Stem cell genetics research may be critical to our understanding of carcinogenesis, as both stem cells and cancer cells possess the ability to self-renew. Recent discoveries have indicated that the piwi family of genes plays an essential role in stem cell selfrenewal in diverse organisms. The hiwi gene, the human homolog of the piwi family, participates in germ cell proliferation and its overexpression may cause the development of germ cell malignancy, but its expression and function in epithelial solid cancers have not been explored. In the present study, we investigated whether there was an association between hiwi expression and human gastric cancer and its potential mechanism. RT-PCR findings demonstrated that hiwi was expressed in different gastric cancer cell lines. To identify the HIWI protein in gastric cancer, we developed a specific monoclonal antibody against HIWI and immunohistochemistry was performed on various gastric tissues. We found that the expression ratio of hiwi in normal gastric tissues, atrophic gastritis, intestinal metaplasia and gastric cancers was 10% (5/50), 36% (18/50), 36% (18/50) and 76% (38/50), respectively, which was consistent with precancerous development. Notably, the expression pattern of hiwi in gastric cancer tissues was similar to that of Ki67, which was used as a marker of proliferation. Moreover, the suppression of hiwi by antisense or RNAi inhibited the growth of gastric cancer cells and induced cell cycle arrest in G 2 /M phase. These results suggest that hiwi may be involved in the development of gastric cancer and is a potential target for cancer therapy. ' 2005 Wiley-Liss, Inc.Key words: hiwi; expression; gastric cancer; proliferation Although there is a high incidence of gastric cancer in Asia and gastric cancer remains one of the leading causes of cancer-related death worldwide, 1 the molecular mechanisms underlying its development are poorly understood. Stem cell research will greatly expand our understanding of the mechanisms of carcinogenesis because the homeostatic mechanisms mediating stem cell proliferation are the same processes that become dysregulated in carcinogenesis.2,3 Therefore, the study of stem cell genes may be critical to furthering our understanding of carcinogenesis and to the development of novel strategies for preventing and managing cancer. 4 Because of this, there is a growing interest in studying the roles of genes, which were initially found to be involved in stem cell selfrenewal, in the development of cancer. 5-7The hiwi gene is a human member of the piwi family, which represents the first class of genes known to be required for stem cell self-renewal in diverse organisms.8 Recent discoveries have shown that hiwi may participate in germ cell proliferation and its overexpression may cause germ cell malignancy development. 9These findings raise the hypothesis that hiwi may be present in other types of stem cells and likewise may be involved in the development of cancers.The hiwi gene, located in 12q24.33, was originally isolated from a h...

BackgroundExosomes are extracellular vesicles released by almost all cell types, including cancer cells, into bodily fluids such as saliva, plasma, breast milk, semen, urine, cerebrospinal fluid, amniotic fluid, synovial fluid and sputum. Their key function being intercellular communication with both neighbouring as well as distant cells. Cancer exosomes have been shown to regulate organ-specific metastasis. However, little is known about the functional differences and molecular consequences of normal cells responding to exosomes derived from normal cells compared to those derived from cancer cells.MethodsHere, we characterised and compared the transcriptome profiles of primary human normal oral keratinocytes (HNOK) in response to exosomes isolated from either primary HNOK or head and neck squamous cell carcinoma (HNSCC) cell lines.ResultsIn recipient HNOK cells, we found that regardless of normal or cancer derived, exosomes altered molecular programmes involved in matrix modulation (MMP9), cytoskeletal remodelling (TUBB6, FEZ1, CCT6A), viral/dsRNA-induced interferon (OAS1, IFI6), anti-inflammatory (TSC22D3), deubiquitin (OTUD1), lipid metabolism and membrane trafficking (BBOX1, LRP11, RAB6A). Interestingly, cancer exosomes, but not normal exosomes, modulated expression of matrix remodelling (EFEMP1, DDK3, SPARC), cell cycle (EEF2K), membrane remodelling (LAMP2, SRPX), differentiation (SPRR2E), apoptosis (CTSC), transcription/translation (KLF6, PUS7). We have also identified CEP55 as a potential cancer exosomal marker.ConclusionsIn conclusion, both normal and cancer exosomes modulated unique gene expression pathways in normal recipient cells. Cancer cells may exploit exosomes to confer transcriptome reprogramming that leads to cancer-associated pathologies such as angiogenesis, immune evasion/modulation, cell fate alteration and metastasis. Molecular pathways and biomarkers identified in this study may be clinically exploitable for developing novel liquid-biopsy based diagnostics and immunotherapies.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0846-5) contains supplementary material, which is available to authorized users.

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These findings indicate that decreased liver adiponectin expression may play a role in the development and progression of NAFLD, from simple steatosis to NASH, in morbidly obese patients.

Although gastric cancer is the second leading cause of cancer death worldwide, specific and sensitive biomarkers that can be used for its diagnosis are still unavailable. Attempting to improve on current approaches to the serological diagnosis of gastric cancer, we subjected serum samples from 245 individuals (including 127 gastric cancer patients, 100 age-and sex-matched healthy individuals, nine benign gastric lesion patients and nine colorectal cancer patients) for analysis by surface-enhanced laser desorption/ionization (SELDI) mass spectrometry. Peaks were detected with Ciphergen SELDI software version 3.1.1 and analyzed with Biomarker Patterns' software 5.0. We developed a classifier for separating the gastric cancer groups from the healthy groups. Three protein masses with 1468, 3935 and 7560 m/z were selected as a potential 'fingerprint' for the detection of gastric cancer. It was able to distinguish the gastric cancer patients from the health volunteers with a sensitivity of 95.6% and a specificity of 92.0% in the training set. In the blinding set, it was capable of differentiating the gastric cancer samples from the others with a specificity of 88.0%, a sensitivity of 85.3%, and an accuracy of 86.4%. These values were all higher than those achieved in a parallel analysis by measuring serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 together. Therefore, the decision tree analysis of serum proteomic patterns has the potential to be used in gastric cancer diagnosis. (Cancer Sci 2007; 98: 37-43)

Objective: To determine whether adipocyte enhancer binding protein (AEBP) 1, a transcriptional repressor that is down-regulated during adipogenesis, functions as a critical regulator of adipose tissue homeostasis through modulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) tumor suppressor activity and mitogen-activated protein kinase (MAPK) activation. Research Methods and Procedures:We examined whether AEBP1 physically interacts with PTEN in 3T3-L1 cells by coimmunoprecipitation analysis. We generated AEBP1-null mice and examined the physiological role of AEBP1 as a key modulator of in vivo adiposity. Using adipose tissue from wild-type and AEBP1-null animals, we examined whether AEBP1 affects PTEN protein level. Results: AEBP1 interacts with PTEN, and deficiency of AEBP1 increases adipose tissue PTEN mass. AEBP1-null mice have reduced adipose tissue mass and enhanced apoptosis with suppressed survival signal. Primary pre-adipocytes from AEBP1-null adipose tissues exhibit lower basal MAPK activity with defective proliferative potential. AEBP1-null mice are also resistant to diet-induced obesity, suggesting a regulatory role for AEBP1 in energy homeostasis. Discussion: Our results suggest that AEBP1 negatively regulates adipose tissue PTEN levels, in conjunction with its role in proliferation and differentiation of pre-adipocytes, as a key functional role in modulation of in vivo adiposity.

Objective This study aimed to investigate the changes in inflammatory biomarkers between newly diagnosed type 2 diabetes (T2DM) patients under one-year acarbose treatments and those under metformin managements. Methods Seventy patients with newly diagnosed T2DM and 32 volunteers with normal glucose tolerance (normal controls, NCs) were enrolled. Seventy patients with T2DM were randomly assigned to two subgroups and treated with acarbose (n=34) or metformin (n=36) for 1 year. Blood glucose, insulin, glycosylated hemoglobin (A1C), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and inflammatory biomarker levels (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), and ferritin) were detected at 0, 6 and 12 months. Results After adjusting for sex, the waist-to-hip ratio (WHR) and body mass index (BMI), higher fasting plasma glucose (FPG), standard meal test 1/2 hr and 2 hr glucose, TG, TC, LDL-C, IL-6, TNF-α, IL-2 and ferritin levels were observed in T2DM group than in NCs ( P <0.05). After 6 months of treatment, TNF-α levels were significantly decreased in both subgroups, and IL-6 and ferritin levels were significantly decreased after 12 months ( P <0.05). However, no significant differences in the IL-6, TNF-α and ferritin levels were observed between the two subgroups. Moreover, significantly higher IL-6 and TNF-α levels were detected in the T2DM group than in NCs after 12 months of treatment ( P <0.05). Conclusion Patients with newly diagnosed T2DM exhibited a marked chronic inflammatory state characterized by increased IL-6, TNF-α, IL-1β, IL-2 and ferritin levels. After 1 year of treatment with acarbose or metformin, IL-6, TNF-α, IL-1β and ferritin levels were significantly decreased compared with the baseline. The anti-inflammatory effects of acarbose and metformin were comparable and required a long-term treatment (1 year), but the characteristics were different. Further investigations are needed to determine whether this effect was independent of the hypoglycemic effects.

Early diagnosis of congenital heart disease (CHD) can improve the prognosis of neonates with CHD. We retrospectively evaluated the value of prenatal diagnosis of CHD by comparing the pregnancy outcomes. Prenatal diagnosis of CHD was established by echocardiographic evaluation of fetal heart. Amniotic fluid and/or cord blood genetic examination, pathological anatomy, casting specimen, and/ or multidisciplinary-joint consultation (MDJC) were performed. A total of 1492 fetuses with CHD were diagnosed by prenatal echocardiography from 67834 pregnant women. There were 445, 236, 583, and 228 cases in groups A (simple CHD), B (simple CHD plus extra-cardiac abnormality), C (complex CHD), and D (complex CHD plus extra-cardiac abnormality), respectively. The pregnancy continuation rate in the four groups was 98.67%, 85.71%, 67.65%, and 36.84%, respectively (P < 0.001). The pregnancy termination rate for fetal CHD with extra-cardiac abnormalities was significantly higher than that for fetuses with only CHD (81.24% vs. 53.6%, P < 0.05). Prenatal genetic test revealed chromosomal abnormalities in 20.43% of fetuses with CHD. MDJC significantly decreased the pregnancy termination rate. In 88 cases, the original decision to terminate the pregnancy was changed after consultation and the pregnancy was continued. Of these, 87 cases culminated in live births; 65 of these children had better prognosis. Nine-segment sequential segment analysis method for prenatal fetal echocardiography was compared with the results of pathological anatomy, cast specimen, postoperative diagnosis, and postnatal ultrasound. The accuracy of prenatal ultrasound for diagnosis of fetal complex CHD and fetal simple CHD was 90.5-91.66% and 98.6%, respectively. Prenatal ultrasound is still the most effective method for fetal CHD diagnosis. According to the "China Birth Defect Prevention Report (2012)" 1 , congenital heart disease (CHD) is the most common type of birth defect in China accounting for 26.7% of all birth defects in 2011. More than 130,000 new cases of CHD are reported each year in China. Globally, a total of 48.9 million cases of CHD were reported in 2015 2. The reported incidence of CHD varies from 4 to 75 per 1,000 live births depending upon the method of diagnosis. About 0.6 to 1.9% of live born infants with CHD have moderate to severe disease 3. CHD is the leading cause of birth defect-related deaths 4. In 2015, an estimated 303,300 infants died around the world due to CHD 5 .