ABSTRACT
OBJECTIVE: To explore the molecular mechanism and prevention of retinoic acid syndrome (RAS). METHODS: SDF-1 alpha mRNA from healthy adult lung tissue was measured by RT-PCR, CXCR4 protein expression on the cell membrane of APL cells induced by ATRA (APL-ATRA) was tested by FCM, and the rotary cell culture system (RCCS) was used to build a modal for in vitro stimulation of APL-ATRA infiltrating human lung tissue. The ability of APL-ATRA in adhesion, migration and infiltration was observed by interference from DEX, Ara-C and DNR. RESULTS: The APL-ATRA cells could evidently infiltrate into normal lung tissue. Mean fluorescence intensity (MFI) of CXCR4 on the cell membrane of APL-ATRA cells was 30.6 +/- 1.8, which was much higher than that on unspecialized APL cells (9.8 +/- 4.2). SDF-1 alpha mRNA expression was detected positive in all 6 lung tissue. Contrary to the control groups, DEX could dramatically restrain the ability of APL-ATRA cells in adhesion and migration [(27.2 +/- 2.6)% vs. (46.0 +/- 3.0)%, (28.1 +/- 4.0)% vs. (48.2 +/- 3.0)%], while Ara-C and DNR could distinctly depress the ability in adhesion, migration and infiltration [(28.1 +/- 3.0)%, (30.2 +/- 3.2)% vs. (46.0 +/- 3.0)%; (29.0 +/- 4.0)%, (23.0 +/- 5.2)% vs. (48.2 +/- 3.0)%; (16.8 +/- 7.6)%, (17.1 +/- 6.0)% vs. (43.6 +/- 5.0)%]. CONCLUSION: In vitro APL-ATRA cells can infiltrate into the human lung tissue. High expression of CXCR4 on APL-ATRA and SDF-1 alpha in the lung tissue may be one of the molecular mechanisms of the lung infiltration and RAS. DEX, Ara-C and DNR can dramatically restrain the ability of APL-ATRA cells in adhesion, migration and infiltration.
Subject(s)
Chemokine CXCL12/metabolism , Leukemia, Promyelocytic, Acute/metabolism , Receptors, CXCR4/metabolism , Tretinoin/adverse effects , Adolescent , Adult , Cell Adhesion , Cell Culture Techniques , Cell Movement , Chemokine CXCL12/genetics , Child , Female , Humans , Leukemia, Promyelocytic, Acute/pathology , Male , Middle Aged , Neoplasm Invasiveness , Receptors, CXCR4/genetics , Tumor Cells, CulturedABSTRACT
OBJECTIVE: To study the main side effects of As(2)O(3) and the way of prevention. METHODS: The changes of body weight and various systems of body were observed after treatment with As(2)O(3) injection. The arsenic content in blood, urine and hair was detected with atom absorbed-spectrum analysis. RESULTS: Mild reactions were observed in 57.43% (147/256) of the patients and they could subside after cessation of arsenic treatment or allotherapy. Chronic mild poisoning manifestations including arsenic furuncle, liver dysfunction and peripheral nerve injury were found in 2.73% (7/256) of the patients and they subsided gradually after treatment. Chronic severe poisoning was found in 1.17% of the patients and all of them died of liver failure. As(2)O(3) might cause decrease of peripheral blood WBC in catabatic patients. There was no infection after allopathy without ceasing arsenic medication. The results showed that As(2)O(3) could distribute over and discharge from the plasma without accumulation in blood. The results also demonstrated the main route of excretion for As(2)O(3) is through urine and there is definite accumulation in the hair 50 days after treatment. CONCLUSION: Most of the side effects of As(2)O(3) are mild and recoverable. Allotherapy could be effective to relieve the complications without stopping arsenic medication. A few patients with complicating hepatitis may suffer from chronic poisoning. As(2)O(3) may cause increase of peripheral blood WBC in induced catabatic APL patients. The side effects must be prevented early.