Although MIF plays multifunctional roles in a broad spectrum of pathophysiological states, little has been done to investigate the role of this protein in association with tumor growth. The current results suggest the possibility that MIF induces tumor cell growth in concert with other growth factors, which encouraged us to investigate a novel approach for tumor therapy using an anti-MIF antibody and an MIF anti-sense plasmid transfection technique.
There is no standard treatment modality for advanced gastric cancer (GC) at the present time. To develop a new treatment modality, we investigated the immunological responses of advanced GC patients (n = = = =13, 9 non-scirrhous and 4 scirrhous types) vaccinated with peptides to a regimen under which pre-vaccination peripheral blood mononuclear cells (PBMCs) were screened for their reactivity in vitro to each of 14 peptides on HLA-A24 or 16 peptides on -A2 allele, then only the reactive peptides (maximum: 4) were administered in vivo. This regimen was generally well tolerated, although grade I levels of fever and local skin reactions were observed in several patients. astric cancer (GC), a leading cause of cancer-related death worldwide throughout the past century, now ranks second only to lung cancer, with an estimated 750,000 new cases diagnosed annually around the world. 1) Except in Japan and a few East Asian countries, the prognosis of GC remains poor, and the overall 5-year survival rate ranges from 5 to 15% despite many clinical trials of chemotherapy and other new therapies. In particular, there is no current treatment modality for disseminated GC histologically of the scirrhous type.2) Therefore, development of a new treatment modality is needed, and one such modality could be specific immunotherapy, given that recent advances in tumor immunology have resulted in identification of many tumor antigens and epitopes recognized by HLA-class-I-restricted cytotoxic T lymphocytes (CTLs) from various cancers, including GC.3-6) However, clinical trials with these peptides have rarely obtained major clinical responses.7-9) This failure could have been due to an insufficient induction of antitumor responses by these vaccine regimens, since peptide-specific memory T cells were not measured in pre-vaccination peripheral blood mononuclear cells (PBMCs). We speculated that vaccination based on pre-vaccination measurement of peptidespecific CTLs in the circulation might be able to induce potent anti-tumor immune responses in cancer patients. [8][9][10][11][12][13] In this report, we describe the safety of such a regimen and the immune responses to peptides and tumor cells in advanced GC patients vaccinated with peptides based on pre-existing cellular response.
Haem is a prosthetic group for haem proteins, which play an essential role in oxygen transport, respiration, signal transduction, and detoxification. In haem biosynthesis, the haem precursor protoporphyrin IX (PP IX) must be accumulated into the mitochondrial matrix across the inner membrane, but its mechanism is largely unclear. Here we show that adenine nucleotide translocator (ANT), the inner membrane transporter, contributes to haem biosynthesis by facilitating mitochondrial accumulation of its precursors. We identified that haem and PP IX specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a known substrate of ANT. Conversely, ADP uptake into mitochondria was competitively inhibited by haem and its precursors, suggesting that haem-related porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of the ANT genes in yeast resulted in a reduction of haem biosynthesis by blocking the translocation of haem precursors into the matrix. Our results represent a new model that ANT plays a crucial role in haem biosynthesis by facilitating accumulation of its precursors into the mitochondrial matrix.
The activities of four heme-biosynthetic enzymes, delta-aminolevulinic acid (ALA) synthase, ALA dehydratase, porphobilogen (PBG) deaminase, and ferrochelatase, were studied in five epithelial cell lines of normal rat liver origin (RL, RLC-10, RLC-24, M, Culb-TC) and five cell lines derived from Yoshida ascites hepatoma (JTC-1, JTC-2, JTC-15, JTC-16, JTC-24). The JTC series of hepatoma-derived cell lines exhibited decreased ALA synthase activity and increased ALA dehydratase activity, although the activities of all four enzymes and the Km values for their respective substrates varied widely from one cell line to another, a finding suggesting that specific regulatory mechanisms for porphyrin metabolism might operate in each cell type. M cells, which were transformed by 4-dimethylaminoazobenzene in vitro, gave the most abnormal Km values of heme-biosynthetic enzymes among all the cell lines studies, and were found to accumulate hematoporphyrin derivative (HpD).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.