV) for the treatment of advanced or recurrent colorectal cancer.

Analysis of the clinical factors associated with anal function after intersphincteric resection for very low rectal cancer.

Background: Intersphincteric resection (ISR) has been used to avoid permanent colostomy in very low rectal cancer patients. This study aimed to assess the surgical safety and oncologic and functional outcomes of ISR.

Methods: The records of 30 consecutive very low rectal cancer patients who underwent ISR without neoadjuvant therapy were retrospectively analyzed; survival and locoregional recurrence rates were calculated by the Kaplan-Meier method.

[Clinical study of Peptide-cocktail vaccination with tegafur-uracil/leucovorin for advanced colorectal cancer].

cDNA microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen(HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different testis cancer antigens, ring finger protein 43(RNF43) and translocase of outer mitochondrial membrane 34(TOMM34). We conducted a clinical trial of vaccines against colorectal cancer specific peptides(RNF43 and TOMM34) with tegafur-uracil/Leucovorin( UFT/LV) for the treatment of advanced or recurrent colorectal cancer.

[New directions in immunotherapy for malignant solid tumors].

Despite advances in treatment modalities, malignant solid tumors remain devastating maladies. Conventional treatment with chemotherapy and radiation is still only partially effective and highly toxic. In the era of increasing knowledge of the molecular biology of tumors and the interaction between the tumor and immune system, the development of targeted agents, including cancer vaccines, has emerged as a promising modality.

Recent advances in active specific cancer vaccine treatment for colorectal cancer.

Cloning techniques to identify genes and peptides of tumor-associated antigens have created new possibilities for the immunotherapy of patients with advanced cancer. Here, we review recent clinical trials of specific cancer vaccines, mainly HLA-restricted peptides, and epitope-encoding vectors for advanced colorectal cancer (CRC). Many researchers initially focused on carcinoembryonic antigen (CEA) as an immunologic target antigen that is overexpressed on virtually all CRCs.

[Preliminary study of Peptide vaccine with UFT/LV as adjuvant setting for stage III colorectal cancer].

cDNA microarray technology has been used to identify HLA-A24-restricted epitope peptides as potential targets for cancer vaccination in metastatic colorectal cancer patients. We conducted a clinical trial of two novel cancer-specific peptides( RNF43, TOMM34) with UFT/LV for the treatment of recurrent colorectal cancer. Among 23 patients, 21 patients had completed the protocol.

Phase I clinical trial of a novel peptide vaccine in combination with UFT/LV for metastatic colorectal cancer.

To test the safety and immune responses of a novel peptide vaccine derived from RNF43 (ring finger protein 43) and TOMM34 (34-kDa translocase of the outer mitochondrial membrane) administered in combination with chemotherapy in patients with metastatic colorectal cancer, a phase I clinical trial with 21 HLA-A2402-positive metastatic colorectal cancer patients was conducted. Patients received a weekly peptide vaccine (1 mg of each peptide in incomplete Freund's adjuvant) in combination with oral UFT (300 mg/m(2)/day) and UZEL (75 mg/day) for 4 weeks, followed by 1 week of rest. The protocol consisted of at least two cycles of this regimen.

Psychosocial factors, disease status, and quality of life in patients with rheumatoid arthritis.

Objective: To explore the interrelationships between the psychosocial and illness factors that determine the disease status of patients with rheumatoid arthritis (RA) and to identify how each factor is associated with quality of life (QOL).

Methods: The study group comprised 120 RA outpatients who completed a series of health examinations and questionnaires. Disease severity, functional disability, counts of swollen and/or tender joints, duration of RA, frequency of arthritis surgery, and C-reactive protein level were assessed by rheumatologists.

Depression, inflammation, and pain in patients with rheumatoid arthritis.

Objective: An association between depression and inflammation has been suggested. In patients with rheumatoid arthritis (RA), pain is a major symptom associated with depression and inflammation. We examined the independent associations between depression, the inflammation marker C-reactive protein (CRP) level, and pain in patients with RA.

A case of peripheral neuropathy and skin ulcer in a patient with rheumatoid arthritis after a single infusion of tocilizumab.

We report a case of peripheral neuropathy and skin ulcer in a patient with rheumatoid arthritis (RA) who received tocilizumab. A 65-year-old woman with a 20-year history of RA participated in a tocilizumab clinical trial. She received a single dose of 8 mg/kg tocilizumab intravenously.

A simple technique for wedge biopsy of the liver during laparoscopic surgery.

A simple technique for wedge biopsy of the liver, which can be performed concomitantly with laparoscopic surgery, is described in this paper. For this technique, the edge of the liver is clamped with two standard laparoscopic bowel graspers at an approximately 90-degree angle to create a wedge of hepatic tissue for biopsy. A pair of endoscopic scissors is used to excise the specimen between the graspers.

The effect of recombinant human bone morphogenetic protein-2 on the osteogenic potential of rat mesenchymal stem cells after several passages.

Background: Since the osteogenic potential of bone marrow derived mesenchymal stem cells (BMSCs) becomes reduced with passage, establishment of culture condition that permit the rapid expansion of BMSCs while retaining their potential for differentiation is needed for clinical application. Bone morphogenetic proteins stimulate osteogenic differentiation in mesenchymal progenitor cells as well as increase stem cell numbers. Thus, we analyzed the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the osteogenic potential of rat BMSCs over several passages.

Anaphylactic reaction to infliximab in two rheumatoid arthritis patients who had previously received infliximab and resumed.

Here we report on two cases of anaphylactic reaction following infliximab infusion in patients with active rheumatoid arthritis (RA). Both individuals had received infliximab treatment during a clinical trial approximately 2 years prior to further therapy; subsequent infusion of this agent led to anaphylactic reactions in both cases. In light of these findings, we recommend that future treatments with infliximab in RA patients who have previously received this agent should be carefully monitored.

Osteogenic potential of rat mesenchymal stem cells after several passages.

Osteogenic potential of serially passaged rat bone marrow derived mesenchymal stem cells (BMCs) was evaluated for clinical feasibility. Osteogenic differentiation in vitro was evaluated by means of the concentration and mRNA expression of alkaline phosphatase and osteocalcin. For in vivo osteogenesis, BMCs in various degrees of differentiation were implanted into the athymic mice.

Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells.

We investigated chondrogenesis of cell-mediated sox9 gene therapy as a new treatment regimen for cartilage regeneration. pIRES2-EGFP vector containing a full-length mouse sox9 cDNA was transfected into bone marrow-derived mesenchymal stem cells (MSCs) by lipofection and chondrogenic differentiation of these cells was evaluated. In vitro high density micromass culture of these sox9 transfected MSCs demonstrated that a matrix-rich micromass aggregate with EGFP expressing MSCs was positively stained by Alcian blue and type II collagen.