All-trans retinoic acid effectively inhibits breast cancer stem cells growth in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the inhibitory effect of all-trans retinoic acid(ATRA) on breast cancer stem cells (CSCs).</p><p><b>METHODS</b>The inhibitory effect of ATRA on MCF-7 and SK-BR-3 cell lines was analyzed using a Cell Counting Kit-8 (CCK-8). The proportion of CD44(+)CD24(-) tumor cells of the two cell lines were measured before and after the ATRA treatment, and the role of ATRA in the regulation of CSC self-renewing ability was evaluated with a tumor sphere assay. The tumor spheres were grown in an adherent culture to evaluate the ATRA-induced differentiation of breast cancer stem cells.</p><p><b>RESULTS</b>ATRA effectively inhibited the unsorted cells and stem cells, but the CSCs were more sensitive to ATRA. At a concentration of 10(-6) mol/L, the inhibitory rate of MCF-7 unsorted cells and stem cells were (8.66 ± 1.06)% and (21.09 ± 3.25)%, respectively (P = 0.004). For SK-BR-3 cells, the rates were (39.19 ± 1.47)% and (51.22 ± 2.80)%, respectively (P = 0.005). The self-renewing ability of the CSCs was impaired by ATRA at a concentration of 10(-6) mol/L. The rate of MCF-7 and SK-BR-3 stem cells to form tumor sphere was 5.2% (5/96) and 13.5% (13/96), respectively. For the control group, it was 86.5% (83/96) and 93.8% (90/96), respectively (P < 0.001). ATRA also promoted the CD44(+)CD24(-) subpopulation to differentiate. SK-BR-3 stem cells were grown in an adherent culture. After using ATRA, the proportion of CD44(+)CD24(-) cells was (48.1 ± 2.5)% and that of the control group was (86.6 ± 2.5)% (P < 0.001).</p><p><b>CONCLUSIONS</b>ATRA effectively inhibits breast NCSCs and CSCs, but CSCs are more sensitive to ATRA. ATRA impairs the self-renewing ability of CSCs and promotes CSCs to differentiate.</p>

Anti-tumor effect of oncolytic herpes simplex virus G47delta on human nasopharyngeal carcinoma / 癌症

Oncolytic herpes simplex virus (HSV) can replicate in and kill cancer cells without harming normal tissue. G47delta is a third-generation HSV vector. In this study, the therapeutic effects of G47delta on human nasopharyngeal carcinoma (NPC) were determined in vitro and in vivo. The human NPC cell lines CNE-2 and SUNE-1, primary normal nasopharyngeal epithelial cells (NPECs), and immortalized nasopharyngeal cells NP-69 and NPEC2/Bmi1 were infected with G47delta at different multiplicities of infection (MOIs). The survival of infected cells was observed daily. Two subcutaneous models of NPC were established with CNE-2 and SUNE-1 in Balb/c nude mice. G47delta or virus buffer as control was injected into the subcutaneous tumors. Tumor size was measured twice a week, and animals were euthanized when the diameter of their tumors exceeded 18 mm or when the animals appeared moribund. For the NPC cell lines CNE-2 and SUNE-1, more than 85% and 95% of cells were killed on day 5 after G47delta infection at MOI = 0.01 and MOI = 0.1, respectively. Similar results were observed for an immortalized cell line NPEC2/Bmi-1. A moderate effect of G47delta was also found on another immortalized cell line NP-69, of which only 27.7% and 75.9% of cells were killed at MOI = 0.01 and MOI = 0.1, respectively. On the contrary, there was almost no effect observed on NPECs. The in vivo experiments showed that tumors in mice in the G47delta-treated group regressed completely, and the mice exhibited much longer survival time than those in the control groups. Our results suggest that the potential therapeutic effects of G47delta would be applicable for treatment of NPC patients in the future.

Selection of the initial surgery extent for differentiated thyroid cancer without metastasis / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the selection of the initial surgery extent for differentiated thyroid cancer (DTC) without metastasis.</p><p><b>METHODS</b>The clinical data of 504 cases with DTC, who accepted the surgical treatment from Jan 1995 to Dec 2004, were analyzed and studied. There were 329 cases without metastasis. The operative extents less than total thyroidectomy were performed on 93 cases (92.1%) with stage T(1), 166 cases (88.3%) with stage T(2), 22 cases (91.7%) with stage T(3) and 12 cases (75.0%) with stage T(4). The recurrence situation after the initial surgery was compared between different T-stage groups and between different surgical extents, total and less than total thyroidectomy.</p><p><b>RESULTS</b>The recurrence of DTC was found in 37 cases of the follow-up cases (8.9%), including 29 cases without metastasis in the initial surgery. There was no significant difference in the recurrent rate between T(1) and T(2) groups (P>0.05). The significant difference was found in recurrent rate between T(1) and T(3) or T(4) groups, T(2) and T(3) or T(4) groups (P<0.05). No significant difference in the ratio of the initial surgical extent less than total thyroidectomy was found between stage T(1) and T(2) cases without metastasis (P>0.05). The rate of the recurrent laryngeal nerve injury was 1.2%. The transient hypoparathyroidism happened in 2% of the cases, without the permanent hypoparathyroidism.</p><p><b>CONCLUSIONS</b>The surgical extent less than total thyroidectomy, especially subtotal thyroidectomy, is rational and available to stage T(1) and T(2) cases of DTC without metastasis. It can effectively remove the tumor and avoid postoperative complications. Total thyroidectomy should be performed on stage T(3) and T(4) cases of DTC.</p>

Oncolytic herpes simplex virus vectors for the treatment of human breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Oncolytic herpes simplex virus (HSV) vectors can be used for cancer therapy as direct cytotoxic agents, inducers of anti-tumor immune responses, and as expressers of anti-cancer genes. In this study, the efficacy of HSV vectors, G47Delta and NV1023 were examined for the treatment of the human breast cancer.</p><p><b>METHODS</b>Human breast cancer MDA-MB-435 cells were cultured or implanted subcutaneously in BALB/c nude mice. The cells or tumors were inoculated with G47Delta or NV1023, and cell killing or inhibition of tumor growth determined. Both viruses contained the LacZ gene and expression in infected cells was detected with X-gal histochemistry.</p><p><b>RESULTS</b>G47Delta and NV1023 were highly cytotoxic to MDA-MB-435 cells in vitro at very low multiplicities of infection. X-gal staining of infected tumor cells in vitro and in vivo illustrated the replication and spread of both viruses. G47Delta and NV1023 inoculation inhibited tumor growth and prolonged mouse survival. Both vectors behaved similarly.</p><p><b>CONCLUSIONS</b>Oncolytic HSV vectors, G47Delta and NV1023, were extremely effective at killing human breast cancer cells in vitro and in tumor xenografts in vivo. This novel form of cancer therapy warrants further investigation and consideration of clinical application.</p>