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We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×109/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.

Destabilizing and reprogramming regulatory T (Treg) cells have become a potential strategy to treat tumor. Mounting evidence indicates that the transcription factor Helios is required for the stable differentiation of Treg lineage. Hence, we investigated whether Helios suppression could be a potential treatment option for pancreatic cancer patients. We found that Helios+ cells were predominantly in Foxp3+ Treg cells. By contrast, Foxp3+ Treg cells can be Helios+ or Helios−, but the level of Foxp3 expression was significantly higher in Helios+Foxp3+ Treg cells than in Helios−Foxp3+ Treg cells. Resected pancreatic tumors were highly enriched with both Helios+Foxp3+ Treg cells and Helios−Foxp3+ Treg cells. Also, the proportion of Helios+ cells in total Foxp3+ Treg cells was significantly higher in peripheral blood mononuclear cells (PBMCs) of patients than in PBMCs of healthy controls and further increased in patient tumors. Using shRNA, we knocked down Helios expression without significant downregulation of Foxp3. After Helios knockdown, CD4+CD25+CD127− Treg cells presented significantly lower levels of TGF-β secretion, lower levels of IL-10 secretion, and higher levels of IFN-γ secretion. In addition, Helios shRNA-transfected CD4+CD25+CD127− Treg cells presented lower capacity to inhibit CD4+CD25−CD127+ T conventional cell proliferation than control shRNA-transfected CD4+CD25+CD127− Treg cells. Of note, CD4+CD25+CD127− Treg cells from pancreatic cancer patients demonstrated higher TGF-β expression and higher suppression capacity than the cells from healthy controls. Overall, these results suggest that in pancreatic cancer patients, Helios may serve as a candidate to suppress Treg function, which could be used as a target to treat pancreatic cancer.

Implant-based breast reconstruction is the most common choice in breast cancer patients. Recently,the acellular dermal matrix (ADM) technique has been widely used in implant-based breast reconstruction in the western countries. This article briefly reviews the biological characteristics,history,types,surgical techniques,and postoperative complications of ADM.

Hypermethylation in the promoter region is an important epigenetic mechanism for the transcriptional repression of a number of cancer-associated genes, and over-expression and/or increased activity of DNA methyltransferases are considered to be the main cause of promoter hypermethylation. In order to explore the roles of two methyltransferase members (DNMT1 and DNMT3b) in the cholangiocarcinoma tumorigenesis, antisense eukaryotic expression plasmid of DNMT1 and DNMT3b gene was constructed respectively, and were co-transfected into the human cholangiocarcinoma cell line QBC-939 to observe their biological effects on the cell growth and proliferation ability, apoptosis, cell cycle alteration, and the tumorigenesis ability in the subcutaneous tissue of nude mouse. The results demonstrated that co-transfection with antisense eukaryotic expression plasmid of DNMT1 and DNMT3b gene and single transfection with antisense eukaryotic expression plasmid of DNMT1 gene can suppress the growth and proliferation of QBC-939, block the cell cycle at G1 phase, increase the apoptosis rate, minimize the tumor size in the subcutaneous tissue of nude mouse. The suppressing biological effect of co-transfection is stronger than single transfection with antisense DNMT1. Meanwhile, single transfection with antisense eukaryotic expression plasmid of DNMT3b gene has no effects on the biological characteristics of QBC-939. This study suggests that DNMT1 gene plays a key role in DNA methylation and DNMT3b gene may act as an accessory to support its function in inactivation of tumor suppressor genes. Combination DNMT1 and DNMT3b will increase their biological effects and have the synergistic effect on suppressing the growth of human cholangiocarcinoma cell line QBC-939.

To evaluate the value of cardiac troponin I (CTnI) measurement in predicting anthracycline-induced cardiotoxicity in patients with breast cancer.This study was conducted among 186 breast cancer patients receiving anthracycline-based chemotherapy. Serum cTnI concentrations before and after each cycle of the chemotherapy and the left ventricular ejection fraction (LVEF) before and at the 2nd, 4th and 6th months of the treatment were recorded. According to serum cTnI concentration, the patients were divided into CTnI+ group (with serum CTnI concentration of no less than 0.1 ng/ml, n=60) and CTnI- (0.1 ng/ml) group (n=126).No patients in this series experienced cardiac heart failure (CHF). The number of patients with a LVEF reduction by over 10% from the baseline was 16 (26.7%) in CTnI+ group, as compared to 7 (5.6%) in CTnI- group, showing a significant difference between the two groups (P0.01).CTnI can be a useful marker for early prediction of anthracycline-induced cardiotoxicity in patients with breast cancer.

To investigate the feasibility of D2-40 labeling for detecting lymphatic vessels in breast cancer tissues and the clinicopathological implications of lymphatic vessel invasion (LVI).Immunohistochemistry was used to detect the expression of D2-40 and lymphatic invasion in 72 cases of breast cancer and 15 benign breast tumor tissues, and their correlations to the clinicopathological factors were analyzed.The positivity rate of LVI was 69.4% in breast cancer tissue. In patients with lymph node metastasis, the positivity rate of LVI was significantly higher than that in patients without lymph node involvement (85.7% vs 54.1%, P0.01), and LVI was found to be positively correlated to axillary lymph node metastasis (r=0.382).D2-40 can specially and reliably mark the lymphatic vessels in breast cancer tissues. LVI is positively correlated to axillary lymph node metastasis and occurs earlier than the latter, therefore should be included in routine clinicopathological testing.

To investigate the expression of D2-40 and CD34 in invasive ductal carcinoma of the breast and the clinical significance.D2-40 and CD34 expressions were detected immunohistochemically in 108 cases of invasive ductal carcinoma of the breast and 30 cases of breast fibroadenoma. The lymphatic microvessel density (LMD) and the microvessel density (MD), marked by D2-40 and CD34, respectively, were calculated and their relationship with the clinicopathological factors was analyzed.The LMD and MD for invasive ductal carcinoma of the breast were significantly higher than those of breast fibroadenoma (P0.01). One-way ANOVA indicated that the LMD differed significantly between tumors of different histological grades, status of lymph node metastasis and TNM stages; the MD also varied significantly with the tumor size, histological grade, lymph node metastasis and TNM stage. The LMD and MD showed a positive correlation to the tumor size (r=0.335, 0.337), histological grade (r=0.580, 0.671), lymph node metastasis (r=0.690, 0.721) and TNM stage (r=0.623, 0.634), but not to ER, PR or Her-2 status (P0.05).D2-40 can specifically mark the lymphatic endothelial cells in invasive ductal carcinoma of the breast. The LMD and MD are positively correlated to the clinicopathological factors of the malignancy. D2-40 and CD34 has the potential for use as the predictors to evaluate the tumor progression and metastasis.

To investigate the effects of mutant exogenous P27(kip1) gene on chemosensitivity of human cholangiocarcinoma cell line.The recombinant vector was constructed and the mutant P27(kip1) gene was transfected into human cholangiocarcinoma cell line (QBC(939)). RT-PCR and Western blot were used to determine the expression of target genes. The effects of 5-fluorouracil (5-FU), mitomycin C (MMC) and cyclophosphamide (CTX) on the transfected cells were detected by assaying the apoptotic rate and growth inhibition by methabenzthiazuron (MTT) assay and flow cytometry (FCM).The mutant exogenous P27(kip1) gene was expressed effectively in the cells, and the expression enhanced the apoptosis and growth inhibition of QBC(939) inducted by 5-FU, MMC and CTX. The ratio of growth inhibiting increased significantly from 41.89% (5-FU), 45.59% (MMC), 38.91% (CTX) to 56.15% (5-FU), 55.65% (MMC), 51.69% (CTX), and apoptosis index from 13.76% +/- 3.03% (5-FU), 11.76% +/- 3.99% (MMC), 10.46% +/- 2.10% (CTX) to 41.39% +/- 4.32% (5-FU), 35.94% +/- 2.71% (MMC), 34.46% +/- 2.32% (CTX) (P0.05).The exogenous P27(kip1) gene transfer can remarkably increase the drug sensibility of the cholangiocarcinoma cells. The strategy targeted to control the cell cycle may be more effective in cancer treatment by combination of P27(kip1) gene therapy.

Hypermethylation of the promoter region is one of the major mechanisms of tumor suppressor gene inactivation. DNA methyltransferase 3b (DNMT3b), an enzyme that participates in the establishment of de novo methylation patterns, is highly expressed in many tumor cells and tissues, and it is closely associated with hypermethylation of the promoter of tumor suppressor genes. The aim of this study was to explore the effect of transfection with antisense DNMT3b gene eukaryotic expression plasmid on the expression of the DNMT3b gene in human biliary tract carcinoma cell.The constructed antisense DNMT3b gene eukaryotic expression plasmid was transfected into the human biliary tract carcinoma cell line QBC-939 with lipofectamine transfection reagent, and positive cell clones were formed using G418 selection after transfection. The constructed recombinant plasmid was transfected into QBC-939 cells successfully and was confirmed by amplification of the exogenous neoR gene with the polymerase chain reaction method. The expression of DNMT3b gene mRNA and protein was detected by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry respectively.Following transfection, the mRNA level of the DNMT3b gene decreased from 0.956+/-0.053 to 0.209+/-0.023, and the protein level of the DNMT3b gene also decreased from (75.38+/-3.22)% to (29.87+/-3.46)%. Very significant differences were observed both at the transcription and post-transcription levels in the expression of the DNMT3b gene between the non-transfection group and the antisense DNMT3b gene eukaryotic expression plasmid transfection group (P0.01).Transfection with the antisense DNMT3b gene eukaryotic expression plasmid can significantly reduce the expression level of the DNMT3b gene in the human biliary tract carcinoma cell line QBC-939. This study may provide a valid method to investigate the function of the DNMT3b gene and its role in biliary tract carcinoma.

Few data are available on the relationship between immune response and the infection caused by gut mucosal barrier dysfunction in patients with severe acute pancreatitis (SAP). The aim of this study was to investigate the immune response to gut mucosal barrier dysfunction in patients with early SAP. The results showed that the levels of endotoxin, the lactulose/mannitol (L/M) ratio, the D(-)-lactate concentration, the proportion of HLA-DR-positive monocytes, and the expression levels of TNF-α, IL-6 and IL-10 all decreased from a high level while the frequency of Tregs increased during the first 14 days. The Th1/Th2 ratio was decreased, with a decreased Th1 and an increased Th2 profile, in the beginning, but it was subsequently increased, with an increased Th1 profile. The data from this study showed that immunosuppression, the shift of the Th1/Th2 balance toward a Th2 response, increased Tregs, and related inflammatory cytokines are involved in the complex process of inflammation and infection caused by gut mucosal barrier dysfunction in patients with early SAP.