Biological formation of 5-aminolevulinic acid by photosynthetic bacteria

In this study, 7 stains of Rhodopseudomonas sp. were selected from 36 photosynthetic bacteria stains storied in our laboratory. Rhodopseudomonas sp. strain 99 28 has the highest 5 aminolevulinic acid(ALA) production ability in these 7 strains. Rhodopseudomonas sp. 99 28 strain was mutated using ultraviolet radiation and a mutant strain L 1, which ALA production is higher than wild strain 99 28 about one times, was obtained. The elements affecting ALA formation of strain 99 28 and L 1 were studied. Under the optimal condition(pH 7 5, supplement of ALA dehydratase(ALAD) inhibitor, levulinic acid(LA) and precursors of ALA synthesis, glycine and succinat, 3000 lx of light density), ALA formation of mutant L 1 was up to 22 15 mg/L. Strain L 1 was used to treat wastewater to remove COD Cr and produce ALA. ALA production was 2 819 mg/L, 1 531 mg/L, 2 166 mg/L, and 2 424 mg/L in monosodium glutamate wastewater(MGW), succotash wastewater(SW), brewage wastewater(BW), and citric acid wastewater(CAW) respectively. More than 90% of COD Cr was removed in four kinds of wastewater. When LA, glycin and succinate were supplied, ALA production was dramatically increased, however, COD Cr could hardly be removed.

COMPARISON OF AMINOLEVULINIC ACID AND ITS METHYL ESTER MEDIATED PHOTOCYTOTOXICITY ON HUMAN NASOPHARYNGEAL CARCINOMA CELLS

Nasopharyngeal carcinoma(NPC)is a prevalent cancer in some areas of southern Asia.To explore the potential of photodynamic therapy(PDT)for the treatment of NPC,a small molecule prodrug 5-aminolevulinic acid(ALA)and its methyl ester(MAL)mediated PDT was studied in vitro.The results showed that human NPC cells were sensitive to both ALA-and MAL-mediated PDT.However,ALA was more effective than MAL,possiblly due to a higher efficiency of ALA on producing endogenous protoporphyrin(PpIX)in NPC cells.Neither ALA nor MAL caused any significant genotoxicity.The ALA-based PDT might be a useful modality in the treatment ofNPC.

Evaluation of photodynamic therapy of skin cancers with δ-aminolevulinic acid

Objective To use δ-aminolevulinic acid induced photodynamic therapy (ALA-PDT) increasingly in treating skin cancers and other diseases in many countries and to explore the efficacy of ALA-PDT for skin cancers in China. Methods Eighty-eight patients, including 34 cases of basal cell carcinoma (BCC), 32 cases of squamous cell carcinoma (SCC), two cases of basal-squamous cell carcinoma (BSCC), one case of verrucuous carcinoma, nine cases of Bowen disease, two cases Paget disease of the nipple and eight cases of extramammary Paget disease, were treated by the δ-aminolevulinic acid induced photodynamic therapy first in China from 1997 to 2000. Results All BCC, including 11 cases of superficial lesions and 29 solid lesions, achieved complete reaction (CR) by 1-4 times of the ALA-PDT. Except one patient with adenoid SCC (grade Ⅲ), all SCC (grade Ⅰ and grade Ⅱ) patients achieved complete remission by 3-6 times of ALA-PDT. All Bowen diseases achieved complete reaction by 1-4 times. Although for Paget diseases it could not cure the disease simply by ALA-PDT, it could control the symptoms. The recurrence rates were 11% (4/34) for BCC, and 22% (7/32) for SCC by following up 1-3 years after the therapy. The continuous therapy is still effective. Conclusions ALA-PDT is an effective, non-traumatic treatment for patients with BCC, SCC, Bowen and Paget diseases. It is especially suitable for older and weaker patients or those who are not tolerable to other therapies. It also has a unique advantage for tumors in specific anatomical areas. It is a new alternative modality for skin cancer therapies.

Photodynamic therapy of condyloma acuminata in pregnant women

Background Photodynamic therapy （PDT） with 5-aminolevulinic acid （ALA） is an emerging technique for the treatment of genital human papillomavirus （HPV）-induced benign and premalignant lesions. We report here in a case series of condyloma acuminata （CA） in pregnancy successfully treated with ALA-PDT. Methods Five pregnant patients with CA received three to four times treatment respectively. Patients were followed up for 6-23 months after treatment. Results The clearance rate of genital warts was 100%. No recurrence was found during the follow-up period. Major adverse events reported were mild erosion, pain, and local edema. All pregnancies resulted in healthy live births without delivery complications. Conclusions PDT with topical ALA seems to be safe and effective in the treatment of CA in pregnancy. It demonstrated high clearance rate of warts, was well-tolerated by patients, and showed no adverse effects on mothers or fetuses. ALA-PDT may be an ideal strategy of treatment for pregnant women with CA.

A non-toxic approach for treatment of breast cancer and its metastases: capecitabine enhanced photodynamic therapy in a murine breast tumor model

Aim: Breast cancer (BCA) in women is a leading cause of mortality and morbidity;distant metastases occur in ~40% of cases. Here, as an alternative to ionizing radiation therapy and chemotherapy and their associated side effects, we explored a new combination approach using capecitabine (CPBN) and aminolevulinate-based photodynamic therapy (PDT). We had previously developed a combination PDT approach in which 5-fluorouracil (5FU), a differentiation-promoting agent, increases the levels of protoporphyrin IX (PpIX) in cancer cells when given as a neoadjuvant prior to aminolevulinic acid (ALA). However, 5FU can be toxic when administered systemically at high levels. We reasoned that CPBN, a known chemotherapeutic for BCA and less toxic than 5FU (because CPBN is metabolized to 5FU specifically within tumor tissues), might work equally well as a PDT neoadjuvant. Methods: Murine 4T1 BCA cells harboring a luciferase transgene were injected into breast fat pads of female nude mice. CPBN (600 mg/kg/day) was administered by oral gavage for 3 days followed by intraperitoneal ALA administration and PDT with red light (633 nm) on day 4. Tumor growth and regression were monitored in vivo using bioluminescence imaging. Histological changes in primary tumors and metastases were assessed by immunohistochemistry after necropsy. ;Results: CPBN pretreatment of 4T1 tumors increased cellular differentiation, reduced proliferation, raised PpIX levels, enhanced tumor cell death, and reduced metastatic spread of 4T1 cells post-PDT, relative to vehicle-only controls. Conclusion: The use of CPBN as a non-toxic PDT neoadjuvant for treatment of BCA represents a novel approach with significant potential for translation into the clinic.