Influence of gut microbiome on metabolic diseases: a new perspective based on microgravity.

Purpose: Microgravity, characterized by gravity levels of 10-3-10-6g, has been found to significantly impair various physiological systems in astronauts, including cardiovascular function, bone density, and metabolism. With the recent surge in human spaceflight, understanding the impact of microgravity on biological health has become paramount. Methods: A comprehensive literature search was performed using the PubMed database to identify relevant publications pertaining to the interplay between gut microbiome, microgravity, space environment, and metabolic diseases. Results: This comprehensive review primarily focuses on the progress made in investigating the gut microbiome and its association with metabolic diseases under microgravity conditions. Microgravity induces notable alterations in the composition, diversity, and functionality of the gut microbiome. These changes hold direct implications for metabolic disorders such as cardiovascular disease (CVD), bone metabolism disorders, energy metabolism dysregulation, liver dysfunction, and complications during pregnancy. Conclusion: This novel perspective is crucial for preparing for deep space exploration and interstellar migration, where understanding the complex interplay between the gut microbiome and metabolic health becomes indispensable.

Maternal Di-(2-ethylhexyl)-Phthalate exposure during pregnancy altered energy metabolism in immature offspring and caused hyperglycemia.

Di-(2-ethylhexyl)-phthalate (DEHP), as distinctive endocrine disrupting chemicals, has become a global environmental pollutant harmful to human and animal health. However, the impacts on offspring and mothers with maternal DEHP exposure are largely unknown and the mechanism remains elusive. We established DEHP-exposed maternal mice to investigate the impacts on mother and offspring and illustrate the mechanism from multiple perspectives. Pregnant mice were administered with different doses of DEHP, respectively. Metagenomic sequencing used fecal and transcriptome sequencing using placentas and livers from offspring have been performed, respectively. The results of the histopathology perspective demonstrated that DEHP exposure could disrupt the function of islets impact placentas and fetus development for maternal mice, and cause the disorder of glucose and lipid metabolism for immature offspring mice, resulting in hyperglycemia. The results of the metagenome of gut microbial communities indicated that the dysbiosis of gut microbiota in mother and offspring mice and the dominant phyla transformed through vertical transmission. Transcriptome analysis found DEHP exposure induced mutations of Ahcy and Gstp3, which can damage liver cells and affect the metabolism of the host. DEHP exposure harms pregnant mice and offspring by affecting gene expression and altering metabolism. Our results suggested that exposure of pregnant mice to DEHP during pregnancy and lactation increased the risk of metabolic disorders by altering key genes in liver and gut microbiota, and these results provided new insights into the potential long-term harms of DEHP.

Metalloestrogens exposure and risk of gestational diabetes mellitus: Evidence emerging from the systematic review and meta-analysis.

BACKGROUND: Metalloestrogens are metals and metalloid elements with estrogenic activity found everywhere. Their impact on human health is becoming more apparent as human activities increase. OBJECTIVE: Our aim is to conduct a comprehensive systematic review and meta-analysis of observational studies exploring the correlation between metalloestrogens (specifically As, Sb, Cr, Cd, Cu, Se, Hg) and Gestational Diabetes Mellitus (GDM). METHODS: PubMed, Web of Science, and Embase were searched to examine the link between metalloestrogens (As, Sb, Cr, Cd, Cu, Se, and Hg) and GDM until December 2023. Risk estimates were derived using random effects models. Subgroup analyses were conducted based on study countries, exposure sample, exposure assessment method, and detection methods. Sensitivity analyses and adjustments for publication bias were carried out to assess the strength of the findings. RESULTS: Out of the 389 articles identified initially, 350 met our criteria and 33 were included in the meta-analysis, involving 141,175 subjects (9450 cases, 131,725 controls). Arsenic, antimony, and copper exposure exhibited a potential increase in GDM risk to some extent (As: OR = 1.28, 95 % CI [1.08, 1.52]; Sb: OR = 1.73, 95 % CI [1.13, 2.65]; Cu: OR = 1.29, 95 % CI [1.02, 1.63]), although there is a high degree of heterogeneity (As: Q = 52.93, p < 0.05, I2 = 64.1 %; Sb: Q = 31.40, p < 0.05, I2 = 80.9 %; Cu: Q = 21.14, p < 0.05, I2 = 71.6 %). Conversely, selenium, cadmium, chromium, and mercury exposure did not exhibit any association with the risk of GDM in our study. DISCUSSION: Our research indicates that the existence of harmful metalloestrogens in the surroundings has a notable effect on the likelihood of GDM. Hence, we stress the significance of environmental elements in the development of GDM and the pressing need for relevant policies and measures.

Sclerosing extramedullary hematopoietic tumor of the colon: A case report and literature review.

Sclerosing extramedullary hematopoietic tumor (SEMHT) is a rare tumor that can occur in association with some chronic myeloproliferative neoplasms, particularly myelofibrosis. The morphology of SEMHT can mimic that of a wide variety of other lesions, both macroscopically and microscopically. SEMHT originating from the colon is extremely rare. The present study reports a case of SEMHT in the colon with involvement of the peri-intestinal lymph nodes. On the basis of the clinical symptoms and endoscopic results, a malignant tumor of colon was suspected. Pathological examination revealed the deposition of collagen and hematopoietic components in the fibrous mucus background. Immunohistochemical staining for CD61 confirmed the presence of atypical megakaryocytes, while immunohistochemical staining for myeloperoxidase and glycophorin A highlighted the existence of granulocyte and erythrocyte precursors, respectively. These findings combined with a clinical history of myelofibrosis led to the final diagnosis of SEMHT. The presence of atypical megakaryocytes with immature hematopoietic cell morphology and a good understanding of the clinical history of the patient are essential to prevent misdiagnosis. The present case emphasizes the necessity of reviewing previous hematological history and considering clinical findings together with the associated pathological results.

Primary adrenal anastomosing haemangioma.

Not required for Clinical Vignette.

Perianal Paget disease associated with non-invasive colorectal adenoma.

Perianal skin Paget disease (PPD) is an unusual subtype of extramammary Paget disease, which is usually caused by a primary intraepithelial adnexal tumor and secondary spread from colorectal adenocarcinoma. The reports of secondary PPD associated with non-invasive colorectal adenoma are rare. We report a rare case of non-invasive colorectal-adenoma-associated PPD. In this case, the intraepithelial Paget cells of perianal skin manifested with colorectal phenotype by immunohistochemistry, and adjacent adenomas had high-grade intraepithelial neoplasia but not invasion. Although this is a rare manifestation of PPD, understanding this phenomenon is important to prevent overdiagnosis and invasive overtreatment. Clinical management is variable and, therefore, close follow-up examination is necessary.

Mediastinal cavernous angioleiomyoma: A case report and review of literature.

Angioleiomyoma is a type of pericyte tumor with a benign biological behavior. It typically features proliferation of mature perivascular smooth muscle cells around blood vessels. Angioleiomyoma may be categorized into solid, cavernous or venous subtypes. Usually, it occurs in the dermis or subcutaneous tissue, while the rare cavernous subtype is most common in the upper extremities. Only a small number of cases of angioleiomyoma located in the mediastinum have been reported to date. In addition, there are few reports of mediastinal angioleiomyoma described as a cavernous histopathological subtype. The present study reported a case of mediastinal angioleiomyoma presenting as an unusual cavernous histopathological subtype. The histopathological and immunohistochemical features, based on which a diagnosis of cavernous angioleiomyoma was confirmed, were desmin- and smooth muscle actin-positive expression in spindle tumor cells, as well as ETS-related gene (ERG)- and CD31-positive expression in vascular endothelial cells. Cavernous angioleiomyoma of the mediastinum rarely occurs in the clinical setting but should be considered as a differential diagnosis of mediastinal tumors.

Axillary Lymph Node Dissection Can Be Omitted in Breast Cancer Patients With Mastectomy and False-Negative Frozen Section in Sentinel Lymph Node Biopsy.

Background: The IBCSG 23-01 and AMAROS trials both reported that axillary lymph node dissection (ALND) did not change survival rates in breast cancer patients with positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether breast cancer patients with mastectomy and false-negative frozen section (FS) in SLNB could forgo ALND. Materials and Methods: This was a retrospective study of cN0 patients diagnosed with primary invasive breast cancer treated by mastectomy and SLNB at our institute between January 2010 and December 2014. Patients with false-negative FS in SLNB were separated by the following management of axillary lymph node dissection in the non-ALND group (nonprocess or axillary radiation only) and ALND group (with or without radiation). Results: A total of 212 patients were included, 86 and 126 patients in the non-ALND and ALND groups, respectively. The positive rate of non-sentinel lymph nodes (SLNs) was 15.87% (20/126) in the ALND group. In multivariate analysis, we found that patients with larger tumor size (>2 cm) (OR, 1.989; p = 0.030) and multifocal lesions (OR, 3.542; p = 0.029) tended to receive ALND. The positivity of non-SLNs in the ALND group was associated with SLN macrometastasis (OR, 3.551; p = 0.043) and lymphovascular invasion (OR, 6.158; p = 0.003). Also, removing more SLNs (≥3) was related to negativity in non-SLNs (OR, 0.255; p = 0.016). After a median follow-up of 59.43 months, RFS and OS of the two groups were similar (p = 0.994 and 0.441). In subgroup analysis, we found that 97 patients who met the inclusive criteria of the IBCSG 23-01 trial had similar RFS and OS between the non-ALND and ALND groups (p = 0.856 and 0.298). The positive rate of non-SLNs was 9.62% (5/52). Also, in 174 patients who met the criteria of the AMAROS trial, RFS and OS in the non-ALND and ALND groups were similar (p = 0.930 and 0.616). The positive rate of non-SLNs was 18.27% (19/104). Conclusion: ALND can be carefully omitted in selected breast cancer patients with mastectomy and false-negative FS in SLNB. SLNB is relatively sufficient in the IBCSG 23-01-eligible patients, and axillary radiation was an effective option in the AMAROS-eligible patients.

Screening of Breast Cancer Methylation Biomarkers Based on the TCGA Database.

OBJECTIVE: Breast cancer has become a fatal disease for women world-wide. Its incidence in China has been increasing yearly, and the identification of early-stage biomarkers is urgently required. METHODS: ANOVA was carried out in the case of a primary tumor, adjacent normal tissue, and tumor metastasis of breast cancer, and on pan-cancer samples using the genome-wide methylation data of 31 solid tumor Illumina Methylation 450K chips downloaded from The Cancer Genome Atlas (TCGA) website in September 2018. Methylation sites showing a significant difference (P ≤ 0.05) were screened and compared with the whole-genome methylation data of 31 other solid tumor species in the TCGA database using t-tests in order to screen the methylation sites of breast cancer-specific expression. The expression of the screened methylation sites was confirmed through pyrosequencing in 45 cases of breast cancer, lung cancer, gastric cancer, and colorectal cancer. RESULTS: A total of 10 specific breast cancer methylation sites (cg13683194, cg07996594, cg21646032, cg07671949, cg21185686, cg03625109, cg16429070, cg23601468, cg24818566, and cg01240931) were analyzed; nine genes (C9orf125, RARB, ESR1, RUNX3, PCDHGB7, DBC1, PDGFRB, TIMP3, and APC) were involved. The overall effect was excellent; a total of 4 methylation sites (2 in the DBC1 gene [cg03625109 and cg24818566], 1 in the C9orf125 gene [cg13683194], and 1 in the PDGFRB gene [cg16429070]) could effectively distinguish breast cancer from 31 other cancer species. The pyrosequencing results revealed that 7 screened methylation sites could significantly distinguish between breast cancer, lung cancer, gastric cancer, and colorectal cancer samples; these sites could also specifically distinguish between luminal A, luminal B, HER2, and Basal-like types of breast cancer. CONCLUSION: The 10 breast cancer methylation sites screened in the present study can effectively distinguish breast cancer from 31 other solid tumors, and they are expected to be used as biomarkers for early screening of breast cancer.

High expression of USP18 is associated with the growth of colorectal carcinoma.

AIM: To investigate whether USP18 can be used as a predictive marker for the diagnosis and development of colorectal cancer. METHODS: The Gene Expression Omnibus (GEO) Dataset and the Cancer Genome Atlas (TCGA) database were used to select differential proteins for the ubiquitin-specific peptidases (USPs). The extensive target prediction and network analysis methods were used to assess the association with the USP18 interacting proteins, as well as the statistical correlation between USP18 and the clinical pathology parameters. The effects of USP18 on the proliferation of colorectal cancer were examined using CCK8. The effects of USP18 on the migration of colorectal cancer were examined using wound healing assays. Immunohistochemistry (IHC) was performed on the tissue microarray. RESULTS: The results showed that the expression of USP18 was related to age (P=0.014). The positive rates of the USP18 protein in T1, T2, T3, and T4 were 0.00%, 22.92%, 78.38%, and 95.35%, respectively (P<0.00). The positive rates of the USP18 protein in I, II, III, and IV were 47.43%, 83.12%, 66.67%, and 100.00%, respectively (P<0.00). The Western blot assay showed that the expression of USP18 in colorectal cancer tissues was significantly higher than that in matched paracancerous tissues (P<0.05). The CCK8 experiments suggested that USP18 promoted the migration of CRC cells. Wound healing assays suggested that USP18 promoted the proliferation of CRC cells. CONCLUSION: This study showed that USP18 can promote the proliferation of colorectal cancer cells and might be a potential biomarker for the diagnosis of CRC.

Multiple Microinvasion Foci in Ductal Carcinoma In Situ Is Associated With an Increased Risk of Recurrence and Worse Survival Outcome.

BACKGROUND: Ductal carcinoma in situ with microinvasion (DCISM) was defined as one or more foci of invasion beyond the basement membrane within 1 mm. The size of primary lesion is associated with axillary status and prognosis in patients with invasive breast cancer; thus, it is of interest to determine whether multiple foci of microinvasion are associated with a higher risk of positive axillary status or worse long-term outcomes in patients with DCISM. METHODS: This study identified 359 patients with DCISM who had undergone axillary evaluation at our institute from January 2006 to December 2015. Patients were categorized as one focus or multiple foci (≥2 foci) according to the pathological results. Clinicopathological features, axillary status, and disease-free survival rate were obtained and analyzed. RESULTS: Of 359 patients, 233 (64.90%) had one focus of microinvasion and 126 (35.10%) had multiple foci. Overall, 242 (67.41%) and 117 (32.59%) patients underwent sentinel lymph nodes biopsy (SLNB) and axillary lymph nodes dissection (ALND), respectively. Isolated tumor cells were found in four (1.11%) patients and axillary metastasis rate was 2.51%. Neither axillary evaluation methods (P = 0.244) nor axillary metastasis rate (P = 0.559) was significantly different between patients with one focus and multiple foci. In univariate analysis, patients with multiple foci tended to have larger tumor size (P < 0.001), higher nuclear grade (P = 0.001), and higher rate of lymphatic vascular invasion (P = 0.034). Also, the proportion of positive HER2 (P = 0.027) and Ki67 level (P = 0.004) increased in patients with multiple foci, while in multivariate analysis, only tumor size showed significant difference (P = 0.009). Patients with multiple foci were more likely to receive chemotherapy (56.35 vs 40.77%; P = 0.028). At median 5.11 years follow-up, overall survival rate was 99.36%. Patients with multiple microinvasive foci had worse disease-free survival rate compared with one-focus patients (98.29 vs 93.01%, P = 0.032). CONCLUSION: Even though the numbers of microinvasion were different and patients with multiple foci of microinvasion tended to have larger tumor size, there was no higher risk of axillary involvement compared with patients with one focus of microinvasion, while patients with multiple microinvasive foci had worse DFS rate. Thus, DCISM patients with multiple foci of microinvasion may be the criterion for more aggressive local-regional treatment. Optimization of adjuvant therapy in DCISM patients is required.

Evaluation of transient elastography in assessing liver fibrosis in patients with advanced schistosomiasis japonica.

Schistosomiasis remains an important public health issue. The presence and extent of liver fibrosis are associated with disease progression and prognosis. The study is aimed at exploring the value of liver stiffness measurement (LSM) by transient elastography in assessing liver fibrosis in patients with advanced schistosomiasis japonica. Seventy-three patients were consecutively recruited for the purpose of this study. The correlation between noninvasive parameters and histological fibrosis stages was analyzed and an area under receiver operating characteristic curve (AUROC) was used to assess diagnostic efficacy. Our results demonstrated that there are significant differences between LSM values of patients with different stages of fibrosis (F1 vs. F2, F2 vs. F3 and F3 vs. F4, P<0.01). The AUROC values of LSM in detecting significant fibrosis (F≥2), advanced fibrosis (F≥3) and cirrhosis (F=4) were 0.96, 0.90, and 0.92 respectively. The optimal cut-off LSM values were 8.0kPa, 9.5kPa, and 18.0kPa for significant fibrosis, advanced fibrosis and cirrhosis. Based on differences between AUROC values, LSM was proven to be superior to several serum models in detecting advanced fibrosis and cirrhosis. In conclusion, our study demonstrates that LSM is a reliable parameter for assessing risk of liver fibrosis in patients with advanced schistosomiasis japonica.

R-spondin 2 promotes proliferation and migration via the Wnt/ß-catenin pathway in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of malignant disease-associated mortality, particularly in China. The RSPO2 (R-spondin 2) gene is evolutionarily conserved in vertebrates and is involved in developmental and physiological processes. Importantly, RSPO2 has been reported to be associated with colon cancer and potentiate the Wnt/ß-catenin signaling pathway. In the present study, enhanced expression of RSPO2 in HCC was observed using tissue microarray. Similarly, the expression level of RSPO2 was higher in HepG2, Huh7 and Hep3B cells but lower in Bel7404 and QGY7703 cells compared with human normal QSG7701 liver cells. Subsequently, gain-of-function studies indicated that RSPO2 promotes the proliferation and migration of QGY7703 cells based on lentivirus-based gene delivery. Furthermore, it was revealed that p21 and leptin, rather than vascular endothelial growth factor-A, are involved in the function of RSPO2 in QGY7703 cells. Particularly, the signal transducer and activator of transcription 3 (STAT3) and Wnt/ß-catenin signaling pathways are involved in this process. Overexpression of RSPO2 resulted in the elevated expression of phosphorylated STAT3, ß-catenin and c-Myc. Therefore, the present study is beneficial to the understanding of RSPO2-involved liver cancer transformation and drug discovery.

RSPOs facilitated HSC activation and promoted hepatic fibrogenesis.

Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear ß-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway.

MiR-340 suppresses cell migration and invasion by targeting MYO10 in breast cancer.

Breast cancer is one of the most common malignant tumors among females, and can seriously affect the physical and mental health and even threaten the lives of women. Recently, research has demonstrated that microRNAs (miRNAs), as a new method of regulation, have been shown to have oncogenic and tumor­suppressive functions in human breast cancer. Detection of their expression may lead to the identification of novel markers for breast cancer. In the present study, we firstly detected miR­340 expression and found lower expression of miR­340 in 6 human breast cancer cell lines by using RT­qPCR. Then by using wound healing assay and Transwell migration and invasion experiments, we focused on the role of miR-340 in the regulation of tumor cell migration and invasion, exploring the relationship between them. The results revealed that induction of miR­340 expression was able to suppress tumor cell migration and invasion, whereas knockdown of miR­340 expression promoted breast cancer cell migration and invasion. At the gene level, MYO10 (myosin X), as a direct miR­340 target gene, mediated the cell migration and invasion. Finally, we verified our research further at the tissue specimen level and in animal experiments. In brief, miR­340 plays an important role in breast cancer progression. Thus, miR­340 may be further explored as a novel biomarker for breast cancer metastasis and prognosis, and potentially a therapeutic target.

The Association of Serum IL-33 and sST2 with Breast Cancer.

Breast cancer is one of the most common malignant diseases in women. The main cause of death from breast cancer is its metastases at distant sites in the body. Interleukin-33 (IL-33) is a cytokine of the IL-1 family and found overexpressed in various cancers. The aim of the present study was to explore the association of serum IL-33 and sST2 with breast cancer. Here, the serum levels of Interleukin-33 (IL-33) and sST2 were found significantly higher in breast cancer patients than in healthy volunteers. Serum levels of vascular endothelial growth factor (VEGF), metalloproteinase-11 (MMP-11), and platelet-derived growth factor-C (PDGF-C) were also greater in breast cancer patients compared to healthy volunteers. We found that serum levels of IL-33 or sST2 were positively correlated with the serum levels of VEGF, MMP-11, and PDGF-C. Moreover, breast cancer dataset downloaded from The Cancer Genome Atlas showed that patients with higher level of MMP-11 or PDGF-C expression had shorter survival time than those with lower level of these proteins. In conclusion, IL-33 and sST2 may serve as noninvasive diagnosis markers for breast cancer. IL-33 and sST2 were significantly associated with MMP-11 or PDGF-C which indicated poor prognosis of breast cancer patients.

[Role of R-Spondin1 in the activation of hepatic stellate cells].

OBJECTIVE: To investigate the role of R-Spondinl in the activation of hepatic stellate cells (HSCs). METHODS: Twenty-four healthy male Kunming mice were randomly divided into the following two groups:fibrosis model group (n=16) and control group (n=8). Hepatic fibrosis was induced by subcutaneous injections of CC14 (20% in olive oil) at a dose of 5 ml/kg twice per week. After 10 weeks, the animals were sacrificed by CO(2) over-exposure and liver tissues were harvested.The protein and mRNA levels of R-Spondin1, alphat-SMA,and collagen I were examined by Western blot assay and real-time PCR respectively. Additionally,HSCs were isolated from the mice liver tissues to examine the time-series expression changes of R-Spondinl, alpha-SMA, and nuclear beta-catenin.TCF activity was analyzed by luciferase reporter assay.Moreover,HSCs were cocultured with recombinant R-Spondin1 and DKK1 to evaluate dose-response. RESULTS: R-Spondinl expression was significantly higher in the fibrosis model group than in the control group (protein level:3.16 ± 0.18 vs. 0.99 ± 0.16, t =13.31, P < 0.01; mRNA level:4.36 ± 0.26 vs. 0.98 ± 0.12, t =21.46, P < 0.01).The culture-activated mouse HSCs showed up-regulated TCF activity (5.33 ± 0.34 vs. non-activated: 1.03 ± 0.09, t =20.93, P < 0.01), nuclear beta-catenin expression (4.47 ± 0.21 vs. 0.97 ± 0.14, t =25.25, P < 0.01), and R-Spondin1 expression (protein level: 4.54 ± 0.18 vs. 1.04 ± 0.12, t =31.17, P < 0.01; mRNA level:5.13 ± 0.15 vs. 1.01 ± 0.16, t=38.06, P < 0.01). Exogenous stimulation of freshly isolated mouse HSCs with recombinant R-Spondin1 induced a dose-dependent increase in both TCF activity and the expression of nuclear beta-catenin and alphat-SMA. DKK1 down-regulated activities of factors in the WNT signaling pathway and repressed activation of HSCs. Conclusion R-Spondin1 may promote HSC activation by enhancing the canonical WNT signaling pathway.

SCYL1BP1 has tumor-suppressive functions in human lung squamous carcinoma cells by regulating degradation of MDM2.

SCY1-like 1-binding protein 1 (SCYL1BP1) is a newly identified transcriptional activator domain containing protein with many unknown biological functions. Recently emerging evidence has revealed that it is a novel regulator of the p53 pathway, which is very important for the development of human cancer. However, the effects of SCYL1BP1 on human lung squamous carcinoma cell biological behavior remain poorly understood. In this study, we present evidence that SCYL1BP1 can promote the degradation of MDM2 protein and further inhibit the G1/S transition of lung squamous carcinoma cell lines. Functional assays found that reintroduction of SCYL1BP1 into lung squamous carcinoma cell lines significantly inhibited cell proliferation, migration, invasion and tumor formation in nude mice, suggesting strong tumor suppressive function of SCYL1BP1 in lung squamous carcinoma. Taken together, our data suggest that the interaction of SCYL1BP1/MDM2 could accelerate MDM2 degradation, and may function as an important tumor suppressor in lung squamous carcinomas.

[Expression and significance of c-Jun activation domain binding protein 1 in human colorectal carcinoma].

OBJECTIVE: To explore the association of Jab1 (c-Jun activation domain binding protein 1) expression during carcinogenesis and clinicopathological characteristics of colorectal carcinoma (CRC) . METHODS: Tissue specimens were obtained from 80 cases of CRC from January 2007 to December 2008. And the expression of Jab1 protein for each specimen was detected by immunohistochemistry (EnVision). Six representative paired samples of cancerous and paired adjacent normal tissues were collected for Western blot. The relationships between the expression level of Jab1 protein and the clinicopathological characteristics of primary CRC were retrospectively analyzed. RESULTS: A high-level expression of Jab1 was present in cancerous tissues but not in paired adjacent normal tissues. The positive expression rate of Jab1 protein was as high as 96.3% (77/80) . And its high expression rate was 82.5% (66/80) , low expression rate 17.5% (14/80) and 8.8% (7/80) in cancerous and paired adjacent normal tissues respectively (P < 0.05) . Its expression was correlated with differentiation, invasion depth, TNM stage and lymph node metastasis (all P < 0.05) . Jab1 was significantly correlated with Ki-67 (r = 0.548, P < 0.01) and inversely with p27(kip1) (r = -0.461, P < 0.01). CONCLUSIONS: An over-expression of Jab1 protein might play an important role in the pathogenesis of CRC. Thus it may become a novel diagnostic marker and a therapeutic target in patients with CRC.