CD147-CD98hc Complex Contributes to Poor Prognosis of Non-Small Cell Lung Cancer Patients Through Promoting Cell Proliferation Via the PI3K/Akt Signaling Pathway

Background

It has been reported that CD147 and CD98 heavy chain (CD98hc) form a complex on the cell plasma membrane of several cancers; however, whether this complex exists in non-small cell lung cancer (NSCLC) cells and affects the prognosis of patients remains to be elucidated.

Methods

The expression of CD147 and CD98hc was assessed in tissue samples from 241 NSCLC patients and NSCLC cell lines. The correlation between CD147 and CD98hc expression and their association with the prognosis of NSCLC patients were analyzed. We also evaluated the impact of CD147 and CD98hc on the growth of NSCLC cells as well as Akt phosphorylation.

Results

Both CD147 and CD98hc were significantly upregulated in NSCLC cells, and their expression levels were significantly correlated (p < 0.001). Immunoflurenece staining and co-immunoprecipitation demonstrated that CD147 and CD98hc could form a complex on NSCLC cells. Compared with NSCLC patients with CD147?/CD98hc?, those with CD147+/CD98hc+ exhibited a significantly poor overall survival (OS) with a hazard ratio (HR) of 1.92 (p = 0.010), and a significantly increased risk of recurrence with a HR of 1.97 (p = 0.004). Also, we demonstrated that the proliferation of lung cancer cell lines was significantly affected by knockdown and force-expression of the CD147-CD98hc complex. Western blot analysis indicated that the phosphorylation of Akt in NSCLC cells was significantly affected by knockdown and overexpression of either or both CD147 and CD98hc.

Conclusions

Our findings indicate that the CD147-CD98hc complex significantly contributes to poor prognosis of NSCLC patients through promoting cell proliferation via the PI3K/Akt pathway.     

彩色多普勒血流成像诊断犬肾移植急性排斥反应

采用彩色多普勒血流成像，以肾动脉阻力指数（ＲＩＮ）为参数，对犬肾移植动物模型的急性排斥反应进行检测。结果显示：肾功能稳定组，ＲＩ值降低；排斥组，ＲＩ值升高，两组相比较有显著性差异（Ｐ＜０．０１）。５例急性血管型排斥反应，ＲＩ值均大于０．８，敏感性为１００％，特异性６６．７％；６例急性细胞型排斥反应，４例ＲＩ值大于０．８，敏感性为６６．７％，特异性为５４．５％。提示彩色多普勒血流成像成为诊断肾移植急     

A novel reference coordinate system to locate the inferomedial point of the transverse-sigmoid sinus junction

Background

A coordinate system was previously developed to identify landmarks on the skull surface to help locate the transverse-sigmoid sinus junction in order to reduce surgical morbidity in retrosigmoid craniotomy; however, in practice we found that this system has important flaws.

Objective

To develop and evaluate a novel reference coordinate system to precisely locate the inferomedial point of the transverse-sigmoid sinus junction (IMTS) and evaluate the effect of gender and skull side (left or right).

Methods

Forty-two adult skulls (84 sides) were obtained for analyses. The X-axis was defined by point A (where the upper edge of the zygomatic arch joins with the frontal process of the zygomatic bone) and point B (where the upper edge of the zygomatic arch blends posterosuperiorly into the supramastoid crest). The Y-axis was defined by the line perpendicular to the X-axis and extending across the tip of the mastoid. The x and y coordinates of IMTS (IMTS-x and IMTS-y) were measured in this coordinate system.

Results

There were 20 male skulls and 22 female skulls. The mean IMTS-x measurements were significantly higher on the right side compared with the left side in both males and females. For the left skull side, the mean IMTS-y measurements were significantly lower in females compared with males.

Conclusion

This novel reference coordinate system may be a reliable and practical method for identifying the IMTS during retrosigmoid craniotomy. There are significant differences in location of the axes with regard to gender and skull side.     

Clinical features and surgical outcomes of intramedullary schwannomas

Object

Intramedullary schwannomas are exceedingly rare. Most previous studies are case reports with an associated literature review. The aim of this study was to discuss the clinical features and the outcomes of microsurgery for these rare lesions.

Methods

The authors retrospectively reviewed the data of twenty patients with intramedullary schwannomas. All patients had performed preoperative and postoperative magnetic resonance imaging (MRI) and underwent microsurgery. The diagnosis of intramedullary schwannomas was based on radiological and pathological criteria. Modified McCormick classification was applied to assess neurological function.

Results

There were 15 males and five females with a mean age of 44.7 years. Ten tumors were located in the cervical cord, five in the thoracic cord, two in the cervicothoracic cord, two in the thoracolumbar cord and one in the conus medullaris. Patients presented with nonspecific symptoms and the mean duration of symptoms was 37.4 months. Intraoperatively, the tumor was connected to the dorsal rootlet in four cases. Gross total resection (GTR) of the tumor with a well-demarcated dissection plane was achieved in 16 cases, and subtotal resection (STR) was achieved in four cases. No patients received postoperative radiotherapy. During a mean follow-up period of 67.9 months, no recurrence or regrowth of the residual tumors was observed on MRI. Ninety percent of patients experienced an improvement in the McCormick grade and 10 % of patients maintained their preoperative status.

Conclusions

Intramedullary schwannomas are benign but clinically progressive lesions. The accurate diagnosis depends on pathology. For symptomatic patients, early surgery should be performed before neurological deficits deteriorate. When GTR cannot be achieved, STR of the tumor for decompression is advised. Postoperative radiotherapy is not recommended for these benign tumors. A good clinical outcome after GTR or STR can be expected.     

Mitogen-Activated Protein Kinase Phosphatase 3 (MKP-3)–Deficient Mice Are Resistant to Diet-Induced Obesity

Mitogen-activated protein kinase phosphatase 3 (MKP-3) is a negative regulator of extracellular signal–related kinase signaling. Our laboratory recently demonstrated that MKP-3 plays an important role in obesity-related hyperglycemia by promoting hepatic glucose output. This study shows that MKP-3 deficiency attenuates body weight gain induced by a high-fat diet (HFD) and protects mice from developing obesity-related hepatosteatosis. Triglyceride (TG) contents are dramatically decreased in the liver of MKP-3^−/− mice fed an HFD compared with wild-type (WT) controls. The absence of MKP-3 also reduces adiposity, possibly by repressing adipocyte differentiation. In addition, MKP-3^−/− mice display increased energy expenditure, enhanced peripheral glucose disposal, and improved systemic insulin sensitivity. We performed global phosphoproteomic studies to search for downstream mediators of MKP-3 action in liver lipid metabolism. Our results revealed that MKP-3 deficiency increases the phosphorylation of histone deacetylase (HDAC) 1 on serine 393 by 3.3-fold and HDAC2 on serine 394 by 2.33-fold. Activities of HDAC1 and 2 are increased in the livers of MKP-3^−/− mice fed an HFD. Reduction of HDAC1/2 activities is sufficient to restore TG content of MKP-3^−/− primary hepatocytes to a level similar to that in WT cells.     

Long-Term Outcomes of Laparoscopic Splenectomy Versus Open Splenectomy for Idiopathic Thrombocytopenic Purpura

The long-term outcomes of laparoscopic splenectomy (LS) versus open splenectomy (OS) in patients with idiopathic thrombocytopenic purpura (ITP) are not known. A retrospective analysis of 73 patients who underwent splenectomy (32 LS and 41 OS) for refractory ITP between April 2003 and June 2012 was conducted. LS was associated with shorter hospital stay (P = 0.01), less blood loss and blood transfusion during surgery, quicker resumption of oral diet (P < 0.0001), and earlier drain removal (P < 0.01). Conversion to OS was required in 4 patients (12.5%). Operation time was significantly longer in LS (P < 0.0001). Deep venous thrombosis (DVT) was observed in 1 patient after LS and in 4 patients after OS (P = 0.52). One patient died from intraperitoneal bleeding after OS, another patient developed pulmonary embolism. Median follow-up of 36 months was performed in LS group (29 of 32, 91%) and of 46 months in OS group (35 of 41, 85%), 25 patients (86%) in LS group and 32 (91%) in OS group reached sustained complete response (P = 0.792). Kaplan-Meier analysis showed that there was no significant difference in the relapse-free survival rate between the groups (P = 0.777). In conclusion, the long-term outcome of laparoscopic splenectomy is not different from that of open splenectomy for patients with ITP.Key words: Idiopathic thrombocytopenic purpura, Splenectomy, Laparoscopy, Postsplenic complications, Relapse-free survival rateIdiopathic thrombocytopenic purpura (ITP) is related to increased platelet destruction along with reduced platelet production via the specific autoantibodies and may cause a potentially life-threatening hemorrhage. Most ITP can be managed medically, yet some patients are refractory to medical agents such as prednisone, or anti-D globulin therapy,¹ and require splenectomy. Splenectomy can be performed as open splenectomy (OS) or laparoscopic splenectomy (LS).^1,2In the past decade, LS has rapidly become recognized as the gold standard for the management of nontraumatic splenic disorders, such as ITP, thrombotic thrombocytopenic purpura, and hemolytic anemia purpuras.^1–3 Systematic review studies have demonstrated a complete response or durable remission following splenectomy in 66% of adult patients with ITP.⁴ Several retrospective studies have compared the outcomes of OS and LS^1,5–7 and have shown comparable perioperative results, and the recent guidelines of the American Society of Hematology for ITP suggested that a similar efficacy is achieved with both LS and OS, the long-term efficacy of LS for this disorder is uncertain. Therefore, we have retrospectively studied 32 consecutive LS (LS group) and compared them with a historical control group of 41 consecutive OS (OS group) performed for ITP in order to compare the outcomes of LS with OS for ITP.     

骨母细胞性肿瘤的免疫组织化学研究

选择３２例骨母细胞性肿瘤，包括１４例良性骨母细胞瘤、２例侵袭性骨母细胞瘤和１６例骨母细胞型骨肉瘤，用ＡＢＣ法作多种抗血清标记（ｖｉｍｅｎｔｉｎ、Ｓ－１００、α－ＡＴ、ｌｙｓｏｚｙｍｅ、Ｌｅｕ－７、Ｋ１２和ＣＥＡ）。结果显示：３２例肿瘤性骨母细胞ｖｉｍｅｎｔｉｎ均呈不同程度的阳性反应；在６例骨母细胞型骨肉瘤和１例侵袭性骨母细胞瘤中散在的单个细胞Ｓ－１００蛋白呈阳性反应，表明肿瘤性的骨母细胞具有软骨分化的潜能１２４例肿瘤中的多核巨细胞α－ＡＴ和１５例肿瘤中的多核巨细胞ｌｙｓｏｚｙｍｅ均呈不同程度的阳性反应，进一步证实这些细胞可能是组织细胞起源；６例骨母细胞型骨肉瘤和４例良性骨母细胞瘤中的骨样基质Ｌｅｕ－７呈阳性反应。