A mobile hemangioblastoma of the cauda equina: Case report and review of the literature

Context: Cases of migratory spinal tumors have been reported since 1963. Most involve spinal schwannomas, which are benign tumors of the lining of nerve cells. We report a rare case of a mobile spinal hemangioblastoma, which is a type of benign vascular tumor.

Findings: A 50-year-old man visited the hospital for painful swelling in his lower back. An MRI scan indicated that a lesion was at the L5 vertebral level. Two weeks later, however, an enhanced MRI showed that the lesion had migrated to the L4 vertebral level. During surgery, the location of the lesion remained consistent with the enhanced MRI reviewed. The histopathological diagnosis was hemangioblastoma.

Conclusion: This is the first known report of a mobile spinal hemangioblastoma. Mobile spinal hemangioblastoma requires careful preoperative and intraoperative evaluation of its real-time location to avoid performing surgery at the wrong vertebral level.     

MIF promoter polymorphism increases peripheral blood expression levels,contributing to increased susceptibility and poor prognosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The etiology and pathogenesis of HCC remain unclear. Macrophage migration inhibitory factor (MIF) plays a critical role in the pathogenesis of hepatocellular carcinoma. The association between MIF polymorphisms and its expression level in HCC has rarely been demonstrated. In the present study, the peripheral blood of 202 patients with HCC (HCC group), 242 patients with chronic hepatitis B (CHB group), 215 patients with liver cirrhosis (LC group) and 227 healthy volunteers (normal group) were collected, DNA was extracted and the target fragment of MIF gene was amplified using PCR. The products were then sequenced, and the expression levels of MIF protein were tested using ELISA. The results showed that the MIF rs755622 polymorphism was associated with an increased susceptibility and metastasis of HCC, and that the genotypes GC and CC were associated with poor prognosis of HCC. Compared with the normal, CHB and LC groups, the expression of MIF in the peripheral blood of the HCC group was significantly increased, and the high expression was associated with to poor prognosis. In the HCC group, MIF protein levels for genotypes GC and CC were increased compared with those of genotype GG. The current study indicated that the MIF rs755622 polymorphism is associated with susceptibility and metastasis of HCC, and that the GC and CC genotypes may be indicators of poor prognosis, which may be ascribed to the MIF rs755622 polymorphism leading to elevated MIF protein expression in peripheral blood.     

High expression levels of centromere protein A plus upregulation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway affect chemotherapy response and prognosis in patients with breast cancer

Centromere proteins (CENPs) are involved in mitosis, and CENP gene expression levels are associated with chemotherapy responses in patients with breast cancer. The present study aimed to examine the roles and underlying mechanisms of the effects of CENP genes on chemotherapy responses and breast cancer prognosis. Using data obtained from the Gene Expression Omnibus (GEO) database, correlation and Cox multivariate regression analyses were used to determine the CENP genes associated with chemotherapy responses and survival in patients with breast cancer. Weighted gene co-expression network and correlation analyses were used to determine the gene modules co-expressed with the identified genes and the differential expression of gene modules associated with the pathological complete response (PCR) and residual disease (RD) subgroups. CENPA, CENPE, CENPF, CENPI, CENPJ and CENPN were associated with a high nuclear grade and low estrogen and progesterone receptor expression levels. In addition, CENPA, CENPB, CENPC and CENPO were independent factors affecting the distant relapse-free survival (DRFS) rates in patients with breast cancer. Patients with high expression levels of CENPA or CENPO exhibited poor prognoses, whereas those with high expression levels of CENPB or CENPC presented with favorable prognoses. For validation between databases, the Cancer Genome Atlas (TCGA) database analysis also revealed that CENPA, CENPB and CENPO exerted similar effects on overall survival. However, according to the multivariate analyses, only CENPA was an independent risk factor associated with DRFS in GEO database. In addition, in the RD subgroup, patients with higher CENPA expression levels had a worse prognosis compared with those with lower CENPA expression levels. Among patients with high expression levels of CENPA, the PI3K/Akt/mTOR pathway was more likely to be activated in the RD compared with the PCR subgroup. The same trend was observed in TCGA data. These results suggested that high CENPA expression levels plus upregulation of the PI3K/Akt/mTOR signaling pathway may affect DRFS in patients with breast cancer.     

A novel mouse model for colitis-associated colon carcinogenesis induced by 1,2-dimethylhydrazine and dextran sulfate sodium

AIM: To develop an efficient animal colitis-associated carcinogenesis model and to detect the expression of β-catenin and p53 in this new model. METHODS: Dysplasia and cancer were investigated in mice pretreated with a single intraperitoneal injection of 20 mg/kg body mass of 1,2-dimethylhydrazine prior to three repetitive oral administrations of 30 g/L dextran sulfate sodium to give conditions similar to the clinically observed active and remission phases. Immunohistochemical staining of β-catenin and p53 was performed on paraffin-imbedded specimens of animals with cancer and/or dysplasia, those without dysplasia and the normal control animals. RESULTS: At wk 11, four early-invasive adenocarcinomas and 36 dysplasia were found in 10 (90.9%) of the 11 mice that underwent 1,2-dimethylhydrazine-pretreatment with 3 cycles of 30 g/L dextran sulfate sodium-exposure. Dysplasia and/or cancer occurred as flat lesions or as dysplasia-associated lesion or mass (DALM) as observed in humans. Colorectal carcinogenesis occurred primarily on the distal portion of the large intestine. No dysplasia and/or cancer lesion was observed in the control groups with 1,2-dimethylhydrazine pretreatment or 3 cycles of 30 g/L dextran sulfate sodium exposure alone. Immunohistochemical investigation revealed that β-catenin was translocated from cell membrane to cytoplasm and/or nucleus in 100% of cases with dysplasia and neoplasm, while normal membrane staining was observed in cases without dysplasia and the normal control animals. Nuclear expression of p53 was not detected in specimens. CONCLUSION: A single dose of procarcinogen followed by induction of chronic ulcerative colitis results in a high incidence of colorectal dysplasia and cancer. Abnormalexpression of β-catenin occurs frequently in dysplasia and cancer. This novel mouse model may provide an excellent vehicle for studying colitis-related colon carcinogenesis.     

Ipsilateral breast metastasis from a pulmonary adenocarcinoma: a case report and a focused review of the literature

Metastases to the breast from extramammary malignancies are extremely rare. Ruling out the diagnosis of primary breast tumor is important in order to decide on clinical management and predict prognosis. We report a case of metastasis to the breast from a pulmonary adenocarcinoma, with extensive micropapillary component, diagnosed concomitantly with the primary tumor. A 52 year-old female patient presented with mammary gland tingling and dyspnea accompanied with fatigued of 4 months duration and a nodular shadows in the front of the upper lobe was found on a chest computed tomography (CT) scan. The original clinical diagnosis was right breast cancer with lung and bone metastasis, or breast and lung double primary cancers. In addition,on physical examination a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent thoracocentesis and breast biopsy. By imageology, cytology, histology and immunohistochemistry, we diagnosed primary lung cancer with metastases to the right breast and bone. The metastatic anatomic sites demonstrated histologically extensive micropapillary component, which is recently recognized as an important prognostic factor. The patient was administered 4 cycles of cisplatin and docetaxel, although no clinical response was seen, the patient is still alive 9 months after diagnosis. The result of immunohistochemistry is a useful supplement in differential diagnosis.     

Knockdown of long noncoding RNA SPRY4-IT1 suppresses glioma cell proliferation,metastasis and epithelial-mesenchymal transition

Long noncoding RNAs (lncRNAs), a class of ribonucleic molecules, participate in various cellular processes. They are highly expressed in several types of cancer and their expression was related to pathophysiological characteristics of tumor growth, therefore, they can be considered as a promising diagnostic tool and a convenient prognostic biomarker. SPRY4-IT1, belonging to a group of intron-retained lncRNAs, was reported to affect tumor development of many types of cancer. However, the expression and the role of SPRY4-IT1 in glioma are still unclear. Therefore, in this study, we examined for the first time the expression and role of SPRY4-IT1 in glioma cells. The results of our study showed that SPRY4-IT1 was up-regulated in human glioma tissues and cell lines. Knockdown of SPRY4-IT1 could inhibit glioma cell growth and migration. Moreover, knockdown of SPRY4-IT1 could inhibit epithelial-mesenchymal transition (EMT) phenotype in glioma cells. Based on these findings, SPRY4-IT1 may be used as a new target for diagnosis and treatment of glioma.     

Berberine Blocks the Relapse of Clostridium difficile Infection in C57BL/6 Mice after Standard Vancomycin Treatment

Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI.     

Development of a new ferulic acid certified reference material for use in clinical chemistry and pharmaceutical analysis

This study compares the results of three certified methods, namely differential scanning calorimetry (DSC), the mass balance (MB) method and coulometric titrimetry (CT), in the purity assessment of ferulic acid certified reference material (CRM). Purity and expanded uncertainty as determined by the three methods were respectively 99.81%, 0.16%; 99.79%, 0.16%; and 99.81%, 0.26% with, in all cases, a coverage factor (k) of 2 (P=95%). The purity results are consistent indicating that the combination of DSC, the MB method and CT provides a confident assessment of the purity of suitable CRMs like ferulic acid.Abbreviations: ASTM, American Society for Testing and Materials; CRM, certified reference material; CT, coulometric titrimetry; DAD, diode-array detector; DSC, differential scanning calorimetry; EDQM, European Directorate for Quality Medicine; GUM, Guide to the Expression of Uncertainty in Measurement; ISO, International Organization for Standardization; MB, mass balance; RM, reference material; SI, International System of Units; WHO, World Health OrganizationKEY WORDS: Differential scanning  calorimetry, Mass balance, Coulometric titrimetry, Certified reference  material, Uncertainty, Ferulic acid     

Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer

HER2 receptor dimerization is a critical step in the HER2 activation process. Here, we demonstrated that heat shock protein gp96 on cell membrane interacts with HER2, facilitates HER2 dimerization and promotes cell proliferation. Cell membrane gp96 levels were observed to correlate with HER2 phosphorylation in primary breast tumors. Finally, we provide evidence that targeting gp96 with a specific monoclonal antibody led to decreased cell growth and increased apoptosis in vitro, and suppression of tumor growth in vivo. Our work represents a new therapeutic strategy for inhibiting HER2 signaling in cancer.