Iron is one of the necessary elements for cell growth, proliferation and functional activities. Iron uptake of the vast majority cells, including tumor cells, is primarily mediated by transferrin receptor (TfR). Studies showed that transferrin receptor expressed on tumor cell surface at a high level, thus can be used in the treatment for malignant tumor combined with many kinds of materials. In this article, recent progress of study on transferrin receptor used in treating hematological malignant tumor are reviewed from aspects of transferrin receptor combined with drugs including artemisinin, doxorubicin, gambogic acid and so on, genes, antibodies, polyethylene glycol and nanoparticles.
Hematologic Neoplasms ; metabolism ; therapy ; Humans ; Receptors, Transferrin ; metabolism ; therapeutic use

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).
Anemia, Aplastic/drug therapy* ; Antilymphocyte Serum/therapeutic use* ; Cyclosporine/therapeutic use* ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/therapeutic use* ; Prognosis ; Receptors, Transferrin/therapeutic use* ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo evaluate the value of serum soluble transferrin receptor (sTfR) concentration in predicting early response to immunosuppressive therapy (IST) in severe aplastic anemia (SAA).

METHODSClinical data and hematologic responses of 140 SAA patients treated with rabbit antithymocyte globulin (rATG) combination with cyclosporine in our hospital were retrospectively analyzed. Correlation of pre-IST baseline of sTfR and IST responses was statistically analyzed and receiver operating characteristic (ROC) curve was used to estimate the sensitivity and specificity of sTfR in prediction of early responses.

RESULTSSerum concentration of sTfR in very SAA (VSAA) patients were significantly lower than SAA and transfusion dependent non-SAA cases (P=0.001). The responders, especially at 3 months, had significantly higher pre- IST baseline of sTfR [median, 0.89 (range, 0.21-2.42) mg/L] than that [median, 0.58 (range, 0.13-1.88) mg/L] of non-responders (P=0.005). The cutoff level of 0.91 mg/L and 0.88 mg/L for predicting responses at 3 and 6 months were established based on the ROC curve, with the degree of accuracy of 65.0% and 60.7% respectively. Multivariate analysis showed that pre-IST baseline of sTfR was the independent factor of predicting response at 3 months (P=0.007) and at 6 months (P=0.021).

CONCLUSIONAs a indicator of bone marrow failure severity, sTfR could predict early response to IST therapy in aplastic anemia.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; therapy ; Antilymphocyte Serum ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; therapeutic use ; Female ; Humans ; Immunosuppression ; Male ; Middle Aged ; Receptors, Transferrin ; immunology ; therapeutic use ; Retrospective Studies ; Sensitivity and Specificity ; Treatment Outcome ; Young Adult

OBJECTIVETo study trend of dynamic change in level of serum transferrin receptor (sTfR) in the process of iron supplementation to provide evidence for sTfR in evaluating the efficacy of iron supplementation.

METHODSTotally, 942 child-bearing-age women aged 18 to 45 years were selected from Longfang City, Hebei Province and Shunyi County, Beijing. Biochemical indicators of iron metabolism were measured for all of them, including serum levels of ferritin (SF) and zinc protoporphyrin (ZPP), and hemoglobin (Hb). According to the current criteria for assessing iron status, women were screened for iron deficiency erythropoiesis (IDE) or iron deficiency anemia (IDA). Seventy-two women agreed to participate in the study, and 59 of them finished whole dynamic observations with signed informed consent. Four capsules of ferrous L-threonate (containing 7 mg of iron element per capsule) were administered for women with IDE every other day and for women with IDA every day, respectively, for 12 weeks. Serum biochemical indicators and level of sTfR were measured in 0 wk, 3 wk, 6 wk, 9 wk and 12 wk, respectively, during the process of iron supplementation, and their dynamic changes were observed.

RESULTSLevel of sTfR in women with IDE and IDA was (26.62 +/- 10.57) nmol/L and (41.25 +/- 21.96) nmol/L, respectively, significantly higher than normal level. During the process of iron supplementation, level of sTfR changed as the following characteristics. In women with IDE, level of sTfR kept stable within the first 3 weeks of iron supplementation, then dropped gradually and progressively, reached to normal, with (17.86 +/- 5.57) nmol/L, in the 12 wk after iron supplementation. In women with IDA, level of sTfR dropped quickly within the first 3 wk of iron supplementation, then dropped slowly until the 9th wk and kept stable, and reached to normal level in the 12 wk, with (19.54 +/- 5.94) nmol/L and a ratio of sTfR/SF of 12.23 +/- 4.34. Ratio of sTfR/SF changed as level of sTfR during the process of iron supplementation. Level of sTfR correlated reversely with levels of Hb and SF and positively with level of ZPP.

CONCLUSIONSerum level of sTfR in child-bearing age women gradually decreased to normal with the restoration of their normal iron status during the process of iron supplementation and could be used as a specific indicator for assessing efficacy of iron supplementation.

Adolescent ; Adult ; Anemia, Iron-Deficiency ; blood ; drug therapy ; Biomarkers ; blood ; Dietary Supplements ; Female ; Hemoglobins ; analysis ; Humans ; Iron ; administration & dosage ; therapeutic use ; Middle Aged ; Protoporphyrins ; blood ; Receptors, Transferrin ; blood

OBJECTIVETo observe the therapeutic effect of shengxuening (SXN) in treating iron-deficiency anemia (IDA) and to explore its molecular mechanism on iron metabolism balance regulation.

METHODSPatients with IDA were randomly divided into the treated group and the control group, 50 in each group. They were treated with SXN (0.1 g, three times per day) and ferrous gluconate (0.1 g, three times per day) respectively, for 30 days. Levels of serum iron (Fe), total iron binding capacity (TIBC), transferrin saturation (TS), serum ferritin (SF), transferrin (Tf), soluble transferrin receptor (sTfR) and blood routine test, as well as scoring of TCM qi-blood deficiency Syndrome were conducted before and after treatment.

RESULTSThe total effective rate in the treated group reached 92%, it was shown that SXN could improve the iron metabolism, increase levels of Fe, TS, SF and reduce levels of TIBC, Tf, sTfR, it has obvious effect in promoting erythrocyte generation and could promote formation of leucocytes and platelets. The total effective rate in the control group was 32%, which was significantly lower than that in the treated group (P < 0.01).

CONCLUSIONThe effect of SXN in treating IDA and qi-blood deficiency Syndrome is evident, it could improve the iron metabolism, increase levels of Fe, TS, SF and lower levels of TIBC, Tf, sTfR.

Adolescent ; Adult ; Anemia, Iron-Deficiency ; blood ; drug therapy ; Child ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Ferritins ; blood ; Humans ; Iron ; blood ; Male ; Middle Aged ; Phytotherapy ; Receptors, Transferrin ; blood

OBJECTIVETo construct the localization system involving anti-TfR monoclonal antibody (McAb) and AFP promoters and assess its effect on human hepatoma cell lines.

METHODSThe conjugate of anti-TfR McAb and polylysine (PLL) was made by SPDP and purified by molecular screen chromatography. DNA blocking test determined that the ratio of one pEBAF/tk to six Ab-PLL was the most suitable to couple them. The pEBAF/tk recombinant plasmid bearing HSV-TK gene was coupled to Ab-PLL by noncovalent bond. The pEBAF/tk was transferred into human hepatoma cell line HepG2, SMMC7721 and pulmonary cancer cell line A549 by receptor-mediated gene delivery (Ab-PLL-DNA) and liposome procedure. The growth inhibitory rates of HepG2, SMMC7721 and A549 cells were measured by MTT assay.

RESULTSThe inhibitory rates of HepG2/tk in 100 mg/L and 1 mg/L of GCV were 60.5% and 24.3%, respectively. The inhibitory rate of GCV to SMMC7721 was 23.2% in 3 days. The pulmonary cancer cell A549, A549/tk (Ab) and A549 /tk (lipo) could not be inhibited by the addition of GCV.

CONCLUSIONThe localization system employed in this paper has high specificity, effectiveness and safety for gene therapy. It would be a promising strategy for gene therapy.

Antibodies, Monoclonal ; therapeutic use ; Carcinoma, Hepatocellular ; therapy ; Cell Line, Tumor ; Ganciclovir ; therapeutic use ; Genetic Therapy ; Humans ; Liver Neoplasms ; therapy ; Receptors, Transferrin ; immunology ; Simplexvirus ; enzymology ; Thymidine Kinase ; genetics ; alpha-Fetoproteins ; genetics