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 non-dormant 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.

Background: There are large individual variations in the responses of risk factors for coronary heart disease to alcohol consumption. To clarify the factors responsible for these individual variations, we studied the relationship between blood pressure, serum lipids, and uric acid and the genetic polymorphisms of alcohol dehydrogenase (ADH) 2 and aldehyde dehydrogenase (ALDH) 2 in alcohol drinkers. Methods: We examined 133 male workers who drank >300 g of alcohol per week. Information regarding lifestyle habits was obtained by questionnaire. The ADH2 genotype was determined by PCR and subsequent digestion with MaeIII. The ALDH2 genotype was determined based on amplified product length polymorphisms. Results: When the workers were divided into three groups: the ADH21/21, ADH21/22, and ADH22/22 groups, the mean triglycerides and γ-glutamyl transpeptidase concentrations were significantly higher in the ADH22/22 group than in the ADH21/21 group. In addition, multiple logistic regression analysis showed that the frequencies of individuals whose systolic blood pressure, triglycerides, and uric acid values were in the highest one third were significantly higher in the ADH22/22 group than in the ADH21/21 group. In contrast, no difference was observed between the ALDH21/21 and (ALDH21/22 + ALDH22/22) groups with regard to the mean value of any variable and to the frequency of individuals with any variable value in the highest one third. Conclusion: Individuals with the ADH21/21 genotype might suffer fewer negative effects of drinking.

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We demonstrate the direct use of benzylic alcohols for a multicomponent reaction of readily available isatoic anhydrides with amines in water, which is a synthetic route for the direct construction of a series of 2‐aryl quinazolinones. This one‐pot synthetic method involves the dehydrative N‐benzylation of in situ generated anthranilamides followed by an amide‐directed benzylic C−H amination process utilizing the π‐benzylPd(II) system. Comparison of independent rate measurements using benzyl alcohol and its deuterated form gave a kinetic isotope effect of 3.5. Therefore, the benzylic C−H bond is cleaved in the rate‐determining step. We successfully carried out a gram‐scale reaction in 85% yield with simplified product isolation.