Tissue factor pathway inhibitor-2 (TFPI-2), a member of the Kunitz-type family, is a broad-spectrum serine proteinase inhibitor. The expression of TFPI-2 is inversely related to increasing degree of malignancy, suggesting a role of TFPI-2 in the mainte-nance of tumor stability and inhibition of the growth of neoplasma. Aberrant methylation of TFPI-2 promoter cytosine-phosphorothio-ate-guanine (CpG) islands has been widely documented to be responsible for diminished expression of TFPI-2 mRNA and protein dur-ing cancer progression. TFPI-2 expression is significantly up-regulated by the ERK1/2 and JNK signaling pathways and modestly in-creased by VEGF, TNF-alpha, and fibroblast growth factor in time-and dose-dependent manners. TFPI-2 can maintain the stability of the tumor environment and inhibit invasiveness and growth of neoplasms. TFPI-2 has also been shown to regulate proliferation, apopto-sis, and vasculogenic mimicry of tumor cells, which may contribute significantly to tumor growth inhibition. Restoration of TFPI-2 ex-pression in tumor tissue inhibits tumor growth and metastasis, which creates a novel possibility of cancer patient treatment. This review focuses on the expression and the molecular regulation mechanisms of TFPI-2 in malignant tumors that control the functions of TFPI-2 in proliferation, apoptosis, and angiogenesis. Insight into these processes will improve our understanding of TFPI-2 and provide new ap-proaches for rational treatment strategies.

Objective:To observe the clinicopathological features of gastrointestinal stromal tumor (GIST) cases with concurrent carcinoma. Methods:Patient data of 24 GIST cases with concurrent carcinoma were collected from the 157 GIST cases reported be-tween 2002 and 2012. The clinicopathological features of the GIST cases with concomitant carcinoma were studied. The expression of CD117, CD34, and SMA by the tumors was assayed using the immunohistochemical EliVision method. In particular, the expression of the proliferation marker Ki-67 was studied. Results:GIST cases with concurrent carcinoma accounted for 15.3%of the total GIST cas-es studied. The GIST patients with concurrent carcinoma included 14 males and 10 females. The male-female ratio of these patients was 1.4∶1. The age of the patients ranged from 41 years to 66 years, with a median age of 55 years. Lesions at the inferior segment of the esophagus were found in 7 of the 24 selected GIST cases;lesions at the gastric wall and in the intestines were observed in 15 and 2 cas-es, respectively. The diameter of the GIST cases with concurrent carcinoma ranged between 0.6 and 3.8 cm, with an average of 1.50 ± 0.85 cm. Slight dysplasia was observed in 4 of the 24 cases; no heteromorphism was present in the remaining 20 cases. The mitotic counts of GIST cases with concurrent carcinoma ranged from 0/50 HPF to 5/50 HPF, with an average of (0.79±1.83)/50 HPF. The pro-liferative index of Ki-67 in the GIST cases with concurrent carcinoma ranged between 0 and 7.72, with an average of 2.16 ± 3.26. The concurrent carcinoma cases included 5 cases with esophageal carcinoma, 2 with cardiac carcinoma, 15 with gastric cancer, and 2 with intestinal cancer. In contrast to the GIST cases with concurrent carcinoma, the GIST cases without carcinoma complications included 74 males and 59 females. The male-female ratio was 1.25∶1. The age of the patients without concurrent carcinoma ranged from 43 years to 71 years, with a median age of 54 years. Among the 133 GIST cases without cancer complications, gastric, intestinal, and esophageal lesions were found in 114, 13, and 6 cases, respectively. The diameter of GISTs without cancerous complications ranged from 2.4 cm to 15.5 cm, with an average of 6.11 ± 7.09 cm. Different degrees of dysplasia were seen in 82 of the 133 cases. The mitotic counts in the GIST cases without cancer complications ranged from 0/50 HPF to 53/50 HPF, with an average of (3.81±23.67)/50 HPF. The prolifera-tive index of Ki-67 for these cases ranged from 0 to 39.21 and averaged at 6.22 ± 16.96. The male-female ratio of the GIST cases with cancer complications was higher compared with the GIST cases without. The average diameter of GISTs with complications was small-er compared with that of GISTs without complications. The mitotic counts and the proliferative index of Ki-67 were significantly lower in the GIST cases with cancer complications than in those without (t=1.981, P<0.05 vs. t=1.993 5, P<0.05). Conclusion:Concurrent car-cinomas were found in 15.3% of the total GIST cases. No special clinical symptoms were observed in most GIST cases with cancer complications, as revealed when the carcinomas were examined. The proliferative index of Ki-67 in the GIST cases with concurrent car-cinoma is significantly lower compared with that of the GIST cases without complications.

Objective To study the clinical,imaging and pathological characteristics and diagnostic methods of pulmonary mucosa-associated lymphoid tissue-derived lymphoma (MALToma),and differentiate from three kinds of pulmonary lymphatic hyperplasia.Methods Medical history,imaging and pathological examination of three cases of pulmonary MALToma were introduced in detail.And differentiated from lymphocytic pseudolymphoma (nodular lymphoid hyperplasia),follicular bronchiolitis and lymphocytic interstitial pneumonia.Results The clinical manifestations and imaging examination of pulmonary MALToma had no special and were not easy to differentiate from cancer.Histopathologically,widened marginal zones encircled one or more germinal centers.The neoplastic lymphocytes invaded germinal center and bronchiole resulting in follicle colonization and lymphoepithelial lesions.Conclusion Pulmonary MALToma is a rare low grade malignant tumor.Histopathology is the key method to diagnosis,while clinical manifestations and imaging examination have no special symptoms at diagnosis.MALToma is differed from pulmonary lymphatic hyperplasia in widened marginal zone encircled one or more germinal centers,follicular colonization,lymphoepithelial lesions,cell types between follicular.

Objective To systematically evaluate the efficacy and safety of enteral nutrition in preoperative bowel preparation for colorectal cancer.Methods We searched in multiple databases (i.e.CNKI,Wanfang Data,VIP,PubMed,Coehrane Library,and Web of Science) for studies up to March 2017 that compared the efficacy and safety of enteral nutrition vs.mechanical bowel preparation before surgical treatment of colorectal cancer.Meta-analysis was conducted with RevMan 5.3 to compare the two approaches in terms of postoperative lymphocyte count,complications,anal exhaust time,intestinal cleaning rate,and levels of prealbumin,albumin,hemoglobin,and transferrin.Results A total of 12 randomized controlled trials involving 617 patients were included in this study,where 308 patients received enteral nutrition and 309 had mechanical bowel preparation.The results showed that enteral nutrition was comparable to mechanical bowel preparation in bowel cleaning rate (OR =1.54,95％ CI=0.98-2.41,P=0.06) and anal exhaust time (WMD =-8.14,95％ CI=-18.25-2.07,P=0.12),and it could lead to higher levels of lymphocytes (WMD=0.19,95％ CI=0.06-0.32,P＜0.01),prealbumin (WMD=20.16,95％ CI=15.77-20.54,P＜0.01),albumin (WMD =2.60,95％ CI=1.69-3.51,P＜0.01),hemoglobin (WMD=7.18,95％ CI=3.61-10.75,P＜0.01),and transferrin (WMD=0.29,95％ CI=0.12-0.47,P＜0.01),and reduce the incidence of postoperative complications (OR=0.18,95％ CI=0.11-0.28,P＜0.01).Conclusions Current evidence showed that using enteral nutrition for bowel preparation before surgical treatment of colorectal cancer could improve postoperative profiles of lymphocyte count,prealbumin,albumin,hemoglobin,and transferrin,and reduce complications.This approach should be adopted in the clinic.

OBJECTIVETo assess clinical and pathological features of ovarian transitional cell tumors.

METHODSFourteen cases of ovarian transitional cell carcinoma (TCC) were selected and investigated for their clinical and pathological features. Their immunohistochemical profiles were compared with 12 cases of serous adenocarcinoma (SC) admixed with TCC and 4 cases of EC admixed with TCC 20 cases of pure high-grade serous adenocarcinoma (HG-SC), 15 cases of endometrioid adenocarcinoma (EC), 6 cases of Brenner tumor (BT, 2 cases of malignant BT and 4 cases of benign BT).

RESULTSThe patients' age ranged from 36-63 years (mean, 56 years). All cases underwent surgery and postoperative chemotherapy with TP or CAP program. Clinical follow-up was available in 9 cases, of which 2 patients died. Histologically, all cases showed features of transitional cell carcinoma without BT component. Immunohistochemically, 13 of 14 TCCs were positive for WT-1 and all were positive for CK7, ER, PR and CA125, but negative for Uroplakin III and CK20.Similar immunohistochemical staining patterns were seen in SC admixed with TCC and pure HG-SC. Percentage of the 14 TCC cases were also diffusely positive for BRCA1. All SCs admixed with TCC and pure HG-SCs were diffusely or heterogeneously positive for WT-1, with a sharp contrast and mottled distribution pattern in the heterogeneous cases. All TCCs were diffusely and strongly positive for p53, while 16 of 20 cases of pure HG-SC were positive. The positive ratio of p53 in SCs admixed with TCC cases was 11/12.WT-1 expression in TCCs was significantly higher than BTs, ECs and ECs admixed with TCC (P < 0.01), while no obvious difference was seen when compared with SCs admixed with TCC and pure HG-SCs.SCs admixed with TCC, TCCs and EC were positive for BRCA1 except pure ECs and BTs. The positive rate of Ki-67 of BTs was low, while it was higher in TCCs, SCs admixed with TCC and pure HG-SCs. Only BTs expressed Uroplakin III.

CONCLUSIONSOvarian TCC has characteristic morphological and immunohistochemical features, similar to SC but different from BT. Therefore, TCC should be considered as a morphological variant of HG-SC.

Adult ; Brenner Tumor ; metabolism ; pathology ; CA-125 Antigen ; metabolism ; Carcinoma, Endometrioid ; pathology ; Carcinoma, Transitional Cell ; pathology ; Cystadenocarcinoma, Serous ; pathology ; Female ; Humans ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neoplasms, Glandular and Epithelial ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Uroplakin III ; metabolism

OBJECTIVETo investigate the expression of apoptotic regulator c-FLIP(L) in invasive breast carcinoma tissues, and to evaluate its correlation with molecular subtyping and clinical prognosis.

METHODSImmunohistochemistry using EnVision staining for c-FLIP(L) was performed in 264 cases of invasive breast carcinomas and matched adjacent normal breast tissue samples from January 1996 to December 1999. ER, PR, HER2, Ki-67, CK5/6 and EGFR were evaluated by immunohistochemistry in order to classify the tumors into five molecular subtypes and the difference of c-FLIP(L) expression in these molecular subtypes was also analyzed. The influence of c-FLIP(L) expression on prognosis was evaluated by Kaplan-Meier curves and multi-factor Cox proportional risk model.

RESULTSHigh expression of c-FLIP(L) was observed in 84.5% (223/264) of cases of invasive breast carcinomas which were significantly higher than the 45.1% (119/264) of cases in adjacent normal epithelium of breast (χ² = 89.78, P = 0.000). The expression of c-FLIP(L) in luminal B (HER2 positive) and basal-like breast cancers was 78.1% (25/32) and 46.2% (18/39), respectively, with significant difference (P < 0.05). Moreover, the expression of c-FLIP(L) in luminal B (HER2 positive) was higher than in luminal A cancers (P < 0.05), and the expression of c-FLIP(L) in HER2 positive cancers was higher than in basal-like cancers (P < 0.01). C-FLIP(L) showed deep yellow staining in node positive breast cancer with a high-expression rate of 93.1% (134/144); whereas the expression was sporadic and light yellow in node negative breast cancer with a lower high-expressed rate of 72.5% (87/120, P < 0.01). C-FLIP(L) expression had significant influence on disease-free survival time, with c-FLIP(L)-positive patients showing poor prognosis (P < 0.01). Multi-factor Cox proportional risk model analysis showed that expression of c-FLIP(L), lymph nodes status and molecular subtypes were independent prognostic factors for invasive breast carcinomas (P < 0.05).

CONCLUSIONSC-FLIP(L) is highly expressed in invasive breast carcinomas, and its expression level is closely related to the molecular subtypes and clinical prognosis of breast cancer patients. Thus, c-FLIP(L) could be used as an important tumor marker for personalized cancer therapy and prognostic prediction.

Aged ; Biomarkers, Tumor ; metabolism ; Breast ; metabolism ; Breast Neoplasms ; classification ; metabolism ; mortality ; CASP8 and FADD-Like Apoptosis Regulating Protein ; metabolism ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Prognosis ; Receptor, ErbB-2 ; metabolism

Lycophytes and seed plants constitute the typical vascular plants. Lycophytes have been thought to have no paleo-polyploidization although the event is known to be critical for the fast expansion of seed plants. Here, genomic analyses including the homologous gene dot plot analysis detected multiple paleo-polyploidization events, with one occurring approximately 13-15 million years ago (MYA) and another about 125-142 MYA, during the evolution of the genome of Selaginella moellendorffii, a model lycophyte. In addition, comparative analysis of reconstructed ancestral genomes of lycophytes and angiosperms suggested that lycophytes were affected by more paleo-polyploidization events than seed plants. Results from the present genomic analyses indicate that paleo-polyploidization has contributed to the successful establishment of both lineages-lycophytes and seed plants-of vascular plants.
Evolution, Molecular ; Genome, Plant ; Genomics ; Phylogeny ; Polyploidy ; Selaginellaceae/genetics*

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.