Flavonoids are a kind of ubiquitous natural products in plants and essential active ingredients of many medicinal plants. They have the characteristics of broad biological activity, high efficiency and low toxicity, with good prevention and cure effects on various types of tumors. Breast cancer is the commonest cancer disease and the main cause of cancer death in women worldwide. In China, the morbidity and mortality are still on the rise. Flavonoids can inhibit the occurrence and development of breast cancer in various aspects. The main mechanisms include the inhibition of aerobic glycolysis, the promotion of apoptosis, the retardation of cell cycle, the suppression of invasion and migration, the induction of DNA damage, and the inhibition of aromatase and microtubule production. Due to its chemical structure similar to estrogen, flavonoids have unique advantages in the prevention and treatment of breast cancer. In this paper, studies on anti-breast cancer of flavonoids in recent years were reviewed, which could provide reference for further studies.

OBJECTIVETo investigate the impact of immunosuppressive therapy (IST) on genetic instabilities of bone marrow hematopoietic cells (BMHCs) in patients with aplastic anemia (AA).

METHODSComet assay as used to detect genetic instabilities of hematopoietic cells from patients, and the percent of DNA in comet tail (TDNA), tail length (TL), tail moment (TM), olive tail moment (OTM) and the rate of comet cells were measured. BMHCs from AA patients were examined with comet assay before and after IST, and the results were compared with those from controls.

RESULTSComet parameters from 91 AA patients including TDNA, TL, TM, OTM comet cell percentage were (5.0 +/- 4.0)%, 11.3 +/- 7.2, 1.7 +/- 2.0, 1.5 +/- 1.4, (16.8 +/- 13.7)%, respectively, which were significantly higher than those from control group (P < 0.05). There were statistical differences between the comet parameters of severe AA (SAA)/non-SAA (NSAA) and those of control group (P < 0.05), but no difference in the comet parameters between SAA and NSAA patients (P > 0.05). The TDNA, TL, TM, OTM and comet cells percentage were (4.4 +/- 3.6)%, 10.4 +/- 7.5, 1.4 +/- 1.6, 1.3 +/- 1.4 and (20.2 +/- 21.2)%, respectively at 3 months after IST in 53 SAA patients and were (3.7 +/- 3.3)%, 10.0 +/- 7.2, 1.2 +/- 1.8, 1.1 +/- 1.3 and (18.5 +/- 19.0)% respectively at 6 months after IST in 30 SAA patients, being no statistical difference from those of 58 SAA patients before IST (P values were all > 0.05).

CONCLUSIONBMHCs of AA had inherent genetic instabilities which were not increased by recent IST. It indicated that there was no correlation between IST and the development of clonal hematologic disorders in AA.

Adolescent ; Adult ; Anemia, Aplastic ; genetics ; therapy ; Child ; Child, Preschool ; Comet Assay ; Female ; Genomic Instability ; Hematopoietic Stem Cells ; cytology ; metabolism ; Humans ; Immunosuppression ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Young Adult

OBJECTIVETo evaluate bone marrow hematopoietic cells genetic instability (BMHCGI) in patients with aplastic anemia (AA) and to explore its influence on immunosupressive therapy for AA and significance on late clonal hematologic disorders.

METHODSGenetic instability of bone marrow mononuclear cells (BMMNC) was measured by Comet assay. The relationship between bone marrow failure parameters and genetic instability results was evaluated. The reciprocity of genetic instability and treatment responses to immunosuppressive therapy (IST) was investigated.

RESULTSComet assay parameters \[tail moment (TM), olive TM (OTM), comet %\] of AA patients were significantly higher than that of control group (P < 0.05). There was no statistic correlation of comet parameters of severe AA (SAA) BM hematopoietic cells with age, gender and peripheral blood cell count (P > 0.05). For the treatment response rate at six months after IST there was no statistical difference between comet cells of < 21.64% and of >/= 21.64%, and so did between OTM < 1.58 and >/= 1.58 in SAA patients. IST had no effect on SAA BMHCGI, whereas, the Comet%, TM and OTM in SAA PR patients and Comet% in CR patients were significantly decreased than those before treatment. Comet parameters of two SAA patients were significantly increased before the development of clonal cytogenetic abnormalities.

CONCLUSIONSIncreased BMHCGI may be one of the elements in the pathogenetic mechanisms in AA. The genetic instability is irrelevant to the SAA patients overall response rate of IST at six months, but IST can alleviate the genetic instabilities in responded SAA patients.

Anemia, Aplastic ; therapy ; Blood Cell Count ; Bone Marrow Cells ; Humans ; Immunosuppression ; Pancytopenia

OBJECTIVETo analyse the efficacy and side-effects of rabbit antithymocyte globulin (ATG) and cyclosporin A (CsA) as the first-line therapy for childhood severe aplastic anemia (SAA).

METHODSSeventy-one childhood SAA patients treated with rabbit ATG + CsA as first line therapy were retrospectively analysed.

RESULTSSeventy-one SAA patients, including 38 SAA and 33 very severe aplastic anemia (VSAA), were enrolled. The median age was 12 years. Of these patients, 3 died within 3 months after the immunosuppressive therapy (IST). The overall response rate was 67.6% (46/68) and the median time to transfusion independent was 53 days. Thirty-three patients (48.5%) obtained remission in 3 months after the IST and 45 (67.2%) in 6 months. The response rates were 57.7% (15/26), 56.5% (13/23) and 94.7% (18/19) for patients less than 10 years old, 10 - 15 year-old and 15 - 18 year-old, respectively. Sixty patients suffered from serum sickness on the IST. Three patients relapsed and another 3 unrespond patients received retreatment of IST, and one patient progressed to myelodysplastic syndromes (MDS).

CONCLUSIONRabbit ATG in combination with CsA as first line therapy for childhood SAA/VSAA can lead to overall response rate of 67.6% with minor adverse effects.

Anemia, Aplastic ; therapy ; Animals ; Antilymphocyte Serum ; Cyclosporine ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Rabbits ; Treatment Outcome

OBJECTIVETo evaluate the effects of cyclosporine A (CsA) whole-blood concentration on the early response to immunosuppressive therapy (IST) in severe and very severe aplastic anemia (SAA/VSAA).

METHODSNinety SAA/VSAA patients treated with rabbit antithymocyte globulin (ATG) plus CsA as first line therapy in our hospital were retrospectively analysed. CsA levels between the response group and non-response group, and response rates of patients with variant CsA levels were compared respectively.

RESULTS(1) There was no significant difference in the beginning unmodified CsA blood concentration between IST responded and non-responded SAA/VSAA patients. The beginning unmodified C(0) 133.91 ug/L in IST 2-month responders was higher than that of 49.9 ug/L in non-responded SAA patients (P = 0.009); (2) The mean CsA C(0) and C(2) levels during the third month following IST were significantly different in responders and non-responders(197.52 µg/L vs 161.49 µg/L, P = 0.024, and 738.76 µg/L vs 615.46 µg/L, P = 0.009), and no significant difference in other periods of IST (P > 0.05); (3) The response rate (87.5%) was significantly higher in patients with CsA C(0) ≥ 200µg/L the third month following IST than those of 55.6% in patients with CsA C(0) 150 - 200 µg/L (P = 0.023) and 59.3% in patients with CsA C(0) < 150 µg/L (P = 0.046), respectively. The response rate was significantly higher of C(2) ≥ 700 µg/L group than that of C(2) < 700 µg/L group (80.5%vs 55.3%, P = 0.012).

CONCLUSIONSThe CsA concentration related to the early IST response. The third month CsA concentrations was the most important for the response and maintaining CsA levels with C(0) ≥ 200 µg/L and C(2) ≥ 700 µg/L may improve the response to IST in SAA/VSAA.

Adolescent ; Adult ; Anemia, Aplastic ; blood ; therapy ; Child ; Child, Preschool ; Cyclosporine ; blood ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult