[Show abstract][Hide abstract] ABSTRACT: A key strategy for the study of the tumor microenvironment is to implant human tumor cells in an immunodeficient rodent strain ubiquitously expressing a fluorescent marker. Here, a novel nude rat expressing a green fluorescent protein (GFP) transgene was established and engrafted with primary human tumor tissue in order to separate tumor from stromal cell populations for subsequent molecular analysis.
SD-TG (GFP) 2BalRrrc transgenic rats were crossed with HsdHan™: rnu/rnu Rowett nude rats to develop a GFP expressing immunocompromised rat. PCR and flow cytometry were used to follow the GFP genotype and phenotype in newborns. After three to four generations, animals were implanted with 4 T1 dsRed murine breast cancer cells or primary human glioblastoma (GBM) biopsies to generate xenografts for subsequent separation by fluorescence-activated cell sorting (FACS).
Fluorecence microscopy and reverse transcription-PCR demonstrated that GFP, under the control of the human ubiquitin C promoter, was stably maintained and expressed in diverse organs over several generations. Immunophenotyping of blood samples by flow cytometry confirmed that the immunodeficient features of the parental rat strain, HsdHan™: rnu/rnu, were retained in the GFP nude rat. Both the murine cell line and human GBM biopsies engrafted, and stromal cell populations were isolated from dissociated xenografts by FACS to > 95% purity.
A GFP transgene was stably introduced into a nude rat background in which human and murine cancer cells successfully engrafted. This animal strain provides a novel in vivo system for detailed cellular and molecular characterization of tumor-stroma interactions.
Cancer Cell International 12/2014; 14(1):541. DOI:10.1186/s12935-014-0146-0 · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the clinical characteristics, diagnosis and treatment regimens for retroperitoneal schwannoma.
Clinicopathological data of 53 retroperitoneal schwannoma patients treated from January 1999 to April 2013 in our hospital were collected and analyzed using SPSS 13.0 statistical software.
Symptoms of the retroperitoneal schwannoma were vague and nonspecific. 12 patients had interrupted abdominal pain, 9 patients had abdominal discomfort, and only 6 patients presented with abdominal mass while 24 patients were detected by health checkup. There were some characteristics but not specific findings in imaging examination such as CT, ultrasonography and MRI, so preoperative diagnosis rate was low with only 9 patients diagnosed as retroperitoneal schwannoma and 21 patients diagnosed as neurogenic tumor. S-100 immunohistochemisty was very important in pathological diagnosis, and the patients with benign retroperitoneal schwannoma got 100% tumor specific 5-year survival after complete excision while the 5-year survival of malignant retroperitoneal schwannoma was only 50.0%.
Retroperitoneal schwannoma is a rare disease. Most of them are benign tumors, and complete surgical excision is the effective treatment.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 11/2014; 36(11):867-870.
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is a systemic autoimmune disease and collagen‑induced arthritis (CIA) is an animal model for RA. Micheliolide (MCL) is a novel compound with strong anti‑inflammatory effects. The present study was conducted to evaluate the therapeutic effects of MCL on RA. Mice were randomly divided into four groups and the CIA model mice were treated with methotrexate (MTX), MCL and dimethyl sulfoxide. A score associated with the severity of arthritis was assigned on alternate days from the 22nd day for 60 days. Histopathological changes and the serum levels of cytokines were measured on day 85. The results demonstrated that the MCL treatment group had arthritis scores lower than the CIA group and higher than the MTX group; compared with the CIA group, MCL and MTX significantly reduced the swelling of the paws and suppressed the degeneration of articular cartilage. Expression levels of macrophage colony‑stimulating factor (M‑CSF), tissue inhibitors of metalloproteinases‑1 (TIMP‑1) and complement component 5a (C5/C5a) were lower in the mice with arthritis compared with normal mice, however, following treatment with MCL and MTX, all the mice exhibited significant recovery to differing degrees. Unlike the MTX group, the MCL group failed to recover the level of soluble intercellular adhesion molecule‑1. In addition, the cytokine of B‑lymphocyte chemoattractant (BLC) solely presented in the MCL group. These results suggest that MCL may be considered for use as a novel therapeutic treatment against RA and that changes in the expression of cytokines C5/C5a, TIMP‑1, M‑CSF and BLC may underlie the mechanism by which MCL effects changes in this disease.
Molecular Medicine Reports 10/2014; 11(1). DOI:10.3892/mmr.2014.2767 · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Although several approaches for identification and isolation of carcinoma cells with tumour initiating properties have been established, enrichment of a population of pure and viable tumour-initiating cells (TICs) is still problematic. This study investigated possibilities to isolate a population of cancer cells with tumour initiating properties based on their adherence properties, rather than expression of defined markers or clonogenicity.
Several human cell lines derived from oral dysplasia and oral squamous cell carcinoma (OSCC), as well as primary cells derived from patients with OSCC were allowed to adhere to collagen IV-coated dishes sequentially. Rapid adherent cells (RAC), middle adherent cells (MAC) and late adherent cells (LAC) were then harvested and further investigated for their morphology, stem cell-like properties and molecular profile while grown in vitro and tongue xenotransplantation in NOD-SCID mice at serial dilutions.
RAC showed significantly higher colony forming efficiency (p < 0.05), sphere forming ability, greater migration ability (p < 0.05), exhibited longer G2 phase and displayed higher expression of integrin β1 and other stem-cell related molecules as compared to MAC and LAC. RAC induced tongue tumours in NOD-SCID mice with the highest incidence. These tumours were also bigger and metastasised more frequently in loco-regional lymph nodes than MAC and LAC.
These findings prove for the first time that OSCC cells with tumour initiating properties can be enriched based on their rapid adhesiveness to collagen IV. This separation procedure provides a potentially useful tool for isolating TICs in OSCC for further studies on understanding their characteristics and drug-resistant behaviour.
European Journal of Cancer 10/2014; 50(18). DOI:10.1016/j.ejca.2014.09.010 · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Although several studies suggest that stromal fibroblasts mediate treatment resistance in several cancer types, little is known about how tumor-associated astrocytes modulate the treatment response in brain tumors. Since traditionally used metabolic assays do not distinguish metabolic activity between stromal and tumor cells as well as 2-dimensional co-culture system does not recreate the formidable complexity of the microenvironment within 3-dimensional structures such as solid tumor tissue, we instead established a glioblastoma (GBM) cell-specific bioluminescent assay for direct measurements of tumor cell viability in the treatment of clinical relevant drugs.Methods
Using lentiviral transfection, we established a panel of human GBM cell lines constitutively expressing a fusion transgene encoding luciferase and the enhanced green fluorescence protein (eGFP). We then initiated co-cultures with immortalized astrocytes, TNC-1, and the eGFP/Luc GBM cell lines. We then treated all eGFP/Luc GBM cell lines with Temozolomide (TMZ) and Doxorubicin, comparing co-cultures of glioblastoma (GBM) cells and TNC-1 astrocytes with mono-cultures of eGFP/Luc GBM cells. Cell viability was quantitated by measuring the luciferase expression.ResultsTitration experiments demonstrated that luciferase expression was proportional to the number of eGFP/Luc GBM cells, whereas it was not influenced by the number of TNC-1 cells present. Notably, the presence of TNC-1 astrocytes mediated significantly higher cell survival after TMZ treatment in the U251, C6, A172 cell lines as well as the in vivo propagated primary GBM tumor cell line (P3). Moreover, TNC-1 astrocytes mediated significantly higher survival after Doxorubicin treatment in the U251, and LN18 glioma cell lines.Conclusion
Glioma cell-specific bioluminescent assay is a reliable tool for assessment of cell viability in the brain tumor cell compartment following drug treatment. Moreover, we have applied this assay to demonstrate that astrocytes can modulate chemo sensitivity of GBM tumor cells. These effects varied both with the cell line and cytotoxic drug that were used, suggesting that several mechanisms may be involved.
Journal of Translational Medicine 10/2014; 12(1):278. DOI:10.1186/s12967-014-0278-y · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are currently no established radiological parameters that predict response to immunotherapy. We hypothesised that multiparametric, longitudinal magnetic resonance imaging (MRI) of physiological parameters and pharmacokinetic models might detect early biological responses to immunotherapy for glioblastoma targeting NG2/CSPG4 with mAb9.2.27 combined with natural killer (NK) cells. Contrast enhanced conventional T1-weighted MRI at 7±1 and 17±2 days post-treatment failed to detect differences in tumour size between the treatment groups, whereas, follow-up scans at 3 months demonstrated diminished signal intensity and tumour volume in the surviving NK+mAb9.2.27 treated animals. Notably, interstitial volume fraction (ve), was significantly increased in the NK+mAb9.2.27 combination therapy group compared mAb9.2.27 and NK cell monotherapy groups (p = 0.002 and p = 0.017 respectively) in cohort 1 animals treated with 1 million NK cells. ve was reproducibly increased in the combination NK+mAb9.2.27 compared to NK cell monotherapy in cohort 2 treated with increased dose of 2 million NK cells (p<0.0001), indicating greater cell death induced by NK+mAb9.2.27 treatment. The interstitial volume fraction in the NK monotherapy group was significantly reduced compared to mAb9.2.27 monotherapy (p<0.0001) and untreated controls (p = 0.014) in the cohort 2 animals. NK cells in monotherapy were unable to kill the U87MG cells that highly expressed class I human leucocyte antigens, and diminished stress ligands for activating receptors. A significant association between apparent diffusion coefficient (ADC) of water and ve in combination NK+mAb9.2.27 and NK monotherapy treated tumours was evident, where increased ADC corresponded to reduced ve in both cases. Collectively, these data support histological measures at end-stage demonstrating diminished tumour cell proliferation and pronounced apoptosis in the NK+mAb9.2.27 treated tumours compared to the other groups. In conclusion, ve was the most reliable radiological parameter for detecting response to intralesional NK cellular therapy.
PLoS ONE 09/2014; 9(9):e108414. DOI:10.1371/journal.pone.0108414 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CIAPIN1 (cytokine-induced antiapoptotic inhibitor 1), was recently identified as an essential downstream effector of the Ras signaling pathway. However, its potential role in regulating myeloid differentiation remains unclear. In this study, we found depletion of CIAPIN1 by shRNAs led to granulocytic differentiation of K562 cells. Meanwhile, the decrease of NHE1 and up-regulation of phosphorylated ERK1/2 were observed after CIAPIN1 depletion. Interestingly, targeted inhibition of NHE1 further promoted the differentiation of K562 cells with CIAPIN1 silencing. Accordingly, ectopic expression of NHE1 reversed this phenotype. Furthermore, ERK1/2 inhibition with the chemical inhibitor, PD98059, abolished CIAPIN1 silencing-induced differentiation of K562 cells after NHE1 inhibition. Thus, our results revealed important mechanism that CIAPIN1 targeted NHE1 to mediate differentiation of K562 cells via ERK1/2 pathway. Our findings implied CIAPIN1 and NHE1 could be new targets in developing therapeutic strategies against leukemia.
Leukemia Research 09/2014; 38(9). DOI:10.1016/j.leukres.2014.06.013 · 2.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In our previous study, we have found that the tumor multidrug resistance mediated by P-glycoprotein could be reversed by sustained intracellular acidification through down-regulating the multidrug resistance gene 1 mRNA and P-glycoprotein expression. However, the molecular events linking the intracellular acidification and the regulation of P-glycoprotein remain unclear. In the present study, the molecular pathways involved in the regulation of P-glycoprotein expression by the intracellular acidification were investigated. We found that the P-glycoprotein expression was down-regulated by the intracellular acidification through inhibition of p38 mitogen-activated protein kinase (MAPK) and the activation of c-Jun N-terminal kinase (JNK) in the resisitant K562/DOX cells. In the sensitive K562 and HL60 cell lines, the changes of the p38 MAPK expression after the acidification are not as obvious as that of K562/DOX cells, but the activation of extracellular signal-regulated kinase (ERK) is also observed, which indicates that the down-regulation of p38 MAPK by the intracellular acidification might be the resistant cell line specific. Blockade of ERK and JNK signaling by the inhibitors or RNA interference increased p38MAPK activities suggesting that cross-talk within MAPKs is also important for this response. Our study provides the first direct evidence that the reversal of P-glycoprotein-mediated multidrug resistance by intracellular acidification is mediated by the crosstalk of MAPK signaling pathways.
The International Journal of Biochemistry & Cell Biology 07/2014; 54. DOI:10.1016/j.biocel.2014.06.016 · 4.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was purposed to investigate the effect of Sam68 gene silence on proliferation of human acute T lymphoblastic leukemia cell line Jurkat. The sequence of shRNA targeting the site 531-552 of Sam68 mRNA was designed and chemically synthesized, then a single-vector lentiviral, Tet-inducible shRNA-Sam68 system (pLKO-Tet-On) was constructed; next the Jurkat cells were infected with lentivirus to create stable cell clones with regulatable Sam68 gene expression. The inhibitory efficiency of Sam68 gene was assayed by Real-time PCR and Western blot; the cell activity of Jurkat cells was detected with MTT assay; the change of colony forming potential of Jurkat cells was analyzed by colony forming test; the cell cycle distribution was tested by flow cytometry. The results indicated that the expression of Sam68 in experimental cells was statistically decreased as compared with that of the control cells; the cells activity and colony forming capacity of the Jurkat cells with Sam68 gene silence were significantly inhibited; with Sam68 gene silencing, the percentage of S phase cells was significantly increased, while the percentage of G2 phase cells was significantly decreased. It is concluded that the silencing Sam68 gene using shRNA interference can effectively inhibit the proliferation of human acute T lymphoblastic leukemia cell line Jurkat.
[Show abstract][Hide abstract] ABSTRACT: The study was aimed to investigate the effect of CIAPIN1 gene on the proliferation of chronic myeloid leukemia (CML) cell line K562. The shRNA eukaryotic expression vector targeting CIAPIN1 gene was constructed and transfected into K562 cells. The inhibitory efficiency on K562 cells was detected by real-time PCR and Western blot; the proliferative activity of K562 cells was detected by MTT assay; the number and size of colonies were assessed by using colony-forming test; the tumorigenic potential was tested in vivo by using nude mice. The results indicated that as compared with control group, the CIAPIN1 gene expression statistically decreased; the proliferative activity of K562 cells in interference group was distinctly weakened; the number and size of colonies were significantly reduced; the tumorigenic potential was also lowered in vivo. It is concluded that inhibition of CIAPIN1 expression can inhibit K562 cell proliferation in vitro and in vivo.
[Show abstract][Hide abstract] ABSTRACT: Chronic myeloid leukemia is a clonal myeloproliferative disorder disease in which BCR/ABL plays an important role as an oncoprotein and molecular target. Despite the success of targeted therapy using tyrosine kinase inhibitors, CML remains largely incurable, most likely due to the treatment resistance after firstly chemical therapy. So know well the unique molecular pathway of CML is very important.
The expressions of CD44 in different leukemia patients and cell lines were detected by real-time PCR and western blotting. The effects of CD44 on proliferation of K562 cells were determined using the MTT and colony formation assays, and even in a nude mouse transplantation model. Then, the cell cycle changes were detected by flow cytometric analysis and the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay. The expressions of the cycles and apoptosis-related proteins p21, Cyclin D1 and Bcl-2 were analyzed by western blot and real-time PCR assay. Finally, the decreased nuclear accumulation of beta-catenin was detected by western blotting and immunefluorescence.
Firstly, we showed that CD44 expression was increased in several kinds of leukemia patients and K562 cells. By contrast, the down-regulation of CD44 resulted in decreased proliferation with a G0/G1 arrest of cell cycle in K562 cells according to the MTT assay and the flow cytometric analysis. And no significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. During this process, p21 and cyclin D1 are the major causes for cell cycle arrest. In addition, we found CD44 down-regulation decreased the expression of beta-catenin and increased the expression of phosphorylated beta-catenin. The instability of Wnt/beta-catenin pathway induced by increased expression of p-beta-catenin resulted in a decreased nuclear accumulation in CD44 silenced K562 cells. In the nude mouse transplantation model, we also found the same results.
These results show that K562 cells depend to a greater extent on CD44 for proliferation, and CD44 down-regulation may induce a cell cycle arrest through Wnt/beta-catenin pathway. CD44 blockade may be beneficial in therapy of CML.
Cancer Cell International 11/2013; 13(1):117. DOI:10.1186/1475-2867-13-117 · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Object. Gamma knife surgery (GKS) may be used for recurring glioblastomas (GBMs). However, patients have then usually undergone multimodal treatment, which makes it difficult to specifically validate GKS independent of established treatments. Thus, we developed an experimental brain tumor model to assess the efficacy and radiotoxicity associated with GKS. Methods. GBM xenografts were implanted intracerebrally in nude rats, and engraftment was confirmed with MRI. The rats were allocated to GKS, with margin doses of 12 Gy or 18 Gy, or to no treatment. Survival time was recorded, tumor sections were examined, and radiotoxicity was evaluated in a behavioral open field test. Results. In the first series, survival from the time of implantation was 96 days in treated rats and 72 days in controls (P < 0.001). In a second experiment, survival was 72 days in the treatment group versus 54 days in controls (P < 0.006). Polynuclear macrophages and fibrosis was seen in groups subjected to GKS. Untreated rats with GBM xenografts displayed less mobility than GKS-treated animals in the open field test 4 weeks after treatment (P = 0.04). Conclusion. GKS administered with clinically relevant doses prolongs survival in rats harboring GBM xenografts, and the associated toxicity is mild.
[Show abstract][Hide abstract] ABSTRACT: Abstract The CCAAT/enhancer binding protein homologous protein (CHOP) expression increased when Na(+)/H(+) exchanger 1 (NHE1) was inhibited. Endoplasmic reticulum (ER) stress has been shown to trigger tumor cell death through CHOP. We therefore hypothesized NHE1 activity correlates with ER stress and confers pharmaceutical potential to NHE1 inhibitor as anti-tumor agent. The current study showed that treatment of NHE1 inhibitor Cariporide led to ER stress-induced up-regulation of the DR5 receptor which is mediated by CHOP at transcriptional level. We also determined that ER stress induced JNK activation was responsible for modulation of CHOP. Combining Cariporide with TRAIL led to a significantly enhanced level of apoptosis that was abrogated by siRNA silencing of CHOP. These studies provide a potential mechanistic rationale for the use of NHE1 inhibitor in combination with DR5 agonists to induce apoptosis in leukemia.
[Show abstract][Hide abstract] ABSTRACT: CUEDC2, a newly reported protein, has been found to be ubiquitously expressed in human tissues and repress NF-κB activity. To study the role of CUEDC2 in chronic myeloid leukemia (CML), we explored the function of CUEDC2 in CML cells through using the CML cell line K562 and its imatinib resistant cells K562/G01. K562 cells expressed a relatively higher level of CUEDC2 compared to K562/G01 cells. Knockdown of CUEDC2 in K562 cells resulted in decreased cell apoptosis after imatinib treatment; when CUEDC2 was overexpressed in K562/G01 cells, imatinib induced more cell apoptosis. By analyzing the activity of NF-κB, the results indicated a negative association between the expression of CUEDC2 and NF-κB signaling pathway in these CML cells. Our data suggested that the expression level of CUEDC2 has an inverse correlation with imatinib resistance and activity of NF-κB signaling pathway in CML cells, CUEDC2 could regulate imatinib sensitivity in CML cells at least partially through NF-κB signaling pathway.
Leukemia research 09/2013; 37(11). DOI:10.1016/j.leukres.2013.08.019 · 2.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glioblastoma (GBM) is the most malignant brain tumor where patients' survival is only 14.6 months, despite multimodal therapy with debulking surgery, concurrent chemotherapy and radiotherapy. There is an urgent, unmet need for novel, effective therapeutic strategies for this devastating disease. Although several immunotherapies are under development for the treatment of GBM patients, the use of natural killer (NK) cells is still marginal despite this being a promising approach to treat cancer. In regard of our knowledge on the role of NG2/CSPG4 in promoting GBM aggressiveness we investigated the potential of an innovative immunotherapeutic strategy combining mAb9.2.27 against NG2/CSPG4 and NK cells in preclinical animal models of GBM. Multiple immune escape mechanisms maintain the tumor microenvironment in an anti-inflammatory state to promote tumor growth, however, the distinct roles of resident microglia versus recruited macrophages is not elucidated. We hypothesized that exploiting the cytokine release capabilities of activated (NK) cells to reverse the anti-inflammatory axis combined with mAb9.2.27 targeting the NG2/CSPG4 may favor tumor destruction by editing pro-GBM immune responses. Combination treatment with NK+mAb9.2.27 diminished tumor growth that was associated with reduced tumor proliferation, increased cellular apoptosis and prolonged survival compared to vehicle and monotherapy controls. The therapeutic efficacy was mediated by recruitment of CCR2low macrophages into the tumor microenvironment, increased ED1 and MHC class II expression on microglia that might render them competent for GBM antigen presentation, as well as elevated IFN-γ and TNF-α levels in the cerebrospinal fluid compared to controls. Depletion of systemic macrophages by liposome-encapsulated clodronate decreased the CCR2low macrophages recruited to the brain and abolished the beneficial outcomes. Moreover, mAb9.2.27 reversed tumor-promoting effects of patient-derived tumor-associated macrophage/microglia(TAM) ex vivo.Taken together, these findings indicate thatNK+mAb9.2.27 treatment may be an amenable therapeutic strategy to treat NG2/CSPG4 expressing GBMs. We provide a novel conceptual approach of combination immunotherapy for glioblastoma. The results traverse beyond the elucidation of NG2/CSPG4 as a therapeutic target, but demonstrate a proof of concept that this antibody may hold potential for the treatment of GBM by activation of tumor infiltrated microglia/macrophages.
[Show abstract][Hide abstract] ABSTRACT: OLIGODENDROGLIOMA POSES A BIOLOGICAL CONUNDRUM FOR MALIGNANT ADULT HUMAN GLIOMAS: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP) positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H) and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.
PLoS ONE 08/2013; 8(3):e59773. DOI:10.1371/journal.pone.0059773 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The surgical management of occult breast cancer is controversial. We compared the outcomes of different treatments of occult breast cancer and evaluated the potential prognostic factors for overall survival and recurrence.
We retrospectively reviewed 77 patients who presented to our hospital from 1968 to 2011 with a diagnosis of occult breast cancer. Patients were divided into three groups: 42 patients (63%) were treated with modified radical mastectomy+axillary lymph node dissection (ALND), 16 patients (24%) were treated with ALND + postoperative radiotherapy, and 9 patients (13%) with only ALND. Survival analyses were undertaken to compare the efficacy of these three treatments.
Of the 77 patients with occult breast cancer, 2 patients were lost to follow-up and 8 patients refused surgical treatment: 67 patients (90.4%) were included in this analysis. The median follow-up was 62.2 (0.6-328.0) months. Kaplan-Meier analyses showed no significant difference in overall survival and recurrence-free survival between the three groups (P = 0.494 and 0.397, respectively). The prevalence of local recurrence was 11.9% for the mastectomy + ALND, 18.8% for ALND + radiotherapy, and 11.1% for ALND-only groups, and those for distant recurrence were 2.4%, 12.5%, and 11.1%, respectively. Compared with progesterone receptor-negative subjects, progesterone receptor-positive patients had better overall survival and lower recurrence rates (P = 0.057 and 0.062, respectively).
There was no significant difference in outcomes between mastectomy and breast-preserving surgery. Expression of the progesterone receptor should be taken into account when evaluating the prognosis of occult breast cancer.
Chinese medical journal 08/2013; 126(16):3026-9. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and Aims: Recently, genetic association studies have linked a number of single nucleotide polymorphisms (SNPs) with liver fibrosis risk of hepatitis C. The present study was designed to validate the association of emerging SNPs with development of liver cirrhosis and chronicity in a Chinese population infected with hepatitis B virus (HBV). Methods: 714 Chinese subjects with persistent HBV infection (429 with evident liver cirrhosis and 285 without cirrhosis clinically or pathologically) and 280 subjects with spontaneous HBV clearance were studied. Six SNPs in five candidate genes were detected with the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The distribution of each polymorphism was compared between the age-matched cirrhotic and noncirrhotic subjects, and between subjects with persistent infection and spontaneous HBV clearance. Results: The rs2679757 polymorphism of antizyme inhibitor 1 (AZIN1) gene was associated with the risk of cirrhosis (odds ratio [OR] for GG+AG versus AA=1.47, 95% confidence interval [CI]=1.08-2.01, p=0.01). So was rs886277 in the transient receptor potential cation channel subfamily M, member 5 (TRPM5) gene (OR for CC versus CT+TT=1.63, 95% CI=1.20-2.22, p=0.002). The frequencies of these two SNPs were also associated with the severity of decompensated cirrhosis based on the Child-Pugh classification. Genotype frequencies of other SNPs were not different between the cirrhotic and noncirrhotic groups. No SNPs were associated with the outcome of spontaneous HBV clearance. Conclusions: AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk of HBV-related liver cirrhosis in Chinese. The emerging SNPs warrant further clinical validation in other cohorts or ethnic groups, and could lead to mechanistic studies to reveal their contributions to fibrosis progression.