SBI Pharmaceuticals Co., Ltd. (SBI) is a pharmaceutical authorization holder of the orally available 5-aminolevulinic acid (5-ALA) in Japan for visualization of glioma and bladder cancer. SBI provides 5-ALA as a research material and makes mutual collaborations with academic institutions. We examined four published studies of 5-ALA-FD (5-ALA fluorescence guided detection) conducted in Japan. 5-ALA was orally administrated at 20mg/kg body weight or 1g per patient at 2-4 hours before surgery or diagnosis. Bladder cancer: The presence of CIS (carcinoma in situ) affects recurrence of non-muscle-invasive bladder cancer. Additional CISs were detected and diagnosed only by 5-ALA-FD in 9 out of 60 patients and they were classified as high risk group. Peritoneal metastasis of gastric cancer: The addition of 5-ALA-FD to conventional laparoscopy enabled us to identify usually invisible peritoneal metastases in 5 of 24 patients with advanced gastric cancer. Pancreatic cancer: Peritoneal nodules suspected to be peritoneal metastases were observed under white light in 9 of 34 patients. The nodules in 4 of 9 patients showed fluorescence by 5-ALA-FD and were histopathologically diagnosed as metastases. Lung cancer: Fluorescence was confirmed in 14 of 14 PL1-PL3 patients and 10 of 24 PL0 patients. PL0 patients showed red fluorescence were preoperatively diagnosed as stage PL1. Accurate intraoperative diagnosis for visceral pleural invasion in lung cancer was performed by 5-ALA-FD. Four studies indicate that 5-ALA-FD is useful for distinction of tumors such as small lesions and contributes to selection of an appropriate therapy without a non-curative resection.
Mitochondria play a fundamental role in generating of energy in cells. Electron transfer in electron transport chain (ETC) involved in mitochondria was one of the biological functions of heme. Heme biosynthesizes increased upon the addition of 5-aminolevulinic acid (ALA). Complex I and II protein expression were downregulated, while complex IV and cytochrome c expression were upregulated by the addition of ALA. Administration of ALA significantly increased Complex IV (COX) activity and cellular ATP level. Surprisingly, the mitochondrial content and mitochondrial membrane potential were unchanged. Consistently, the relative mRNA-expression of transcription factors affecting mitochondrial biogenesis was unchanged after the addition of ALA.
Aminolevulinic acid–based photodynamic therapy (ALA-PDT) has emerged as a new alternative for chemotherapy in cancer treatment due to its high specificity and low side effects. We added siRNAs and inhibitors of transporters to study the roles of transporters in ALA uptake in sets of normal and cancer cell lines. PEPT1 and PAT1 were expressed only in normal lung and prostate cells, respectively, but not in their cancerous counterparts. Inhibition of these transporters showed a significant decrease in PpIX production only in normal cells. PEPT1 and PAT1 transporter inhibitors could be possible new drugs to increase the specificity of ALA-PDT.
Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to drive the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. However, the tendency to accumulate PpIX is not well understood. Patients with cancer can develop recurrent metastatic disease with latency periods. This pause can be explained by cancer dormancy. Here we created uniformly sized PC-3 prostate cancer spheroids using a 3D culture plate (EZSPHERE). We demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner not only in spheroids but also in 2D culture. Dormant cancer cells accumulated high PpIX levels and were sensitive to ALA-PDT. In dormant cancer cells, transporter expressions of PEPT1, ALA importer, and ABCB6, an intermediate porphyrin transporter, were upregulated and that of ABCG2, a PpIX exporter, was downregulated. PpIX accumulation and ALA-PDT cytotoxicity were enhanced by G0/G1-phase arrestors in nondormant cancer cells. Our results demonstrate that ALA-PDT would be an effective approach for dormant cancer cells and can be enhanced by combining with a cell-growth inhibitor.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.